Core Insights - Tenaya Therapeutics announced interim data from the RIDGE™-1 Phase 1b/2 clinical trial of TN-401 gene therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC), showing promising safety and efficacy results in early patients [1][3] Group 1: Clinical Trial Results - TN-401 was well tolerated at a dose of 3E13 vg/kg, with no dose-limiting toxicities observed [4] - Initial data indicated a significant increase in PKP2 protein expression from baseline in two of three patients, with a mean increase of 10% by Week 8 [12] - Clinically meaningful reductions in arrhythmia burden were observed, with Patient 1 experiencing a 46% decrease in premature ventricular contractions (PVCs) and Patient 2 showing an 89% decrease, along with a reduction of non-sustained ventricular tachycardia (NSVT) counts from 78 to zero [12] Group 2: Safety and Tolerability - Adverse events were generally mild and asymptomatic, with no serious adverse events (SAEs) related to TN-401 treatment reported in the cohort [6][5] - No incidents of thrombotic microangiopathy (TMA) or cardiotoxicities were observed, and all patients have tapered off immunosuppressive medicines [6] - Biopsies demonstrated robust transduction and expression of TN-401 in all patients within the first eight weeks [6] Group 3: Future Developments - Tenaya management plans to host a webcast conference call to discuss the TN-401 data on December 11, 2025 [9] - The RIDGE-1 trial aims to enroll up to fifteen adults diagnosed with PKP2-associated ARVC, assessing the safety, tolerability, and preliminary clinical efficacy of TN-401 [14] - TN-401 has received Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration, indicating its potential significance in treating ARVC [13]

Core Insights - The five-year results from the Phase 3 HOPE-B study confirm the long-term durability and safety of HEMGENIX, a gene therapy for adults with hemophilia B, demonstrating sustained therapeutic benefits and a favorable safety profile [2][3][4] Efficacy and Safety - 94% of patients remained free from continuous prophylaxis treatment five years after a single infusion of HEMGENIX, indicating its effectiveness in providing sustained bleed protection [1][5] - Mean factor IX activity levels were maintained at 36.1% at year five, showcasing the therapy's durable efficacy [1][5] - The mean adjusted annualized bleeding rate (ABR) for all bleeds decreased by approximately 90% from the lead-in period (4.16) to year five (0.40) [5] Real-World Adoption - More than 75 individuals across eight countries have received HEMGENIX in real-world settings, reflecting its growing global adoption [1][7] Clinical Study Details - The pivotal Phase 3 HOPE-B trial involved 54 adult male participants with severe or moderately severe hemophilia B, with 50 completing five years of follow-up [3][9] - The study's primary endpoint was the ABR measured from month seven to month 18 post-infusion, ensuring a steady-state factor IX expression [9] Regulatory Status - HEMGENIX has received regulatory approval in multiple countries, including the United States, Canada, and the European Union, indicating its acceptance in various markets [7][21]

Company Overview - uniQure N.V. develops treatments for rare and devastating diseases, focusing on Huntington's disease (HD) with its AMT-130 gene therapy [2] Scientific and Strategic Challenges - AMT-130 faces significant challenges in the evolving HD landscape, with competitors like Wave Life Sciences' WVE-003 showing comparable or superior results while preserving wild-type HTT [2] - The huntingtin hypothesis is increasingly questioned, with disease progression influenced by various genetic factors, leading to variability among patients [3] Risks and Concerns - Non-selective HTT lowering may disrupt essential wild-type functions, potentially causing neuroinflammation or compensatory responses, as seen in previous failed attempts like tominersen [4] - AMT-130 carries risks associated with miRNA and AAV, including off-target effects and potential long-term immune responses [4] Clinical Trial Limitations - Current human trials are small (n=12), rely on external controls, and lack key mechanistic endpoints, weakening the evidence for AMT-130's efficacy [5] - Operational constraints due to debt and regulatory timelines limit the feasibility of a rigorous Phase 3 trial [5] Market Sentiment and Regulatory Environment - Market optimism is driven by hope, FDA alignment, and the "right to try" framework, but significant data gaps and uncertainties remain [6] - The gene therapy sector is facing heightened scrutiny and higher regulatory standards, necessitating robust evidence for validating permanent interventions in HD [6] - AMT-130 is viewed as a high-risk approach amid the development of safer, more targeted therapies [6]

