PLYMOUTH MEETING, Pa., March 18, 2025 /PRNewswire/ -- INOVIO (NASDAQ: INO) a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases today announced its financial results and operational highlights for the fourth quarter and full year ended December 31 2024 and provided a business update and description of operational highlights during the year "INOVIO's recent progress puts us on the cusp of achieving several long-term goals for our DNA medicines most importantly the submission of our first BLA and potential transition to a commercial-stage company," said Dr INOVIO's President and Chief Executive Officer "By resolving the previously announced device array component issue we are back on track to submitting our first BLA for INO-3107 to the FDA We anticipate starting our submission in mid-2025 with non-device related modules under the agency's rolling submission program with the goal of having the complete submission accepted for priority review before the end of the year We continue to believe that INO-3107 has the potential to be the preferred product candidate offering durable clinical benefit tolerability and a patient-centric dosing regimen and are moving forward with urgency."   "While delivering INO-3107 to patients remains our primary focus we are extremely pleased with recently announced data from a proof-of-concept trial with our DMAb technology that showed durable in vivo antibody production DMAbs represent a potential breakthrough as they have the ability to overcome traditional monoclonal antibody production challenges such as short half-life and anti-drug immune responses They have the potential to transform treatments for infectious diseases as well as cancer and metabolic disorders by enabling long-term production of therapeutic antibodies and other proteins our DNA-based approach has demonstrated sustained antibody production without generating anti-drug antibodies making it a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery We look forward to continuing to advance this technology and other promising pipeline candidates through collaborations and other potential strategic opportunities." INO-3107 – Recurrent Respiratory Papillomatosis (RRP) INO-3112 - Oropharyngeal Squamous Cell Carcinoma (OPSCC) INOVIO's balance sheet and statement of operations are provided below. Additional information is included in INOVIO's annual report on Form 10-K for the year ended December 31, 2024, which can be accessed at: http://ir.inovio.com/financials/default.aspx Cash GuidanceINOVIO estimates its current cash cash equivalents and short-term investments balances to support the company's operations into the first quarter of 2026 This projection includes an operational net cash burn estimate of approximately $27 million for the first quarter of 2025 These cash runway projections do not include any further capital-raising activities that INOVIO may undertake.  About INOVIO's DNA Medicines PlatformINOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids delivered by INOVIO's proprietary investigational medical device INOVIO uses proprietary technology to design its DNA plasmids which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms Forward-Looking StatementsThis press release contains certain forward-looking statements relating to our business including the planned initiation and conduct of pre-clinical studies and clinical trials and the availability and timing of data from those studies and trials the completion of the FDA-required device verification testing  the planned submission of a BLA in mid-2025 and request for priority review and goal of FDA's acceptance of the submission by the end of 2025 the potential commercial launch of INO-3107 if regulatory approval is obtained the potential benefits of our product candidates and the expected sufficiency of our cash resources into the first quarter of 2026 Actual events or results may differ from the expectations set forth herein as a result of a number of factors including uncertainties inherent in pre-clinical studies product development programs and commercialization activities and outcomes the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines our ability to support our pipeline of DNA medicine products the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute assessments of our technology by potential corporate or other partners or collaborators the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31 2024 and other filings we make from time to time with the Securities and Exchange Commission There can be no assurance that any product candidate in our pipeline will be successfully developed that the results of clinical trials will be supportive of regulatory approvals required to market products or that any of the forward-looking information provided herein will be proven accurate Forward-looking statements speak only as of the date of this release and we undertake no obligation to update or revise these statements ContactsMedia: Jennie Willson, (267) 429-8567, [email protected]Investors: Peter Vozzo, ICR Healthcare, 443-213-0505, [email protected]  Accounts receivable from affiliated entities Accounts payable and accrued expenses due to affiliated entities Preferred stock—par value $0.001; Authorized shares: 10,000,000 issued and outstanding shares: 9 at December 31 Common stock—par value $0.001; Authorized shares: 600,000,000 at December 31 issued and outstanding: 36,099,991 at December 31 Total liabilities and stockholders' equity Revenue from collaborative arrangements and other contracts Change in fair value of common stock warrant liability (Loss) gain on investment in affiliated entity Net unrealized gain on available-for-sale equity securities       Basic and diluted Weighted average number of common shares outstanding       Basic and diluted  a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from.. Pharmaceuticals Health Care & Hospitals Medical Pharmaceuticals Biotechnology Do not sell or share my personal information: a biotechnology company developing DNA medicines has announced its participation in several major scientific and investor conferences in May 2025 The company will present at the Citizens JMP Life Sciences Conference in New York through a fireside chat on May 8 INOVIO will showcase new data about their lead candidate INO-3107 at multiple venues Abstracts will be available on INOVIO's website after presentations with the JMP conference webcast replay accessible for 90 days un'azienda biotecnologica specializzata nello sviluppo di farmaci a base di DNA ha annunciato la sua partecipazione a importanti conferenze scientifiche e per investitori nel maggio 2025 L'azienda presenterà al Citizens JMP Life Sciences Conference di New York con una chiacchierata informale l'8 maggio INOVIO presenterà nuovi dati sul suo candidato principale INO-3107 in diverse sedi Gli abstract saranno disponibili sul sito web di INOVIO dopo le presentazioni mentre la replica in webcast della conferenza JMP sarà accessibile per 90 giorni una empresa biotecnológica que desarrolla medicamentos de ADN ha anunciado su participación en varias conferencias científicas y de inversores importantes en mayo de 2025 La compañía presentará en la Citizens JMP Life Sciences Conference en Nueva York mediante una charla informal el 8 de mayo INOVIO mostrará nuevos datos sobre su candidato principal INO-3107 en múltiples eventos Los resúmenes estarán disponibles en el sitio web de INOVIO después de las presentaciones y la repetición en webcast de la conferencia JMP estará accesible durante 90 días 2025년 5월에 열리는 주요 과학 및 투자자 컨퍼런스에 참가한다고 발표했습니다 회사는 5월 8일 뉴욕에서 개최되는 Citizens JMP Life Sciences Conference에서 파이어사이드 채팅 형식으로 발표할 예정입니다 특히 INOVIO는 주력 후보물질 INO-3107에 대한 새로운 데이터를 여러 행사에서 선보입니다 une entreprise de biotechnologie développant des médicaments à base d'ADN a annoncé sa participation à plusieurs grandes conférences scientifiques et investisseurs en mai 2025 La société présentera lors de la Citizens JMP Life Sciences Conference à New York à travers une discussion informelle le 8 mai INOVIO mettra en avant de nouvelles données concernant son candidat principal INO-3107 lors de plusieurs événements Les résumés seront disponibles sur le site web d'INOVIO après les présentations la rediffusion du webinaire de la conférence JMP étant accessible pendant 90 jours hat seine Teilnahme an mehreren bedeutenden wissenschaftlichen und Investorenkonferenzen im Mai 2025 angekündigt Mai auf der Citizens JMP Life Sciences Conference in New York in einem Fireside-Chat präsentieren dass INOVIO neue Daten zu ihrem führenden Kandidaten INO-3107 an mehreren Veranstaltungsorten vorstellen wird Abstracts werden nach den Präsentationen auf der INOVIO-Website verfügbar sein und die Webcast-Wiedergabe der JMP-Konferenz ist für 90 Tage zugänglich today announced that it will be presenting at several upcoming conferences including a fireside chat at the Citizens JMP Life Sciences Conference in New York INOVIO will also present for the first time data on the long-term clinical effect of lead candidate INO-3107 at the American Broncho-Esophagological Association (ABEA) program at the Combined Otolaryngology Spring Meetings (COSM) the largest meeting of otolaryngologists in the U.S Citizens JMP Life Sciences Conference (NY)Date: May 8Time: 11:30am EDTFormat: Fireside Chat(audio webcast available here: https://wsw.com/webcast/jmp65/ino/1544620) European Laryngological Society Annual Congress (Warsaw PL)Date: May 9Oral presentation: DNA immunotherapy generates targeted immunologic response and results in surgery reduction for 81% of adults with recurrent respiratory papillomatosis in year 1 American Society of Gene and Cell Therapy (New Orleans LA)Date: May 13Poster Abstract Session: Successful Treatment of Recurrent Respiratory Papillomatosis with INO-3107 is Irrespective of Papilloma Microenvironment and Molecular Subtype LA)Date: May 15Oral Presentation: DNA Immunotherapy (INO-3107) Durability and Long-Term Clinical Effect in Treatment of Recurrent Respiratory Papillomatosis Caused by HPV 6 & 11 Available abstracts will be shared on INOVIO's website following presentations An audio replay of the Citizens JMP webcast will be available for 90 days after the event About INOVIOINOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com ContactsMedia: Jennie Willson, (267) 429-8567, communications@inovio.com Investors: Peter Vozzo - ICR Healthcare, (443) 213-0505, investor.relations@inovio.com View original content to download multimedia:https://www.prnewswire.com/news-releases/inovio-to-present-at-upcoming-scientific-and-investor-conferences-302442322.html Already have an account? Login Chart for Inovalis Real Estate Investment Trust (INO.UN:CA) Providing the latest insights and updates for stock traders across Canada Metrics details Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV) DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11 was evaluated in a 52-week Phase 1/2 study for efficacy Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation The primary endpoint was safety and tolerability as assessed by treatment-emergent adverse events (TEAEs) Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction RNA sequencing identified an inflammatory response in papillomas inclusive of cytolytic CD8 + T-cell signatures T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response INO-3107 is a DNA immunotherapy encoding for antigens from both HPV-6 and HPV-11 as well as encoding for an interleukin-12 (IL-12) immune adjuvant we report full study results from a DNA-based therapy in development for RRP from a completed Phase 1/2 trial demonstrating the safety 50.0%) patients were infected with HPV-6 only 6.3%) were co-infected with both HPV-6 and HPV-11 12.5%) patients’ genotypes could not be distinguished between HPV-6 and HPV-11 per assay standards at Screening but were known from prior diagnostic history to be HPV-6 and/or HPV-11 positive which was subsequently confirmed through on-study assessment All patients in the trial had complete follow-ups for efficacy and safety data A Waterfall plot indicating a change in the frequency of clinically indicated surgical interventions during the year of study as compared with the year before Change in the number of interventions is indicated for each individual patient Complete responders (CR) are labeled dark blue partial responders (PR) are labeled light blue and patients who exhibited a decrease in surgical intervention but contributed only to the calculation of overall clinical response (OCR) are green Non-responders are labeled gray (increase in surgery) or with 0 (no change) B Top left panel: Airway pictures taken before treatment with INO-3107 or after the completion of treatment The top row is a complete responder before treatment and at Week 52 the middle and bottom rows are partial responders taken before treatment and Week 26 Top right panel: Bar graphs indicating efficacy breakouts for patients infected with HPV-6 Complete (dark blue) and partial response (light blue) are separated within the overall response rate (ORR) stack for clarity OCR (all patients exhibiting a decrease in surgical frequency of any magnitude in green) is graphed separately to allow for comparison Bottom panel: Responses are also broken out in tabular fashion When comparing the median number of surgeries in the year prior to treatment with the year following Day 0 patients had a median of four surgeries (range 2–8) there was a median decrease of three surgeries with a 95% confidence interval of 2 to 3 which indicates a statistically significant decrease Treatment with INO-3107 resulted in reductions in RRP Severity Score (modified) from pretreatment through the treatment assessment period as assessed by laryngoscopy throughout the trial Anatomical disease severity was measured by a modified Derkay Score Scores were obtained prior to surgery at or near Day 0 and again at each visit when laryngoscopy was performed there was a mean change in total site score of −10.7 (95% CI −16.3 −5.0) and a mean change in total symptom score of −0.4 (95% CI −0.7 The mean change in total clinical score (total site and total symptom score) was −11.0 (95% CI −16.7 Grade 3 TEAEs were observed in four (4) patients (12.5%) Serious adverse events (SAE) were observed in three (3) patients (9.4%) none of which were considered treatment-related No patient experienced a Grade 4 or 5 TEAE or TEAE leading to treatment discontinuation or death A Interferon-gamma ELISpot T-cell response displayed as peak log2 fold change above pretreatment responses against the HPV-6 (open black circles) and HPV-11 (open black squares) components for N = 32 patients Box and whiskers extend from 25th–75th percentile and minima to maxima B Top left panel: Representative staining of markers assessed for lytic granule loading (LGL) in HPV-specific multiparametric flow cytometry of CD8 + T-cells Percentile of indicated cell populations are noted in each quadrant Top right panel: peak frequency (%) of HPV-specific cytotoxic CD8 + T-cells (CTLs) above pretreatment responses as determined by flow cytometry and observed for N = 32 study patients Values at zero represent true zero values as well as negative values normalized to zero based on Y axis description Bottom left panel: Peripheral T-cell profiling employing uniform manifold approximation and projection (UMAP) on all CD8 + T-cells and with activation as determined by flow cytometry at Week 26 for n = 29 patients; no Week 26 data available for three patients Bottom right panel: Heatmap of HPV-specific peak changes (Δ) in frequencies (%) of indicated parameters of CD8 + T-cells grouped by clinical response Infecting strain(s) of HPV noted in papilloma tissue are also indicated for n = 31 patients; one outlier is absent for improved visualization C Left panel: Longitudinal frequency (%) of significantly expanded T-cell clonal populations as defined by CloneTrack for n = 27 patients each represented by an open black diamond at any timepoint Data were normalized to Screening (pretreatment) to specifically visualize on-study clonal expansion Line denotes point-to-point geometric mean Right panel: Absolute number of unique significantly expanded clonal populations observed during the study on a per-patient basis for n = 27 patients D Tracking of CDR3 clonotypes longitudinally across the study via Immunarch E Break out of peripheral T-cell response frequencies by assay and in aggregate indicating engagement of peripheral T-cell clonal populations after treatment with INO-3107 Aggregate assessment of ELISpot, flow cytometry and significant T-cell clonal expansion data determined that 100% of patients (32/32) exhibited peripheral immune response during the conduct of the study (Fig. 2E) Taken together these results suggest that INO-3107 robustly engaged peripheral T-cells inclusive of the induction of HPV-6 and HPV-11-specific activity A Gene set enrichment analysis (GSEA) results for hallmark interferon gamma and inflammatory signatures comparing pretreatment papilloma tissue with end of study tissue as determined by one-sided false discovery rate (FDR) correction for multiple comparisons Core enriched genes are displayed with an intensity of color-coding tracking to rank metric scores of those genes Non-core enriched genes are found in the supplement B Heatmap of 280 differentially expressed genes (DEGs) in responders using one minus Spearman rank correlation with average linkage for hierarchical clustering and samples grouped by study visit; this gene set was analyzed using ingenuity pathway analysis (IPA) which confirmed the activation of interferon-gamma and interferon alpha signaling pathways in responder tissue at end of study versus screening via p value and z-score as determined using one-sided Fisher’s exact test and reported in the inset table A Bubble plot of various IPA outputs relevant to inflammation as well as adaptive and innate immune responses that are enriched in airway tissue after INO-3107 treatment p value and z-score (orange = activated; blue = inhibited) determined by one-sided Fisher’s exact test B Network diagram of IPA data from tissue-localized T-cell activity inclusive of p value and z-score as determined using one-sided Fisher’s exact test and reported in the inset table Networks are defined by central nodes with bold names differentially expressed genes (DEGs) that are upregulated (red) or downregulated (green) and connected to nodes they contribute to with dashed lines Single sample GSEA comparison of Screening (pretreatment) to end of study for total CD8+ (top left) CD8+ central memory (bottom left) and CD8+ cytotoxic (bottom right) T-cell signatures Selected core enriched genes for these assessments are identified in the inset table: CD3D/E/G and CD8A are T-cell identification markers CD27 encodes a receptor required for activation of CD8 + T-cells EOMES and TBX21 are transcription factors expressed in activated CD8 + T-cells and PRF1 encode lytic proteins that induce T-cell killing of target cells Both CX3CR1 and CXCR6 chemokines promote the survival p values are from a two-sided Wilcoxon signed-rank test of n = 17 patients each represented by an open black diamond at both timepoints A Regression analysis for TCRβ sequencing of tissue-localized T-cells in papilloma tissue from screening (pretreatment left panel) and end of study (right panel) assessed against percent (%) change in surgical frequency during the study year (post-) relative to the year prior (pre-) to study start Data were displayed as total TCRβ clone counts as determined by summed total reads from n = 17 patients p values and r values are determined by two-sided Spearman correlation analysis B Left panel: Direct comparison of total TCRβ clone reads in papilloma tissue from Screening (pretreatment) and end of study from n = 17 patients Right panel: TCRβ clone reads in papilloma tissue from Screening (pretreatment) and end of study additionally broken out by clinical outcome where n = 5 non-responders (open red circles) and n = 12 Responders (open green squares) p values are determined by a two-sided Wilcoxon signed-rank test C Regression analysis of change (Δ) in TCRβ clone reads above Screening (pretreatment) to end of study against change in surgical frequency (%) on the study (post-) as compared to the year prior (pre-) to study start p value and r value are determined by a two-sided Spearman correlation analysis of n = 17 patients A Venn diagram displaying limited overlap (25 shared clones) between TCRβ clones identified in end of study papilloma tissue as compared to Screening (pretreatment) tissue for n = 13 patients B Left panel: Emergent T-cell clones are identified and tracked longitudinally for n = 14 on study patients each represented by lines connecting open diamonds color-coded by the left panel No clone was detectable at Screening (pretreatment) Right panel: Assessment of emergent T-cell clone peak frequencies show statistical significance via two-sided Wilcoxon signed-rank test for n = 14 patients each represented by a green line connecting an open black diamond at each timepoint C Left panel: peak emergent T-cell clones in blood identified on a per-patient basis for n = 14 patients each represented by a color-coded bar and black diamond Right panel: Venn diagram of considerable overlap between unique TCRβ clones in end of study airway tissue with emergent clones identified in the blood of n = 13 patients we report results for a DNA immunotherapy for RRP from a completed Phase 1/2 trial demonstrating the safety When compared to the year prior to treatment with INO-3107 26 RRP patients (81.3%) treated with INO-3107 exhibited reductions in clinically indicated surgical interventions in the year following treatment Clinical response was seen across both HPV-6 and/or HPV-11 infections suggesting that INO-3107 efficiently addresses both viral genotypes Despite the small trial population of 32 patients enrolled patients were inclusive of a broad age group ranging from 25 to 82 representing the general adult RRP population and supporting the generalizability of the results INO-3107 treatment was well-tolerated and allowed for partial or complete control of disease in the context of reducing surgical interventions during the monitoring period of the trial with a four-dose regimen spanning only 9 weeks are not expanded on here as the current report is focused on CD8 + T-cell-based contribution to the proposed mechanism of action the possibility remains open for re-administration of INO-3107 to augment the immune response to further improve clinical response Such an undertaking would also allow for continued research into immune responsiveness in RRP patients over time which may have broader implications for understanding the mechanisms underpinning changes in disease state The results presented here make a strong rational case for use of INO-3107 as a non-surgical approach to RRP treatment from both a clinical and mechanistic standpoint future clinical trials are being planned to further address prolonged efficacy and redosing to expand the potential impact of this approach for the benefit of RRP patients The study was conducted in accordance with the Declaration of Helsinki and local and national regulatory requirements The protocol was reviewed and approved by the relevant Institutional Review