Core Viewpoint - InMed Pharmaceuticals has announced new preclinical data indicating that its drug candidate INM-901 significantly reduces neuroinflammation in ex vivo models, supporting its potential as a therapeutic option for Alzheimer's disease [1][5]. Group 1: Study Findings - The study evaluated INM-901 in an ex vivo model of lipopolysaccharide (LPS)-induced inflammation, showing that INM-901 treatment can reduce pro-inflammatory cytokines such as IL-6, IL-1β, IL-2, and KC/Gro, and the inflammasome marker NLRP3 [2][7]. - INM-901 demonstrated a statistically significant reduction in levels of NLRP3 and IL-1β, which are implicated in the pathogenesis of Alzheimer's disease and other neuroinflammatory conditions [8][4]. - The results suggest that INM-901's effects on neuroinflammation are independent of amyloid beta or tau pathology, indicating its potential to treat a broader range of dementia-related diseases [8][4]. Group 2: Implications for Alzheimer's Disease - The study highlights INM-901 as a promising therapeutic candidate for Alzheimer's disease, with plans for further preclinical studies and IND-enabling studies to follow [5][9]. - NLRP3-driven inflammation is recognized as a key contributor to neurodegenerative disease progression, and INM-901's ability to reduce this inflammation could have significant implications for treating Alzheimer's and other neurodegenerative diseases [4][8]. Group 3: Drug Characteristics - INM-901 is a proprietary small molecule drug candidate with multiple mechanisms of action, including neuroprotective effects and the ability to improve cognitive function and memory [14][9]. - The drug can be administered orally, achieving therapeutic levels in the brain comparable to those obtained through intraperitoneal injection, which may offer advantages over currently approved products [14].

Summary of NewAmsterdam Pharma Company (NAMS) 2025 Update Company Overview - **Company**: NewAmsterdam Pharma Company (NAMS) - **Event**: R&D Day held on June 11, 2025 - **Focus**: Updates on Alzheimer's research and drug development, particularly obacetropib Key Points Discussed 1. Corporate and Clinical Updates - 2024 was a successful year with the completion of three Phase III trials: Brooklyn, Tandem, and Broadway [5] - The company has expanded its commercial team to nearly 100 people across the U.S. and Amsterdam [5] - New Composition of Matter IP secured exclusivity until February 1943 [6] - Data from Broadway and Tandem trials published in reputable journals, enhancing credibility [6] 2. Alzheimer's Disease Research - The company is focusing on HDL raising as a potential treatment pathway for Alzheimer's disease [9] - Obacetropib is being studied for its LDL lowering effects, which may also benefit Alzheimer's patients [10] - The brain's cholesterol metabolism is distinct, with HDL being crucial for brain health [11][12] - The company is exploring the relationship between HDL levels and amyloid beta plaque formation, which is linked to Alzheimer's [13][14] 3. APOE4 Gene and Alzheimer's Risk - APOE4 carriers have a significantly increased risk of cardiovascular disease and Alzheimer's [15] - The company aims to determine if obacetropib can effectively prevent Alzheimer's in APOE4 patients [16] - The urgency for treatment is heightened in APOE4 patients due to their family history of Alzheimer's [28] 4. Clinical Trial Insights - The Broadway trial included 3,000 patients and showed promising results in reducing Alzheimer's biomarkers [22] - The pTal217 biomarker is highlighted as a significant predictor for Alzheimer's progression [20] - The company plans to present further data at the AIC conference on July 30 [7] 5. Drug Mechanism and Benefits - Obacetropib targets the CETP protein, inhibiting its activity by 97%, which may influence both heart and brain health [44] - The drug has shown a reduction in small LDL particles, which are more harmful to arterial health [73] - The reduction in small particles is believed to contribute to the observed MACE (major adverse cardiovascular events) reduction in trials [78] 6. Future Directions - The PREVAIL study is ongoing, designed to evaluate the long-term benefits of obacetropib [35] - The company is considering expanding the MACE endpoint to include ischemic stroke and other cardiovascular events [43] - There is a focus on the potential of obacetropib to replace existing therapies like PCSK9 inhibitors due to its broader benefits [31] 7. Market Positioning - Obacetropib is positioned as a complementary therapy to statins, addressing limitations such as increased Lp(a) levels and diabetes risk associated with statins [29][30] - The company is optimistic about the drug's market potential, especially among high-risk populations [32] Additional Important Insights - The company has received positive feedback from the medical community regarding the efficacy and safety profile of obacetropib [30] - The integration of new biomarkers into patient care is expected to enhance diagnosis and treatment monitoring for Alzheimer's [21] - The company emphasizes the importance of understanding lipid metabolism in developing effective therapies for both cardiovascular and neurodegenerative diseases [63][64] This summary encapsulates the critical updates and insights shared during the NewAmsterdam Pharma Company R&D Day, highlighting the company's strategic focus on Alzheimer's research and the development of obacetropib as a potential therapeutic option.

