Scaling new heights in the fight against heart disease November 10, 2025 Forward-looking statement This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our management's beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or qua ...

Core Insights - The third quarter of 2025 was significant for uniQure, presenting topline three-year data for AMT-130, a gene therapy for Huntington's disease, showing statistically significant slowing of disease progression [3][4] - The company raised approximately $323.7 million in net proceeds from a public offering, enhancing its financial position with cash and equivalents totaling $694.2 million as of September 30, 2025 [7][9] - uniQure plans to urgently interact with the FDA regarding AMT-130 following unexpected feedback that introduced uncertainty in the timing of the Biologics License Application (BLA) submission [4][8] Recent Developments - AMT-130 for Huntington's disease met primary and key secondary endpoints, showing a 75% slowing in disease progression and a 60% slowing in Total Functional Capacity at 36 months [5][4] - Enrollment for AMT-260 in mesial temporal lobe epilepsy has commenced, with updated data expected in the first half of 2026 [6][8] - Initial data for AMT-191 in Fabry disease showed a 27- to 208-fold increase in α-Gal A enzyme activity, with further results anticipated in 2026 [6][8] Financial Performance - Revenue for Q3 2025 was $3.7 million, up from $2.3 million in Q3 2024, primarily due to increased license revenues [10] - Research and development expenses rose to $34.4 million in Q3 2025 from $30.6 million in Q3 2024, driven by preparations for the BLA submission for AMT-130 [12] - The net loss for Q3 2025 was $80.5 million, compared to a net loss of $44.4 million in the same period in 2024, reflecting increased operating expenses and non-operating items [17][28]

Core Insights - Tenaya Therapeutics announced significant advancements in its gene therapy programs, TN-201 and TN-401, aimed at treating serious genetic cardiomyopathies, with positive recommendations from Data Safety Monitoring Boards for both products [2][3]. Business and Program Updates - TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), showed robust transduction and durable expression, with a dose-dependent increase in MyBP-C protein. Cohort 1 patients exhibited decreases in circulating biomarkers and reductions in left ventricular hypertrophy over time [3]. - The MyPEAK-1 trial for TN-201 is currently on clinical hold, with the company working with the FDA to resolve the issue and resume dosing [4]. - TN-401, targeting PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), has completed dosing in Cohort 2 of the RIDGE-1 trial, with initial safety and biopsy data expected to be shared by year-end 2025 [5][6]. Research and Development Updates - A seroprevalence study indicated that nearly 95% of MYBPC3-associated HCM patients had low pre-existing immunity to AAV9, suggesting a favorable patient eligibility for the MyPEAK-1 trial [7]. - The MyClimb study, focusing on pediatric patients with MYBPC3-associated HCM, revealed that 93% of participants had the nonobstructive HCM phenotype, highlighting the need for treatment options [7]. - Tenaya presented new preclinical data on cardiac function improvement in a pig model of ischemic heart failure, achieved through a proprietary in vivo reprogramming cocktail [7]. Financial Highlights - As of September 30, 2025, Tenaya reported cash, cash equivalents, and marketable securities totaling $56.3 million, sufficient to support operations into the second half of 2026 [12]. - Research and Development (R&D) expenses for Q3 2025 were $15.4 million, down from $20.4 million in Q3 2024. General and Administrative (G&A) expenses also decreased to $5.6 million from $6.4 million in the same period [12][16]. - The net loss for Q3 2025 was $20.3 million, or $0.12 per share, compared to a net loss of $25.6 million, or $0.30 per share, in Q3 2024 [12][16].

Core Insights - 4D Molecular Therapeutics, Inc. (NASDAQ:FDMT) is a clinical-stage company focused on gene therapy, utilizing adeno-associated virus vectors for treatments in ophthalmology, cardiology, and pulmonology [1] - The company has several candidates in clinical trials, including 4D-125 for X-linked retinitis pigmentosa and 4D-310 for Fabry disease, along with investigational new drug candidates like 4D-150 for wet age-related macular degeneration [1] Price Target and Analyst Sentiment - The stock's consensus target price has increased from $16.33 to $21.5 over the past year, indicating growing optimism among analysts [2][5] - Wall Street analysts have set an average price target for FDMT, suggesting a potential upside of 208.5%, supported by positive trends in earnings estimate revisions [3][5] - Factors contributing to this positive outlook include advancements in clinical trials and successful collaborations with partners such as uniQure and Roche [2][5] Monitoring Developments - Investors are advised to monitor upcoming news or results from FDMT's clinical trials, as these could further influence the stock's target price and market performance [4]