Board/Ethics Committee at each participating site (NYU Langone; University of Texas Southwestern; Washington University School of Medicine; University of California Davis; Johns Hopkins University School of Medicine; Mayo Clinic Arizona; Emory University; University of Cincinnati Medical Center) All patients provided written informed consent Eligible patients were men and women aged ≥18 years with histologically documented HPV-6 and/or HPV-11 positive disease historically and/or at baseline as assessed by SPF10 LiPA25 HPV DNA genotyping followed by HPV-6 and HPV-11 specific qPCR conducted by DDL Diagnostic Laboratory (Rijswijk Netherlands) and were enrolled across eight sites to reduce potential selection bias Patients could have presented as either Juvenile-onset (JO; diagnosed before age 12 years) or Adult-onset (AO; diagnosed at or after 12 years of age) RRP who exhibited moderate to severe disease based on a history of required frequent RRP interventions to remove papilloma defined as ≥2 RRP surgical interventions (in the operating room or office-based) in the year prior to treatment Patients must have been judged by the investigator to be appropriate candidates for an upcoming surgical intervention Key exclusion criteria included the use of off-label adjuvant therapy for RRP disease (e.g. anti-angiogenic therapy [including bevacizumab] and prophylactic HPV vaccination) within 3 months of study start; immunosuppression; high risk of bleeding; and any illness or condition that may affect patient safety or evaluation of study endpoints (full inclusion and exclusion criteria are listed in Supplementary Information and full protocol is available on clinicaltrials.gov and appended at the end of the Supplementary Information) All patients were required to undergo a clinically necessary surgical intervention which included predominantly laser-based techniques or microdebridement within 14 days of the first dose (Day 0) to maximize standardization of baseline disease burden across patients All patients underwent an assessment of the RRP Severity Score (modified) immediately prior to baseline surgery (see below) No compensation was provided for patient participation Patients received one 6.25 mg dose of INO-3107 (a DNA plasmid-based immunotherapy composed of a plasmid encoding for HPV-6 and HPV-11 E6 and E7 antigens as well as a plasmid encoding for interleukin-12) on Day 0 and Weeks 3 INO-3107 was administered intramuscularly (IM) in the deltoid (or anterolateral quadriceps muscle if the deltoid muscle was not possible or appropriate) in a 1 mL volume followed immediately by electroporation (EP) using the CELLECTRA proprietary device designed to enable local transfection of DNA plasmids into the cells (Inovio Pharmaceuticals; Plymouth Meeting Clinically significant changes in laboratory parameters and vital signs from baseline assessments were also assessed There were no missing or incomplete safety data There were no missing or incomplete efficacy data Data was collected according to GCP/ICH standards at each of the enrolling investigational sites by qualified personnel representative of the Sponsor and overall clinical response (reduction of at least one surgery in the year following first dose when compared with the year prior) The decision to perform surgery among individual patients was made by their treating laryngologist in order to maintain consistency in the time period prior to and following administration of INO-3107 The clinical trial protocol mandated that prior to surgery both anatomical and symptom severity (modified Derkay) scores be obtained and that the rationale for surgery be clearly documented in the case report forms was revised by Pransky (S.M.P.) to provide a more detailed anatomical map of sites to be scored Guidelines were issued to all investigators to assess lesions as surface (<3 mm) Photo documentation of each laryngoscopy was required The assessment form subdivided the true vocal cords (using both the free edge and superior surface as separate locations) and false vocal cords into three subsections from anterior to posterior The epiglottis and posterior glottis were divided into left and right The aryepiglottic folds were clearly delineated a definition and grading score were created for an extensive carpet of papilloma the same laryngeal assessment form was utilized along with assessment of the subglottis (divided into left and right and posterior segments) and the trachea (divided into superior The staging assessment was further expanded to include a symptom score that identified the presence of voice changes and the severity scores were retrospectively verified by independent otolaryngologists with extensive experience in RRP not participating in the study Patients underwent office laryngoscopy and staging at Screening and Weeks 6 No formal power analysis was applicable to the study; descriptive statistics were used to summarize data The trial planned to treat approximately 30 patients which would enable the trial to provide 95% confidence that the true incidence of SAEs was <12% if no SAEs were observed the main summary of safety data was based on TEAEs with a frequency of preferred term events computed The safety population comprised all patients who received at least 1 dose of INO-3107 the number of RRP surgical interventions in the year following the first dose of INO-3107 compared with the number in the year prior on a per-patient basis was summarized descriptively using median change and associated 95% confidence interval (CI) Mean changes and associated 95% CIs were computed for RRP severity scores from baseline pre-dose to each post-dose evaluation The modified intention-to-treat population comprising all patients who received at least one dose of INO-3107 was used for the secondary efficacy analyses Immunological and correlative statistical analysis was post hoc in nature data represent single assay runs from distinct samples obtained from each individual patient at specific timepoints during the conduct of the study data represent N = 32 patients for immunology assays and n = 27 patients with both pre- and post-treatment samples remaining for TCR sequencing unless otherwise stated in the figure legend due to sample availability 17 patients had sufficient samples for use: n = 5 non-responders and n = 12 responders per the overall clinical response definition Graphing and statistical analyses were performed using GraphPad Prism (v9) software T cell clones were identified and tracked via their CDR3 nucleotide sequence The total number of effective cells sequenced was estimated as the summation of all productive TCRβ reads for a given sample productive reads being defined as sequences in frame and without stop codons was estimated as the number of reads of the corresponding CDR3 nucleotide sequence with the frequency of that clone defined as \({f}_{x}=\frac{{n}_{x}}{N}\) We required that a specific clone demonstrate at least a twofold increase compared to pretreatment visits (M) to warrant further investigation Clones demonstrating a fold change \( < 2(\frac{{m}_{x}}{M} < 2\times \frac{{n}_{x}}{N})\) were assigned default p values = 1 otherwise p values were calculated using an adapted Fisher’s exact test with the repertoire size of the initial sample rescaled by half p values were adjusted using Bonferroni correction:\({P}_{{adjusted}}=P\times \left|N\cup M\right|\) where \(\left|N\cup M\right|\) is the number of unique clones in the union of the two samples being tested A TCRβ clone was considered expanded were Padjusted < 0.05 RNA-based T-cell receptor (TCR) clonotype nucleotide sequences were derived from both FFPE tissue and a minimum of 1 × 106 viable PBMCs using a universal software platform to analyze and process raw TCR repertoire sequencing data Default settings and downstream filters were applied at reporting levels to remove false positives Only productive TCR sequences are analyzed and reported here Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article The sequencing data generated in this study have been deposited in the Gene Expression Omnibus database under accession code GSE275788 The de-identified individual patient clinical data are available under restricted access for ongoing research and privacy reasons due to ethical concerns related to the sensitive nature of the participant information Interested investigators can obtain and certify a data transfer agreement and submit requests by emailing Jeffrey Skolnik (Jeffrey.Skolnik@inovio.com) The raw individual patient data were protected and are not available due to data privacy laws The processed de-identified immunology data are available under restricted access for privacy Interested investigators can obtain and certify a data transfer agreement and submit requests by emailing Matthew Morrow (Matthew.Morrow@inovio.com) Responses to data requests will be provided within 30 days of receipt Custom code used in this analysis can be found on GitHub (https://github.com/Inovio-Pharmaceutical/CloneTrack.Adopted.git) Sexually transmitted human papillomavirus: update in epidemiology Oncogenic viruses as 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I. et al. immunarch: bioinformatics analysis of T-cell and B-cell immune repertoires. R package version 0.9.0. https://CRAN.R-project.org/package=immunarch (2022) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes Causal analysis approaches in ingenuity pathway analysis xCell: digitally portraying the tissue cellular heterogeneity landscape 9-Gene signature correlated with CD8+ T cell infiltration activated by IFN-γ: a biomarker of immune checkpoint therapy response in melanoma Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis Sicca syndrome associated with immune checkpoint inhibitor therapy Angiogenesis inhibitor drug-induced benign migratory glossitis in a patient of juvenile-onset recurrent respiratory papillomatosis under maintenance therapy Renal implications of long-term systemic bevacizumab for recurrent respiratory papillomatosis Interim results of a phase 1/2 open-label study of INO-3107 for HPV-6 and/or HPV-11-associated recurrent respiratory papillomatosis Profiling of VEGF receptors and immune checkpoints in recurrent respiratory papillomatosis Durable response in a patient with recurrent respiratory papillomatosis treated with immune checkpoint blockade PD-L1 expression and CD8+ infiltration shows heterogeneity in juvenile recurrent respiratory papillomatosis Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100 US Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE) A staging system for assessing severity of disease and response to therapy in recurrent respiratory papillomatosis R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing. https://www.R-project.org/ (2022) edgeR v4: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation edgeR: a Bioconductor package for differential expression analysis of digital gene expression data GSVA: gene set variation analysis for microarray and RNA-seq data Download references This study was funded by INOVIO Pharmaceuticals The authors would like to thank the RRP-001 trial patients and site staff involved in this study Department of Otolaryngology-Head and Neck Surgery New York University Grossman School of Medicine Department of Otolaryngology/Head and Neck Surgery Johns Hopkins University School of Medicine University of Texas Southwestern Medical Center Department of Otolaryngology – Head and Neck Surgery Department of Hematology and Medical Oncology contributed to the study design and development concept and drafted the manuscript directed analyses of all immune and sequencing assays were responsible for analyses of immune and sequencing data via CloneTrack contributed to the conception of the program All authors contributed to the acquisition and performed critical revision of the manuscript for intellectual content are employees of and may hold stock and/or stock options in Inovio Pharmaceuticals received honoraria for consultancy for Inovio Pharmaceuticals received honoraria for consultancy for Inovio Pharmaceuticals and Precigen receives support from the RRP Foundation for attending an RRPF Research meeting receives honoraria for consultancy and advice for Inovio Pharmaceuticals; and is a member of the Recurrent Respiratory Task Force of the American Society of Pediatric Otolaryngology provides advice for Inovio Pharmaceuticals; and provided compensated or non-compensated advisory role for Astra Zeneca received remuneration as a member of the Board of Directors and consultant for Inovio Pharmaceuticals and received honoraria for consultancy for Geneos All authors declare to have competing interests None of the other authors have any competing interests who co-reviewed with Liu Kai; Everardo Saad reviewer(s) for their contribution to the peer review of this work Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41467-025-56729-6 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Data shows that INO-3107 induced new populations of T cells in the blood that traveled to airway tissue and were associated with clinical benefit as measured by reduced need for surgeries In the trial, treatment with INO-3107 induced new populations of T cells in the blood that traveled to the airway and papilloma tissue and were correlated with a reduction in the number of post-treatment surgeries 26 patients (81%) required fewer surgeries post-treatment when compared to the year prior to treatment INO-3107 treatment was also well tolerated in the trial INOVIO plans to submit its biologics license application (BLA) for INO-3107 in mid-2025 and request rolling submission and priority review under the FDA's accelerated approval program INO-3107 would be the first DNA medicine approved for any indication in the United States The Phase 1/2 study showed the majority of participants experienced a reduced need for surgery providing great hope for RRP patients who face both risk of vocal cord damage and immense impact on their daily lives with every surgery," said Dr Director of the Center for Voice & Swallowing at UC Davis Health and a principal investigator on the trial "INO-3107 was designed with those patient needs in mind and has the potential to transform the treatment paradigm for RRP." INOVIO's Vice President of Translational Science stated "The combination of the full clinical data set and the immunological evaluation described in this publication allows for a complete view of the immunological impact of INO-3107 which is a compelling story of a T cell-based mechanism of action that drives clinical benefit The publication describes in detail how INO-3107 engaged both the innate and adaptive arms of the immune system of treated patients and directly points to the emergence of new T cell populations after treatment that traveled to infected tissue to fight RRP." "These important data characterizing the cytotoxic T cell-based mechanism of action of INO-3107 in conjunction with our recently reported durability data showing that clinical benefit continued to improve through year two and into year three after initial treatment with half of  patients not requiring any surgeries in year two are part of the growing body of evidence that INO-3107 has the potential to be the preferred product of choice for both patients and healthcare providers," said Dr "The primary goal for RRP patients is to reduce or eliminate the need for surgery and INO-3107 has the potential to do just that for the majority of patients Every surgery matters and a safe and effective therapeutic alternative to surgery would be truly life-changing for RRP patients and their caregivers."   Highlights from the Nature Communications Paper About RRPRRP is a debilitating and rare disease caused primarily by HPV-6 and/or HPV-11 RRP is characterized by the development of small While papillomas are generally benign life-threatening airway obstruction and respiratory complications RRP can also significantly affect quality of life for patients by affecting the voice box Surgery to remove papillomas is the standard of care for RRP; however INOVIO's market research to date with patients and healthcare professionals indicates that a reduction of even one surgery matters because every surgery poses a significant risk of causing permanent damage to the vocal cords epidemiology data published in 1995 estimated that there were 14,000 active cases and about 1.8 per 100,000 new cases in adults each year About INO-3107INO-3107 is an investigational DNA medicine designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins These targeted T cells seek out and kill HPV-6 and HPV-11 infected cells with the aim of potentially preventing or slowing the growth of new papillomas In a Phase 1/2 clinical trial conducted with INO-3107 in patients requiring ≥2 RRP surgical interventions in the year prior to initiating treatment 81.3% (26/32) of patients had a decrease in surgical interventions in the year after INO-3107 administration compared to the prior year including 28.1% (9/32) that required no surgical intervention (Complete Response) during or after the dosing window Patients in the trial had a median range of 4 surgeries (2-8) in the year prior to dosing there was a median decrease of 3 surgical interventions (95% confidence interval -3 patients had a clinically warranted procedure to have RRP tissue surgically removed but any surgery performed after Day 0 during the dosing window was counted against the efficacy endpoint Treatment with INO-3107 generated a strong immune response in the trial inducing activated CD4 T cells and activated CD8 T cells with lytic potential T cell responses were also observed at Week 52 indicating a persistent cellular memory response with trial participants experiencing mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue INO-3107 has shown the ability to generate antigen-specific T cells that is not affected by anti-vector immunity impacting immunogenicity either before administration or after the first dose unlike other T cell generating platforms such as viral vectors This feature of DNA medicines is anticipated to allow INO-3107 to maintain T cell response and overall efficacy which could make it an important therapeutic option for a majority of RRP patients The FDA previously granted INO-3107 Orphan Drug designation and Breakthrough Therapy designation and has advised INOVIO that it can submit a biologics license application under the FDA's accelerated approval program using data from INOVIO's already completed Phase 1/2 trial The European Commission granted INO-3107 Orphan Drug designation INOVIO has CE-marked its CELLECTRA® delivery device in the EU which allows INOVIO to commercialize the device in the EU and other geographies that recognize CE-marking The United Kingdom awarded INO-3107 the Innovation Passport This designation serves as the entry point to the Innovative Licensing and Access Pathway (ILAP) which aims to accelerate time to market and facilitate patient access to medicines including the planned submission of a BLA in mid-2025 and plan to request rolling submission and priority review under the FDA's accelerated approval program and the potential clinical benefit of INO-3107 if approved our Quarterly Report on Form 10-Q for the quarter ended September 30 and other filings we make from time to time with the Securities and Exchange Commission ContactsMedia: Jennie Willson (267) 429-8567 [email protected] Investors: Peter Vozzo, ICR Healthcare, 443-213-0505 [email protected]  Metrics details We have previously developed a DNA-based vaccine encoding the Lassa lineage IV glycoprotein precursor and conferred 100% protection in cynomolgus non-human primates we expanded the characterization of INO-4500 assessing immunogenicity and protective efficacy of lower doses and single immunization The study was divided into three arms evaluating INO-4500 vaccination: Arm 1 – Dosing regimen; Arm 2 – Single immunization; and Arm 3—Durability of immune responses and protective efficacy Humoral and T cell responses were assessed by IgG binding ELISA IFNγ ELISpot and flow cytometry-based T cell activation assays NHPs were challenged with a lethal dose of Lassa lineage IV 8 weeks (Arms 1 and 2) or one year (Arm 3) after immunization NHPs were assigned clinical scores and monitored for survival virus neutralization and release of soluble mediators were assessed post-challenge as well as disease pathology following NHPs death or euthanasia INO-4500 induces dose-dependent immune responses and protective efficacy Animals receiving two doses of 2 mg of INO-4500 show complete short- and long-term LASV protection NHPs receiving 1 mg of INO-4500 are protected from LASV challenge one year after vaccination but are only partially protected 8 weeks post-vaccination LASV-specific memory T cells are present in vaccinated NHPs one year after vaccination INO-4500 vaccination prevents NHPs from developing severe disease These studies demonstrate that INO-4500 can provide short- and long-term protection in NHPs from lethal LASV challenge Lassa Fever is an infection that leads to excessive bleeding and often that protected monkeys from becoming infected with Lassa we tested whether different vaccine schedules we evaluated the long-term protection of INO-4500 and confirmed that INO-4500 protects monkeys from infection with Lassa one year after vaccination These findings confirm that our vaccine prevents infection with Lassa and provides long-term protection from Lassa Fever in this animal model of the disease This work supports further investigation being undertaken into whether the vaccine can prevent Lassa fever in humans these factors have led to Lassa fever being categorized as a priority pathogen for countermeasure research and development by the World Health Organization The development of effective vaccines and vaccine delivery technologies to protect against potential biothreat agents like LASV is of extreme importance the Coalition for Epidemic Preparedness Innovations (CEPI) has become the largest funder of research in the development and licensure of vaccines against Lassa fever The studies reported herein demonstrate the durability of protection in NHP one year after initial vaccination the ability of the vaccine to protect against long-term effects of disease and offer insights into potential immune mechanisms associated with protection Virus challenge occurred 4 weeks after the final vaccination timepoint NHPs were administered a target dose of 1000 PFU (plaque forming units) of LASV Josiah suspended in 1 mL of sterile saline via intramuscular (IM) injection to the upper arm Blood samples were collected prior to virus challenge on Day 0 and on Days 3 Blood samples were used for blood chemistry and blood cell population assessments Serum was isolated and used for virus titration by plaque assay and plaque reduction neutralization tests (PRNTs) Post-challenge clinical scoring was performed daily by the same operator Clinical scoring for euthanasia determinations at RML was based upon appearance Predetermined euthanasia criteria were established based on ACUC-approved scoring criteria Animals were euthanized when predefined endpoint criteria were met Brainstem Auditory Evoked Response (BAERCOM®) analysis was performed on each animal under anesthesia at the start of the study