Lexeo Therapeutics Conference Call Summary Company Overview - **Company**: Lexeo Therapeutics (NasdaqGM:LXEO) - **Focus**: Cardiac genetic medicines - **Clinical Programs**: Two main programs targeting Friedreich's ataxia and arrhythmogenic cardiomyopathy Key Points on Friedreich's Ataxia (FA) Program - **Current Status**: Advanced therapy for Friedreich's ataxia showing promising results in Phase I/II trials - **Clinical Data**: - All patients with abnormal left ventricular mass index (LVMI) returned to normal range - Improvement of 1.5 to 2 points on neurologic scales, comparable to approved treatments [1][2][27] - **Regulatory Alignment**: - FDA alignment on accelerated approval path with co-primary endpoints being LVMI and frataxin expression - Required effect size: at least 10% reduction in LVMI and increased frataxin expression post-treatment [5][6] - **Next Steps**: - Moving towards a registrational study in 2026 with a focus on pivotal study design and statistical plan [15][16] Key Points on Arrhythmogenic Cardiomyopathy (PKP2) Program - **Patient Population**: Approximately 60,000 patients in the U.S. with PKP2 mutation, a significant commercial opportunity [2] - **Clinical Data**: - Completed enrollment of Phase I/II study with 10 patients, focusing on high-dose data readout in January [2][36] - Initial data shows variability in PKP2 expression among patients, with some achieving up to 70% of normal levels [36][41] - **Regulatory Considerations**: - Ongoing discussions with the FDA regarding registrational endpoints, focusing on multiple clinical endpoints related to quality of life and arrhythmia [42][44] - **Safety Profile**: - No significant treatment-related adverse events reported, with a favorable safety profile compared to other gene therapies [32][50] Commercial Strategy and Market Potential - **Target Market**: - Early adopters for FA are patients with abnormal LVMI (40% of adult population) and those with elevated cardiac markers [28][29] - For PKP2, younger patients with symptoms are expected to be early adopters, with potential for broader market reach as safety data supports wider use [57][59] - **Cost Considerations**: - Gene therapy could offset costs associated with transplants, which can exceed $2 million, making it attractive from a payer perspective [60] Financial Position - **Cash Reserves**: - As of Q3, Lexeo had $122 million in cash and marketable securities, with an additional $154 million raised in October, providing runway into 2028 [61] Additional Insights - **Neurologic Benefits**: The therapy shows potential for neurologic improvement alongside cardiac benefits, indicating a comprehensive treatment approach for FA [27] - **Manufacturing and Safety**: The company emphasizes a low empty capsid ratio in its gene therapy production process, contributing to its safety profile [52][56] This summary encapsulates the key insights from the Lexeo Therapeutics conference call, highlighting the company's strategic direction, clinical advancements, and market potential.

Financial Data and Key Metrics Changes - As of September 30, 2025, the company had cash, cash equivalents, restricted cash, and short-term investments totaling $207.5 million, providing significant financial flexibility for the ZEVASKYN commercial launch [15] - Research and development (R&D) spending for Q3 2025 was $4.2 million, a decrease from $8.9 million in Q3 2024, primarily due to costs capitalized into inventory and reclassification of certain costs to selling, general, and administrative expenses (SG&A) [16] - SG&A expenses increased to $19.3 million in Q3 2025 from $6.4 million in Q3 2024, reflecting the reclassification of R&D expenses and increased costs associated with the commercial launch [16] - The net loss for Q3 2025 was $5.2 million, or -$0.10 per share, compared to a net loss of $30.3 million, or -$0.63 per share, in Q3 2024 [16] Business Line Data and Key Metrics Changes - The ZEVASKYN commercial launch is progressing, with growing patient demand and the activation of a third qualified treatment center (QTC), Children's Hospital Colorado [5][12] - The number of identified eligible patients at QTCs has more than doubled to approximately 30, up from over 12 previously reported [11] - The company has received ZEVASKYN Product Order Forms (ZPOFs) for 12 patients, indicating strong interest and movement towards treatment [10] Market Data and Key Metrics Changes - ZEVASKYN has received coverage decisions from all major commercial payers, covering over 80% of commercially insured lives, and has baseline coverage across all 51 state Medicaid programs [13] - A permanent product J-code for ZEVASKYN will be