Alzheimer's Disease Update - Emerging evidence suggests a vascular component in multi-infarct dementia, implying LDL-lowering could reduce atherosclerosis in the brain [15] - Alzheimer's disease affects over 50 million people worldwide, with an economic burden exceeding $1 trillion [15] - ApoE4 carriers exhibit a 22-45% elevated risk for CVD [28] - In a proof-of-concept study in 13 ApoE4 carriers with MCI and biomarker-proven AD, obicetrapib showed significant reductions in plasma and CSF levels of 24S- and 27-hydroxycholeterol [41, 43] PREVAIL and MACE Reduction - BROADWAY study showed a 21% observed MACE reduction [98, 99] - In BROADWAY, patients on Obicetrapib had a 42% first 4-point MACE compared to 52% in the placebo group [90] - BROADWAY + BROOKLYN pooled data showed a 75% first 4-point MACE in the Obicetrapib group compared to 49% in the placebo group [91] - Mediation analysis predicts 26% of MACE reduction from Lp(a) in BROADWAY [132, 133] Market Opportunity and Commercial Launch - The lipid-lowering therapy market has shown growth each year for the last 5 years [172] - Repatha® experienced a +47% Rx growth in the last 12 months [172] - The company estimates an $8 billion+ potential worldwide market opportunity for Obicetrapib [247]

Core Viewpoint - Sanofi has agreed to acquire Vigil Neuroscience for approximately $470 million, enhancing its neurology pipeline with the addition of VG-3927, an investigational treatment for Alzheimer's disease [1][4]. Group 1: Acquisition Details - The acquisition involves Sanofi purchasing all outstanding shares of Vigil at $8 per share in cash, with Vigil shareholders also eligible for a contingent value right of $2 per share upon the first sale of VG-3927 [3]. - The transaction is expected to close in the third quarter of 2025, subject to customary closing conditions, and will not affect Sanofi's financial guidance for 2025 [4]. Group 2: Product Information - VG-3927 is a TREM2 agonist aimed at enhancing the neuroprotective function of microglia in Alzheimer's patients, differing from existing FDA-approved drugs that target amyloid beta plaque accumulation [2][8]. - Sanofi is not acquiring Vigil's other candidate, iluzanebart (VGL101), which is in mid-stage development for a rare neurodegenerative disease [5]. Group 3: Market Context - Year-to-date, Sanofi's shares have increased by 9.7%, contrasting with a 3.9% decline in the industry [2]. - Currently, there are two FDA-approved drugs for Alzheimer's disease: Biogen's Leqembi and Eli Lilly's Kisunla, both targeting amyloid beta accumulation [8][9].