to obtain baseline measurements and prior to euthanasia to assess outcome The one vs two-dose study was conducted at USAMRIID in Frederick Eighteen cynomolgus macaques of Vietnamese and Cambodian origins (7 male and 11 female ranging between 2.1 and 8.8 kg) were divided in three groups of six NHPs/group One group was left unimmunized and the other two groups received one or two doses of INO-4500 at 2 mg per dose intradermally Both groups were immunized at week 0; the second dose for the two-dose group was administered four weeks after the first dose Blood samples were collected at multiple time-points following immunization after which NHPs were challenged with a target of 1000 PFU of LASV Josiah via IM injection at week 8 Blood samples were collected just prior to virus challenge on Day 0 and on Days 3 as well as at the end of study on Day 30 post-challenge Serum samples were separated and used for virus titration by plaque assay and PRNTs Post-challenge clinical scoring was performed daily by members of the study team who were blinded to the study groups Clinical scoring for euthanasia determinations at USAMRIID were based upon recumbency Predetermined clinical scoring and euthanasia criteria were established based on USAMRIID’s IACUC-approved protocol Animals were monitored for body weight and temperature changes and evaluated for clinical signs of disease Animals were humanely euthanized when moribund according to predefined criteria in the IACUC protocol NHPs were also monitored for hearing loss using BAERCOM® at the start and at the end of the study to assess outcome A total of eighteen cynomolgus macaques of Chinese origin (50% male and female ranging between 2.3 and 5.2 kg) were randomly assigned (stratified by weight and sex) to two groups consisting of six NHPs per group An age/weight-matched control group consisting of six NHPs was populated prior to challenge The control group was unvaccinated and the other two groups received two doses of 2 mg or 1 mg of INO-4500 + IP-EP four weeks apart All NHPs were challenged with a target IM dose of 1000 PFU LASV (Josiah) 59 weeks after the final vaccination was administered Blood samples were collected as described for Arms 1 and 2 Post-challenge assessments were performed as described for Arm 1 study All animals were euthanized at the end of the study on Day 35 post-challenge Tissue samples were collected for histopathology after euthanasia NHPs were housed at BIOQUAL facility following the approved ACUP protocol ranging from 3.2 to 9.5 kg) received 2 mg of INO-4500 with ID-EP at weeks 0 Serum and PBMCs were collected at selected time-points for assessment of cross-reactive antibody and T cell responses Blood was collected in K2 EDTA tubes and shipped overnight to Inovio for peripheral blood mononuclear cell (PBMC) isolation Whole blood was diluted 1:1 with an equal volume of PBS supplemented with 2% FBS PBMCs were isolated using a 50 mL SepMate tube (Stemcell Technologies) pre-filled with 15 mL of 90% Ficoll (GE Healthcare) and 10% PBS Red blood cells present in the PBMC suspension were lysed with 5 mL ACK buffer for 5 min before the addition of 1x PBS to stop the reaction Cells were then centrifuged at 1500 rpm for 5 min and resuspended in 10 mL of RPMI supplemented with 10% FBS and 10% PenStrep (R10 medium) for ELISpot assay To assess the cellular IFNγ responses to vaccinations monkey interferon (IFN)-γ ELISpot assays were performed using a Mabtech IFNγ ELISpotPRO (ALP) kit (Mabtech 96-well ELISpot plates were blocked with R10 medium overnight at 4 °C 200,000 freshly isolated PBMCs from NHPs were added to each well and incubated at 37 °C in 5 % CO2 in the presence of media with DMSO (negative control) PMA/ Ionomycin (positive control for monkey or media with peptide pools consisting of 15-mers overlapping by nine amino acids and spanning the length of LASV lineages I Antigen-specific responses were determined by subtracting the number of spots in the negative control wells from the wells containing peptide pools To determine antigen-specific antibody responses in sera 96-well ELISA plates were coated with 1 µg/ml recombinant LASV lineage IV GP prefusion protein (Zalgen Labs) or 1 µg/ml recombinant LASV lineages I II and III GP prefusion protein (kindly donated from Dr La Jolla Institute for Immunology) in 1x PBS overnight at 4 °C Plates were then washed with 1x PBS + 0.05% Tween 20 and blocked with 3% BSA PBS-Tween 20 for 2 h at 37 °C plates were washed and serum was serially diluted in 1% BSA PBS-Tween 20 and incubated for 2 h at 37 °C Plates were washed and incubated with 1:10,000 dilution of secondary anti-human IgG HRP (BD Bioscience cat #555788) for 1 h Plates were washed and SureBlue TMB peroxidase substrate (ref# 95059-286 after which the reaction was stopped with TMB stop solution (ref# 5150-0020 The absorbance signal was acquired at 450 nm using an automated plate reader (Biotek) Pseudovirus production: HIV-based LASV IV pseudovirus carrying a luciferase reporter gene was generated by co-transfecting 293T cells with pLASV-GPC IV and envelope-defective HIV-1 pNL4-3.Luc.R-E plasmids (NIH AIDS reagent program) using Lipofectamine 3000 (Life Technologies) Pseudovirus-containing culture supernatant was harvested 72 h post-transfection Supernatants were filtered using a 0.22 μm filter (Sigma-Millipore) NHP sera samples were heat inactivated for 1 h at 56 °C and serial dilutions of heat-inactivated sera were mixed with equal volumes of LASV pseudovirus and incubated 1 h at 37 °C Pseudovirus-sera mixture was added to 96-well plates with 293 T cells and luciferase signal acquired by luminescence using an automated plate reader T-cell activation assay was performed as previously described with modifications35 PBMCs from study Arm 3 were thawed (Day 0 pre-immunization 270 and 379 pre-challenge) and resuspended in complete RPMI (cRPMI) medium supplemented with 10% FBS and allowed to rest overnight at 37 °C and 5% CO2 PBMCs were washed with cRPMI and resuspended in medium containing overlapping peptides spanning the Josiah GPC for 24 h and supplemented with 10 U/mL IL-2 and 10 ng/mL of IL-7 every 2 days for 6 days The next day cells were incubated with peptide megapools or DMSO control for 20 h PBMCs were stained for 1 h at 4 °C with LIVE/DEAD stain (ThermoFisher) Staining was removed and cells were fixed with 1% paraformaldehyde until acquisition PBMCs were acquired by flow cytometry using LSRFortessa cytometer (BD Biosciences) Data were analyzed with FlowJo V10 Software Rhesus macaques were single-housed in adjacent primate cages to allow social interactions Animals were subject to a fixed 12 h/12 h light-dark cycle Commercial monkey chow was provided twice daily and water was available ad libitum Environmental enrichment included a variety of human interactions Animals were monitored at least twice daily throughout the experiment Vero-76 cells plated on six-well plates were incubated with gentle rotation at 37 °C 5% CO2 with ten-fold serial dilutions of serum for 1 h 0.8% molecular grade agarose in EBME (basal medium Eagle with Earle’s salts) with 10% FBS and 20 μg/ml gentamicin was applied to each well and allowed to solidify then stained with a neutral red overlay (Invitrogen Plates were incubated overnight at 37 °C in the staining overlay Lower limit of detection for the LASV plaque assay has been empirically determined to be 10 PFU two-fold dilutions of sera (in 100 µl volumes) were incubated for 1 h at 37 °C with LASV diluted to approximately 100 PFU per serum dilution each serum dilution/virus mixture was then added to Vero-76 cells at ~90% confluency in six-well tissue culture plates The downstream procedure was performed as described above for the standard plaque assay Plaques were counted and compared to control wells containing cells infected with 100 PFU LASV pre-incubated with a LASV naïve NHP serum Neutralizing antibody titers yielding a 50% reduction (PRNT50) in plaques were determined Vero-76 CRL-1587 was obtained from ATCC (Manassas VA) and tested free of mycoplasma HEK293T (Lenti-X™ 293T cat# 632180) was obtained from Takara Bio (San Jose CA) and validated free of mycoplasma by the manufacturer Serum samples collected from NHPs were analyzed for glucose 100 μl of serum was added to a General Chemistry 13-panel rotor and evaluated in a Piccolo point-of-care blood chemistry analyzer (Abaxis) hematology analysis was performed using an IDEXX Instrument using a volume of 500 µl of EDTA-treated whole blood hematology analysis was performed using an DxH 520 instrument (Beckman Coulter) using a volume of 100 µl of EDTA-treated whole blood and 35 were used to assess fold change in cytokine/chemokine levels post-challenge using a 23-plex magnet immunology multiplex panel kit specific for nonhuman primates (EMD Millipore) This kit allows for simultaneous measurements of G-CSF 25 µl of undiluted serum from each NHP at the time-points listed above was added to the 96-well plate according to manufacturer’s instructions 25 µl of magnetic bead conjugates were added to the wells and plates were incubated for 2 h at room temperature Plates were washed with a magnetic plate washer then 25 µl of detection antibodies were added to each well followed by a 1 h incubation with agitation at RT A final incubation of 30 min after addition of 25 µl of Streptavidin-Phycoerythrin was performed 150 µl sheath fluid was added to each well and mixed prior to plate reading plates were loaded onto the Magpix instrument (Luminex) Fluorescence intensity values were recorded for each multiplexed cytokine/chemokine per well and exported to an Excel file Values of all 23 cytokines/chemokines per time-point for each NHP were obtained and analyzed Tissue samples collected at necropsy were inactivated with 10% buffered formalin for 30 days prior to removal from the containment laboratory tissues were processed and embedded in paraffin The paraffin-embedded tissues were sectioned to 5 μm thick and placed on glass slides stained with hematoxylin and eosin (H&E) and labeled in accordance with USAMRIID SOPs Inactivated tissue samples for studies conducted at RML were shipped to USAMRIID for analysis Immunohistochemistry (IHC) was performed in accordance with USAMRIID SOPs using the Dako Envision system (Dako Agilent Pathology Solutions sections were covered with mouse anti-Lassa virus monoclonal antibody (clone 52-2074-7 A USAMRIID) diluted 1:8000 and incubated for 45 min at RT and the peroxidase-labeled secondary antibody added for 35 min Slides were washed and the chromogenic substrate 3,3′ Diaminobenzidine (DAB) solution (Dako Agilent Pathology Solutions) added and incubated for 80 min after which substrate-chromogen solution was removed and samples were counterstained with hematoxylin Slides were evaluated using a Nikon Eclipse 600 light microscope Hearing screenings for the DR and One vs Two studies were performed using a BAERCOM® device (UFI Inc.) according to manufacturer’s instructions needle probes were placed sub-dermally into the skin above each ear around the temporal bones An additional probe was placed sub-dermally on the crown of the head The probes were plugged into the BAERCOM device which was set to medium resolution recording An earplug was placed into one ear at a time and audiometric readings were collected at 0 dB to obtain a baseline measurement The BAERCOM® software recorded waveforms for each reading GraphPad Prism 7.02 was used to analyze and plot the data the statistical difference between immunization groups at each time point was assessed using parametric one-way ANOVA t-test or nonparametric Kruskal-Wallis Mann-Whitney test and p < 0.05 was defined as significant Two-way ANOVA was used to compare differences between time-points and treatment groups Technical duplicates were used to run experimental assays Predicted probability of survival plots were generated using SAS software Survival was analyzed using logistic regression statistical model P-value from this model was used to determine whether there was strong association between peak antibodies and overall survival Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article a NHPs were divided into four groups of 6 animals/group 1 or 0.1 mg of INO-4500 (with intradermal (ID) EP; groups 1 and a fourth group served as unvaccinated control after which animals were challenged with LASV Josiah at week 8 Serum and PBMCs were collected to assess the presence of LASV-specific antibody and T cell responses before and after immunizations b LASV-specific antibody responses were assessed at week 6 by IgG Binding ELISA to lineage IV Prefusion GPC IgG titers were calculated based on the highest serum dilution with OD450 equal to or higher than 0.150 times 2.5 standard deviations of the experimental duplicates Error bars represent the geometric mean (GMT) ± 95% confidence interval (CI) c IFNγ T cell responses at week 6 for each group was measured in PBMCs stimulated with lineage IV Josiah GPC peptide megapools by IFNγ ELISpot assay Data were calculated after DMSO subtraction from peptide-stimulated wells Error bars represent the mean ± standard error of the mean (SEM) b-c Each datapoint represents the mean of technical duplicates for each NHP d Kaplan-Meier survival curves for vaccinated and control animals after challenge with 1000 PFU LASV Josiah at week 8 e Quantification of LASV Josiah in PFU per mL of serum by group Serum samples were collected every 3–5 days to monitor viremia in vaccinated and control NHPs Surviving NHPs were monitored until Day 38 post-challenge Shaded areas indicate viral levels above 4 log10 PFU/mL Animals noted with a black X indicate vaccinated NHPs that were euthanized during critical phase f LASV neutralization in serum as measured by plaque reduction neutralization test (PRNT) Viremia levels in all control animals and in 4/5 vaccinated non-survivors continued to increase until euthanasia vaccinated NHPs that did not survive LASV challenge had no detectable nAb suggesting that nAb may play an important role at controlling viremia and preventing death Animals received one or two 2 mg doses of INO-4500 with ID-EP at week 0 or weeks 0 and 4 All animals were challenged at week 8 with a target of 1000 PFU LASV Josiah b LASV-specific antibody response was assessed by IgG Binding ELISA to LASV lineage IV Prefusion GPC at weeks 4 and 6 IgG titers were calculated based on the highest serum dilution with OD450 equal to or higher than 0.250 + 2.5 standard deviations of the experimental duplicates c IFNγ responses at week 4 and 6 for each group were measured in PBMCs stimulated with lineage IV Josiah GPC peptide megapools by IFNγ ELISpot assay c Each datapoint represents the mean of technical duplicates for each NHP e Quantification of LASV in PFU per mL of serum by group viremia was monitored until the time of death or euthanasia Surviving NHPs were monitored until Day 30 post-challenge Shaded areas indicate peak viremia levels above 4 log10 PFU/mL at critical phase Animals noted with a black X indicate vaccinated NHPs that succumbed to disease We measured the levels of IFNγ-producing T cells in isolated PBMCs stimulated with LASV lineage IV peptide megapools. Cellular responses peaked 2 weeks after the second immunization (week 6) in the two-dose group (mean [min-max]: 354 [17-1397] SFU per 106 cells), and at week 4 for the one-dose group (mean [min-max]: 115.8 [11.7-348] SFU per 106 cells) (Fig. 2c) T cell data suggest that immunization with two doses of 2 mg of INO-4500 generates higher levels of LASV-specific cellular responses compared to a single dose and TP decreased for all groups initially but stabilized in vaccinated groups after Day 10 post-challenge No neutralizing activity above background was detected in the control NHPs nor for the two non-surviving NHPs in the one-dose group (1v2-7 and 1v2-12) the same two non-surviving NHPs in the one-dose group had viremia titers above 104 PFU/mL and low to undetectable binding antibodies and T cells at weeks 4 and 6 following INO-4500 vaccination pre-challenge and post-challenge immune response profiles suggest a potential recall of memory immune cells and their reactivation upon antigen re-exposure following LASV challenge To determine the durability of INO-4500-mediated protection we assessed the outcome of LASV Josiah challenge 1 year after vaccination in a study Arm 3. NHPs were separated into two vaccinated (2 doses of 2 mg and 1 mg of INO-4500) and one control groups (Fig. 3a). NHPs were immunized with INO-4500 + ID-EP at weeks 0 and 4 b LASV-specific IgG responses by IgG Binding ELISA to LASV Clade IV Prefusion GPC for 2 mg and 1 mg groups LASV IgG antibody response was assessed at baseline c Individual IFNγ cellular responses after INO-4500 immunization for NHPs from 2 mg and 1 mg groups at week 6 and prior to LASV challenge at week 54 PBMCs were stimulated with Clade IV Josiah GPC peptide megapools Quantification of d LASV-specific CD4+ and e CD8 + T cells upon stimulation with peptide megapools spanning the Josiah lineage IV GPC Cells were stained with antibodies against markers that are upregulated upon T cell activation Frequency of LASV + T cells were calculated based on any T cell expressing at least two AIM markers Percentage of positive CD4+ and CD8 + T cells were calculated after DMSO subtraction from peptide-stimulated samples Each symbol represents an individual NHP test sample f Kaplan-Meier survival curves following LASV challenge with Josiah strain one year post-initial immunization a Quantification of LASV Josiah replication in PFU per ml of serum for each individual group Serum samples were collected every 3-5 days to monitor viremia in vaccinated and control NHPs viremia was monitored until their time of death or euthanasia Surviving NHPs were monitored until Day 35 post-challenge b LASV neutralization in the serum by plaque reduction and neutralization test (PRNT) c Levels of cytokines and chemokines post-challenge are expressed as fold changes in median fluorescence intensity (MFI) values compared to Day 0 values Cytokines were placed into the following basic functional groupings: Adaptive Immunity (IL-2 A reduction in sCD-40L levels in control NHPs indicates that there are fewer activated T cells present to release sCD-40L thus preventing antigen-specific B cell production These results indicate that control NHPs experienced an acute and fatal disease characterized by an uncontrolled immune response as evidenced by the elevation of pro-inflammatory cytokines a–c Analysis of 70% probability of survival calculated based on serum viremia titers as log10 PFU/mL for (a) Dose-ranging (Arm 1) (b) One vs Two dose (Arm 2) and (c) Durability (Arm 3) studies d–f Analysis of 70% probability of survival calculated based on PRNT50 titers for (d) Dose-ranging (e) One vs two dose and (f) Durability studies Predicted probability plots were generated using SAS software Survival was analyzed using a logistic regression statistical model Blue lines indicate predictive survival probability at a given measurement The value beside circular symbols indicates the number of NHPs with corresponding assay readout We evaluated the relation of nAbs after LASV exposure with survival. Peak PRNT50 values were plotted against survival status for all NHPs across the three studies (Fig. 5d–f) All three studies followed a similar pattern where minimal PRNT50 values ranging from 17.6 and 23.2 predict 70% survival from LASV challenge INO-4500 vaccinated NHPs demonstrated increased levels of nAbs post-challenge; this was shown to be associated with survival suggesting potential memory B cell recall after LASV exposure were unable to generate LASV-specific nAbs above the minimum protective threshold The generation of nAbs against LASV may be an important component involved in disease protection and prevention from death in this model we expanded our knowledge to investigate the protective efficacy and immunogenicity of INO-4500 at low doses in addition to assessing durability of immune response durable protection from Lassa fever in NHPs INO-4500 also induces cross-reactive humoral and cellular responses against heterologous LASV lineages Despite LASV-specific antibody levels waning INO-4500 protected NHPs from Lassa fever one year after initial immunization The presence of long-term LASV-specific CD4 and CD8 T cells suggests a potential recall of immune memory cells after LASV exposure that may be critical to prevent the acute onset of symptoms and ultimately to protect NHPs from succumbing to disease The lowest (1 mg) vaccine dose used to assess protective durability induced 100% protection in NHPs one year after vaccination but only partial protection (67%) 4 weeks after vaccination We hypothesized this phenomenon may be due to the development of memory immunity LASV-specific T cell responses quantified one year after immunization indicated the presence of a population of LASV-specific CD4 T cells that were recalled upon LASV peptide exposure This suggests a potential T-cell mediated activation of B cells to rapidly engage the production of neutralizing antibodies observed after challenge assessment of cytokine/chemokine release post-challenge indicate that a programmed response occurred in vaccinated NHPs compared to the uncontrolled release of pro-inflammatory mediators observed in control NHPs Here we showed that INO-4500 vaccination can rapidly induce production of neutralizing antibodies after LASV exposure in NHPs and that presence of neutralizing antibodies is associated with survival from LASV challenge It is possible that the observed difference is because study Arm 1 was conducted at a different institute (RML) and is a result of Institute-to-Institute variability in available resources the studies presented here indicate that vaccination with INO-4500 induces long-term protective efficacy in NHPs and that protection is associated with a synergy of antibodies and T cells against Lassa virus T cell activation and cytokine release assays Additional histopathology images and all other datasets are available from the corresponding author upon reasonable request Lassa fever in the Eastern Province of Sierra Leone Clinical observations and virological studies on selected hospital cases Acute sensorineural deafness in Lassa fever Historical Lassa fever reports and 30-year clinical update Lassa fever-induced sensorineural hearing loss: a neglected public health and social burden Sensorineural hearing loss in Lassa fever: two case reports Lassa fever induced hearing loss: the neglected disability of hemorrhagic fever Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective Disease Outbreak News; Lassa Fever—Nigeria (2023) Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area Mortality among confirmed Lassa fever cases during the 2015-2016 outbreak in Nigeria Hospital-based surveillance for Lassa fever in Edo State Lassa fever: the first confirmed case imported into Canada Releve epidemiologique hebdomadaire/Section d’hygiene du Secretariat de la Societe des Nations = Weekly epidemiological record/Health Section of the Secretariat of the League of Nations 75 The first case of Lassa fever was imported from Mali to the United Kingdom Fifty years of imported Lassa fever: a systematic review of primary and secondary cases Imported viral haemorrhagic fever with a potential for person-to-person