Financial Data and Key Metrics Changes - The company is focused on the upcoming data readout for setrusumab, which is expected by the end of December or January, marking a significant near-term value driver [2][34] - The company has achieved a 67% reduction in fracture rates from baseline in the phase 1/2 study, indicating strong efficacy [7][15] Business Line Data and Key Metrics Changes - The company is advancing its Osteogenesis Imperfecta (OI) program, which targets a patient population of at least 60,000 in the covered geographies, aiming to replicate the success of Crysvita [3][4] - The ORBIT trial has enrolled an additional 159 patients, maintaining a two-to-one randomization of setrusumab to placebo, with a focus on patients aged 5 to 26 [10][12] Market Data and Key Metrics Changes - The company is preparing for a market launch of setrusumab, which is positioned as a superior treatment compared to bisphosphonates, currently the only available treatment for OI [2][11] - The potential market for Sanfilippo is estimated at 3,000 to 5,000 patients, while GSD1A is slightly larger at 6,000 patients, indicating a strategic focus on rare disease markets [42] Company Strategy and Development Direction - The company is committed to not compromising the quality of data for the OI filing, despite the ambitious timeline for approval by the end of September [30][32] - The strategy includes leveraging AI for data analysis and document preparation to enhance efficiency in the filing process [32] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the probability of success for the final data readout, maintaining that the interim analyses have not negatively impacted their outlook [20][28] - The company is optimistic about achieving profitability within the timeframe of their recent monetization deal, which allows for revenue generation without immediate repayment obligations [93] Other Important Information - The company is actively working on gene therapy programs, with a focus on Sanfilippo and GSD1A, both of which are expected to have PDUFA dates within the PRV window [38][39] - The company has learned from previous regulatory feedback, applying those lessons to improve the quality of their gene therapy programs [40][42] Q&A Session Summary Question: What is the timeline for the data readout for setrusumab? - The company has defined the end of year as December or January for the data readout [34] Question: How does the company view the efficacy of bisphosphonates compared to setrusumab? - Management estimates the treatment effect of bisphosphonates to be around 20%, while setrusumab has shown a 67% reduction in fracture rates [14][15] Question: What is the company's approach to the upcoming regulatory filings? - The company plans to ensure high-quality data packages for regulatory submissions, emphasizing that they will not rush the process [30][32] Question: How does the company plan to address the market for Sanfilippo and GSD1A? - The company is confident in the clinical data for both programs and is preparing for timely submissions to the FDA [38][39]