Financial Data and Key Metrics Changes - REGENXBIO ended Q3 2025 with cash, cash equivalents, and marketable securities of $302 million, an increase from $245 million as of December 31, 2024, primarily driven by a $110 million upfront payment from Nippon Shinyaku and $145 million in net proceeds from royalty monetization [17][18] - Revenues for Q3 2025 were $30 million, compared to $24 million in Q3 2024, mainly due to development service revenue under the Nippon Shinyaku partnership [17] Business Line Data and Key Metrics Changes - The RGX-202 program for Duchenne muscular dystrophy is progressing well, with enrollment completed in the Affinity Duchenne Pivotal Trial, and top-line pivotal data expected in early Q2 2026 [5][11] - RGX-121, a potential gene therapy for MPS II, is on track for FDA approval by early 2026, with positive 12-month data delivered to the FDA [8][14] - The retinal disease franchise, particularly the ABBV-RGX-314 program for wet AMD, has completed enrollment in two global phase 3 studies, representing the largest global gene therapy program ever conducted [9][10] Market Data and Key Metrics Changes - The anticipated market for RGX-202 is significant, with the ability to produce 2,500 doses per year, positioning the company for clinical and commercial success [7] - The prevalent market for Duchenne is expected to be around 14,000 patients by 2027, with approximately 3,000 eligible for gene therapy [82] Company Strategy and Development Direction - The company is focused on advancing its late-stage pipeline of gene therapies, with a commitment to bringing new medicines to patients in need [4] - REGENXBIO is preparing for a commercial launch of RGX-202 in 2027 and is exploring opportunities to expand the program outside the U.S. [6][14] - The company aims to leverage its manufacturing capabilities and innovative science to deliver best-in-class therapeutics [10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing BLA review for RGX-121, highlighting productive interactions with the FDA and a strong safety profile [8][32] - The company anticipates a transformational year ahead, with multiple product launches and significant unmet needs being addressed by its gene therapies [19] Other Important Information - The company has a strong financial position, with cash runway expected to extend into early 2027, not including potential non-dilutive financing opportunities [18] - The manufacturing facility in Rockville is capable of producing high-purity gene therapies, which is crucial for commercial readiness [7][35] Q&A Session Summary Question: Update on RGX-202 interactions with FDA - Management indicated that top-line data will be available in early Q2 2026, with a pre-BLA meeting expected around that time [21][23] Question: Cash runway and non-dilutive financing - The company expects non-dilutive financing options to extend cash runway well into 2027 or early 2028 [24][25] Question: Confirmatory trial enrollment for DMD - Enrollment for the confirmatory study has begun, and management expects substantial progress by mid-2026 [26][27] Question: Regulatory interactions for DMD and MPS II - Management confirmed a late cycle meeting with the FDA for RGX-121 and a pre-BLA meeting for RGX-202 is anticipated [30][32] Question: Manufacturing capacity and production volume - The Rockville site has a 2,000-liter bioreactor, capable of producing up to 2,500 doses of RGX-202 annually [34][35] Question: Use of FDA natural history as a control in DMD - Management confirmed that propensity score matching is prospectively specified in the protocol for RGX-202 [38][40] Question: Interest in gene therapy from retina specialists - There is significant excitement about gene therapy among retina specialists, with half of surveyed specialists expressing interest in gene therapy approaches [42][44] Question: Expectations for black box warnings - Management does not expect a black box warning for RGX-202 due to its strong safety profile [48][49] Question: EMA plans and requirements - The company is evaluating the EMA's requirements for RGX-121 and RGX-202, with ongoing discussions about potential placebo control needs [52][54] Question: Diabetic retinopathy study adjustments - The company is considering the ordinal two-step DRSS change as a potential primary endpoint for their pivotal studies [58][61] Question: Enrollment for suprachoroidal delivery program - The company is looking to enroll 20 patients in the suprachoroidal delivery arm, with expectations for increased enrollment speed following the completion of the subretinal program [63][66]

Core Insights - Solid Biosciences has received an Innovation Passport for its investigational gene therapy SGT-003, aimed at treating Duchenne muscular dystrophy, under the new Innovative Licensing and Access Pathway (ILAP) in the UK [1][2][3] - The ILAP is designed to accelerate the development and access of transformative medicines, facilitating early engagement with regulatory bodies [4] - SGT-003 is currently undergoing clinical trials, including the Phase 1/2 INSPIRE DUCHENNE trial and the Phase 3 IMPACT DUCHENNE trial, with the aim of becoming the first gene therapy for Duchenne in the UK [3][8][9] Company Overview - Solid Biosciences is focused on developing precision genetic medicines for neuromuscular and cardiac diseases, with a portfolio that includes SGT-003 for Duchenne muscular dystrophy [10] - The company aims to improve the lives of patients with rare diseases through innovative gene therapy solutions [10] Clinical Development - SGT-003 is designed with a differentiated microdystrophin construct and a proprietary capsid, AAV-SLB101, which targets integrin receptors and enhances muscle transduction [7] - The ongoing INSPIRE DUCHENNE trial is evaluating the safety and efficacy of SGT-003 in pediatric participants with Duchenne, while the IMPACT DUCHENNE trial is focused on supporting regulatory authorizations outside the US [8][9] Regulatory Framework - The ILAP, launched in 2021, provides a unique end-to-end regulatory access pathway, allowing for early multi-stakeholder engagement and support for clinical development and market access [4] - The Innovation Passport designation enables Solid Biosciences to work closely with the UK's MHRA and other regulatory bodies to expedite the development of SGT-003 [1][3]

