Summary of ProMIS Neurosciences FY Conference Call Company Overview - **Company Name**: ProMIS Neurosciences - **Ticker Symbol**: PMN - **Focus**: Development of antibody therapies targeting protein misfolding, particularly in neurodegenerative diseases like Alzheimer's [3][4] Core Points and Arguments - **Technology Platform**: ProMIS utilizes the EpiSelect platform to generate highly selective antibodies aimed at misfolded proteins, which are implicated in various diseases [4][10] - **Lead Program**: The lead program, PMN310, is currently in a Phase 1b/2 study for Alzheimer's disease, with over 100 patients enrolled across 22 sites in the US [7][8] - **Differentiation**: The company emphasizes the importance of having a differentiated product in the competitive Alzheimer's space, particularly regarding efficacy and safety profiles [5][6] - **Safety Profile**: ProMIS claims that PMN310 has a better safety profile compared to existing treatments, particularly concerning ARIA (Amyloid-related imaging abnormalities), which is a significant side effect associated with current Alzheimer's therapies [6][30] - **Clinical Study Design**: The Phase 1b study is designed to last 12 months, focusing on both biomarker and clinical endpoints, with an interim analysis expected in Q2 of the following year [8][34] - **FDA Fast Track Designation**: PMN310 has received fast track approval from the FDA, indicating the agency's recognition of the potential therapeutic benefit of the drug [8][35] Pipeline and Future Programs - **Additional Candidates**: Besides PMN310, ProMIS is developing other candidates targeting misfolded proteins associated with ALS (PMN267) and Parkinson's disease [12] - **Vaccine Program**: The company is also exploring a vaccine program that follows a similar approach to their therapeutic candidates [12] Market Context - **Unmet Medical Need**: There is a significant unmet medical need in Alzheimer's treatment, with existing products showing modest efficacy and challenging risk-benefit profiles [38] - **Commercial Validation**: Despite the challenges, existing Alzheimer's drugs are generating substantial revenue, indicating a market opportunity for safer and more effective treatments [37][38] Important but Overlooked Content - **Interim Analysis**: The interim analysis will focus on biomarker profiles rather than clinical endpoints, which may provide early insights into the drug's efficacy [32][34] - **Patient Population**: The current study focuses on patients with mild Alzheimer's disease and mild cognitive impairment (MCI), with plans to expand to more moderate to severe cases in future studies [41][42] - **Robust Study Design**: The Phase 1b study is designed to be more comprehensive than typical Phase 2 studies, potentially allowing ProMIS to skip a traditional Phase 2 trial if results are favorable [42] This summary encapsulates the key points discussed during the ProMIS Neurosciences FY Conference Call, highlighting the company's focus on innovative therapies for Alzheimer's disease and its strategic positioning within the market.

Financial Data and Key Metrics Changes - The company closed the quarter with $307.3 million in cash, which is expected to provide runway into 2027 [38] - Updated financial guidance for 2025 includes collaboration revenue anticipated between $13 million and $18 million, total research and development guidance between $130 million and $140 million, and total general and administrative guidance between $55 million and $65 million [38] Business Line Data and Key Metrics Changes - The pivotal Phase III INFROM3 trial of Latozinimab is expected to provide top-line data by mid Q4 2025, focusing on frontotemporal dementia due to the GRN gene mutation [5][6] - The Phase II trial of AL-101, targeting early Alzheimer's disease, completed enrollment in April 2025, with trial completion expected in 2026 [7][30] Market Data and Key Metrics Changes - FTD GRN accounts for approximately 5% to 10% of all FTD cases, representing about 8,000 to 17,000 cases in the US and EU [22] - The incidence of FTD in the US is estimated to be 15 to 22 cases per 100,000 person-years, resulting in a prevalence of about 50,000 to 60,000 concurrent cases [15] Company Strategy and Development Direction - The company aims to deliver therapies that eradicate neurodegeneration and improve patient outcomes, focusing on building a durable biotechnology company [9] - The proprietary Electric Brain Carrier technology platform is designed to enable effective delivery of therapies across the blood-brain barrier [8][33] Management's Comments on Operating Environment and Future Outlook - Management emphasized the urgent unmet need in treating frontotemporal dementia and the importance of their clinical programs [10][22] - The company is preparing for potential BLA and MAA submissions in 2026 based on the strength of their trial design and clinical data [29] Other Important Information - The INFROM3 trial is a 96-week randomized, double-blind, placebo-controlled global trial evaluating Latozinimab in symptomatic and at-risk individuals with confirmed GRN mutations [25] - The company has received breakthrough therapy and fast track designations from the FDA for Latozinimab [28] Q&A Session Summary Question: Clarification on the statistical analysis plan changes - The change to include progranulin as a co-primary endpoint was made at the request of the FDA, recognizing its mechanistic role [42] Question: Concerns about plasma progranulin levels - The FDA did not specify a threshold for progranulin levels but emphasized its importance as a biologically meaningful marker [51] Question: Thoughts on the potential for a 25% slowing of cognitive decline - A 25% reduction would be meaningful in a disease with no other therapeutic options, and the safety profile appears favorable compared to anti-amyloid therapies [56][58] Question: Discussion on the open-label extension of the INFROM study - The company is satisfied with the number of subjects opting into the open-label extension, which will provide meaningful data on treatment persistence [108]