Core Insights - Eli Lilly and Company has received marketing authorization for Kisunla (donanemab) in Australia, marking it as the first amyloid-targeting therapy for Alzheimer's registered in the country [1][3] - Kisunla is indicated for adult patients with mild cognitive impairment and mild dementia due to Alzheimer's disease, specifically targeting Apolipoprotein E ε4 heterozygotes or non-carriers [1][6] - The drug has shown significant efficacy in slowing cognitive and functional decline in early symptomatic Alzheimer's disease, with a 35% reduction in decline compared to placebo over 18 months [3][9] Regulatory and Clinical Data - The authorization in Australia is based on data from the TRAILBLAZER-ALZ 2 and TRAILBLAZER-ALZ 6 clinical trials, which demonstrated the drug's effectiveness and safety profile [3][4] - Kisunla has been approved in multiple countries, including the United States, Japan, and the United Kingdom, totaling 13 regulatory authorizations [5][10] - The TRAILBLAZER-ALZ 2 study involved 1,736 participants and showed a 39% reduced risk of progressing to the next clinical stage of Alzheimer's disease [3][7] Patient Population and Impact - Approximately 600,000 Australians are living with Alzheimer's disease, with around 450,000 in early stages eligible for Kisunla treatment [3][4] - Alzheimer's disease is the third leading cause of death in Australia, highlighting the urgent need for effective treatments [3][4] - The earlier patients are diagnosed and treated with Kisunla, the better their response to the therapy, emphasizing the importance of timely intervention [3][10] Safety and Side Effects - Kisunla can cause amyloid-related imaging abnormalities (ARIA), which are generally asymptomatic but can lead to serious complications [4][12] - A modified titration schedule has been approved to reduce the incidence of ARIA while maintaining the drug's efficacy [4][9] - The product information includes warnings about potential serious side effects, including infusion-related reactions and ARIA [12][16]

Core Insights - Alpha Cognition is a relatively unknown pharmaceutical company that launched its first commercial product, Zunveyl (benzgalantamine), in March for the symptomatic treatment of mild-to-moderate Alzheimer's disease [1] - The company received FDA approval for Zunveyl in July 2024, marking a significant milestone in its product development [1] Company Overview - Alpha Cognition operates in the pharmaceutical industry, focusing on treatments for Alzheimer's disease [1] - The launch of Zunveyl represents the company's entry into the market with a product aimed at addressing a critical health issue [1] Product Details - Zunveyl is specifically designed for the symptomatic treatment of mild-to-moderate Alzheimer's disease, indicating a targeted approach to a prevalent condition [1] - The approval from the FDA is a crucial step for the company, as it allows for commercial sales and distribution of Zunveyl [1]

Core Insights - BioVie Inc. is hosting a virtual key opinion leader event to discuss the unmet needs and treatment landscape for Parkinson's disease on May 28, 2025 [1] - The event will provide updates on BioVie's Phase 2 trial (SUNRISE-PD) evaluating bezisterim (NE3107) for Parkinson's disease treatment [2] Company Overview - BioVie Inc. is a clinical-stage company focused on developing innovative drug therapies for neurological and neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and Long COVID [12] - The company's drug candidate, bezisterim, is designed to inhibit inflammatory activation and insulin resistance, which are key drivers of neurodegenerative diseases [12] Clinical Trials and Research - BioVie is currently enrolling patients for the Phase 2 SUNRISE-PD trial, which aims to evaluate bezisterim's safety and efficacy in patients recently diagnosed with Parkinson's disease [9] - Previous Phase 2 studies indicated significant improvements in motor control and "morning on" symptoms when bezisterim was combined with levodopa, with no drug-related adverse events reported [9] Key Opinion Leaders - The event will feature Dr. Suzanne de la Monte and Dr. Mark Stacy, both of whom have extensive backgrounds in neurology and Parkinson's disease research [4][5] - Dr. de la Monte has published over 300 peer-reviewed articles and is known for her research on brain insulin resistance and neurodegenerative disorders [4] - Dr. Stacy has also published extensively on Parkinson's disease and has held various leadership roles in related research centers [5] Parkinson's Disease Insights - Parkinson's disease is characterized by the loss of dopamine-producing neurons, leading to motor and non-motor symptoms that significantly impact patients' quality of life [6] - Chronic inflammation and insulin resistance are emerging as critical factors in the onset and progression of Parkinson's disease, highlighting the potential for anti-inflammatory and insulin-sensitizing therapies [7] Bezisterim Overview - Bezisterim is an orally bioavailable modulator that can cross the blood-brain barrier, targeting inflammation and insulin resistance without immunosuppression [8] - The drug has shown promise in treating not only Parkinson's disease but also Alzheimer's disease and neurological symptoms associated with Long COVID [8][10]

