NRx Pharmaceuticals (NasdaqCM:NRXP) Q3 2025 Earnings Call November 17, 2025 08:30 AM ET Speaker1Good morning, ladies and gentlemen, and welcome to the NRx Pharmaceuticals Q3 2025 earnings conference call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Monday, November 17, 2025. I would now like t ...

Core Insights - Denali Therapeutics Inc. (DNLI) announced that the FDA has extended the review timeline for its Biologics License Application (BLA) for tividenofusp alfa, a treatment for mucopolysaccharidosis type II (MPS II) [1][3][7] - The new target date for the BLA review is now April 5, 2026, pushed back from January 5, 2026, due to the submission of updated clinical pharmacology information [3][7] - The extension is classified as a major amendment and is not related to the drug's efficacy, safety, or biomarkers [3][4][7] Company Performance - Denali's stock experienced a decline of 26.5% year to date, contrasting with the industry average gain of 9.2% [2] Drug Development Details - Tividenofusp alfa is designed to deliver the iduronate 2-sulfatase (IDS) enzyme to address symptoms of Hunter syndrome [4][5] - The FDA has previously granted Fast Track and Breakthrough Therapy designations to tividenofusp alfa, and the European Medicines Agency has given it Priority Medicines designation [8] Other Pipeline Candidates - Denali is also developing DNL126 for Sanfilippo syndrome type A (MPS IIIA), with the FDA considering cerebrospinal fluid heparan sulfate as a potential surrogate endpoint for accelerated approval [9] - Another candidate, TAK-594/DNL593, is in collaboration with Takeda for treating frontotemporal dementia (FTD) [10] - Denali and Biogen are jointly evaluating BIIB122/DNL151 for Parkinson's disease, with a global phase IIb study currently ongoing [11][12] Market Position - Denali currently holds a Zacks Rank 3 (Hold), while competitors Amicus Therapeutics and CorMedix have higher rankings of 1 (Strong Buy) and 2 (Buy) respectively [13]

Core Viewpoint - Disc Medicine, Inc. has submitted a New Drug Application (NDA) to the FDA for bitopertin, targeting patients aged 12 and older with erythropoietic protoporphyria (EPP), aiming for accelerated approval due to significant unmet medical needs [1][2][3] Company Overview - Disc Medicine is a clinical-stage biopharmaceutical company focused on developing novel treatments for serious hematologic diseases, with a portfolio targeting heme biosynthesis and iron homeostasis [9] Product Details - Bitopertin is an investigational, orally administered inhibitor of glycine transporter 1 (GlyT1), designed to modulate heme biosynthesis and potentially serve as the first disease-modifying therapy for erythropoietic porphyrias [4][5] - The NDA submission is supported by Phase 2 BEACON and AURORA studies, which showed significant reductions in protoporphyrin IX (PPIX) and improvements in light tolerance and quality of life for EPP patients [2][4] Regulatory Pathway - The NDA includes a request for Priority Review, which could shorten the FDA review period to six months, highlighting the potential for significant improvement in treatment effectiveness [3][7] Disease Context - Erythropoietic protoporphyria (EPP) is a rare and debilitating disease caused by mutations affecting heme biosynthesis, leading to severe reactions to sunlight and potential liver complications [6][8]

Core Viewpoint - OS Therapies is advancing its regulatory submissions for OST-HER2, focusing on obtaining marketing authorizations in the UK and US for the treatment of pulmonary metastatic osteosarcoma, with submissions expected in late 2025 and early 2026 [3][7]. Regulatory Update - The company has updated its regulatory filing sequence to prioritize the UK MHRA conditional Marketing Authorisation Application (MAA) submission, which is expected to be completed in December 2025, followed by the US FDA Biologics Licensing Application (BLA) submission in January 2026 [3][7]. - A conditional MAA Pre-Submission Request has been submitted to the MHRA, and the company anticipates receiving formal acceptance for a rolling review request soon [4]. Clinical Trial Insights - The information in the MHRA conditional MAA submission aligns closely with the planned US FDA BLA submission, with the exception of the acceptable comparator arm for efficacy data [5]. - The company aims to use immune activation biomarker data as a surrogate marker correlated with overall survival to support its Accelerated Approval request [5][7]. Company Background - OS Therapies is a clinical-stage oncology company focused on developing treatments for osteosarcoma and other solid tumors, with OST-HER2 being its lead asset [8]. - OST-HER2 has received several designations from the FDA, including Rare Pediatric Disease Designation and Fast-Track designation, and has shown statistically significant benefits in its Phase 2b clinical trial [8]. Future Developments - The company is also advancing its next-generation Antibody Drug Conjugate (ADC) platform, known as tunable ADC (tADC), which utilizes proprietary technology for enhanced drug delivery [9].