established by CMS effective January 1, 2026, which is expected to simplify claims and reimbursement processing [14] Company Strategy and Development Direction - The company is focused on scaling the ZEVASKYN commercial launch to meet patient demand and expanding its QTC network [5] - The management is actively discussing the onboarding of additional EB centers across the U.S. to further expand ZEVASKYN's geographic footprint [12] - The company aims to achieve profitability in the first half of 2026, despite the delay in the first patient treatment [30] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving 2026 launch goals based on trends in patient demand and market access, despite a temporary delay in the first patient treatment [5][6] - The management highlighted the importance of maintaining high-quality standards in manufacturing personalized drug products [8] - The company is encouraged by the doubling of identified patients and the favorable payer landscape for ZEVASKYN [19] Other Important Information - The company has paused collecting additional patient biopsies to investigate and optimize a release assay that encountered performance issues [9] - The gene therapy program for X-linked retinoschisis, ABO-503, has been selected for the FDA Rare Disease Endpoint Advancement Pilot Program, which may accelerate development [18] Q&A Session Summary Question: Expected timeline for patients to receive treatment - Management indicated that several patients have already been scheduled for biopsy in November and early 2026, with treatment expected to follow if all paperwork is completed [24][26] Question: Impact on profitability timeline due to treatment delays - Management does not foresee a significant impact on the timeline for achieving profitability, maintaining guidance for the first half of 2026 [30] Question: Status of routine maintenance shutdown - The company confirmed a planned shutdown for routine maintenance starting mid-December and lasting about a month [34][35] Question: Biopsy collection during optimization pause - No biopsies were collected during the pause; the company prioritized resolving the assay issue before proceeding [36] Question: Lead time for ZEVASKYN Product Order Forms - Management expects the lead time to decrease as more patients progress through the treatment process and payer policies become established [39][42] Question: Attrition rate among patients with ZPOFs - Management anticipates a high conversion rate for patients with ZPOFs, as these are motivated patients who have expressed interest in treatment [47][49] Question: Prior authorization process for RDEB patients - The prior authorization process involves clinical and financial discussions, with most payers following inclusion/exclusion criteria from clinical trials [52] Question: Revenue recognition timeline - Revenue is recognized when the product is administered to the patient, with cash flow considerations varying by site [58]

Financial Data and Key Metrics Changes - As of September 30, 2025, the company had cash, cash equivalents, restricted cash, and short-term investments totaling $207.5 million, providing significant financial flexibility for the ZEVASKYN commercial launch [15] - Research and development (R&D) spending for Q3 2025 was $4.2 million, a decrease from $8.9 million in Q3 2024, primarily due to costs capitalized into inventory and reclassification of certain costs to selling, general, and administrative expenses (SG&A) [16] - SG&A expenses increased to $19.3 million in Q3 2025 from $6.4 million in Q3 2024, reflecting the reclassification of R&D expenses and increased costs associated with the commercial launch [16] - The net loss for Q3 2025 was $5.2 million, or negative $0.10 per share, compared to a net loss of $30.3 million, or negative $0.63 per share, in Q3 2024 [16] Business Line Data and Key Metrics Changes - The ZEVASKYN commercial launch is progressing, with the first patient treatment delayed to Q4 2025 due to optimization of a product release assay, but demand is growing [5][6] - The number of identified eligible patients at qualified treatment centers (QTCs) has more than doubled to approximately 30, up from over 12 previously reported [11] - The activation of Children's Hospital Colorado as a QTC brings the total to three, alongside Lurie Children's Hospital of Chicago and Lucille Packard Children's Hospital Stanford [12] Market Data and Key Metrics Changes - ZEVASKYN has received positive coverage decisions from major commercial payers, covering over 80% of commercially insured lives, and has baseline coverage across all 51 state Medicaid programs effective October 1, 2025 [13] - A