Financial Data and Key Metrics Changes - As of March 31, 2025, the company had $197.9 million in cash and marketable securities, which is expected to support current clinical and operational activities into early 2027 [12] - Research and Development (R&D) expenses were $25.3 million in the first quarter, an increase attributed to spending for the ALTITUDE AD trial [12] - General and Administrative (G&A) expenses were $5.1 million, roughly flat compared to the same period last year, leading to a loss from operations of $30.4 million and a net loss of $28.8 million for the quarter [13] Business Line Data and Key Metrics Changes - The company completed enrollment of its 542-participant Phase II study, ALTITUDE AD, designed to evaluate the clinical efficacy and safety of sabernatog in patients with early Alzheimer's disease [6][11] - The rapid enrollment was attributed to interest in sabernatog's therapeutic potential, innovative participant screening methods, and strong execution by the team [6][9] Market Data and Key Metrics Changes - The company presented at two major Alzheimer's medical conferences, highlighting the innovative use of plasma phospho tau217 screening in the ALTITUDE AD study [8] - The study aims to reduce the number of negative PET scans, improving enrollment efficiency and reducing costs [9] Company Strategy and Development Direction - The company aims to establish sabernatog as a next-generation treatment option for early Alzheimer's disease [6] - Future steps include ongoing formulation drug delivery assessments for subcutaneous administration of sabernatog, with plans to integrate this into ongoing or standalone studies [11][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in sabernatog as an innovative treatment for Alzheimer's disease and is excited to share Phase II results expected in late 2026 [11] - The management noted that the enrollment rate for the ALTITUDE study was much higher than projected, indicating strong interest despite the presence of FDA-approved drugs in the market [36] Other Important Information - The company is focused on the use of biomarkers in clinical studies, emphasizing the importance of synaptic biomarkers in understanding Alzheimer's disease progression [29][30] - Management acknowledged the advancements in blood-based plasma biomarkers and their potential role in assessing drug effects and disease progression [39][41] Q&A Session Summary Question: Inquiry about the incorporation of subcutaneous administration into future development plans - Management indicated that options include incorporating subcutaneous administration into an ongoing Phase III study or conducting a standalone study [19] Question: Clarification on powering assumptions for ALTITUDE and interim analysis - Management confirmed there is no interim analysis in the study, and the powering is appropriate for a Phase II study with 542 participants [21][22] Question: Discussion on the impact of recent advancements in Alzheimer's biomarkers - Management noted that recent advances in biomarkers provide valuable insights and that their Phase II study will focus on clinical measures while also considering biomarker data [27][30] Question: Concerns about competition from newly approved drugs - Management reported that the enrollment rate for the ALTITUDE study was higher than expected and that discontinuation rates are currently low, indicating no significant impact from competing drugs [36][37] Question: Inquiry about the potential of pTau217 as a treatment biomarker - Management suggested that multiple biomarkers will likely be used to assess disease progression and treatment efficacy, rather than relying on a single marker [39][40]