Core Insights - Denali Therapeutics reported a second-quarter 2025 loss of $0.72 per share, which was narrower than the Zacks Consensus Estimate of a loss of $0.74, but wider than the loss of $0.59 in the same quarter last year [1][8] - The company did not generate any collaboration revenues in the reported quarter, missing the Zacks Consensus Estimate of $25 million [2] - Year-to-date, shares of Denali have declined by 31.7%, while the industry has only seen a 0.6% decline [2] Financial Performance - Research and development expenses increased by 12.4% to $102.7 million, primarily due to higher spending on multiple preclinical programs and increased costs for consultants and general facilities [4] - General and administrative expenses rose by 28% to $32.3 million, driven by preparations for the potential launch of tividenofusp alfa [4] - As of June 30, 2025, the company had cash, cash equivalents, and marketable securities totaling approximately $977.4 million [5] Pipeline Developments - The FDA accepted Denali's biologics license application (BLA) for tividenofusp alfa for priority review, with a target action date set for January 5, 2026 [6][8] - The BLA seeks accelerated approval based on data from a phase I/II study in individuals with Hunter syndrome, with previous designations from the FDA including Breakthrough Therapy and Fast Track [7] - Denali is also advancing DNL126 for Sanfilippo syndrome type A, with alignment from the FDA on using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval [10] Ongoing Studies - Data from the ongoing phase I/II study of DNL126 shows a significant reduction in cerebrospinal fluid heparan sulfate levels, supporting continued development [11] - Denali is conducting a phase I/II study of DNL593 for frontotemporal dementia, in collaboration with Takeda [12] - The company is also evaluating BIIB122/DNL151 in partnership with Biogen for Parkinson's disease, with a global phase IIb study fully enrolled [13][14] Future Plans - Denali plans to submit regulatory applications for one to two TV-enabled programs each year over the next three years across its various franchises [15] - The most advanced programs include DNL952 for Pompe disease and DNL111 for Parkinson's/Gaucher disease, among others [15] Overall Assessment - Denali's recent pipeline progress is viewed positively, with potential approval of tividenofusp alfa expected to significantly boost the company [16] - The strong cash position is seen as a positive factor for funding ongoing programs [16]

Summary of Laramar Therapeutics Conference Call Company Overview - **Company**: Laramar Therapeutics - **Focus**: Development of nonlobofusp (formerly CTI-16-01) for the treatment of Friedreich's Ataxia (FA), a rare neurodegenerative disease [doc id='13'][doc id='16'] Industry Context - **Disease**: Friedreich's Ataxia (FA) is characterized by low levels of frataxin, leading to severe neurological symptoms and a life expectancy of 30 to 50 years [doc id='15'][doc id='14'] - **Current Treatments**: The FDA approved omevaloxolone in 2023, but it does not affect frataxin levels, highlighting the unmet need for therapies that address the underlying deficiency [doc id='16'] Key Regulatory Updates - **FDA Recommendations**: Laramar received FDA guidance on the safety database for the Biologics License Application (BLA) submission, requiring data from at least 30 participants exposed to the drug for six months and 10 participants for one year [doc id='7'][doc id='8'] - **BLA Submission Timeline**: The company plans to submit the BLA in Q2 2026, with a U.S. launch targeted for early 2027 [doc id='25'][doc id='31'] Clinical Development - **Clinical Trials**: Ongoing studies include a global Phase 3 trial and an open-label extension study to evaluate long-term safety and efficacy [doc id='11'][doc id='12'] - **Patient Population**: The Phase 3 study will include patients aged 2 to 40, with a focus on younger patients [doc id='28'][doc id='29'] - **Efficacy Data**: Initial data from the 25 mg dose showed increases in frataxin levels and early trends towards clinical improvement [doc id='19'][doc id='20'] Safety Profile - **Adverse Events**: Nonlobofusp has been generally well tolerated, with mild injection site reactions being the most common adverse events [doc id='20][doc id='21'] - **Allergic Reactions**: Anaphylaxis has been reported, particularly in patients with prior exposure, leading to the introduction of antihistamine premedication [doc id='21'][doc id='22'] Financial Position - **Cash Balance**: As of March 31, the company reported $158 million in cash, sufficient to support operations through the BLA filing [doc id='61'] - **Funding Strategy**: Laramar is exploring non-dilutive financing options, including royalty financing [doc id='61] Future Plans - **Expansion of Studies**: The company plans to enroll children aged 2 to 11 directly into the open-label study, pending FDA discussions [doc id='26'][doc id='105'] - **Data Reporting**: Upcoming data cuts in September will include safety and pharmacokinetic data from 30 to 40 participants [doc id='26'][doc id='39'] Conclusion - Laramar Therapeutics is making significant progress in the development of nonlobofusp for FA, with clear regulatory guidance from the FDA and a robust clinical program aimed at addressing the unmet needs of patients with this debilitating disease [doc id='30'][doc id='31']