transmission: review and recommendations for initial management of a suspected case in Belgium DNA vaccines delivered by dermal electroporation elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs A DNA vaccine delivered by dermal electroporation fully protects cynomolgus macaques against Lassa fever Enhanced efficacy of a codon-optimized DNA vaccine encoding the glycoprotein precursor gene of Lassa virus in a guinea pig disease model when delivered by dermal electroporation Animal models of highly pathogenic RNA viral infections: hemorrhagic fever viruses Comparative pathology of Lassa virus infection in monkeys Immunogenicity of a protective intradermal DNA vaccine against Lassa virus in cynomolgus macaques A single-shot Lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains Guide for the Care and Use of Laboratory Animals (The National Academies Press Standardization of a plaque assay for Lassa virus DNA vaccination with hantavirus M segment elicits neutralizing antibodies and protects against seoul virus infection Immune-mediated systemic vasculitis as the proposed cause of sudden-onset sensorineural hearing loss following Lassa virus exposure in Cynomolgus Macaques Pathogenesis of Lassa fever in cynomolgus macaques Activation-induced markers detect vaccine-specific CD4(+) T cell responses not measured by assays conventionally used in clinical trials Lassa and Mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on IL-8 and TNF-alpha gene expression Low levels of interleukin-8 and interferon-inducible protein-10 in serum are associated with fatal infections in acute Lassa fever Early and strong immune responses are associated with control of viral replication and recovery in lassa virus-infected cynomolgus monkeys Severe human Lassa fever is characterized by nonspecific T-cell activation and lymphocyte homing to inflamed tissues Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals Robust T cell immunity in convalescent individuals with asymptomatic or Mild COVID-19 A case of human Lassa virus infection with robust acute T-cell activation and long-term virus-specific T-cell responses A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits Treatment of Lassa virus infection in outbred guinea pigs with first-in-class human monoclonal antibodies Human-monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever Enhanced detection of antigen-specific T cells by a multiplexed AIM assay Download references These authors contributed equally: Viviane M United States Army Medical Research Institute of Infectious Diseases (USAMRIID) National Institute of Allergy and Infectious Diseases (NIAID) United States Army Medical Research Institute of Infectious Diseases Rocky Mountain Laboratory Veterinary Branch (RMVB) are employees of Inovio Pharmaceuticals and as such receive salary and benefits including ownership of stock and stock options from the company All other authors declare no competing interest Communications Medicine thanks Peter Okokhere and the other Download citation DOI: https://doi.org/10.1038/s43856-024-00684-8 Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research PLYMOUTH MEETING, Pa., Jan. 9, 2025 /PRNewswire/ -- INOVIO (NASDAQ: INO) today highlighted anticipated milestones for 2025 and key accomplishments from 2024 in advance of upcoming investor meetings we anticipate 2025 to be a transformational year for INOVIO as we move closer to our goal of becoming a commercial-stage company providing a breakthrough therapy for patients suffering from a devastating rare disease and delivering on the promise of DNA medicines," said Dr "Our top priorities for the coming year are the submission of our biologics license application (BLA) for INO-3107 and preparing to expedite the launch of the product commercially We also look forward to making progress with our pipeline through collaborations and other potential strategic opportunities." Anticipated Milestones for 2025 and Key 2024 Accomplishments the planned submission of a BLA in mid-2025 and the potential commercial launch of INO-3107 if regulatory approval is obtained ContactsMedia: Jennie Willson (267) 429-8567 [email protected]Investors: Peter Vozzo, ICR Healthcare, 443-213-0505 [email protected] PLYMOUTH MEETING, Pa., Dec. 3, 2024 /PRNewswire/ -- INOVIO (NASDAQ:INO) today announced data from a retrospective trial showing that the number of RRP patients meeting the criteria for a Complete Response increased to 50% by the end of the second year following initial treatment with INO-3107 in a previously reported Phase 1/2 52-week trial where the Complete Response rate was 28% the Complete Response rate had risen to 54% 95% of patients maintained or enhanced their original Overall Response Rate two years following initial treatment with INO-3107 86% of patients had maintained or enhanced their initial response to INO-3107 "These new data provide further support that INO-3107 has the potential to provide RRP patients with a durable non-surgical therapeutic option in treating this chronic disease," said Dr "These results are particularly meaningful because patients tell us that reducing the number of surgeries is of utmost importance The durability data will help inform future research to establish re-dosing schedules that could further maintain or enhance clinical response for patients across the disease spectrum We plan to share these data with the FDA as part of our BLA package targeted for submission in mid-2025." "Viewed in the context of our recently presented immunology data these promising durability results are consistent with the mechanism of action for INO-3107 including establishment of a memory T cell response that could drive continued antiviral activity resulting in a further reduction or potential elimination of surgical interventions in RRP patients," said Dr "We believe INO-3107's profile supports its potential to become the preferred product by healthcare providers and patients We plan to publish and present these new durability data at upcoming scientific conferences and in medical publications." Durability of Response to Treatment with INO-3107 INOVIO investigated the long-term clinical and safety response of 28* of the 32 patients treated with INO-3107 in a previously reported 52-week Phase 1/2 trial (RRP-001) The retrospective trial collected patient data for nearly three years (median time of follow-up 1,025 days) following initial treatment in RRP-001 Twenty-one of the 23 patients who achieved the criteria for Overall Response Rate (ORR; Complete Response + Partial Response) in RRP-001 agreed to participate in the retrospective study 20 of 21 patients (95%) maintained or improved upon their initial response by the end of year two and 18 of the 21 patients (86%) did so in year three All data presented is from the modified intent-to-treat dataset defined as subjects who received at least one dose of INO-3107.** Complete Responses (CR) were defined as requiring no surgeries and a Partial Response (PR) was defined as greater than or equal to 50% reduction in the number of surgeries compared to the year prior to treatment but less than a 100% reduction in surgeries The number of patients treated with INO-3107 who met the CR criteria increased to 50% by the end of year two This compares to the initial CR rate of 28% observed at the end of the 52-week period in RRP-001 the number of patients with a CR increased to 54% No treatment-emergent serious adverse events were identified during the retrospective trial Phase 1/2 Trial (RRP-001) – Overall Clinical Benefit (Previously Reported) Retrospective Trial (RRP-002) – Long-Term Maintenance of Patients in ORR Group  Retrospective Trial (RRP-002) – Change in CR Met CR Criteria in Year 3 (median 295 days) *Four of the original 32 patients were not able to be consented in the retrospective trial.**The number of patients treated with INO-3107 who met the CR criteria increased to 55% by the end of year two in the per protocol population the number of patients with a CR was 52% per protocol limiting the ability to speak effectively because every surgery poses a significant risk of causing permanent damage to the vocal cords In a Phase 1/2 clinical trial conducted with INO-3107 INOVIO has CE-marked its CELLECTRA® delivery device in the EU INOVIO's proprietary CELLECTRA delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms including our plans to develop and commercialize DNA medicines and expectations regarding our research and development programs including timelines and prospects for regulatory approval expectations regarding INO-3107's ability to maintain T cell response and overall efficacy ContactsMedia: Jennie Willson (267) 429-8567 [email protected]Investors: Thomas Hong (267) 440-4298 [email protected] PLYMOUTH MEETING, Pa., April 9, 2025 /PRNewswire/ -- INOVIO (NASDAQ:INO) and infectious diseases, today announced that it will highlight key data associated with its lead candidate including an opportunity to join other leading voices at the inaugural National HPV Conference INOVIO will also discuss its novel DNA-encoded monoclonal antibody technology at a preconference workshop at the World Vaccine Congress About INOVIOINOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com Media: Jennie Willson, (267) 429-8567, [email protected]Investors: Peter Vozzo - ICR Healthcare, (443) 213-0505, [email protected] PLYMOUTH MEETING, Pa., Dec. 13, 2024 /PRNewswire/ -- INOVIO Pharmaceuticals, Inc. (Nasdaq: INO) a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases today announced the pricing of an underwritten public offering of 10,000,000 shares of its common stock and accompanying warrants to purchase 10,000,000 shares of its common stock at an exercise price of $3.76 per share of common stock at a combined public offering price of $3.00 per share of common stock and accompanying warrant All of the securities in the offering are being sold by INOVIO The offering is expected to close on December 16 subject to the satisfaction of customary closing conditions before deducting the underwriting discounts and commissions and offering expenses payable by INOVIO and assuming no exercise of the accompanying warrants and Citizens JMP are acting as joint book-running managers for the offering is acting as lead manager for the offering This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools This release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995 These forward-looking statements are not based on historical fact and include statements regarding the public offering of INOVIO's securities including the timing of the closing of the offering as well as the anticipated proceeds of the offering Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements risks and uncertainties related to market conditions and satisfaction of customary closing conditions related to the proposed public offering For a discussion of other risks and uncertainties any of which could cause our actual results to differ from those contained in the forward-looking statements see the section entitled "Risk Factors" in INOVIO's Annual Report on Form 10-K for the year ended December 31 INOVIO's Quarterly Report on Form 10-Q for the quarter ended September 30 2024 and in other filings that INOVIO makes with the SEC from time to time There can be no assurance that any of the forward-looking information provided herein will be proven accurate These forward-looking statements speak only as of the date hereof and INOVIO undertakes no obligation to update forward-looking statements and readers are cautioned not to place undue reliance on such forward-looking statements Media: Jennie Willson (267) 429-8567 [email protected]Investors: Peter Vozzo, ICR Healthcare, 443-213-0505 [email protected] PLYMOUTH MEETING, Pa., Dec. 12, 2024 /PRNewswire/ -- INOVIO Pharmaceuticals, Inc. (Nasdaq: INO) today announced that it intends to offer and sell shares of its common stock and accompanying warrants to purchase shares of its common stock All of the securities in the proposed offering will be sold by INOVIO The proposed offering is subject to market conditions and there can be no assurance as to whether or when the offering may be completed or the actual size or terms of the offering statements regarding INOVIO's anticipated public offering including the completion of the public offering on the anticipated terms Media: Jennie Willson (267) 429-8567 [email protected]Investors: Peter Vozzo, ICR Healthcare, 443-213-0505 [email protected] PLYMOUTH MEETING, Pa., Nov. 14, 2024 /PRNewswire/ -- INOVIO (NASDAQ: INO) a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases today announced its financial results for the third quarter of 2024 and provided an update on recent company developments "We continue to be focused on advancing INO-3107 and delivering a non-surgical option to RRP patients we expect to have all non-device modules for our BLA completed by year end while in parallel we continue to implement the plan to resolve the previously announced manufacturing issue with the single-use array component of the device we continue to target the submission of our BLA in mid-2025," said Dr "Our development of INO-3107 is supported by a growing body of research that collectively points to INO-3107's potential to be an important therapeutic option for all RRP patients regardless of the severity of their disease We recently presented new immunology data highlighting the ability of INO-3107 to induce new populations of T cells that travel to the airway tissue and papilloma and correspond with clinical benefit We've also presented our full safety and efficacy data demonstrating that INO-3107 was shown to be well tolerated and have clinical benefit in the Phase 1/2 trial we anticipate announcing long-term clinical durability data We continue to believe INO-3107 has the potential to become the preferred choice for the broadest number of RRP patients INO-3107 – Recurrent Respiratory Papillomatosis INOVIO's primary focus is driving toward the regulatory approval and commercialization of its lead product candidate Recent progress includes advancing preparations for submitting the BLA New Immunology Data: INOVIO presented additional immunology data demonstrating the ability of INO-3107 to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of those T cells into airway tissues and papilloma of RRP patients which could potentially slow or eliminate papilloma regrowth These data were presented at the American Association for Cancer Research (AACR) Special Conference and at the 36th International Papillomavirus Conference Full Safety and Efficacy Data: INOVIO presented its full safety and efficacy data set for the Phase 1/2 trial in which INO-3107 was shown to be well tolerated and have clinical benefit experienced a decrease in the number of surgical interventions in the year after treatment when compared to the year before treatment These data were presented at both the International Society of Vaccines Conference and the Fall Voice Conference the overall clinical response (OCR) was 81% with 26 of the 32 enrolled patients experiencing a decrease in the number of surgical interventions in the year after INO-3107 administration compared to the prior year including 28% (9/32) that required no surgical intervention (i.e. 44% (14/32) of patients had a partial response (PR) in the number of surgeries when compared to the prior year The overall response rate (ORR) of patients (CR+PR) was therefore 72% (23/32). Other key data points presented include: INOVIO's balance sheet and statement of operations are provided below. Additional information is included in INOVIO's quarterly report on Form 10-Q for the quarter ended September 30, 2024, which can be accessed at: http://ir.inovio.com/financials/default.aspx Cash GuidanceINOVIO estimates its cash runway to extend into the third quarter of 2025 This projection includes an operational net cash burn estimate of approximately $24 million for the fourth quarter of 2024 Contact:Media: Jennie Willson (267) 429-8567 [email protected]Investors: Thomas Hong (267) 440-4298 [email protected] including our plans to develop and commercialize DNA medicines and our expectations regarding our research and development programs including the planned initiation and conduct of clinical trials and the availability and timing of data from those trials expectations regarding INO-3107's potential to be an important therapeutic option for RRP patients and the preferred choice of RRP patients as well as plans for discussions with regulatory authorities the planned commercial launch of INO-3107 if regulatory approval is obtained and expectations with respect to our cash resources into the third quarter of 2025 and expected cash burn for the fourth quarter of 2024 Prepaid expenses and other current assets from affiliated entity Accounts payable and accrued expenses due to affiliated entity Grant funding liability from affiliated entity CONSOLIDATED STATEMENTS OF OPERATIONS  Gain (loss) on investment in affiliated entity Net unrealized gain (loss) on available-for-sale equity securities           Basic and diluted (1) Weighted average number of common shares used to compute net loss per share (1)  Share and per share amounts have been restated to reflect the 1-for-12 reverse stock split effected in January 2024 on a retroactive basis for all periods presented Earnings Poster will describe loss of detectable HPV-6 in Recurrent Respiratory Papillomatosis patients following treatment with INO-3107 PLYMOUTH MEETING, Pa., Feb. 10, 2025 /PRNewswire/ --  INOVIO (NASDAQ:INO) today announced that an abstract describing the immunological activity of INO-3107 will be presented as a poster at the following scientific conference: American Association for Cancer Research – Immuno-Oncology Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy (February 23-26 2025) Poster entitled: "Loss of Detectable HPV-6 Following Induction of Emergent T cells in Patients with Durable Complete Clinical Response to Treatment for Recurrent Respiratory Papillomatosis using INO-3107" The abstract will be made available on INOVIO's website following the conference About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com Contacts Media: Jennie Willson, (267) 429-8567, [email protected] Investors: Peter Vozzo, ICR Healthcare, 443-213-0505, [email protected] PLYMOUTH MEETING, Pa., April 30, 2025 /PRNewswire/ -- INOVIO (NASDAQ:INO) and infectious diseases, today announced that it will be presenting at several upcoming conferences Citizens JMP Life Sciences Conference (NY)Date: May 8Time: 11:30am EDTFormat: Fireside Chat(audio webcast available here: https://wsw.com/webcast/jmp65/ino/1544620) ContactsMedia: Jennie Willson, (267) 429-8567, [email protected] Investors: Peter Vozzo - ICR Healthcare, (443) 213-0505, [email protected] PLYMOUTH MEETING, Pa., Oct. 21, 2024 /PRNewswire/ -- INOVIO (NASDAQ:INO) today announced the presentation of new data at scientific conferences for its lead candidate for which the company is preparing a Biologics License Application for targeted submission in mid-2025 under the U.S Food and Drug Administration's Accelerated Approval Pathway Program At AACR's Tumor and Immunology Conference on October 19 INOVIO presented new immunology data demonstrating the ability of INO-3107 to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of those T cells into airway tissues and papilloma of RRP patients which could ultimately slow or eliminate papilloma regrowth INOVIO will tomorrow present its full safety and efficacy data set for the Phase 1/2 trial for INO-3107 at the International Society of Vaccines Conference INO-3107 was found to be well tolerated and immunogenic "The new immunology data support the proposed mechanism of action of INO-3107 which is to generate an immune response that can seek out and eliminate HPV-6 and HPV-11 infected cells that are the underlying cause of papilloma growth," said Dr INOVIO's Vice President of Translational Science. "Our analysis shows that INO-3107 induced significant clonal T cell expansion in the blood Investigators also observed T cell infiltration into airway tissue which is positively associated with clinical response." "The collective story these data sets provide is compelling Over 81% of patients who received INO-3107 required fewer surgical procedures compared to baseline a result that is further supported by the new immunology data demonstrating the ability of INO-3107 to stimulate the immune system and generate antigen-specific T cells that travel to the airways and could eliminate the underlying disease," said Dr "We believe these data continue to demonstrate that INO-3107 has the potential to significantly improve the lives of patients living with RRP and become the preferred choice for the broadest number of RRP patients and healthcare providers." AACR Special Conference in Cancer Research: Tumor Immunology and ImmunotherapyAbstract: Reduction in Surgical Interventions for the Treatment of Recurrent Respiratory Papillomatosis by INO-3107 is Associated with Enriched Macrophage Dendritic cell and T cell Signatures in Patient Airways New Immunology data for INO-3107 demonstrated:  International Society of Vaccines ConferenceAbstract: Clinical Assessment of Adjuvant Immunotherapy in Adult Patients with Recurrent respiratory papillomatosis (RRP) Clinical Results of Phase 1/2 Study with INO-3107 in Adult RRP PatientsIn the trial complete response or "CR") during or after the dosing window 44% (14/32) of patients had a partial response ("PR") The overall response rate (ORR) of patients (CR+PR) was therefore 72% (23/32) The abstracts from the poster and presentations are available on the INOVIO events page: [tbd link] About INO-3107INO-3107 is a DNA immunotherapy designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins These targeted T cells are designed to seek out and kill HPV-6 and HPV-11 infected cells including 28.1% (9/32) that required no surgical intervention during or after the dosing window T-cell responses were also observed at Week 52 INO-3107 was well tolerated by participants in the trial resulting in mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue INO-3107 has demonstrated the ability to generate antigen-specific T cells that is not affected by anti-vector immunity impacting immunogenicity either before administration or after the first dose unlike other T-cell generating platforms such as viral vectors This feature of DNA medicines is expected to allow INO-3107 to maintain T cell response and overall efficacy which would make it an important therapeutic option for a majority of RRP patients The FDA granted INO-3107 Orphan Drug designation and Breakthrough Therapy designation and advised INOVIO that it could submit its BLA under the accelerated approval program using data from its already completed Phase 1/2 trial The European Commission granted INO-3107 Orphan Drug designation and assigned INOVIO's delivery device CELLECTRA® a CE marking a regulatory standard that certifies that a product has met European Union's safety ContactsMedia: Jennie Willson (267) 429-8567 [email protected]Investors: Thomas Hong (267) 440-4298 [email protected] PLYMOUTH MEETING, Pa., March 13, 2025 /PRNewswire/ -- INOVIO (NASDAQ: INO) today announced promising interim results from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs for COVID-19 100% (24/24) of participants who have reached week 72 maintained biologically relevant levels of DMAbs confirming the durability of in vivo antibody production no participant developed anti-drug antibodies (ADA) a common challenge observed in other gene-based delivery platforms such as adeno-associated virus (AAV) mediated antibody expression with the most common side effects being mild The trial is being led by The Wistar Institute in collaboration with INOVIO and clinical investigators at the Perelman School of Medicine at the University of Pennsylvania "This study provides the first clinical proof-of-concept that DNA-encoded monoclonal antibodies can be durably and tolerably expressed in humans," said David B Executive Vice President of The Wistar Institute and lead investigator for the study "These findings could represent a breakthrough as they demonstrate the potential of DMAb technology to overcome traditional monoclonal antibody production challenges making it a promising platform for a broad range of diseases This technology has the potential to transform treatments for infectious diseases as well as cancer and metabolic disorders by enabling long-term expression of therapeutic antibodies and other proteins." "One of the biggest hurdles for gene-based antibody delivery has been the immune system's response to the vector or the antibody itself leading to anti-drug antibodies that can limit how long a treatment will be effective," said Pablo Tebas a professor of Infectious Diseases at Penn "Our DNA-based approach has demonstrated sustained antibody expression without generating ADA And because antibodies are remaining active for longer our approach may be a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery." added: "We believe these data highlight the potential to apply our DNA Medicines technology to deliver a broad spectrum of therapeutic proteins that could be used to treat diseases with missing or defective proteins We'd like to thank our partners in advancing this important new technology and we look forward to working with them to complete this trial and on future research where we anticipate exploring broader applications of our technology for long-term therapeutic protein delivery." A manuscript describing interim results from the trial has been uploaded to Research Square for early dissemination and is under peer review by a leading scientific journal for publication The consortium plans to present interim results from the trial at upcoming scientific conferences in 2025.  