Financial Data and Key Metrics Changes - As of March 31, 2025, the company had $197.9 million in cash and marketable securities, expected to support operations into early 2027 [10] - Research and Development (R&D) expenses were $25.3 million in Q1 2025, an increase attributed to the ALPITUDE AD trial [10] - General and Administrative (G&A) expenses were $5.1 million, roughly flat compared to the same period last year, leading to a loss from operations of $30.4 million and a net loss of $28.8 million for the quarter [11] Business Line Data and Key Metrics Changes - The company completed enrollment of its 542-participant Phase II study, ALTITUDE AD, designed to evaluate the efficacy and safety of sabernatog in patients with early Alzheimer's disease [5][6] - The rapid enrollment was attributed to interest in sabernatog's therapeutic potential and innovative participant screening methods [6] Market Data and Key Metrics Changes - The company presented at two major Alzheimer's medical conferences, highlighting the use of plasma phospho tau217 as a sensitive indicator of amyloid pathology [6][8] - The study showed that screening for pTau217 improved enrollment efficiency and reduced screening costs [7] Company Strategy and Development Direction - The company aims to establish sabernatog as a next-generation treatment option for early Alzheimer's disease [5] - Future steps include ongoing formulation drug delivery assessments for subcutaneous administration of sabernatog [9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in sabernatog's potential as an innovative treatment for Alzheimer's disease and is excited to share Phase II results in late 2026 [9][11] - The management noted that the enrollment rate for the ALTITUDE study was higher than projected, and the discontinuation rate looks favorable [32] Other Important Information - The company completed a Phase I study comparing subcutaneous and intravenous administration of sabernatog, which was well tolerated [8] - Management emphasized the importance of biomarkers in understanding Alzheimer's disease progression and treatment efficacy [25][26] Q&A Session Summary Question: Incorporation of SubQ administration into future plans - Management discussed options for integrating subcutaneous administration into ongoing studies or conducting a standalone study [15][16] Question: Powering assumptions for ALPITUDE and interim analysis - Management confirmed no interim analysis is planned and that the powering is appropriate for a Phase II study with 542 participants [18][19] Question: Impact of recent advances in Alzheimer's biomarkers - Management acknowledged the rapid advancements in blood-based plasma biomarkers and their relevance to the development plan for sabernatog [21][22] Question: Risks posed by commercial antibodies to the trial - Management indicated that the presence of FDA-approved drugs has not negatively impacted the ALTITUDE study, with good enrollment and discontinuation rates [31][32] Question: Usefulness of pTau217 as a treatment biomarker - Management suggested that multiple biomarkers will likely be used to assess disease progression and treatment efficacy, rather than a single marker [35][36]

Core Viewpoint - InMed Pharmaceuticals reported its financial results for the third quarter of fiscal year 2025, highlighting advancements in its drug development pipeline, particularly INM-901 for Alzheimer's disease and INM-089 for dry age-related macular degeneration, while also addressing financial performance and operational challenges [1][2]. Financial Performance - For the three months ended March 31, 2025, InMed reported a net loss of $2.12 million, an increase from a net loss of $1.72 million in the same period the previous year, primarily due to higher research and development expenses [6][9]. - General and administrative expenses decreased to $1.33 million from $3.75 million year-over-year, attributed to lower accounting fees and share-based payments [10]. - As of March 31, 2025, the company's cash, cash equivalents, and short-term investments totaled $4.68 million, down from $6.57 million at June 30, 2024, indicating a need for additional funding sources [11]. Revenue Generation - BayMedica's commercial business generated revenues of $1.26 million for the three months ended March 31, 2025, reflecting an 8% increase from $1.18 million in the same period last year, driven by expanded marketing efforts and increased demand for cannabinoid products [12]. - Despite stable revenues, gross margins declined due to competitive pricing pressures and increased sales of lower-margin products [12]. Drug Development Updates - INM-901 is under development for Alzheimer's disease, targeting neuroinflammation through multiple biological pathways, with positive preclinical data indicating its potential to significantly reduce neuroinflammation [3][4]. - INM-089 is being developed for dry age-related macular degeneration, showing promise in preserving retinal function and improving retinal structure in preclinical studies [6][8]. Future Outlook - The company expects its cash reserves to be sufficient to fund operations into the third quarter of calendar year 2025, contingent on the timing of commercial revenues and operating expenses [11]. - InMed plans to seek additional funding through equity and debt financings, collaborations, and other strategic transactions to support its pharmaceutical pipeline [11].