permanent product J-code for ZEVASKYN will be established by CMS effective January 1, 2026, simplifying claims and reimbursement processing [14] Company Strategy and Development Direction - The company is focused on scaling the ZEVASKYN commercial launch to meet patient demand and expanding its QTC network [5][6] - The management team has been strengthened with the appointment of Dr. James A. Gao as Senior Vice President, Head of Clinical Development and Medical Affairs, to advance the pipeline [18] Management's Comments on Operating Environment and Future Outlook - Management remains confident in achieving 2026 launch goals despite the delay in the first patient treatment, citing trends in patient demand and market access [5][6] - The company expects to maintain a profitable business in the first half of 2026, with no significant impact from the treatment delay [29] Other Important Information - The company paused collecting additional patient biopsies to investigate a performance issue with a release assay, resuming in November 2023 [9] - The company plans to participate in the Stifel 2025 Healthcare Conference following the earnings call [16] Q&A Session Summary Question: Expected timeline for patients to receive treatment - Management indicated that several patients have already received prior authorizations and are scheduled for biopsies in November and early 2026 [24] Question: Impact on profitability timeline due to treatment delay - Management does not foresee a significant impact on the timeline to profitability, maintaining guidance for the first half of 2026 [29] Question: Routine maintenance shutdown of the plant - A shutdown for routine maintenance is scheduled for mid-December to early January, as mandated by the FDA [32] Question: Current lead time for ZEVASKYN Product Order Forms - The current lead time is about three months, but management expects this to decrease as more patients progress through the process [36] Question: Attrition rate among patients with ZEVASKYN Product Order Forms - Management expects a high conversion rate among patients who have received ZPOFs, as these are motivated patients [44] Question: Prior authorization process for RDEB patients - The prior authorization process involves clinical and financial discussions, with most payers following inclusion/exclusion criteria from clinical trials [50] Question: Biopsies and sterility release criteria - Management confirmed that they have resumed biopsies and are not guiding on the number of biopsies completed yet [54] Question: Patients on background Vyjuvek or Filsuvez - Management does not have visibility into the exact number of patients currently on these treatments but expects many to be [58] Question: UMass not listed as a QTC - Different sites have various reasons for not being onboarded, including financial constraints and trade policy differences [62]

Financial Data and Key Metrics Changes - As of September 30, 2025, the company reported cash, cash equivalents, restricted cash, and short-term investments totaling $207.5 million, providing significant financial flexibility for operations over the next two years [13][14] - Research and development (R&D) spending for Q3 2025 was $4.2 million, a decrease from $8.9 million in Q3 2024, primarily due to costs capitalized into inventory [14] - Selling, general and administrative (SG&A) expenses increased to $19.3 million in Q3 2025 from $6.4 million in Q3 2024, reflecting the reclassification of R&D expenses and increased costs associated with the commercial launch [15] - The net loss for Q3 2025 was $5.2 million, or negative $0.10 per share, compared to a net loss of $30.3 million, or negative $0.63 per share, in Q3 2024 [15] Business Line Data and Key Metrics Changes - The company is focused on the commercial launch of ZEVASKYN, the first autologous cell-based gene therapy for recessive dystrophic epidermolysis bullosa (RDEB), with growing patient demand and an expanding network of qualified treatment centers (QTCs) [4][10] - The number of identified eligible patients at QTCs has more than doubled to approximately 30, up from over 12 previously reported [10] - The activation of Children's Hospital Colorado as a QTC brings the total to three, alongside Lurie Children's Hospital of Chicago and Lucille Packard Children's Hospital Stanford [11] Market Data and Key Metrics Changes - ZEVASKYN has received coverage decisions from all major commercial payers, covering over 80% of commercially insured lives, and has baseline coverage across all 51 state Medicaid programs effective October 1, 2025 [12] - A permanent product J-code for ZEVASKYN will be established by CMS effective January 