Summary of Solid Biosciences FY Conference Call Company Overview - **Company**: Solid Biosciences (NasdaqGS:SLDB) - **Focus**: Gene therapy, primarily targeting Duchenne muscular dystrophy (DMD), Friedreich's ataxia, catecholaminergic polymorphic ventricular tachycardia (CPVT), and TNNT2-related cardiac diseases [5][6] Key Points and Arguments Pipeline and Differentiation - Solid Biosciences is developing a next-generation gene therapy platform, emphasizing the importance of delivery systems, including custom capsids and dual plasmids for improved purity [5][6] - The lead program, SGT-003, is a gene therapy for DMD, utilizing a novel capsid (SLB101) that has not been previously tested in humans [7][9][13] - The company has rebuilt its gene therapy program from the ground up, focusing on safety and efficacy, with early data showing promising results in cardiac output improvements in treated patients [14][15][46] Clinical Trials and FDA Interaction - The company plans to meet with the FDA in early 2026 to discuss data from 30 patients and the use of external controls for regulatory approval [17][18][32] - Solid Biosciences aims to initiate a registrational trial soon, with hopes of filing for accelerated approval based on the FDA's guidance [18][33] - The company is cautious about dosing older, sicker patients and intends to work closely with the FDA to ensure safety and efficacy [44][45] Safety and Efficacy Data - As of the latest update, 23 patients have been dosed, with plans to reach 28-30 by year-end [15][26] - No drug-induced liver injuries have been reported, although there was one case of grade three myositis linked to a specific genetic mutation [46][49] - The company is committed to excluding certain mutations from future dosing to mitigate risks [51] Future Developments - Solid Biosciences is preparing to dose patients in additional programs for Friedreich's ataxia and CPVT, with expectations to release safety data in early 2026 [72][75] - The company believes its gene therapy could significantly impact the treatment landscape for DMD and other conditions, with a potential market value of $4.5 billion based on competitor pricing [42] Research and Innovation - The company is exploring the unique properties of its capsid, which may have implications for gene therapy beyond its current applications [59][60] - Solid Biosciences is pursuing method of use patents related to its dosing strategies, which could influence future gene therapy protocols [62] Additional Important Insights - The company is focusing on younger patient cohorts (ages 0-3) for DMD, which presents a significant opportunity given the lack of existing treatments for this age group [41][42] - Solid Biosciences is also adapting its dosing strategies based on findings from ongoing trials, indicating a responsive approach to clinical data [64][70] - The company anticipates that its findings will not only benefit its own programs but could also influence the broader field of gene therapy [59][60] This summary encapsulates the key discussions and insights from the Solid Biosciences FY Conference Call, highlighting the company's strategic focus, clinical developments, and future opportunities in the gene therapy landscape.

Summary of Prime Medicine FY Conference Call Company Overview - **Company**: Prime Medicine (NasdaqGM:PRME) - **Focus**: Gene editing technology, specifically prime editing Key Points on Prime Editing Technology - **Definition**: Prime editing is described as the most versatile and safest method for genome editing, allowing for precise and permanent corrections in the DNA sequence [6][14] - **Comparison with Other Technologies**: - **CRISPR**: Effective for knocking out genes but has limitations such as off-target effects and potential immunogenicity [6][7][9] - **Base Editing**: Allows for single-letter changes in DNA but is limited to specific types of mutations [9][10][14] - **Prime Editing Advantages**: Capable of correcting larger mutations and multiple mutations simultaneously, with lower off-target effects [14][15] Industry Context - **Competitive Landscape**: Other companies, such as Tessera and Regeneron, are also developing prime editing technologies, indicating a competitive market [34] - **Market Need**: There is a significant unmet need for therapies targeting conditions like Wilson disease and alpha-1 antitrypsin deficiency, which are suitable for prime editing [32][33] Corporate Strategy and Pipeline - **Recent Changes**: The company underwent restructuring to focus on high-value areas, reducing the number of programs from 18 to prioritize those with higher probabilities of success [31][32] - **Key Programs**: - **Wilson Disease**: Targeting specific mutations with no existing gene editing therapies [32] - **Alpha-1 Antitrypsin Deficiency**: A competitive area where prime editing is believed to provide superior outcomes [33] - **Cystic Fibrosis and Ex Vivo CAR T Programs**: Continued focus on these areas, while deprioritizing ocular and neurological programs [38][40] Development and Clinical Trials - **IND Timeline**: The company aims to submit an Investigational New Drug (IND) application for Wilson disease in the first half of 2026, with proof of concept data expected by 2027 [48][49] - **Trial Design**: The Wilson disease trial will be a dose escalation study focusing on safety and efficacy measures, targeting patients with specific mutations [52][54] - **Biomarkers**: Various biomarkers will be used to assess treatment efficacy, including copper PET studies and ceruloplasmin levels [54] Off-Target Editing and Safety - **Off-Target Analysis**: Prime Medicine has conducted extensive off-target analysis for its programs, reporting no evidence of off-target effects in their first program for chronic granulomatous disease [16][31] - **Assay Development**: The company has developed its own assays for measuring off-target effects, which may differ from those used by competitors [17][30] Future Outlook - **Partnerships**: While the company is open to partnerships, it sees significant value in independently advancing its key programs [41][42] - **Long-Term Vision**: Prime Medicine aims to expand its portfolio beyond single products and diseases, leveraging its technology for a broader range of genetic conditions [41] Conclusion - Prime Medicine is positioned as a leader in the gene editing space with its prime editing technology, focusing on high-value therapeutic areas with significant unmet needs. The company is preparing for upcoming clinical trials and aims to establish itself as a key player in the competitive landscape of gene editing therapies.