About the Phase 1 TrialThe Phase 1 trial is the first clinical study to report using synthetic DNA technology to enable in vivo production of monoclonal antibodies directly from muscle cells Participants received an intramuscular (IM) injection of synthetic DNA plasmids encoding AZD5396 and AZD8076 (derived from AstraZeneca's cilgavimab and tixagevimab) delivered via INOVIO's proprietary CELLECTRA 2000 electroporation (EP) device This delivery method temporarily increases cell permeability which is intended to facilitate efficient DNA uptake and enable sustained antibody production Enrollment began in May 2022 and was completed in March 2024 The most common side effects observed were temporary local injection site reactions associated with the administration of the study product There were three SAEs all of which were considered unrelated to the study product the trial is led by The Wistar Institute in collaboration with INOVIO and clinical investigators at the University of Pennsylvania and Economic Security Act (CARES Act) and the Defense Advanced Research Projects Agency (DARPA) which are small circular DNA molecules that work like software that the body's cells can download to produce specific proteins to target and fight disease Forward-Looking StatementsThis press release contains certain forward-looking statements relating to INOVIO's business including the planned publication of data from clinical trials and the potential benefits of INOVIO's DMAb technology platform This project was supported by the Joint Program Executive Office for Chemical Radiological and Nuclear Defense (JPEO-CBRND) Joint Project Lead for Enabling Biotechnologies (JPL CBRND EB) in collaboration with the Defense Health Agency (DHA) COVID funding initiative for (Phase 1 dose-escalation trial of the safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies (DMAb) in healthy adults The views expressed in this press release reflect the views of the authors and do not necessarily reflect the position of the Department of the Army References to non-federal entities do not constitute or imply Department of Defense or Army endorsement of any company or organization financial consideration related to the licensing of certain Penn intellectual property to INOVIO Weiner is a member of the Scientific Advisory Board and Board of Directors for INOVIO ContactsMedia: Jennie Willson, (267) 429-8567, [email protected]Investors: Peter Vozzo - ICR Healthcare, 443-213-0505, [email protected] a biotechnology company specializing in DNA medicines for HPV-associated diseases has scheduled the release of its fourth quarter and year-end 2024 financial results for March 18 The company will host a live conference call and webcast at 4:30 p.m ET on the same day to discuss the financial results and provide a business update The webcast will include a Q&A session with analysts and will be available for replay for 90 days through the investor relations section of INOVIO's website un'azienda biotecnologica specializzata in medicine a base di DNA per malattie associate all'HPV ha programmato la pubblicazione dei suoi risultati finanziari del quarto trimestre e dell'anno 2024 per il 18 marzo 2025 L'azienda ospiterà una call e webcast dal vivo alle 16:30 ET lo stesso giorno per discutere i risultati finanziari e fornire un aggiornamento aziendale Il webcast includerà una sessione di domande e risposte con gli analisti e sarà disponibile per il replay per 90 giorni nella sezione delle relazioni con gli investitori del sito web di INOVIO una empresa biotecnológica especializada en medicamentos de ADN para enfermedades asociadas al VPH ha programado la publicación de sus resultados financieros del cuarto trimestre y del año 2024 para el 18 de marzo de 2025 La empresa llevará a cabo una conferencia telefónica y webcast en vivo a las 4:30 p.m ET el mismo día para discutir los resultados financieros y proporcionar una actualización empresarial El webcast incluirá una sesión de preguntas y respuestas con analistas y estará disponible para su repetición durante 90 días a través de la sección de relaciones con inversores del sitio web de INOVIO 암 및 감염성 질병을 위한 DNA 의약품을 전문으로 하는 생명공학 회사가 2024년 4분기 및 연간 재무 결과를 2025년 3월 18일 회사는 같은 날 오후 4시 30분 ET에 라이브 컨퍼런스 콜 및 웹캐스트를 개최하여 재무 결과를 논의하고 비즈니스 업데이트를 제공할 것입니다 INOVIO 웹사이트의 투자자 관계 섹션을 통해 90일 동안 다시 볼 수 있습니다 une entreprise biotechnologique spécialisée dans les médicaments à ADN pour les maladies associées au VPH a prévu de publier ses résultats financiers du quatrième trimestre et de l'année 2024 le 18 mars 2025 L'entreprise organisera une conférence téléphonique et un webinaire en direct à 16h30 ET le même jour pour discuter des résultats financiers et fournir une mise à jour sur l'entreprise Le webinaire comprendra une session de questions-réponses avec des analystes et sera disponible en rediffusion pendant 90 jours dans la section des relations avec les investisseurs du site Web d'INOVIO das sich auf DNA-Medikamente für HPV-assoziierte Krankheiten Krebs und Infektionskrankheiten spezialisiert hat hat die Veröffentlichung seiner Finanzergebnisse für das vierte Quartal und das Jahr 2024 für den 18 Das Unternehmen wird am selben Tag um 16:30 Uhr ET eine Live-Konferenzschaltung und einen Webcast veranstalten um die Finanzergebnisse zu diskutieren und ein Unternehmensupdate zu geben Der Webcast wird eine Fragerunde mit Analysten beinhalten und ist für 90 Tage über den Bereich für Investorenbeziehungen auf der Website von INOVIO verfügbar a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-associated diseases today announced that fourth quarter and year-end 2024 financial results will be released after the market close on March 18 INOVIO will host a live conference call and webcast at 4:30 p.m ET to discuss financial results and provide a general business update The live webcast will be available online at http://ir.inovio.com/events-and-presentations/default.aspx This is a listen-only event but will include a live Q&A with analysts The webcast will be archived and available for replay for 90 days following the event ContactsMedia: Jennie Willson, (267) 429-8567, communications@inovio.comInvestors: Peter Vozzo - ICR Healthcare, (443) 213-0505, investor.relations@inovio.com  View original content to download multimedia:https://www.prnewswire.com/news-releases/inovio-to-report-fourth-quarter-and-year-end-2024-financial-results-on-march-18-2025-302400150.html « Back INOVIO Pharmaceuticals (Nasdaq: INO) has announced the pricing of a $30 million public offering consisting of 10,000,000 shares of common stock and accompanying warrants The combined offering is priced at $3.00 per share with warrants exercisable at $3.76 per share and Citizens JMP as joint book-running managers The gross proceeds of $30 million are calculated before deducting underwriting discounts INOVIO Pharmaceuticals (Nasdaq: INO) ha annunciato il prezzo di un offerta pubblica da 30 milioni di dollari composta da 10.000.000 azioni ordinarie e relativi warrant L'offerta combinata è fissata a 3,00 dollari per azione con warrant esercitabili a 3,76 dollari per azione Si prevede che l'offerta si chiuda il 16 dicembre 2024 I proventi lordi di 30 milioni di dollari sono calcolati prima di dedurre sconti di sottoscrizione INOVIO Pharmaceuticals (Nasdaq: INO) ha anunciado el precio de una oferta pública de 30 millones de dólares que consiste en 10.000.000 acciones ordinarias y garantías asociadas La oferta combinada se fija en 3,00 dólares por acción con garantías ejercitables a 3,76 dólares por acción Se espera que la oferta cierre el 16 de diciembre de 2024 Los ingresos brutos de 30 millones de dólares se calculan antes de deducir descuentos de suscripción INOVIO Pharmaceuticals (Nasdaq: INO)는 가격을 발표했으며 INOVIO Pharmaceuticals (Nasdaq: INO) a annoncé le prix d'une offre publique de 30 millions de dollars composée de 10 000 000 actions ordinaires et de bons de souscription associés L'offre combinée est fixée à 3,00 dollars par action les bons de souscription étant exerçables à 3,76 dollars par action L'offre devrait se clôturer le 16 décembre 2024 et Citizens JMP en tant que co-gestionnaires Les produits bruts de 30 millions de dollars sont calculés avant déduction des remises de souscription INOVIO Pharmaceuticals (Nasdaq: INO) hat den Preis für ein Öffentliches Angebot von 30 Millionen Dollar bekannt gegeben das aus 10.000.000 Stammaktien und damit verbundenen Warrants besteht Das kombinierte Angebot wird mit 3,00 Dollar pro Aktie festgesetzt wobei die Warrants bei 3,76 Dollar pro Aktie ausgeübt werden können Dezember 2024 abgeschlossen werden und wird von Oppenheimer & Co und Citizens JMP als Joint Book-Running Manager verwaltet Die Bruttoeinnahmen von 30 Millionen Dollar sind vor Abzug von Underwriting-Rabatten 2024 /PRNewswire/ -- INOVIO Pharmaceuticals a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases Media: Jennie Willson (267) 429-8567 jennie.willson@inovio.comInvestors: Peter Vozzo, ICR Healthcare, 443-213-0505 peter.vozzo@icrhealthcare.com View original content to download multimedia:https://www.prnewswire.com/news-releases/inovio-announces-pricing-of-30-million-public-offering-302331073.html INOVIO Pharmaceuticals (Nasdaq: INO) announced plans for a proposed public offering of common stock and accompanying warrants focused on DNA medicines for HPV-related diseases and Citizens JMP are serving as joint book-running managers The offering is subject to market conditions It will be conducted under a shelf registration statement filed with the SEC on November 9 INOVIO Pharmaceuticals (Nasdaq: INO) ha annunciato piani per una proposta di offerta pubblica di azioni ordinarie e relativi warrant focalizzata sulla medicina genetica per malattie correlate all'HPV e Citizens JMP agiscono come joint book-running managers L'offerta è soggetta a condizioni di mercato Sarà condotta sotto un modulo di registrazione di shelf depositato presso la SEC il 9 novembre 2023 INOVIO Pharmaceuticals (Nasdaq: INO) anunció planes para una oferta pública propuesta de acciones ordinarias y warrants asociados enfocada en medicamentos de ADN para enfermedades relacionadas con el VPH y Citizens JMP están sirviendo como gerentes conjuntos de libro La oferta está sujeta a condiciones del mercado Se llevará a cabo bajo una declaración de inscripción de estante presentada ante la SEC el 9 de noviembre de 2023 y declarada efectiva el 31 de enero de 2024 INOVIO Pharmaceuticals (Nasdaq: INO)는 일반주식과 관련된 워런트를 제안하는 공모 계획을 발표했습니다 이 공모는 2023년 11월 9일 SEC에 제출된 선반 등록 명세서에 따라 진행되며 INOVIO Pharmaceuticals (Nasdaq: INO) a annoncé des projets pour une offre publique proposée d'actions ordinaires et de warrants associés axée sur les médicaments à ADN pour les maladies liées au VPH vendra tous les titres dans le cadre de l'offre et Citizens JMP agissent comme co-responsables de la gestion L'offre est soumise aux conditions de marché sans aucune garantie concernant son achèvement Elle sera réalisée dans le cadre d'une déclaration d'enregistrement de shelf déposée auprès de la SEC le 9 novembre 2023 INOVIO Pharmaceuticals (Nasdaq: INO) hat Pläne für ein proposed öffentliche Angebot von Stammaktien und den dazugehörenden Warrants angekündigt das sich auf DNA-Medikamente gegen HPV-bedingte Krankheiten Krebs und Infektionskrankheiten konzentriert wird alle Wertpapiere im Angebot verkaufen und Citizens JMP agieren als gemeinsame Buchführer Das Angebot unterliegt den Marktbedingungen November 2023 eingereichten Shelf-Registrierungsmitteilung durchgeführt View original content to download multimedia:https://www.prnewswire.com/news-releases/inovio-announces-proposed-public-offering-302330740.html has announced its participation in multiple high-profile scientific and investor conferences scheduled for May 2025 The company's focus will be on presenting new data regarding their promising lead candidate which is being developed to treat recurrent respiratory papillomatosis (RRP) caused by human papillomavirus (HPV) types 6 and 11 Key events on the agenda include the Citizens JMP Life Sciences Conference in New York on May 8 where a fireside chat will discuss the latest advancements and findings related to INO-3107 INO-3107 clinical results will be shared at the European Laryngological Society Annual Congress in Warsaw the American Society of Gene and Cell Therapy conference in New Orleans and the American Broncho-Esophagological Association (ABEA) program at COSM the largest meeting of otolaryngologists in the US INO-3107 has demonstrated a significant 81% reduction in surgeries for adults dealing with recurrent respiratory papillomatosis within the first year of treatment The DNA immunotherapy showcases potential irrespective of papilloma microenvironment and molecular subtype suggesting broad applicability across patient populations Abstracts of these presentations will be made available on INOVIO's website after the events and an audio replay of the Citizens JMP webcast will remain accessible for 90 days following the conference Add Comment|1INOInovio Pharmaceuticals Inc$1.951.56%Stock Score Locked: Want to See it?Benzinga Rankings give you vital metrics on any stock – anytime Inovio Pharmaceuticals Inc INO shares are trading higher by 17.9% to $2.27 Tuesday afternoon amid growing concerns about respiratory illnesses Increased attention to vaccine and therapeutic solutions this week has increased interest in biotechnology stocks focused on infectious diseases The Louisiana Department of Health also reported the first U.S a patient over 65 with underlying conditions who contracted the virus from birds with no further cases or person-to-person spread This may increase demand for avian flu vaccines and research Read Also: US Records First Human Bird Flu Death, High Levels Of Respiratory Illnesses: Vaccine Stocks Rally What Else: Inovio is known for its DNA-based vaccine technology platform particularly for markets seeking alternatives to traditional mRNA vaccines Inovio's portfolio extends beyond COVID-19 The company is advancing research on vaccines targeting a variety of infectious diseases and cancers with recent progress in its RSV and MERS vaccine programs enables the design and production of new vaccine candidates potentially positioning Inovio as a player in responding to emerging global health threats Read Also: Why Novavax Stock Is Rising By now you're likely curious about how to participate in the market for Inovio Pharmaceuticals – be it to purchase shares or even attempt to bet against the company Buying shares is typically done through a brokerage account. You can find a list of possible trading platforms here. Many will allow you to buy ‘fractional shares,' which allows you to own portions of stock without buying an entire share can cost thousands of dollars to own just one share if you only want to invest a fraction of that which is trading at $2.33 as of publishing time Stock Score Locked: Want to See it?Benzinga Rankings give you vital metrics on any stock – anytime Momentum3.06Growth-Quality-Value2.84Price TrendShortMediumLongOverviewMarket News and Data brought to you by Benzinga APIs© 2025 Benzinga.com Benzinga does not provide investment advice Posted In: Newswhy it's movingBenzinga simplifies the market for smarter investingTrade confidently with insights and alerts from analyst ratings free reports and breaking news that affects the stocks you care about and trade ideas delivered to your inbox every weekday before and after the market closes The following is a summary of “Impact of low dose inhaled nitric oxide treatment in spontaneously breathing and intubated COVID-19 patients: a retrospective propensity-matched study,” published in the October 2024 issue of Critical Care by Isha et al The effectiveness of inhaled nitric oxide (iNO) therapy for COVID-19-related ARDS is still unclear Researchers conducted a retrospective study assessing how iNO affects patients with COVID-19 needing respiratory support using data from a multicenter retrospective study They analyzed patients with COVID-19 from the SCCM VIRUS COVID-19 registry who were admitted to Mayo Clinic sites (March 2020 – June 2022) and needed high-flow nasal cannula (HFNC) patients were grouped as “spontaneously breathing” or “intubated.” Outcomes were examined using propensity score matching (PSM) and inverse propensity of treatment weighting (IPTW) analysis The results showed that among 2,767 patients 1,879 were spontaneously breathing (153 received iNO) and respiratory rate improved within 48 hours of iNO use iNO did not lower intubation risk in patients breathing spontaneously (PSM OR 1.08 It also showed that iNO reduced in-hospital mortality risk for spontaneously breathing patients (PSM HR 0.49 The use of iNO was also linked to longer hospital and ICU stays  Investigators concluded that iNO therapy lowered the in-hospital mortality risk for patients with spontaneous breathing suffering from COVID-19 on HFNC/NIV and improved oxygenation in both breathing groups Source: ccforum.biomedcentral.com/articles/10.1186/s13054-024-05093-w  The latest articles and insights from your colleagues in your specialty(ies) of choice SUBSCRIBE NOW View all newsletters Insights from the leaders in medical research Subscribe to our free Newsletters to receive weekly emails and even get a laugh or two from our medical cartoons SUBSCRIBE NOW About Physician’s Weekly Careers Memberships & Verifications Advertise With Us Our Partners Blog Terms & Conditions Privacy Policy Editorial Policy Contact Us The content of this site is intended for healthcare professionals Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views A profile showcasing an individual's professional experience A profile for companies that LinkedIn users can follow sit down on another episode of the NeuroOp Guru to discuss how modern high-resolution MRIs may miss up to a third of internuclear ophthalmoplegia (INO) lesions Editor's note - This transcript has been edited for clarity and welcome to another edition of the NeuroOp Guru And today we're going to be talking about how even modern high-resolution MRI could miss up to a third of internuclear ophthalmoplegia lesions So an internuclear ophthalmoplegia is caused by a lesion in the medial longitudinal fasciculus which connects the sixth nerve nucleus and contralateral third nerve sub-nucleus of the medial rectus And this is an important structure because it helps helps maintain lateral gaze you need your left eye sixth nerve to innervate your lateral rectus and your right third nerve to innervate the medial rectus And they have to do it in a coordinated manner So both eyes move at the same time as opposed to one eye and then the other eye oftentimes you see the one eye has an abduction deficit so it doesn't look well towards the nose and the other eye moves pretty well except it has a AB ducting nystagmus It can be associated with other findings like skew deviation But there's it's very well localizing and depending on your age group has very typical causes that we may need to identify because of other neurologic implications of this disease processes And it's different from our ischemic cranial nerve palsy is because this is in the brainstem you're at risk of having further strokes and assessments to decrease the risk of having further strokes And so what were the results of this study with MRI with INO So they looked at this the single institution and they looked at patients who had an INO and they had to have an MRI imaging on a 1.5 Tesla or three Tesla magnet They had to have good quality scans less than or equal to three millimeter axial slices And they were looking for T2 lesion and a newly diagnosed INO patient and so They had an independent review of of all of these MRIs by a neuroradiologist and they said that only 64% of them on the original report they did see a T2 hyperintense lesion on 73% of those MRI scans And in patients with demyelinating disease they were able to find a lesion of T2 hyperintensity in 76% And they only had diffusion weighted imaging changes in 43% shouldn't you see restricted diffusion or it's too small a lot of times these lesions are really small And I think that's the problem and it may not be quite as good in the brainstem because when you get to tissue interfaces there's a lot of distortion like it's really hard to see that in an ischemic optic nerve injury And you have–it's a small area and surrounded by cerebral spinal fluid and then you have the aqueduct there so you can get a lot of artifacts Shouldn't the demyelinating lesion that's acute be enhancing we'd like to think that the slices are perfectly correlated on your T2 and on your T1 post contrast but they might not be perfect and so you may miss it Do you admit the INO if it's a stroke I think most of them do get admitted for rapid stroke workup to see what risk factors they