1, 2026, simplifying claims and reimbursement processing [12] Company Strategy and Development Direction - The company aims to achieve its 2026 launch goals for ZEVASKYN despite a temporary delay in the first patient treatment, focusing on expanding treatment center networks and ensuring market access [4][5] - The company is also advancing its pipeline, with a gene therapy program for X-linked retinoschisis selected for the FDA Rare Disease Endpoint Advancement pilot program [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ability to meet 2026 launch goals based on trends in patient demand and treatment center expansion, despite the delay in the first patient treatment [4][5] - The management team highlighted the importance of maintaining high-quality standards in manufacturing and the proactive measures taken to optimize release assays [6][7] Other Important Information - The company has strengthened its management team with the appointment of Dr. James A. Gao as Senior Vice President, Head of Clinical Development and Medical Affairs, bringing over 20 years of industry experience [17] Q&A Session Summary Question: Expected timeline for patients to receive treatment after ZEVASKYN Product Order Forms - Management indicated that many patients have already received prior authorizations and are scheduled for biopsies in November and early 2026, with treatment expected to follow if all paperwork is completed [20][22] Question: Impact of treatment delays on profitability timeline - Management stated that the timeline for achieving profitability remains unchanged, with expectations for profitability in the first half of 2026 [26][28] Question: Routine maintenance shutdown of the plant - Management confirmed a mandated FDA-required shutdown for general maintenance from mid-December to early January [29][30] Question: Status of biopsies collected before optimization pause - Management clarified that no biopsies were collected during the pause to ensure patient safety and product quality [31] Question: Lead time for ZEVASKYN Product Order Forms - Management expects the lead time to decrease as more patients progress through the treatment process, currently estimated at about three months [34] Question: Attrition rate among patients with ZEVASKYN Product Order Forms - Management expressed confidence in a high conversion rate for patients with ZPOFs, as these are motivated patients eager to proceed with treatment [40][41] Question: Prior authorization process for RDEB patients - Management described the prior authorization process as involving clinical and financial discussions, with most payers following inclusion/exclusion criteria from clinical trials [44][46]

Financial Data and Key Metrics Changes - Revenue for Q3 2025 was $3.7 million, an increase from $2.3 million in Q3 2024, resulting in a $1.5 million increase in license revenues and a slight decrease in collaboration revenues [17] - Research and development expenses rose to $34.4 million in Q3 2025 from $30.6 million in Q3 2024, driven by a $10.1 million increase in direct R&D expenses, primarily for BLA submission preparation [18] - Selling, general, and administrative expenses increased to $19.4 million in Q3 2025 from $11.6 million in Q3 2024, mainly due to higher employee-related expenses and professional fees [18] - Cash, cash equivalents, and investment securities totaled $649.2 million as of September 30, 2025, up from $376.5 million at the end of 2024, primarily due to net proceeds from public offerings [19] Business Line Data and Key Metrics Changes - AMT-130 for Huntington's disease showed a statistically significant 75% slowing of disease progression at three years compared to an external control, meeting the pivotal study's primary endpoint [9] - AMT-260 for mesial temporal lobe epilepsy has activated 17 recruiting sites in the U.S. and completed enrollment of the first three patients in the first cohort, with updated data expected in the first half of 2026 [11] - AMT-191 for Fabry disease demonstrated supra-physiological alpha-galA enzyme activity in treated patients, with all successfully withdrawn from enzyme replacement therapy [12] Market Data and Key Metrics Changes - The company is focusing on building a foundational strategy for the U.S. market for AMT-130 while also exploring potential markets in the European Union and the United Kingdom [16] Company Strategy and Development Direction - The company remains committed to working with the FDA to clarify next steps for AMT-130 and is also planning discussions with other regulatory agencies [20] - The management emphasizes the importance of stakeholder engagement and education to prepare