Core Viewpoint - Larimar Therapeutics, Inc. is progressing towards the submission of a Biologics License Application (BLA) for nomlabofusp, a potential treatment for Friedreich's Ataxia, with a planned submission in the second quarter of 2026 following FDA recommendations for safety data inclusion [1][4][9] FDA Recommendations - The FDA has provided clear recommendations for the safety database, requiring at least 30 participants with continuous exposure for 6 months, including a subset of at least 10 participants with 1-year exposure, primarily from the 50 mg dose group [4][5] - The FDA is open to the use of skin frataxin (FXN) concentrations as a reasonably likely surrogate endpoint for the BLA submission, acknowledging the relationship between increased skin FXN and relevant tissues [5][9] Clinical Development Progress - Enrollment in the open label extension (OLE) study is ongoing, with plans to include adolescents and patients who have not previously participated in clinical studies [2][4] - Data from the OLE study, expected in September 2025, will include results from 30-40 participants who received at least one dose of nomlabofusp, focusing on the 50 mg dose [4][9] - Adolescent pharmacokinetic (PK) run-in data is also anticipated in September 2025 from 14 participants, some of whom received a placebo [4][9] Global Phase 3 Study - Activities for the global Phase 3 study are ongoing, with site identification and qualification in the U.S., Europe, U.K., Canada, and Australia [4][9] - The Phase 3 study is intended to serve as a confirmatory study to verify clinical benefit as required by the FDA's accelerated approval pathway [9] Company Overview - Larimar Therapeutics is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, with nomlabofusp as its lead compound targeting Friedreich's Ataxia [7]

Core Viewpoint - Dyne Therapeutics has received Breakthrough Therapy Designation from the FDA for DYNE-101, aimed at treating myotonic dystrophy type 1 (DM1), and has outlined a revised plan for U.S. Accelerated Approval based on new long-term functional data [1][2][10]. Group 1: FDA Designations and Approvals - The FDA granted Breakthrough Therapy Designation to DYNE-101 for DM1, which expedites development and review for drugs showing substantial improvement over existing therapies [10]. - Dyne is pursuing U.S. Accelerated Approval for DYNE-101, with a revised protocol submitted to the FDA following a Type C meeting [6][5]. Group 2: Clinical Trial Updates - The ongoing Registrational Expansion Cohort of the ACHIEVE trial will enroll 60 participants, with video hand opening time (vHOT) as the primary endpoint for potential Accelerated Approval [6][5]. - New long-term data from the ACHIEVE trial indicate that DYNE-101 led to a 3.3 seconds improvement in vHOT at 6 months compared to placebo, with sustained improvements observed at 12 months [12]. - The trial's secondary endpoints include various measures of muscle strength and performance, with a reported 20% improvement in strength at 12 months relative to baseline [12]. Group 3: Financial Guidance - As of March 31, 2025, Dyne reported cash, cash equivalents, and marketable securities totaling $677.5 million, expected to fund operations into Q4 2026 [7]. Group 4: Future Plans - Dyne plans to complete enrollment in the Registrational Expansion Cohort by Q4 2025, with data expected in mid-2026 to support a potential U.S. Accelerated Approval submission in late 2026 [6]. - A confirmatory Phase 3 clinical trial is anticipated to begin in Q1 2026 [6].