Core Insights - REGENXBIO Inc. reported significant progress in its late-stage gene therapy programs, highlighting advancements in treatments for Duchenne muscular dystrophy, Hunter syndrome, wet AMD, and diabetic retinopathy [2][3]. Financial Performance - Cash, cash equivalents, and marketable securities totaled $302.0 million as of September 30, 2025, an increase from $244.9 million at the end of 2024, primarily due to a $110.0 million upfront payment from Nippon Shinyaku and $144.5 million from royalty monetization [7]. - Revenues for Q3 2025 were $29.7 million, up from $24.2 million in Q3 2024, driven by $5.9 million in development service revenue from the Nippon Shinyaku partnership [8]. - Research and development expenses rose to $56.1 million in Q3 2025 from $54.4 million in Q3 2024, mainly due to increased personnel and manufacturing costs [9]. - General and administrative expenses increased to $20.3 million in Q3 2025 from $19.4 million in Q3 2024, attributed to professional services and consulting [10]. - The net loss for Q3 2025 was $61.9 million, compared to a net loss of $59.6 million in Q3 2024, resulting in a basic and diluted net loss per share of $1.20 [11]. Program Highlights - RGX-202, a gene therapy for Duchenne muscular dystrophy, is advancing rapidly with topline results expected in early Q2 2026 and a Biologics License Application (BLA) submission planned for mid-2026 [5][6]. - Clemidsogene lanparvovec (RGX-121) is on track to be the first gene therapy for Hunter syndrome, with a PDUFA date set for February 8, 2026 [4][12]. - Surabgene lomparvovec (sura-vec) is positioned to be the first gene therapy for chronic retinal diseases, with pivotal trial enrollment completed and topline data expected in Q4 2026 [5][7]. Operational Developments - Enrollment in the pivotal trial for RGX-202 was completed in October 2025, with ongoing confirmatory studies for ambulatory patients [6]. - REGENXBIO has begun manufacturing RGX-202 for commercial supply, anticipating a launch in 2027 [6]. - The company presented positive 12-month data for RGX-121, showing significant biomarker reductions and correlations with neurodevelopmental outcomes [12]. Future Outlook - REGENXBIO expects its cash position to fund operations into early 2027, excluding potential milestone payments from partners [13]. - The company is preparing for a conference call to discuss these results and operational highlights [14].

Core Insights - Opus Genetics has successfully completed a Type B Regenerative Medicine Advanced Therapy (RMAT) meeting with the FDA regarding its gene therapy candidate OPGx-LCA5 for Leber congenital amaurosis (LCA) caused by mutations in the LCA5 gene [1][2][8] - The FDA provided constructive feedback on Opus's registration strategy, including Chemistry, Manufacturing and Controls (CMC), and pivotal trial design, acknowledging the significant unmet medical need for individuals with LCA5-related blindness [2][3] - The company plans to advance its ongoing trial using an adaptive design that includes a Phase 3 portion, which will avoid the need for a separate registrational trial [3][4] Clinical Development - Six late-stage participants have been treated in the Phase 1/2 trial of OPGx-LCA5, with all experiencing clinically meaningful improvements in vision [3][9] - The Phase 3 trial will include a run-in period to evaluate the natural history of each participant, serving as their own control [5][4] - Efficacy and safety will be assessed using various measures, including visual acuity and microperimetry, with dosing anticipated in the second half of 2026 [5][8] Financial Position - Opus Genetics has secured recent financing of $23 million, which will support the advancement of its LCA5 program and fund current operating plans into the second half of 2027 [6][8] Regulatory Environment - The FDA's introduction of the Rare Disease Evidence Principles (RDEP) review process aims to facilitate the approval of drugs for rare diseases, and Opus believes its LCA5 program meets the eligibility criteria for this process [7][8] - OPGx-LCA5 has the potential to be the first gene therapy and one-time treatment for LCA type 5, addressing a significant unmet medical need [8][11] Company Overview - Opus Genetics is a clinical-stage biopharmaceutical company focused on developing gene therapies for inherited retinal diseases and small-molecule therapies for other ophthalmic disorders [12] - The company's pipeline includes AAV-based gene therapies targeting conditions such as LCA and bestrophinopathy, with OPGx-LCA5 currently in a Phase 1/2 clinical trial [12][9]