for a potential launch of AMT-130 [15] Management's Comments on Operating Environment and Future Outlook - Management expressed disappointment regarding the FDA's feedback on the BLA submission for AMT-130 but remains confident in the data and its potential to benefit patients [5][10] - The company plans to engage urgently with the FDA to discuss the next steps and remains committed to transparency and collaboration [6][11] Other Important Information - Enrollment in the phase I-II trial of AMT-162 for SOD1 ALS has been paused due to safety concerns, with ongoing data collection from treated patients [13] Q&A Session Summary Question: Treatment effect and external control arm construction - The company conducted rigorous propensity score matching with Enroll-HD and performed various sensitivity analyses to ensure robustness of findings [27] Question: Details on AMT-162 and dose differences - The middle dose of AMT-162 was about three-fold higher than the low dose, and the company is monitoring data to determine next steps [31] Question: Expectations from final meeting minutes with the FDA - The company hopes the minutes will outline FDA concerns and provide guidance on addressing those in future meetings [34] Question: Confirmation of prior meeting minutes regarding accelerated approval - The company confirmed that previous meetings indicated the data could support a BLA submission and that the composite UHDRS was an acceptable endpoint [37] Question: Future investment in Huntington's program - The company is committed to collaborating with the FDA to find an expedited path for BLA submission, emphasizing the urgency of patient needs [41] Question: EMA or MHRA feedback on AMT-130 - The company has not yet engaged with EMA or MHRA but plans to prioritize discussions with the FDA first [47]

Core Insights - uniQure reported a quarterly loss of $1.38 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.85, marking a 62.35% earnings surprise [1] - The company's revenues for the quarter were $3.7 million, missing the Zacks Consensus Estimate by 46.62%, but showing an increase from $2.29 million a year ago [2] - The stock has gained approximately 57.4% year-to-date, outperforming the S&P 500's gain of 14.4% [3] Financial Performance - The company has surpassed consensus EPS estimates two times over the last four quarters [2] - The current consensus EPS estimate for the upcoming quarter is -$0.40 on revenues of $40.73 million, and for the current fiscal year, it is -$3.12 on revenues of $39.82 million [7] Market Outlook - The sustainability of the stock's price movement will depend on management's commentary during the earnings call [3] - The Zacks Rank for uniQure is currently 3 (Hold), indicating expected performance in line with the market in the near future [6] - The Medical - Biomedical and Genetics industry is currently in the top 36% of Zacks industries, suggesting a favorable outlook compared to the bottom 50% [8]

Core Viewpoint - MeiraGTx Holdings has entered into a strategic collaboration with Eli Lilly to develop and commercialize gene therapies for eye diseases, leading to a significant pre-market stock price increase of 13.22% [1] Group 1: Collaboration Details - The agreement grants Eli Lilly global exclusive rights to MeiraGTx's AAV-AIPL1 gene therapy project, targeting Leber Congenital Amaurosis Type 4 (LCA4), a severe hereditary retinal disease caused by a defect in the AIPL1 gene [1] - Eli Lilly will also gain rights to additional gene therapy technologies from MeiraGTx as part of the collaboration [1] Group 2: Financial Terms - MeiraGTx will receive a $75 million upfront payment and could earn over $400 million upon achieving certain milestones [1] - The company will also be eligible for tiered royalties from potential sales of the licensed products [1]

Core Insights - Moderna reported a quarterly loss of $0.51 per share, significantly better than the Zacks Consensus Estimate of a loss of $2.15, representing an earnings surprise of +76.28% [1] - The company generated revenues of $1.02 billion for the quarter ended September 2025, exceeding the Zacks Consensus Estimate by 18.13%, although this is a decline from $1.86 billion in the same quarter last year [2] - Moderna has surpassed consensus EPS estimates in all four of the last quarters and has topped consensus revenue estimates three times during the same period [2] Financial Performance - The earnings report indicates a loss of $0.51 per share compared to a profit of $0.03 per share a year ago, adjusted for non-recurring items [1] - The company has shown a mixed trend in estimate revisions ahead of the earnings release, currently holding a Zacks