Financial Performance & Guidance - Lantheus' Q1 2025 revenues reached $372.8 million, reflecting a 0.8% increase[9] - The company's updated full-year 2025 revenue guidance is $1.55 billion to $1.585 billion[17] - The updated adjusted fully diluted EPS guidance for 2025 is $6.60 to $6.70[17] - As of March 31, 2025, Lantheus had $938.5 million in cash on hand and $750 million available in revolving credit[17, 18] Acquisitions & Divestments - Lantheus closed the acquisition of Evergreen Theragnostics in April 2025[9] - The company anticipates closing the acquisition of Life Molecular Imaging in Q2 2025[9] - Lantheus plans to finalize the divestment of its SPECT business by the end of 2025[9] Key Products & Market - PYLARIFY net sales were $257.7 million in Q1 2025, and it is the 1 utilized PSMA PET imaging agent[26, 24] - 99% of enrolled patients in the CONDOR study experienced a change in intended patient management based on PYLARIFY results[29] - The PSMA PET market may exceed $3.5 billion by the end of the decade[38] - DEFINITY net sales were $79.2 million in Q1 2025, with a 3.5% year-over-year growth, remaining the 1 utilized ultrasound enhancing agent[61] - The U S Ultrasound Enhancing Agent TAM is $600M+[68] Pipeline & Development - Lantheus is advancing a diversified radiotherapeutic and radiodiagnostic pipeline, including MK-6240 for Tau imaging and NAV-4694 for β amyloid imaging in Alzheimer's disease[71, 74] - PNT2003, a somatostatin receptor (SSTR)-targeted radiotherapeutic, has a potential launch in 2026[75] - LNTH-2401/2402 (GRPR-targeted) are in development for metastatic prostate cancer, with an IND filing for LNTH-2401 expected in Q4 2025 and Phase 1 initiation for LNTH-2402 planned for 2026[141]

Core Insights - Axsome Therapeutics is collaborating with the Alzheimer's disease advocacy community to raise awareness about the increasing impact of Alzheimer's disease in the U.S. and the significance of brain health during Alzheimer's & Brain Awareness Month [1][2] Industry Overview - There are currently over 7 million Americans living with Alzheimer's disease, a number projected to rise to approximately 14 million by 2060 [2] - Alzheimer's disease is the most common form of dementia, characterized by cognitive decline and various behavioral symptoms [2] - Nearly 12 million individuals serve as caregivers for those affected by Alzheimer's disease, highlighting the extensive burden on public health [2] - The Global Burden of Disease classification indicates that Alzheimer's disease has escalated from the 12th to the 6th most burdensome disease in the U.S. from 1990 to 2016, based on disability-adjusted life years (DALYs) [2][8] Company Initiatives - Axsome Therapeutics is actively participating in raising awareness and sharing resources related to Alzheimer's disease, alongside advocacy and patient communities [2] - The company is involved in scientific and medical conferences throughout the year to further its mission [2] Research and Development Focus - Axsome Therapeutics is dedicated to addressing central nervous system (CNS) disorders through innovative treatments, focusing on novel mechanisms of action to improve patient outcomes [3][5] - The company's neuroscience portfolio includes FDA-approved treatments for various conditions, including major depressive disorder and narcolepsy [5]

Commercial Portfolio Performance - PYLARIFY achieved blockbuster status in 2024 with over $1 billion in sales[154], and Q1 2025 net sales reached $257.7 million[13] - DEFINITY remains the 1 utilized ultrasound enhancing agent, with Q1 2025 net sales of $79.2 million, a 3.5% year-over-year growth[24] Market Opportunities - The U S PSMA PET imaging market has a potential of over $3.5 billion by 2030, driven by expansion of radiotherapeutics and increasing clinical utility in BCR population[19, 20] - The U S ultrasound enhancing agent total addressable market is over $600 million[35] Pipeline Development - Lantheus is advancing an innovative pipeline of radiopharmaceuticals, including diagnostic and therapeutic candidates for prostate cancer, neuroendocrine tumors, and Alzheimer's disease[38, 40] - LNTH-2402, a GRPR-targeted radiotherapeutic, is expected to have an IND filing in Q4 2025, with Phase 1 initiation planned for 2026[109] Financial Highlights - As of March 31, 2025, Lantheus had $938.5 million in cash on hand and $98.8 million in free cash flow in Q1 2025[10] - The updated interim corporate financial guidance for the full year 2025 projects revenue between $1.550 billion and $1.585 billion, and adjusted fully diluted EPS between $6.60 and $6.70[142] Strategic Transactions - The acquisition of Evergreen Theragnostics closed in April 2025, strengthening radiodiagnostic and therapeutic capabilities[10, 165] - The acquisition of Life Molecular Imaging is expected to close by 2Q 2025, expanding the commercial portfolio and pipeline in Alzheimer's disease[10, 144]