have and what we can do to minimize them But that doesn't mean they can't also have atrial fibrillation embolic disease from cardioembolic etiologies we definitely need to coordinate with their neurologist to say; Hey they're having active brainstem complications and that has a really poor long term prognostic factor or postdose IV steroids do help to speed recovery then usually they're gonna end up being admitted So what do you think the take home message for our audience is from this study I think the major take home point is the clinical exam is really crucial in these patients because it's going to tell you where the lesion is and tell you that it's a brainstem parenchymal lesion And that just because you don't see it on the MRI doesn't mean it's not real and the patient doesn't have a real disease and that does not have serious neurologic complications if it's not diagnosed and treated appropriately So I think all our general ophthalmologists and neuro ophthalmologists need to remember that the exam is important and coordinate with our neurology colleagues for the appropriate care of these patients The MRI just confirms what we already think And that MRI can tell us other things like is it multiple sclerosis or do they have other silent strokes occurring that you know but that specific lesions is a clinical diagnosis that concludes another edition of NeuroOp Guru Don’t miss out—get Ophthalmology Times updates on the latest clinical advancements and expert interviews ASCRS 2025: Visual and patient-reported outcomes following bilateral Odyssey implantation California dreaming: 2025 Glaucoma 360 brings celebration, innovation, and education to San Francisco (Part 1) From ophthalmology’s lockdown to lasting change: Five Aprils ago Connect, learn, and innovate in a family-friendly atmosphere: What to expect at EnVision Summit 2025 Piecing it together: Does semaglutide fit the NAION puzzle? Presbyopia treatment success begins with patient-centered care 609-716-7777 This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page 2024 (GLOBE NEWSWIRE) -- In a Fast-Track SWIFT challenge brought by competitor Vero Biotech BBB National Programs’ National Advertising Division recommended that Beyond Air discontinue the challenged comparative superiority safety claims for its iNO (inhaled nitric oxide) products or modify its advertising to avoid conveying the message that Beyond Air’s products are safer than Vero’s and/or that Vero’s products are unsafe Fast-Track SWIFT is an expedited process designed for single-issue advertising cases brought to the National Advertising Division (NAD) Vero and Beyond Air are competitors in the market for iNO delivery systems used to treat neonates with hypoxic respiratory failure associated with pulmonary hypertension At issue for NAD were Beyond Air’s claims that its products are safer than Vero’s including marketing materials in its Corporate Presentation and Fact Sheet which Vero argued misrepresented its products as unsafe or containing hazardous materials NAD recommended that Beyond Air discontinue or modify the challenged comparative superiority claims to avoid conveying the message that Beyond Air’s products are safer than Vero’s and/or that Vero’s products are unsafe Nothing in this decision precludes Beyond Air from making truthful and non-misleading safety claims about its products Beyond Air advised NAD that as of February 2024 it had permanently discontinued use of the “Fact Sheet.” NAD will treat the permanently discontinued “Fact Sheet” and claims contained therein as if NAD recommended that they be discontinued This press release shall not be used for advertising or promotional purposes About BBB National Programs: BBB National Programs currently operating more than a dozen globally recognized programs that have been helping enhance consumer trust in business for more than 50 years These programs provide third-party accountability and dispute resolution services that address existing and emerging industry issues create a fairer playing field for businesses BBB National Programs continues to evolve its work and grow its impact by providing business guidance and fostering best practices in arenas such as advertising About the National Advertising Division: The National Advertising Division (NAD) of BBB National Programs provides independent self-regulation and dispute resolution services guiding the truthfulness of advertising across the U.S NAD reviews national advertising in all media and its decisions set consistent standards for advertising truth and accuracy delivering meaningful protection to consumers and leveling the playing field for business Egge brings over 25 years of biopharmaceutical experience building commercial organizations and successfully launching novel therapeutic products INOVIO poised to become a commercial-stage company with plans to submit a Biologics License Application for INO-3107 in second half of 2024 under U.S Food and Drug Administration's Accelerated Approval Pathway PLYMOUTH MEETING, Pa., July 2, 2024 /PRNewswire/ -- INOVIO (NASDAQ:INO) today announced the appointment of Steven Egge as Chief Commercial Officer Egge will lead the company's commercial strategy and operations as it prepares to potentially launch its first DNA medicine product INO-3107 as a treatment for recurrent respiratory papillomatosis (RRP) "We are delighted to welcome Steve to INOVIO and look forward to adding his expertise to our leadership team as we continue advancing our preparations to commercially launch INO-3107 in 2025 should it receive approval by the FDA as a treatment for RRP," said Dr as we prepare to become a commercial-stage company while advancing multiple product candidates targeting unmet medical needs driving market share in competitive environments and growing overall therapeutic areas will be advantageous to the development and implementation of our commercial plans as will his experience across immunology and vaccines "This is a great time to join INOVIO as the company has the opportunity to market the first therapeutic option for patients suffering from RRP a rare and debilitating HPV-related disease that significantly impacts quality of life," said Mr "I look forward to working with the talented team at INOVIO and continuing the ongoing efforts to build out the company's commercial strategies and capabilities." Egge comes to INOVIO from Sumitomo Pharma (formerly Myovant Sciences where as Senior Vice President and General Manager for Women's Health he was responsible for building the commercial leadership team accelerating the launch of Myfembree® and helping lead the company's expansion into new indications where he held a number of senior commercial leadership roles including leading Merck's HPV Vaccines Franchise as well as Chief Marketing Officer for the Vaccine Division where he oversaw launches for new indications for GARDASIL® and launch planning for GARDASIL9® and VAXELIS® Egge also served as Global Commercial Head for Merck's Fertility Franchise where he oversaw the launch of ELONVA® in ex-U.S Egge served as Senior Vice President at Genfit Corp. a French biotech company focused on liver diseases where he led commercial planning and business development CELLECTRA® is a trademark of INOVIO.GARDASIL® ZOSTAVAX® and ELONVA® are trademarks of Merck and Co. Inc.VAXELIS® is trademark of The MSP Vaccine Company.Myfembree® is trademark of Sumitomo Pharma Switzerland GmbH including the planned submission of a BLA in the second half of 2024 and the planned commercial launch of INO-3107 if regulatory approval is obtained our Quarterly Report on Form 10-Q for the quarter ended March 31 ContactsMedia: Jennie Willson (267) 429-8567 [email protected]Investors: Thomas Hong (267) 440-4298 [email protected] 2024 (GLOBE NEWSWIRE) -- SROA Capital announced today its partnership with INOArmor a pioneer in bio-materials packaging and protection SROA Capital owns and operates 650 self-storage facilities across 31 states under its flagship brand and other initiatives to reduce its carbon footprint and costs over time It is in the process of exploring the addition of EV charging stations at some of its facilities SROA considers two goals— pursuing economic value and positive social and environmental impacts SROA will be the first in its industry to offer a 100% biodegradable packing product to replace bubble wrap across all its stores in the USA INOArmor’s innovative lightweight padding material uses natural silk cocoons known for their dome structure and natural strength providing excellent impact absorption and biodegrading completely at the end of their useful life a non-toxic bioplastic produced by bacteria which composts readily in various environments INOArmor launched a home compostable bag with Pantalones Organic Tequila co-founded by Matthew and Camila McConaughey for Earth Day 2024 and has since expanded to other partners in multiple industries “We are honored to partner with such forward-looking and successful partners like Ben Macfarland and SROA Capital We are very excited to collaborate and build multiple products with SROA over the next few years to help them meet their sustainability initiatives.” By incorporating INOArmor’s patented Silk Pillow Technology SROA is initiating a multi-year strategy to offer more sustainable home-compostable alternatives at all of its stores Biodegradable Packing Material by SROA Capital and INOArmor About SROA CapitalSROA Capital is a vertically integrated private equity real estate and technology platform that has an established track record of providing risk adjusted returns to its partners through its focused strategy of investing in self storage on behalf of its principals and partners and developed self storage across the risk spectrum in major and secondary markets across the United States under the brand Storage Rentals of America and the United Kingdom under the brand Kangaroo Self Storage For more information, please visit SROACapital.com About INOArmorINOArmor has innovated a patented and impact-resistant material composite that can be used as an alternative to synthetic foam for protecting and insulating products during shipment and storage INOArmor’s founder suffered a life-threatening brain injury and partnered with the neurosurgeon who saved his life along with a renowned Oxford materials scientist For more information, please visit INOArmor.com or follow us on Instagram at @inoarmor Media Details:INO Armor, LLCwww.inoarmor.comhello@inoarmor.comNew York Add Comment|1INOInovio Pharmaceuticals Inc$1.86-%Stock Score Locked: Want to See it?Benzinga Rankings give you vital metrics on any stock – anytime Shares of Inovio Pharmaceuticals Inc INO pulled back by 5.3% to $2.16 during Wednesday's session, following a strong rally Tuesday The decline may be attributed to profit-taking, as investors assess renewed focus on respiratory illnesses, with increased cases of influenza, COVID-19 and RSV driving interest in vaccine developers particularly as alternative vaccine technologies gain traction The company is also advancing its broader pipeline While Wednesday's profit-taking reflects typical market volatility following a sharp rise Inovio's long-term prospects remain tied to its ability to advance its portfolio and demonstrate the effectiveness of its DNA-based vaccine platform in addressing global health challenges Read Also: Quantum Stocks Tumble: Why Rigetti, IonQ and D-Wave Are Falling Besides going to a brokerage platform to purchase a share – or fractional share – of stock you can also gain access to shares either by buying an exchange traded fund (ETF) that holds the stock itself or by allocating yourself to a strategy in your 401(k) that would seek to acquire shares in a mutual fund or other instrument An ETF will likely hold shares in many liquid and large companies that help track that sector allowing an investor to gain exposure to the trends within that segment According to data from Benzinga Pro, INO has a 52-week high of $14.75 and a 52-week low of $1.74. Momentum3.01Growth-Quality-Value2.83Price TrendShortMediumLongOverviewMarket News and Data brought to you by Benzinga APIs© 2025 Benzinga.com Our #1 AI Stock Pick is on a steep discount - 29.99$ instead of 99.99$! Click here to access exclusive research Inovio Pharmaceuticals, Inc. (NASDAQ:INO) Q4 2024 Earnings Call Transcript March 18 and welcome to the Inovio Pharmaceuticals Fourth Quarter 2024 Financial Results Conference Call we will conduct a question-and-answer session [Operator Instructions] This call is being recorded on Tuesday 2025 And I would now like to turn the conference over to Ms and thank you for joining the Inovio fourth quarter 2024 financial results conference call Joining me on today’s call will be Jacqui — Dr Today’s call will review our corporate and financial information for the quarter and year ended December 31 as well as provide a general business update we will conduct a question-and-answer segment we will be making forward-looking statements regarding future events and the future performance of the company These events relate to our business plans to develop Inovio’s DNA medicines platform which include clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions along with capital resources and strategic matters All of these statements are based on the beliefs and expectations of management as of today Actual events or results could differ materially We refer you to the documents we file from time-to-time with the SEC identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon’s press release And a replay will be made available shortly after this call is concluded I will now turn the call over to Inovio’s President and CEO and thank you to everyone for joining today’s call we remain focused on transforming Inovio into a commercial stage company and delivering on the promise of DNA medicines for patients and shareholders alike our work this year will be driven by three main strategic priorities: submitting our BLA for INO-3107 a lead candidate for recurrent respiratory papillomatosis; advancing our commercial plan and preparing for a fast and efficient launch; and leveraging the strengths of our platform to drive progress across our diversified pipeline and I’m very pleased to report that we have resolved the previously announced manufacturing issues involving the single-use array component of the CELLECTRA device Our next step is to perform the FDA required device verification testing known as DV testing for the combined handset and single use array required for our IND and BLA submission We now plan to begin submitting our BLA under the FDA’s rolling submission process as well as commencing our confirmatory trial and requesting priority review in mid-2025 we anticipate being able to complete rolling submission in the second half of the year to enable the FDA to accept our BLA filing before the end of the year 3107 could be the preferred non-surgical treatment for RRP for both patients and their physicians a position that is strengthened by the year two and year three clinical data announced in December and the detailed immunology data we published in February Mike will provide more detail later in the call patients showed continued improvement in reduction in surgery after year one with 50% meeting criteria for complete response in the second 12 month period or year two the mean number of surgeries across the patient population continued to decrease into year three The ongoing efficacy was observed — observed is also supported by the immunology data published in Nature Communications demonstrating the ability of 3107 to drive an anti-viral immune response in airway tissue that correlated with a reduced or eliminated need for surgery We also have published the full safety and efficacy data set for the completed Phase 1/2 trial which shows that the administration of 3107 was well tolerated 3107 offers significant and durable clinical benefits tolerability and a simple patient centric dosing regimen that does not require scoping or surgery during the dosing window all of which we believe could be compelling advantages once on the market While our immediate focus is on advancing 3107 I’m also pleased to provide an important update from our work on next generation DNA medicines we recently announced top line interim results from an ongoing Phase 1 trial with our DNA-Encoded Monoclonal Antibodies technology This proof-of-concept trial involves two DMAbs targeting SARS-CoV-2 and showed that they can be durably and simultaneously produced in humans at biologically relevant levels We believe this technology has the potential to overcome some of the biggest challenges with traditional recombinant monoclonal antibodies and could also transform treatment for broad range of diseases by enabling long-term in-vivo production of therapeutic antibodies or other proteins Now I’ll turn it over to Mike for some additional insights on our progress and new data on 3107 we have made tremendous progress towards our primary goal We have now completed the drafting of all non-device modules And after extensive testing and internal quality sign-off we have resolved the previously announced manufacturing issue involving the single use array component of the CELLECTRA device our device team strengthened key components and refined the production process for the plastic molded part of the array We have tested the new array under similar testing conditions to when the issue was first identified and have not been able to reproduce the breakage which gives us great confidence that the modifications have resolved the issue We began manufacturing our new commercial grade arrays which will now be utilized in the design verification testing so we can move forward to completing our IND and BLA submissions the full Phase 1/2 clinical data and accompanying detailed immunology data were recently published in Nature Communications These data further support the T-cell mechanism of action for 3107 which underpins the efficacy results we’ve seen We also announced some very exciting clinical durability data showing that patients treated with 3107 continue to show further reduction in the need for surgery to manage their disease in the second and third year This data will be the subject of an oral presentation at the Combined Otolaryngology Spring Meeting to be held in New Orleans this May one of the most frequented meetings by our target physicians treating RRP We’ve also made important progress in preparing for our Phase 3 confirmatory trial this will be a randomized placebo controlled trial enrolling patients with two or more surgeries in the prior year conducted at approximately 20 sites at major U.S This progress to date will enable us to enroll in a timely manner following submission of our updated IND I’d like to spend some time now discussing the new data as it paints a compelling product profile that strengthens our belief that 3107 could be the preferred product for RRP patients and their physicians we completed a Phase 1/2 open label trial of 3107 in patients who required at least two surgeries in the previous year for the removal of HPV-6 and 11 related papillomas It’s important to note that based on our understanding of the risk and cost to the patient of every single surgery every surgery performed after day zero was counted against the efficacy endpoint in our trial where we followed the patients for 12 months a retrospective trial in which we were able to collect data on 28 of the original 32 patients to assess the longer-term treatment effect with a median follow-up of 2.8 years and duration of efficacy is clearly important looking at the longer-term efficacy results we observed in the trial We were very pleased to see that patients continue to show improvement into years two and three following their initial dosing regimen the complete response rate increased to 50% for the second 12 month period when evaluated at the end of year two that is the number of patients that had 50% to 100% fewer surgeries compared to their pretreatment baseline increased from 72% in the first 12 month treatment period or year one to 86% for the second 12 month period or year two When you look at this in terms of the average or mean number of surgeries this patient group faced it reduced by more than half from a mean of 4.1 surgeries per year prior to treatment to a mean of 1.7 surgeries at the end of year one and then reduced further by the end of year two to a mean of 0.9 surgeries Across the population of patients treated with 3107 this is a reduction of greater than 75% following the initial treatment regimen alone one of the core strengths of our DNA medicines platform is the ability to administer additional doses to continue to drive an amplify strong T-cell based immune responses without having to worry about the impact of an anti-vector response Looking again at the mean surgeries per year across the population we saw a significant decrease in the year following treatment and then a further decrease in the second 12 month period or year two the improvement seems to be holding steady And what we would like to be able to do is consider a longer term treatment strategy that supports both the maintenance of that complete or partial response and potentially extending clinical improvement including the potential for non-responders to mount a clinical response We have published data from a similar DNA medicine that targeted the E6 and E7 antigens of HPV-16 and 18 that demonstrated we were able to augment the CD8 T-cell responses with a single additional dose given after completion of the primary treatment course when compared to pre dose levels This further increase in cytotoxic T-cells supports the potential of extending the duration and improving upon the already excellent clinical response that we have seen to date and our vision for INO-3107 is to further minimize or eliminate future surgeries for all RRP patients the immunology data we’ve recently published becomes important here as it underpins the mechanism of action of 3107 and how we believe treatment is providing the favorable efficacy results we observed we found that all the patients were generating the right kind of anti-viral immune responses to fight HPV specifically antigen specific cytotoxic T-cells And then we saw that these T-cells really got where they needed to go traveling from the blood into the airway and papilloma tissue which we believe is responsible for reducing or eliminating the need for surgery by eradicating HPV infected cells I would also like to note that while other investigators have suggested that multiple factors such as high viral loads or neutrophil infiltration in the papilloma microenvironment can be barriers to immunotherapy treatment of RRP We didn’t see any such factors impacting the efficacy we observed in the trial While all patients were generating the right kind of immune response this response wasn’t as large and tended to decrease faster than in our responders which again is why we believe continued treatment may improve clinical outcomes in these patients our immunology data provide a clear demonstration of the mechanism of action behind INO-3107 showing that it is doing exactly what is needed to treat the underlying HPV infection that causes RRP I want to provide some additional detail on our next