Summary of Compass Therapeutics Conference Call Company Overview - **Company**: Compass Therapeutics (NasdaqCM:CMPX) - **Industry**: Biotechnology, specifically focused on oncology and monoclonal antibody development - **Location**: Boston Key Clinical Programs Tevesemig (DLL4 VEGFA Bispecific Antibody) - **Current Status**: In a randomized trial for advanced biliary tract cancer - **Primary Endpoint Achievement**: Reported a tripling of the overall response rate compared to the control arm [4][10] - **Response Rate**: Achieved one of the highest response rates in second-line treatment for advanced biliary tract cancer [4] - **Disease Control Rate**: Significantly higher in the Tevesemig arm, suggesting potential improvements in progression-free survival (PFS) [5][10] - **Expected Data Release**: PFS and overall survival (OS) data anticipated by the end of Q1 2026 [8][11] - **Crossover Impact**: Approximately half of the control arm patients crossed over to receive Tevesemig, which may affect OS event accrual [16][22] 8371 (PD-1/PD-L1 Bispecific Antibody) - **Current Status**: Completed phase one dose escalation with no dose-limiting toxicities [5][6] - **Response Rate**: Three confirmed responses in 15 patients treated, including significant tumor reduction in a triple-negative breast cancer patient [6][7] - **Next Steps**: Moving to cohort expansions for non-small cell lung cancer and triple-negative breast cancer, with potential for approval studies in 2026 [30][32] 10726 (PD-1/VEGF Bispecific Antibody) - **Current Status**: Expected IND filing and phase one initiation in the first half of 2026 [33] - **Target Indications**: Hepatocellular cancer, gastric cancer, renal cell cancer, and endometrial cell cancer [33] Market Potential - **Biliary Tract Cancer**: Approximately 25,000 new cases annually in the U.S., with an increasing incidence projected [24] - **Eligible Patients for Tevesemig**: Estimated 15,000 patients annually in the U.S. alone, significantly larger than the platinum-resistant ovarian cancer market [24][25] - **Global Market**: Over 100,000 patients diagnosed annually across the U.S., EU, and Japan [25] Regulatory and Commercialization Strategy - **BLA Submission Timeline**: Expected in the second half of 2026, following positive interactions with the FDA [23] - **Commercialization Plans**: Preparing to launch Tevesemig independently in the U.S., with potential partnerships for ex-U.S. markets [26] Statistical Analysis and Methodology - **Statistical Techniques**: Utilizing Rank Preserving Structural Failure Time (RPSFT) for OS analysis to account for crossover patients [16][17] - **Hierarchical Testing**: Employed to control alpha spending across multiple endpoints [20] Additional Insights - **Clinical Operations**: Low patient loss to follow-up (approximately 5%) indicates strong clinical management [13] - **Future Outlook**: 2026 is anticipated to be a pivotal year for Compass Therapeutics with multiple potential approvals and market entries [32][33]