Rank 3 (Hold), suggesting expected performance in line with the market [6] - Current consensus EPS estimate for the upcoming quarter is -$2.90 on revenues of $805.49 million, and for the current fiscal year, it is -$9.74 on revenues of $1.9 billion [7] Market Context - Moderna shares have declined approximately 43.3% since the beginning of the year, contrasting with the S&P 500's gain of 15.6% [3] - The Medical - Biomedical and Genetics industry, to which Moderna belongs, is currently ranked in the top 41% of over 250 Zacks industries, indicating a favorable outlook compared to lower-ranked industries [8] - The performance of Moderna's stock may also be influenced by the earnings outlook and trends in earnings estimate revisions, which have shown a strong correlation with near-term stock movements [5]

Financial Data and Key Metrics Changes - Research and development expenses increased to $25.7 million for Q3 2025, up from $14.9 million in Q3 2024, driven by BLA-enabling manufacturing initiatives and higher compensation expenses due to increased headcount [21] - General and administrative expenses rose to $8.3 million in Q3 2025 from $7.9 million in Q3 2024, primarily due to debt issuance costs [22] - Net loss for Q3 2025 was $32.7 million, or $0.09 per share, compared to a net loss of $25.5 million, or $0.10 per share, in Q3 2024 [23] - As of September 30, 2025, the company had $297.3 million in cash and cash equivalents, expected to support operations into 2028 [23] Business Line Data and Key Metrics Changes - The company is focusing on the TSHA-102 program for Rett Syndrome, which received FDA breakthrough therapy designation, highlighting its potential to address significant unmet medical needs [7][8] - The REVEAL Phase 1/2 trials showed a 100% response rate in Part A, with all 10 patients achieving developmental milestones [10][11] Market Data and Key Metrics Changes - The estimated patient population for Rett Syndrome in the U.S. is between 15,000 and 20,000, indicating a significant market opportunity for TSHA-102 [17] Company Strategy and Development Direction - The company regained full global rights to TSHA-102, allowing for strategic flexibility and focus on long-term value [14] - The company is building out its infrastructure to support late-stage development and potential commercialization of TSHA-102 [15] - The appointment of a new Chief Commercial Officer aims to strengthen the commercial leadership team as the company prepares for market entry [16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory clarity and progress achieved, which positions the company well for the REVEAL pivotal trial and BLA submission [6][24] - The company anticipates reporting longer-term clinical data from Part A of the REVEAL trials in the first half of 2026 [24] Other Important Information - The company is enrolling 15 patients in the pivotal trial, with a primary endpoint of a 33% response rate, which is the minimum threshold for success [10] - The FDA's guidance emphasizes the importance of aligning the statistical analysis plan before starting clinical trials, which the company has adhered to [35] Q&A Session Summary Question: Interest and demand for the pivotal trial - Management noted exceptionally high demand for participation in the trial, with over 15 identified sites having significant patient populations [26][27] Question: Expectations for longer-term data and FDA discussions - Management plans to provide updates on safety and efficacy as data matures, with a focus on the 12-month data for all patients [32][34] Question: Data from younger patients and safety expectations - The company aims to include the two- to five-year-old population in the BLA submission, with safety-focused studies planned for this cohort [41][42] Question: Updates on European plans and EMA discussions - The primary focus remains on the U.S. market, with ongoing discussions to enable future opportunities in Europe [50][51] Question: Statistical plan and interim analysis - The evaluations for the trial are objective, based on a natural history analysis accepted by the FDA, with a clear process for interim analysis [81][82]

U.S. stocks traded higher this morning, with the Nasdaq Composite gaining 1% on Monday.Following the market opening Monday, the Dow traded up 0.04% to 47,583.87 while the NASDAQ rose 1.01% to 23,964.61. The S&P 500 also rose, gaining, 0.48% to 6,872.88.Check This Out: How To Earn $500 A Month From Pfizer Stock Ahead Of Q3 EarningsLeading and Lagging SectorsConsumer discretionary shares jumped by 1.8% on Monday.In trading on Monday, utilities stocks fell by 0.8%.Top HeadlineON Semiconductor Corporation (NASD ...