steps for 3107 we have commenced the manufacturing of the new arrays which we will subsequently age condition and utilize in the conduct of the FDA required design verification or DV testing process which we anticipate will be completed in the first half of this year This testing is required to update the IND before we can dose patients in our confirmatory trial and is also part of the last remaining module of our BLA package we need to complete We plan to request rolling submission and priority review of our BLA we will begin submitting our modules in mid-2025 and complete the full submission three to four months later with the goal of having the FDA accept our complete BLA for filing by the end of the year we plan to finalize our long-term dosing study strategy and submit a proposed protocol to the FDA to support a supplemental BLA in the future We also look forward to commencing onboarding of our field medical science liaison team and presenting this exciting data package at several upcoming conferences this spring I will now turn it over to our Chief Commercial Officer Mike shared by reviewing why our work on RRP is so important why 3107 could be the product of choice for patients and providers and what we’re doing to prepare for potential commercialization RRP is a rare HPV related disease that affects around 14,000 people in the U.S It’s characterized by work like growth called papilloma to grow in the respiratory tract and can cause difficulty speaking swallowing and breathing and repeated surgery is the standard of care today Every one of these surgeries matters to patients because every surgery poses a risk of irreversible damage to the vocal cords and carries costs the significant time and stress of preparing for and recovering from each surgery Patients and their providers want a non-surgical option for RRP that addresses the underlying disease and that ultimately helps them avoid additional surgeries We designed 3107 with the patient experience in mind and we believe it has the potential to become the preferred treatment option for RRP based on the efficacy and tolerability results we’ve observed to date as well as the simple patient centric treatment regimen not only do we observe favorable efficacy results in patients treated with 3107 we saw continued improvement into the second 12 month period or year two for both complete and overall response rates 3107 was well tolerated in the trial and there were no discontinuation 3107 offers a simple patient centric treatment regimen that does not require additional potentially unnecessary scoping and procedures during the treatment window 3107 offers office based administration without the need for referral a preference that many physicians shared with us in market research We’ve shared a few other insights on this slide from that research reinforcing our belief in the strength of 3107’s product profile Laryngologist told us the complete response rate of 50% is good but a 50% to 100% reduction in surgeries in eight out of 10 patients is the most compelling they quickly move to think about how they would describe the product to their patients And they indicate they like being able to say the vast majority of patients see significant benefit from treatment both the tolerability profile and simple patient focused treatment regimen were very well received by laryngologists I’d like to share just a few updates on our commercial launch preparations including developing our distribution channel strategy and identifying channel partners developing our initial pricing strategy and completing targeting segmentation and product positioning work to establish positive differentiation We’re currently developing our go-to-market model and planning a further build out of the commercial organization Given the RRP market is highly concentrated with the majority of RRP patients treated by relatively few laryngologists we believe we will need a small and efficient field force footprint but I’m energized by what we’ve built so far and look forward to providing an update on our progress next quarter While 3107 is at the forefront of our work we are excited about the opportunities to leverage the strengths of our platform across the pipeline including what we see as the next generation of DNA medicine technology Harnessing the power of in vivo protein production and enabling the body to generate its own disease fighting tools is a key strength of our DNA medicine platform and our DMAb technology leverages that strength in another way Using our proprietary gene sequence optimization technology we can create precisely designed DNA plasmids that encode for specific monoclonal antibodies can then be delivered directly into muscle cells in the arm using our CELLECTRA delivery system The heavy and light chain proteins that make up the DMAbs are produced and then assembled into functional antibodies within the muscle cells and are then secreted into the blood where they can circulate within the body This contrasts with conventional monoclonal antibodies which are manufactured in in-vitro systems and then need to be administered through regular infusion or injection We recently announced top line interim clinical data from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs for COVID-19 led by Wistar Institute in collaboration with AstraZeneca the University of Pennsylvania and INOVIO and funded by DARPA and JPEO this trial has provided the first clinical proof-of-concept that DMAbs can be durably and simultaneously produced inside the human body we saw long lasting in-vivo antibody production with DMAb levels remaining stable for 72 weeks in all participants who have reached that time point No antidrug antibodies or immune rejection of the DMAb was detected across approximately 1,000 blood samples unlike other gene based antibody delivery approaches And treatment was well tolerated with the most common side effects being mild temporary injection site reactions such as pain and redness and no serious adverse events related to study drug And we saw that the express DMAbs successfully balanced the SARS CoV-2 spike protein receptor-binding domain confirming functional activity through week 72 I also just want to point out that the panel on the right hand side of the slide shows the representative data from one dose level cohort from the trial The consortium plans to present its important clinical data in the first half of the year at various scientific conferences and has submitted a manuscript to a leading peer review journal which is currently available in preprint on Research Square We believe this technology could have the potential to be a breakthrough that could overcome many of the challenges seen with traditional monoclonal antibody production temperature stable storage and distribution and the ability to redose reduce cost and enable access in low resource settings our DNA based approach has demonstrated sustained antibody production without generating antidrug antibodies making it a potentially promising long term solution for conditions requiring continuous therapeutic protein delivery We see broad potential for this technology and we and our partners at Wistar have been investigating the feasibility of DMAb across multiple disease targets mostly in a preclinical setting from flu to HIV to cancers and to the most recent clinical trial targeting COVID-19 I believe this is an excellent example of how we’ve been able to work through partnerships with non-dilutive funding to advance our DNA medicines platform We look forward to continuing working with our partners to complete the current Phase 1 trial and on future research where we plan to explore a number of these broader applications of our technology for long-term therapeutic protein delivery You’ll see here that we have two other novel technologies in the preclinical stage DNA launch nanoparticle or DLNP candidates addressing infectious diseases And following on from my comments on DMAb DNA encoded protein replacement candidates or DPROT addressing various disease targets where disease is caused by missing or defective protein These fall into that next generation category of our technology and we’re very excited about what the future holds for these novel approaches we’re leveraging the opportunity to build on our extensive experience in HPV related diseases and advancing plans for a Phase 3 trial to evaluate INO- 3112 in combination with the FDA approved PD-1 inhibitor LOQTORZI high risk HPV-16 and 18 positive throat cancer With the trial planned across both North America and Europe we’ve discussed the trial design with FDA and most recently received some initial feedback from the European regulators on the trial design We believe our current sign will be sufficient to address those comments and our next steps include finalizing the trial protocol and completing manufacture of the candidate We’re also advancing discussions on the design for a Phase 2 trial of INO-5401 in newly diagnosed glioblastoma and we look forward to advancing this and other promising candidates through collaboration and other potential strategic opportunities I will now turn it over to our Chief Financial Officer I’d like to provide an overview of Inovio’s financial results for the fourth quarter and full year of 2024 being ready to begin the submission of our BLA in mid-2025 and ensuring that we have the resources to support this critical work we raised more than $72 million in gross proceeds from two equity offerings in April and December of 2024 and from equity sales from our ATM We also continue to decrease operational spending with our total operating expenses dropping from $27.5 million in fourth quarter of 2023 to $20.5 million in the fourth quarter of 2025 Our full year operational expenses decreased 22% from $144.8 million in 2023 to $112.6 million in 2024 Inovio’s net loss for the fourth quarter of 2024 was $19.4 million or $0.65 per share basic and dilutive and our total net loss for the full year of 2024 was $107.3 million or $3.95 per share basic and dilutive We finished the fourth quarter of 2024 with $94.1 million in cash cash equivalents and short-term investments compared to $145.3 million We estimate our cash runway to take us into the first quarter of 2026 our first quarter operational net cash burn runs higher than other quarters These cash projections — this cash runway projections do not include any further capital raise activity that Inovio may undertake you can find our full financial statements in this afternoon’s press release as well as in our Form 10-K filed with the SEC I’d now like to open up the call to answer any questions you might have [Operator Instructions] And your first question comes from the line of Roy Buchanan from Citizens Glad to hear you’re on track with 3107 So we actually held a pre-BLA meeting with the FDA prior to the single-use array breakage that we found and have now resolved we actually had very good alignment with all the remaining modules we — as soon as we complete the device modules we plan to hopefully start rolling submission in the middle of next — of this year as all the other remaining modules are complete we don’t need to have another meeting but we do need to request the rolling submission but is that a single test or do you need to repeat a whole battery of tests And are you doing that yourself or is it a third-party So we need to repeat a number of the tests required for device verification or DV testing where we’re testing the array in combination with the handset So we need to repeat a number of those different tests And we use an external testing house to do that So we’ve previously worked extensively with the testing house And there’s also some external certification that’s required as part of this process that goes into our BLA as well I think you’ve covered all the major points I thought the data in the publication is pretty compelling clearly differentiated from mRNA even self-amplifying RNAs in terms of durability But I didn’t see anything in the publication about half life Seems like it’s clearly longer than even the extended half-life antibodies that you’re expressing Do you have any sense of what the half-life from the DNA constructs themselves might be in people I’m not sure if we’ve released all of that data yet What we do have in the publication is some details of some modifications we’ve made for these particular monoclonals to extend half-life So happy to follow-up with you after the call on the specific details of those I know you mentioned some other wide range of potential applications for the technology and the publication mentions [Indiscernible] for example Do you have any — anything you can disclose today about potential programs over the next 24 months or so we were really excited to see that the level of functional antibody production that we saw over such a long time period and the fact that we didn’t see any antidrug antibodies at all coming up we shared with you a broad range of other targets that we previously worked on and are working on and we hope to provide further updates on those targets in due course But we’re really excited by the power of this technology and the level that we’re producing these antibodies at the moment is biologically relevant and spans the levels needed for a wide range of targets And your next question comes from the line of Jay Olson from Oppenheimer congrats on resolving the manufacturing issues with the CELLECTRA device We had a question about the timeline for testing and validation of the new manufacturing process and how long it takes for validation before including the new manufacturing information in your filing package I’m just really thrilled and delighted that we fixed the snap frame part the single use array component of the device that broke The process did take a little longer than we initially expected as we needed to make some design changes to the part which also required us to improve the actual molding process we started manufacturing new arrays and we plan to start device verification testing very soon And we anticipate we’re going to complete all of that in the first half of this year we’ll reach out to the FDA and request rolling submission of the BLA Since we have all of the other modules completed and ready for submission we expect to begin submitting the modules in mid-year and anticipate being able to complete the submission three to four months later with the expectation that FDA will accept full BLA for review prior to the end of the year Thank you so much for that detailed explanation Do you need to initiate the confirmatory study before the BLA submission Jacqui Shea: So we — do need to initiate the confirmatory trial before the BLA submission but we’ve made really good progress in terms of doing that we’ve previously talked that we have identified the majority of the sites We’ve actually advanced contracts and actually have IRB approvals at several sites So the whole reason the FDA usually ask you to commence that trial is so that they can feel confident that you are going to meet the commitment to complete the study We’ll be very easily able to demonstrate to the FDA the seriousness we’re approaching the study and the fact that we want to complete enrollment and the study as quickly as possible Thanks again for taking the questions and congrats on all the progress And your next question comes from the line of Sudan Loganathan from Stephens and thank you for giving this update and congrats again on the great progress here with this CELLECTRA device and resolving those issues aside from the initiation of the confirmatory trial needed to submit for the BLA is there anything else holding you back from just starting to submit the non-device component modules of the BLA now and starting the rolling process that way versus waiting a few more months to start submitting everything we have all of the other modules ready to go FDA normally once you’ve started rolling submission FDA normally like you to submit all of your modules in a three to four month timeframe But it is a discussion that we can have with the FDA as to when we can start rolling submission And I think the important thing is that we start our DV testing have made good progress on the DV testing before we set that end timeline for when we’re going to deliver all of the modules to the BLA So I think the guidance that we’re providing at the moment is that we’re going to start rolling submission mid-year and we expect to complete that within three to four months we’re going to try and accelerate things as much as possible Everyday matters to our RRP patients and we’re very conscious of that And quickly just to hopefully jog my memory better the breakage of the CELLECTRA device component was discovered previously or did — yeah were you able to get to the DV testing point last time we were pretty far through our DV testing when I believe we identified the issue with the single use array we identified the issue following the age conditioning with the — as part of the progress that we made and how we develop this We actually have already aged some of the arrays in similar manner and actually performed the testing So we really are confident that we will — we’ve resolved the issue have to actually repeat the formal aging and the formal testing once we have actually signed off the fix which we have done and we’ve started manufacturing those sort of commercial grade arrays But we do not expect to see any issues going forward with the array Just given the context for the RRP patients often require multiple surgeries per year and the substantial health care costs and risks associated with that Has there been any health economist or payer research conducted yet on the potential pricing or the advantages of therapeutics such as 3107 that would in savings providers and/or the health care facilities and the system in general Or is that something that could come maybe after approval once we kind of get a better idea of pricing if that’s anything has been done on your end on that So we’ve done a fair amount of research with payers where we reviewed product profile reviewed budget impact models and talked to them about kind of price ranges So kind of what we’ve shared is that could be a pretty big range anywhere from $200,000 to $2 million a year But one analogy that we look at that’s pretty close The standard-of-care kind of prior to that launching was repeated surgeries They’re in the price range of $360,000 per year that’s kind of a price that we referenced And the feedback that we’ve gotten from payers is that that kind of rare disease pricing range is very acceptable to them kind of with rare disease pricing if that helps Thank you again for all the answers here and congrats again on all the progress and looking forward to the progress going forward And your next question comes from the line of Yi Chen from H.C Regarding the utility of the DMAb technology particularly in terms of the Phase 1 proof-of-concept trial evaluating DMAb causing COVID-19 could you tell us how durable is the in-vivo antibody production in case the produced antibody has some undesirable effects is there a way that you can turn off the antibody production So in terms of how durable the antibody production is we presented and if you take a look at the preprint as well we’re now out for 72 weeks and we’re not seeing any drop in terms of the levels that we’re seeing secreted into the serum So our production seems to be holding up over 72 weeks So we think that’s really excellent durability And then in terms of future clinical trials we’re excited by what this technology could mean across a wide range of targets There are either inducible or repressible [indiscernible] that you could use to turn off the genes or turn on the genes to be able to control expression we’ll be focused on targets that were already in the right therapeutic range and where there’s less concern about potentially turning off those antibodies So I think those will be the targets that we focus on initially is it primarily produced in certain parts of the body or it’s produced throughout the body So we’re administering our DMAbs into the deltoid muscle in the arm And the DMAbs are actually produced within the myocytes within the muscle cells They’re produced as heavy and light chain proteins which then are self-assembled and then are secreted into the bloodstream from the myocytes So it’s actually production in these muscle cells And your next question comes from the line of Gregory Renza from RBC Capital Markets Congrats on the progress this quarter and thanks for taking our questions what are your going assumption for labeling And what particular points would you like to see that could play to the strengths of your program both on its own merits and even over competitors really confident in the very strong product profile that we’re seeing with INO-3107 with — we’ve observed great and durable efficacy The treatment’s been very tolerable we’ve designed really 3107 with the patients in mind So we have a very patient centric treatment regimen We don’t require any scoping or any surgery during the dosing window We’re able to administer the treatment in the doctor’s office to an infusion center to receive the product So we think that product profile is really we’re still very close to filing our BLA And so I think we can’t really comment at the moment about the potential label implications the phase that we’ve generated in this patient population who previously had two or more surgeries is I when you have these discussions with the agency it is about sharing the risk benefit ratio for the physician and for the patient we’re able to now really demonstrate the durable clinical effect of INO-3107 And I would hope we’ll be able to discuss that with the agency and get that taken into account because RRP is not a disease that’s defined by a 12 month period and these patients have multiple surgeries So I think it’ll be an interesting discussion that we’ll have with the agency in the future And your next question comes from the line of Roger Song from Jefferies So I guess two questions from us regarding RRP and the 3107 really great to see the durability data of the 3107 up to two years So just wondering how should we think about the redosing commercially if you think about the durability and increased response there as we think about the treatment of RRP disease in a longer term the epidemiology and addressable market there I caught your first question about the redosing strategy I didn’t quite catch your second question So as we have now have those 3107 and those treatment — new treatment for RRP And how should we think about the addressable market there and then I’ll take the EPI question we’re actually still deciding on the redosing strategy I think as we looked to our sort of excellent efficacy it did make us think about how we could design the clinical trial to get a future labeling change I think we’re also sort of in the position now that we started off this process looking at it very much from a sort of regulatory lens of complete remission But really that isn’t how the physicians look at this They look at this at a totality of the surgeries that these patients have see what — see how we can reduce the surgeries to hopefully zero and how we can maintain that