Core Insights - Beam Therapeutics (BEAM) and Intellia Therapeutics (NTLA) are both clinical-stage companies in the gene therapy sector, with BEAM focusing on early-stage development and NTLA advancing late-stage candidates [1][9] Group 1: Beam Therapeutics Overview - Beam Therapeutics utilizes proprietary base-editing technology to develop precision genetic medicines, minimizing errors by targeting a single base in the genome [2] - The company is evaluating BEAM-101 for sickle cell disease (SCD) in a phase I/II study, with initial data showing a significant increase in fetal hemoglobin and a reduction in sickle hemoglobin [3] - BEAM has initiated a phase I study for BEAM-103, an experimental anti-CD117 monoclonal antibody for SCD treatment [4] - The company is also developing in vivo therapies, BEAM-301 and BEAM-302, for glycogen storage disease type 1a and alpha-1 antitrypsin deficiency, respectively [5] - Beam has partnerships with major pharmaceutical companies like Eli Lilly and Pfizer, providing financial support through collaboration revenues [6] - The primary challenge for Beam is the absence of an approved product, making it reliant on collaboration partners for growth [7] Group 2: Intellia Therapeutics Overview - Intellia Therapeutics focuses on in vivo gene editing, advancing two late-stage candidates: lonvo-z for hereditary angioedema and nex-z for transthyretin amyloidosis [8] - The pivotal phase III HAELO study for lonvo-z has completed enrollment, with top-line data expected by mid-2026 and a potential commercial launch planned for the first half of 2027 [10] - Intellia faced a setback with nex-z due to a clinical hold imposed by the FDA after a patient experienced significant liver enzyme elevations [11][12] - The company is undergoing a strategic reorganization to prioritize late-stage candidates and reduce cash burn, including workforce reductions [13] Group 3: Financial Estimates and Performance - The Zacks Consensus Estimate predicts a nearly 37% decline in BEAM's 2025 sales, while loss estimates per share are expected to improve by 3% [14] - NTLA's 2025 sales are expected to decline about 4%, with loss estimates narrowing by nearly 24% [15] - Year-to-date, BEAM shares have gained 1%, while NTLA shares have decreased by 27%, contrasting with a 20% rise in the industry [17] - From a valuation perspective, BEAM's price/book (P/B) ratio is 2.63, compared to NTLA's 1.22, indicating that BEAM is more expensive [19] Group 4: Investment Considerations - Both companies hold a Zacks Rank 3 (Hold), complicating the decision for investors [22] - Despite Intellia's closer proximity to a commercial launch, the setback with nex-z has negatively impacted its stock sentiment, while BEAM's diversified pipeline offers a safer investment option [23] - There is potential for growth in BEAM stock, supported by solid fundamentals and a recent positive trend in stock price movement [24]

Table of Contents As filed with the Securities and Exchange Commission on November 26, 2025 Registration No. 333-291722 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 1 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 GENPREX, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 2834 90-0772347 (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Identifi ...

Core Insights - REGENXBIO Inc. will participate in the Piper Sandler 37th Annual Healthcare Conference with a fireside chat scheduled for December 2, 2025, at 8:30 a.m. ET [1] - The company is focused on advancing gene therapy, particularly in treating rare and retinal diseases, with a late-stage pipeline that includes several investigational therapies [2] Company Overview - REGENXBIO, founded in 2009, specializes in AAV gene therapy and aims to improve lives through its curative potential [2] - The company has developed treatments such as RGX-202 for Duchenne muscular dystrophy, RGX-121 for MPS II, and RGX-111 for MPS I, in collaboration with Nippon Shinyaku [2] - REGENXBIO is also working with AbbVie on surabgene lomparvovec (ABBV-RGX-314) for wet AMD and diabetic retinopathy [2] - Thousands of patients have been treated using REGENXBIO's AAV platform, including those receiving Novartis' ZOLGENSMA® [2] Recent Developments - The company announced the completion of pivotal enrollment in the AFFINITY DUCHENNE® trial for RGX-202, marking a significant milestone in its Duchenne gene therapy program [5]