Summary of Akero Therapeutics (AKRO) 2025 Conference Call Company Overview - **Company**: Akero Therapeutics (AKRO) - **Industry**: Biotechnology, specifically focused on liver diseases such as NASH (Non-Alcoholic Steatohepatitis) and cirrhosis Key Points and Arguments Phase III Program Updates - Akero is currently executing multiple Phase III programs, including: - **Synchrony Real World Study**: Non-invasive study completed enrollment, results expected in the first half of 2026 [4] - **Synchrony Histology Study**: F2F3 study, results expected in the first half of 2027 [4] - **Synchrony Outcomes Study**: F4 study, first patient enrolled in September 2024, no guidance on results yet [5] Positive Phase II F4 Cirrhosis Data - Akero reported statistically significant improvement in fibrosis for cirrhotic patients, a first in the industry [7] - The effect size increased from 20% to 52% in pre-cirrhotic patients, indicating strong efficacy [8] - The company has not yet received FDA feedback on the Phase II data [10] FDA Interactions and Breakthrough Designation - Akero has breakthrough therapy designation for both pre-cirrhotic and cirrhotic patients [16] - The likelihood of filing for accelerated approval based on the recent data is considered low, but the company intends to share the data with the FDA [18] Competitive Landscape - Akero faces competition from Madrigal Pharmaceuticals, which has already received approval for its drug in the F2F3 space [57] - Other companies, including those developing FGF21 compounds, are also in the pipeline, indicating a competitive market [76] Study Design and Endpoints - The primary endpoint for the F2F3 study is a combination of fibrosis improvement and NASH resolution, which is different from other companies that may only focus on one [70] - The company is considering interim analyses based on strong data from the ongoing studies [25] Enrollment and Market Position - Enrollment for the F2F3 studies is tracking well, with expectations to complete enrollment by the first half of 2026 for a readout in the first half of 2027 [59][60] - Akero's strong F4 data has helped distinguish it from competitors, making enrollment easier [58] Pharma Interest in NASH - Recent acquisitions, such as GSK's purchase of Boston Therapeutics, indicate growing interest from large pharmaceutical companies in the NASH space [80] - Novo Nordisk is also entering the market, which could increase disease awareness and excitement in the field [82] Other Important Insights - Akero is actively engaging with large pharma companies for potential collaborations and investments [85] - The company is focused on ensuring patient safety and monitoring bone mineral density in ongoing studies [51][46] This summary encapsulates the key discussions and insights from the Akero Therapeutics conference call, highlighting the company's progress, competitive landscape, and future outlook in the biotechnology sector focused on liver diseases.

Core Insights - uniQure N.V. is advancing its investigational gene therapy AMT-130 for Huntington's disease, with a Biologics License Application (BLA) submission planned for the first quarter of 2026, following alignment with the FDA on key components of the statistical analysis plan and Chemistry, Manufacturing and Controls (CMC) information [1][2][8] Regulatory Update - The FDA has supported the use of the composite Unified Huntington's Disease Rating Scale (cUHDRS) as an acceptable clinical endpoint for accelerated approval, with the primary efficacy analysis focusing on the 3-year change in cUHDRS in high-dose AMT-130 patients compared to an external control arm [3][4] - The ENROLL-HD dataset, which includes approximately 33,000 patients, will serve as the external control dataset for the primary analysis, enhancing the robustness of the statistical analysis plan due to its larger sample size and lower attrition rates [4][5] Chemistry, Manufacturing and Controls (CMC) - The FDA has agreed that the validation of the AMT-130 manufacturing process can leverage prior knowledge from the HEMGENIX® process, along with additional full-scale AMT-130 GMP batches and a single Process Performance Qualification (PPQ) batch [6][7] Next Steps - The company plans to submit an updated statistical analysis plan to the FDA in Q2 2025, initiate the PPQ run and present topline Phase I/II data in Q3 2025, hold a pre-BLA meeting in Q4 2025, and submit the BLA in Q1 2026 with a request for priority review designation [15] Clinical Program Overview - uniQure is conducting two multi-center, dose-escalating, Phase I/II clinical studies to evaluate the safety and efficacy of AMT-130, with a total of 26 patients in the U.S. study and 13 patients in the European study, exploring both low and high doses [10][11] - AMT-130 has received the FDA's Regenerative Medicine Advanced Therapy (RMAT) designation and Breakthrough Therapy designation, marking it as the first therapy for Huntington's disease to achieve RMAT designation [11] Huntington's Disease Context - Huntington's disease is a rare neurodegenerative disorder affecting approximately 70,000 diagnosed individuals in the U.S. and Europe, with no approved therapies currently available to slow its progression [12] Company Background - uniQure is focused on gene therapy, with a pipeline that includes treatments for Huntington's disease, refractory temporal lobe epilepsy, ALS, and Fabry disease, building on its historic achievement in gene therapy for hemophilia B [13]