excellent clinical response that we’ve seen So I mean hopefully we’ll have some more details in upcoming calls we really are still thinking about how best to accomplish the goals knowing exactly what our platform is capable of doing with the redosing and being able to boost that CDA response that we’ve seen with 3107 in the past I think that’s a really excellent point we’re able to redose from a previous product We’ve shown that we can boost the existing T cell responses by going in with a single dose laser So we’re really confident that we can continue to maintain the immune response that’s associated with clinical benefit very excited by what that means for potential long term treatment for RRP So being able to provide durable clinical benefits is really incredibly important what we’re seeing is in most developed countries where the vaccination rates are around sort of 50% or 60% we’re still seeing large numbers of RRP cases in adults which don’t seem to be affected by the vaccination rates yet The level of cases in adult seems to be holding pretty steady And if you think about the epidemiology of RRP you see a peak of disease cases around age five to seven another peak in the age sort of 30 group and then another peak in the late 50s vaccination for HPV is only around 50% in males So a large proportion of the adult population I think it’s been estimated at around 70% And it’s also not entirely clear how long the vaccine the vaccine protective effects remain as well I think it looks as though RRP is going to be with us for several generations to come Where we are seeing a decrease in the number of patients and the impact of vaccination is in pediatric RRP where the number of pediatric cases are declining But we’re not seeing any impact on cases in the adult population we think this is actually an under diagnosed disease in the adult population And there are no further questions at this time we are moving into 2025 with very focused strategic priorities First and foremost is completing the next steps necessary for submitting our BLA for 3107 we’ll be continuing to advance our commercial readiness plan so we can hit the ground running and use our compelling product profile to its full advantage we’ll continue driving progress across our pipeline advancing commenting programs like 3112 and leveraging potential partnership opportunities This includes building on the breakthrough potential of our DMAb program and other next gen DNA medicine technology I’ll close today by noting that the inspiration for all of this work continues to be the patients around the world who could benefit from the power and potential of DNA medicines For those suffering from RRP in particular we’re strongly motivated by the understanding that every day and every surgery matters Thank you for your attention and good evening everyone And that concludes our conference for today Artificial intelligence is the greatest investment opportunity of our lifetime The time to invest in groundbreaking AI is now My #1 AI stock pick delivered solid gains since the beginning of 2025 while popular AI stocks like 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system Which determines whether a stock could shoot sky-high in the next three to six months… or come crashing down That’s why Marc’s work appears in every Bloomberg and Reuters terminal on the planet… and brokerages to track the billions of dollars flowing in and out of stocks each day He’s used this system to survive nine bear markets… create three new indices for the Nasdaq… and even predict the brutal bear market of 2022 Click to continue reading… Get our editor’s daily picks straight in your inbox CU Boulder Classics scholars identify previously unknown fragments of two lost tragedies by Greek tragedian Euripides two University of Colorado Boulder scholars have deciphered and interpreted what they believe to be the most significant new fragments of works by classical Greek tragedian Euripides in more than half a century In November 2022, Basem Gehad, an archaeologist with the Egyptian Ministry of Tourism and Antiquities, sent a papyrus unearthed at the ancient site of Philadelphia in Egypt to Yvona Trnka-Amrhein, assistant professor of classics The two scholars have also recently discovered the upper half of a colossal statue of the ancient Egyptian Pharaoh Ramesses II in their joint excavation project at Hermopolis Magna She began to pore over the high-resolution photo of the papyrus (Egyptian law prohibits physically removing any artifact from the country) CU Boulder classicists Yvona Trnka-Amrhein (left) and John Gibert (right) spent months studying a small square of papyrus and became confident it contains previously unknown material from two fragmentary Euripides plays Using the Thesaurus Linguae Graecae digitized database of ancient Greek texts maintained by the University of California Trnka-Amrhein confirmed she was looking at previously unknown excerpts from mostly lost Euripidean plays I realized I should call in an expert in Euripides fragments,” she says my mentor in the department is just that!” Working together, Trnka-Amrhein and renowned classics Professor John Gibert embarked on many months of grueling work meticulously poring over a high-resolution photo of the 10.5-square-inch papyrus They made out words and ensured that the words they thought they were seeing fit the norms of tragic style and meter they became confident that they were working with new material from two fragmentary Euripides plays Twenty-two of the lines were previously known in slightly varied versions but “80 percent was brand-new stuff,” Gibert says “We don’t think there has been a find of this significance since the 1960s,” he says “This is a large and unusual papyrus for this day and age,” Trnka-Amrhein says Polyidus retells an ancient Cretan myth in which King Minos and Queen Pasiphaë demand that the eponymous seer resurrect their son Glaucus after he drowns in a vat of honey It’s not one of these tragedies where everyone winds up dead,” Trnka-Amrhein says: Polyidus is able to revive the boy using an herb he previously saw one snake use to revive another The papyrus contains part of a scene in which Minos and Polyidus debate the morality of resurrecting the dead found in 1704 CE in the Esquiline Hill at Rome and dated to the 2nd century CE lists several of the tragedian's works on the back panel It is on display at the Louvre-Lens Museum in France Ino came close to being one of Euripides’ best-known plays Part of the text was inscribed on cliffs in Armenia that were destroyed in modern conflict early 20th-century Russian scholars had preserved the images in drawings The eponymous character is an aunt of the Greek god Dionysus and part of the royal family of Thebes In previously known fragments of a related play Ino is an evil stepmother intent on killing her husband the Thessalian king’s children from a previous marriage “The third wife of the king is trying to eliminate Ino’s children causing her to kill her own children and commit suicide and such bold claims will receive careful scrutiny from other experts Gibert and Trnka-Amrhein decided not to pull any punches with their conclusions and on top of that we are sticking our necks out a little.” They’ve already entered the gauntlet of scrutiny making their case to 13 experts in Washington in June and having their first edition of the fragment accepted for publication in August instead of having the guests give hour-long papers we’re going to present for 20 to 25 minutes each Gibert says he and Trnka-Amrhein will “take the show on the road” to such places as Dartmouth and Harvard “John’s contacts and readers in the Euripides world have given us reassurance we’re not going to have too much pie on our faces,” Trnka-Amrhein says “We feel extremely lucky to have worked on this material and look forward to the world’s reactions.” Top image: A marble bas-relief show Euripides (seated) a standing woman holding out a theater mask to him (left) and the god Dionysus (right) dated to between the 1st century BCE and the 1st century CE from the Misthos collection in the Istanbul (Turkey) Archaeological Museum Did you enjoy this article? Subscribe to our newsletter. Passionate about classics? Show your support. 275 UCB, Boulder, CO 80309Email the magazineCollege of Arts & Sciences main website University of Colorado Boulder Privacy • Legal & Trademarks • Campus Map University of Colorado Boulder You have successfully subscribed to our newsletter Comunicação social - todos os direitos reservados For the complete transcript of the earnings call, please refer to the full earnings call transcript III Grand Prix Angers Loire Metropole (purse 64,000€ 16 starters ages 6-11) saw 2/1 odds favorite Ino du Lupin (7g Scipion du Goutier-Tina d’Hermes) score in 1.12.5kr overcoming his 25 meter handicap owned and bred performer that now has 23 victories in 35 starts for 631,560€ earned The 4.3/1 odds Ibiki de Houelle (7m Love You-Sawasde de Houelle) was second also overcoming a 25 meter handicap with Eric Raffin driving the Franck Leblanc trainee for owner Daniel Angereau Imperator d’Ela (7g Carat Williams-Reville) landed third at 11/1 with Anthony Barrier driving the Matthieu Varin trainee that finished ahead of two more 25 meter handicapped horses 7.7/1 Greco Bello with Franck Nivard up and 19/1 Hasard d’Erable that David Thomain piloted nine starters ages 5-6) saw 2.1/1 Jacquard (6g Up And Quick-Valse d’Avignere-Look de Star) score timed in 1.12.9kr with Mathieu Mottier the jockey of this nine time career winner in 27 starts for 163,550€ earned This Thierry Duvaldestin trainee has won two straight for owner Charles Bourratiere Katina Aimef (5f Singalo) was second for jockey Guilllaume Martin at 7.4/1 odds Franck Leblanc trains this one for owner Michel Fitoussi Kentucky Ideal (5g Alto de Viette) was third at 37/1 odds Adrien Lamy trainer Charley Heslouin and proprietor P-M Rimbert Race replay  https://www.letrot.com/courses/2025-04-01/7500/3 Also on the Vincennes program was the Prix Alcyone (purse 46,000€ eight three year old females) where 2.2/1 odds Magic Night (3f Helgafell-Byblis du Goutier) scored timed in 1.16.7kr Paul Philippe Ploquin handled this Philippe Allaire trainee to her second career victory in seven starts for 40,170€ Gitte Poulsen-Allaire owns the winner that bested 16/1 Mamjack Sacha (3f Golden Bridge) that Mathieu Mottier drove for conditioner A.P Grimault and owner/breeder Chantelle Mottier Malice Speed (3f Hohneck) was third at 14/1 for driver/trainer F.P Race replay  https://www.letrot.com/courses/2025-04-01/7500/5 seven three year olds open) went to 39/1 Melody de Vivoin (3f Seigneur Aimef-Bacchante du Beryl) ridden by jockey J.Y The easy winning filly won for the first time in eight starts with this 1.18.1kr timed score The 23/1 Mentalist AR (3m Frisbee d’Am) was second for jockey Louis Jublot and owner/trainer Richard Westerink Moon Star (3f Dragon des Racques) was third as the 1.2/1 odds favorite ridden by Florion Desmigneux Race replay https://www.letrot.com/courses/2025-04-01/7500/6 Three year olds were also on stage at Bologna Arcoveggio Italy on March 30 Here the 4.5/1 Gandhi Mail (3m And Al Sheba-Taylor EK-Varenne) scored in 1.14.0kr with Andrea Farolfi at the lines for his fourth career victory for 33,597€ The 2.5/1 Galileo Ferm (4m Maharajah-Zima Axe) was second for Marco Stefani and 3.1/1 Ginger Gio (3m Tony Gio-Doris Deo) landed third for Alessandro Gocciadoro 2025) was the companion Gran Premio Italia-Femmine (purse 25,300€ 2060 meters autostart) where 7.1/1 Glory Winner (3f Vivid Wise As-Victoire Winner) scored in 1.16.8kr Francesco Facci handled this winner to her fifth victory for 49,598€ earned that defeated 10/1 Goldie Home (3f Muscle Mass-Ain’t She Sweet) reined by  Davide DiStefano Third home was 14.9/1 Giulia OP (3f Wishing Stone-Venus Ferm) with Vincenzo Luongo driving followed by 54.5/1 odds Giulia Play (3f Victor Gio-Vitesse Play) handled by Edoardo Loccisano On another European note there are now five 2025 Elitloppet invitees that include Francesco Zet by Thomas H. Hicks Harnesslink.com is the only harness racing website dedicated to covering news and events in the Standardbred Industry world-wide © 2024 Harnesslink | All Rights Reserved | NV © 2024 Harnesslink | All Rights Reserved | NV won the gold medal at the second International Nanotechnology Olympiad (INO 2024) which was held from October 17 to 18 in Kuala Lumpur The Iranian team competed with participants from Thailand student of metallurgy engineering; and Nima Dehqan proposed a project named ‘Using sunlight to produce clean hydrogen fuel’ the presented projects focused on global challenges facing nanotechnology applications in the development and production of new (alternative) energies including hydrogen fuel The INO aims to provide a platform for young innovators and researchers to showcase their talents and address some of the world’s most pressing environmental and technological challenges The promotion of scientific and technological interactions with related organizations in Malaysia is the most important peripheral goal of the event The third INO is set to take place in Taiwan in 2026 the first INO was held from April 10 to 15 at Tehran’s Pardis Technology Park and nine teams from four foreign countries competed at the event The participants presented their solutions for the global challenges related to water and wastewater treatment information and communication through nanotechnology Students of Iran University of Science and Technology have managed to win first place in Eurasia Federation of International RoboSports Association (FIRA) Open competition 2024 The competition was held from November 6 to 9 in Van bringing together 130 teams from eight countries.  They ranked first in innovation and entrepreneurship Iran grabbed five gold medals and two special awards in the International Science and Invention Fair (ISIF) 2024 which was held in Indonesia from November 5 to 10 A total of 18 students from Iran attended the 47th WorldSkills Competition winning 9 medals including a silver medal and medallions for excellence The competition was held from September 10 to 15 in Lyon Some 1,500 competitors from more than 65 countries and regions around the world gathered in Lyon to compete in different skills Hasan Mohammadi and Hamid-Reza Hamidi won the silver medal and a bronze medal at the 36th International Olympiad in Informatics (IOI) the event started on September 1 and concluded on September 8 Each participating country selected a team of up to four contestants to represent their nation The team competed in a two-day competition Each contestant competed individually to maximize their score by solving three algorithmic problems within five hours Iranian students attended the event online and ranked ninth globally.  ranking first in the 17th International Olympiad on Astronomy and Astrophysics (IOAA) which was held from August 17 to 27 in Vassouras Silkworm cocoons serve as a protective layer in the home-compostable packaging Ino is working to scale up production and gain more customers InoArmor initially came about following a traumatic head injury Maddock sustained after being hit by a car in New York City and the two started a nonprofit focused on helping people who have experienced traumatic brain and spinal cord injuries They aimed to find a replacement for the expanded polystyrene foam used in bike helmets whose research includes the use of silk in medical products due to the natural material’s strength and other properties The team developed a concept for using silk as a cushioning element in bike helmets Testing on the bike helmet made with InoArmor “silk pillows” scored higher on performance metrics than competing helmets made from EPS That prompted the partners to “go to companies with fragile items “We saw the packaging world as a cohort of people who would use a lot of this product and who ideally would start to be interested in a better solution Ino performed extensive testing on the silk-filled bag for Pantalones including drop tests onto concrete from a height of about nine feet Employees have joked that “no one should be afraid to drop their Pantalones with InoArmor,” Maddock said The silk pillows inside the packaging are designed differently than those used in the helmets or other products similar to how EPS density differs across products But all the silkworm cocoons come from silk farms with whom INO contracts Ino has worked with five farms spanning North America noting that Ino’s current plan does not involve owning its own silk farm “All of the cocoons are slightly different so we had to develop kind of an in-house QC process,” he said “We can receive just a minimal amount of silk from a farm and put it through some impact testing to see how well it could potentially act.” altering the shape to be a fit for each application Ino sources its PHA from a separate supplier and that product must protect against water Silk absorbs water it is exposed to and then becomes less effective at protecting against impacts Another challenge is that “we're dealing with a natural product that no one had ever used before,” he said So the Ino team had to try to prove to potential customers that people care about more effective sustainable protective packaging — and that they’d use it and the pandemic slowed down progress with getting products to market the founders’ focus is turning toward scaling up production of InoArmor for mass-market products and gaining more customers “We want to make products that have an impact on our planet,” Maddock said “We’re always trying to make sure that we have most sustainable option possible.” Get the free daily newsletter read by industry experts Squared-off designs often are better for densification or waging the “war on air,” according to sources from Smurfit Westrock Geometry grows more important as robots and SIOC proliferate Growing regulatory and public pressure on single-use plastic is creating market opportunities for fiber products DS Smith and others are helping clients innovate bottles The free newsletter covering the top industry headlines VO65 Sisi (AUT) skippered by Oliver Kobale finished the RORC Transatlantic Race in the early hours of Thursday 23rd January completing the 3000-mile race in an elapsed time of 10 Days 19 Hrs 53 Mins 11 Secs Consisting of group of professional Austrian sailors and amateurs from all over the world the Sisi crew is the first pro-am team to finish the race Twenty five year old German sailor Christine Kurz is the first women sailor to complete the race this year at 25 years of age is the youngest skipper in the race and virtually lives on board all the time: “I probably only go home to Austria for a few weeks a year so yes she is my home,” commented Oliver who competed on the boat in the 2022-23 Ocean Race This was a high-speed race with challenging conditions The pro crew did a great job ensuring safety and guiding the team While we can’t compete at the grand prix level the crew performed incredibly well and had an amazing experience We arrived in Grenada with the crew and boat in great shape James Neville’s Carkeek 45 Ino Noir (GBR) was the fourth boat to finish the RORC Transatlantic Race completing the course in an elapsed time of 10 Days Ino Noir is virtually assured of winning IRC One and is currently estimated to be third overall in IRC This was the first transatlantic race for Ino Noir which will represent the RORC in the upcoming Admiral’s Cup The all-British crew brought extensive experience to the race having collectively completed numerous transatlantic crossings Tactician Mike Henning and navigator Jack Trigger noted that the defining moments of the race occurred during its early and final days gusty conditions at the start caused damage to their smallest spinnaker forcing the team to adjust their approach and prioritise preserving their sail inventory Ino Noir’s routing software suggested they had a chance to beat overall winner Volvo 70 Tschuss 2 on IRC corrected time but further sail damage dashed their hopes of an overall victory the Ino Noir team arrived at Camper & Nicholson’s Port Louis Marina in high spirits but we chose this race because it promised to be a real adventure,” said Neville with a variety of wind conditions and scenarios surfing waves – there’s nothing quite like it dark nights where you’re flying along at speed in pitch black It’s exhilarating and relentless at the same time and then the thrill of speed pulls you back in This race was a fantastic opportunity to test the boat in various conditions and we’ve discovered some new modes we’re excited to try out in the RORC Caribbean 600.” 2025-05-06T08:37:00+12:00May 6th Switzerland’s Eric Monnin and his Capvis Swiss Match Racing Team of Ute Monnin Wagner and Maxime Mesnil today clinched a long awaited win of the 60th Anniversary Long Beach Yacht Club Congressional Cup stage three of the 2025 World Match Racing Tour season 2025-05-05T11:35:57+12:00May 5th The eyes of the sailing world will turn to Qingdao as the city prepares to host the 2025 ILCA 6 Women’s and ILCA 7 Men’s World Championships 2025-05-04T20:29:35+12:00May 4th Light airs and overcast conditions brought high-stakes racing to the penultimate day of the 60th Congressional Cup in Long Beach as the final four teams advanced to the semi-finals 2025-05-04T20:23:07+12:00May 4th and claimed Antigua Sailing Week’s most coveted prize 3 or 4 class winner with the fastest overall corrected times calculated on a time-on-distance basis 2025-05-03T17:34:46+12:00May 3rd The final day of racing at Antigua Sailing Week saw a return to steady winds of 10-12 knots that gradually built to 13-14 knots The big boats in CSA Racing Class 1 had a 20-mile course in conditions that had Roy Disney’s Volvo 70 Pyewacket hitting speeds of 15-17 knots 2025-05-03T17:28:09+12:00May 3rd The race to the semi-finals at the 60th Long Beach Yacht Club Congressional Cup is going down to the wire With just two flights remaining in the double round robin stage four teams are locked in a high-stakes battle for the final semi-final slots with crucial races to count Check your inbox or spam folder to confirm your subscription Sign up to receive awesome content in your inbox We don’t spam!Read our privacy policy for more info We keep your data private and don't spam. Read our full Privacy Policy © Copyright © 2005-document.write(new Date().getFullYear()) Live Sail Die Limited The views and opinions expressed on this web site are soley those of the original authors and other contributors These views and opinions do not necessarily represent those of official sailing agencies Live Sail Die is a recognised member of the NZ Marine Industry Association.Live Sail Die drone pilots are CAA Part 102 Certificated Discover the world's largest classical music catalogue with Presto Music If you are a library, university or other organisation that would be interested in an institutional subscription to Gramophone please click here for further information. Ino said through a translator that he was focused on villains this season. But, rather, it seemed like he was focused on righteousness and its impact on people. Everyone has a defect, but should everyone be villainized for it? 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