Financial Data and Key Metrics Changes - The company's cash, cash equivalents, and restricted cash totaled $32.9 million as of September 30, 2025, down from $58.8 million as of December 31, 2024 [13] - Total operating expenses for the three months ended September 30, 2025, were $19.4 million, compared to $14.4 million for the same period in 2024 [14] Business Line Data and Key Metrics Changes - The OCU400 phase three LI M EL IGHT clinical trial is on track for BLA and MAA submissions in 2026, addressing multiple genetic mutations with a single therapeutic approach [7] - OCU410 is designed to address multiple pathways implicated in dry age-related macular degeneration, showing a 23% reduction in lesion growth at 12 months [12] Market Data and Key Metrics Changes - Approximately 300,000 people in the U.S. and Europe combined live with Retinitis Pigmentosa (RP), with OCU400 targeting the remaining 98-99% of RP patients [7][8] - There are an estimated 7,000 individuals in South Korea with RP, representing about 7% of the U.S. market [9] Company Strategy and Development Direction - The company aims to file three BLAs in the next three years, with a focus on addressing unmet medical needs for patients facing vision loss [5] - Ocugen is pursuing regional partnerships to maximize patient reach while generating returns for shareholders, including an exclusive licensing agreement with Kwang Dong Pharmaceutical for OCU400 in South Korea [9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress of clinical trials and the potential for OCU400 to provide a therapeutic option for a large patient population [8] - The company anticipates commercialization of OCU400 in 2027, with brand planning and marketing initiatives already underway [8] Other Important Information - The company closed a registered direct offering with Janus Henderson in August, raising approximately $20 million to extend its runway through the second quarter of 2026 [6] - The interim data from the ongoing phase two three study for OCU14ST is expected mid-2026, further advancing the goal of bringing the treatment to patients [11] Q&A Session Summary Question: Timing of BLA completion for OCU400 - Management indicated that resources are ready to turn around pivotal data to the FDA in weeks [15] Question: Manufacturing readiness for commercial production - The company confirmed that process validation runs are on target and materials for registration can be commercialized [16] Question: Endpoints for OCU410ST interim readout - The primary endpoint is lesion growth compared to untreated controls, with visual acuity as a secondary endpoint [17] Question: Statistical design of the LIMELIGHT study for OCU400 - The study includes a control arm and has a planned enrollment of 150 subjects, with a 97% power for the study [19] Question: Enrollment progress for OCU410ST - Enrollment is on track with no geographical restrictions, covering a pediatric population [24] Question: Commercial strategy for OCU400 - The company is targeting a broad indication for RP, including various mutations to maximize treatment potential [25] Question: Regulatory path for OCU400 in South Korea - Approval in South Korea is expected to follow FDA approval without the need for additional clinical trials [29] Question: Manufacturing capacity for larger indications - The company has a facility in Pennsylvania and plans to produce all U.S. supply from this site by 2027 [30]

Core Insights - Pacira BioSciences has completed patient enrollment in Part A of its Phase 2 ASCEND study for PCRX-201, a novel gene therapy for knee osteoarthritis, with topline results expected by the end of 2026 [1][6][10] Study Overview - The ASCEND study is a two-part, multicenter trial involving approximately 135 patients aged 45 to 80 with painful knee osteoarthritis at Kellgren-Lawrence Grades 2, 3, or 4 [4] - Part A randomizes about 45 patients to evaluate two doses of PCRX-201, with a 1:1:1 randomization to Dose A, Dose B, or saline, all receiving corticosteroid pretreatment [5][6] - The primary endpoint includes treatment-emergent adverse events and secondary endpoints assess pain and physical function changes at Weeks 38 and 52 [7] Product Details - PCRX-201 is designed to enhance IL-1Ra production locally in the knee joint, targeting chronic inflammation and pain associated with osteoarthritis [2][9] - The therapy utilizes a high-capacity adenovirus vector platform, allowing for efficient gene delivery and the potential for redosing [12][17] - The product has received RMAT designation from the FDA and ATMP designation from the EMA, highlighting its clinical promise [11] Company Background - Pacira BioSciences focuses on innovative, non-opioid pain therapies, with existing products including EXPAREL, ZILRETTA, and iovera° [15] - The company aims to address prevalent diseases like osteoarthritis through advanced gene therapy solutions [15]