Summary of Alpha Cognition Conference Call - October 08, 2025 Company Overview - **Company**: Alpha Cognition (NasdaqCM: ACOG) - **Lead Product**: Zunvil, approved by the FDA for mild to moderate Alzheimer's disease in Q3 2024 [2][3] Industry Context - **Target Market**: Long-term care facilities, specifically nursing homes, which represent a $2 billion opportunity for Zunvil [13][14] - **Alzheimer's Disease**: Affects memory, cognitive function, and behavior; approximately 40% of Alzheimer's patients spend their lifespan in assisted living or long-term care [4][14] Core Product Insights - **Zunvil Characteristics**: - A prodrug of galantamine, designed to minimize gastrointestinal side effects [5][6] - Demonstrates improved tolerability with less than 2% of patients reporting GI issues [11] - 0% incidence of insomnia compared to 30% for leading competitors [12] - Proven cognitive effects and functional performance, targeting behavioral symptoms common in Alzheimer's patients [12][13] Commercialization Strategy - **Launch Details**: - Launched in April 2025, generating over 1,500 prescriptions in the first quarter [3][19] - Focused on long-term care market due to high concentration of Alzheimer's patients and fewer payer restrictions [13][14] - **Sales Strategy**: - 50 salespeople targeting nursing homes and medical directors [16] - Engaged with nearly 2,000 nursing homes, with 15% writing prescriptions for Zunvil [17] - Plans for strategic partnerships with pharmacies and long-term care facilities [18] Financial Outlook - **Revenue**: Generated approximately $1.7 million in the first quarter, with expectations for steady growth [19] - **Expense Guidance**: Projected expenses between $34 to $38 million, targeting profitability by 2027 [3][20] - **Market Potential**: If Zunvil captures 10% to 25% of the market, it could generate $200 to $600 million in sales [20][31] Pipeline and Future Developments - **Additional Products**: - A sublingual formulation for patients with swallowing difficulties, expected to enter clinical studies in early 2026 [21] - A product targeting cognitive impairment from concussions, with data expected mid-next year [22] - **Market Expansion**: Plans to enter the neurology segment, representing a $1.5 billion opportunity, post achieving break-even status [25][26] Competitive Landscape - **Market Size**: The acetylcholinesterase inhibitor market is estimated at $6 to $7 billion, with historical products achieving billion-dollar sales [29][30] - **Differentiation**: Zunvil's unique formulation and tolerability profile position it as a disruptive force in the market [33] Key Takeaways - **Management Team**: Experienced team with a strong track record in drug launches [24] - **Future Focus**: Continued education for healthcare providers and strategic partnerships to enhance market penetration [33] This summary encapsulates the key points discussed during the Alpha Cognition conference call, highlighting the company's strategic direction, product differentiation, and market potential.

Core Insights - NewAmsterdam Pharma is advancing its oral, low-dose CETP inhibitor obicetrapib, targeting cardiovascular disease and Alzheimer's pathology, with significant clinical data supporting its efficacy [3][4][10] - The company reported a substantial increase in revenue for Q2 2025, recognizing $19.1 million compared to $2.3 million in Q2 2024, primarily due to development cost contributions from Menarini [7][19] - NewAmsterdam's cash position as of June 30, 2025, was $783.3 million, down from $834.2 million at the end of 2024, reflecting ongoing operating expenditures [7][19] Clinical Development Updates - The PREVAIL Phase 3 cardiovascular outcomes trial has completed enrollment of over 9,500 patients, focusing on those with a history of ASCVD [9][10] - Positive topline data from the BROADWAY trial indicated a statistically significant reduction in p-tau217 levels, a key Alzheimer's biomarker, in patients treated with obicetrapib [4][12] - The company plans to launch the Phase 3 RUBENS trial later in 2025, evaluating obicetrapib in combination with ezetimibe for patients with type 2 diabetes and metabolic syndrome [3][4] Financial Performance - NewAmsterdam reported a net loss of $17.4 million for Q2 2025, an improvement from a net loss of $39.0 million in Q2 2024 [7][19] - Research and development expenses decreased to $27.5 million in Q2 2025 from $38.4 million in the same period in 2024, attributed to reduced clinical expenses [7][19] - Selling, general, and administrative expenses rose to $27.3 million in Q2 2025, up from $16.5 million in Q2 2024, driven by increased personnel costs and marketing investments [7][19] Market Context - Cardiovascular disease remains a leading global health issue, with a projected increase in affected U.S. adults to over 184 million by 2050, highlighting the need for effective LDL-C lowering therapies [11] - Despite the availability of lipid-lowering therapies, many patients remain undertreated, with only 10% of very high-risk ASCVD patients achieving LDL-C goals below 55 mg/dL [11] - The company aims to address this unmet need with obicetrapib, which has shown promising LDL-C reduction and a favorable safety profile in clinical trials [10][11]

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Core Insights - INmune Bio Inc. announced additional analyses from its Phase 2 MINDFuL trial for XPro™, a selective soluble TNF inhibitor, to be presented at the Alzheimer's Association International Conference in Toronto on July 29, 2025 [1] - The MINDFuL trial is a double-blind, Phase 2 proof-of-concept study aimed at evaluating XPro™'s potential to slow cognitive decline in early-stage Alzheimer's disease by targeting neuroinflammation [2] - Although the primary endpoint was not met in the overall modified-intent-to-treat group, significant benefits were observed in a subpopulation with confirmed amyloid-beta pathology and systemic inflammation biomarkers [3] Study Details - The MINDFuL trial enrolled 208 participants with early Alzheimer's disease, requiring at least one biomarker of inflammation [2][6] - Participants received XPro™ or placebo in a 2:1 ratio for 24 weeks, with cognitive changes measured using the Early Mild Alzheimer's Cognitive Composite [2][6] - The trial's findings suggest a potential therapeutic approach for Alzheimer's by targeting inflammation [4] Future Plans - INmune Bio plans to submit a publication of the MINDFuL Phase 2 study results by mid-August [4] - The company is seeking strategic partnerships to expedite the development of XPro™ for Alzheimer's treatment [4] Product Information - XPro™ is designed to inhibit soluble TNF while preserving trans-membrane TNF and TNF receptors, potentially enhancing cognitive function and neuronal communication [7] - INmune Bio focuses on developing treatments that target the innate immune system, with XPro™ being part of its Dominant-Negative Tumor Necrosis Factor product platform [8][9]

Core Insights - The Phase 2 MINDFuL trial of XPro™ in early Alzheimer's Disease (AD) patients with inflammation biomarkers did not meet the primary cognitive endpoint in the modified intent-to-treat (mITT) population, but showed cognitive, behavioral, and biological benefits in a predefined subgroup of amyloid-positive patients with two or more inflammation biomarkers [1][3][4] Group 1: Trial Results - The MINDFuL trial enrolled 208 participants with early-stage AD, assessing XPro™'s potential to slow cognitive decline by targeting neuroinflammation [4] - In the predefined subgroup of amyloid-positive early AD patients with two or more inflammation biomarkers (n=100), XPro™ demonstrated a cognitive benefit on the primary endpoint EMACC (effect size: 0.27) and a behavioral benefit on the Neuropsychiatric Inventory (effect size: -0.24) [7] - A biological benefit was observed in blood levels of pTau217 (effect size: -0.20), indicating a positive impact on AD pathology [7] Group 2: Safety and Tolerability - XPro™ treatment was well-tolerated and safe, with no occurrences of ARIA-E or ARIA-H reported [2][7] - The most common adverse events were injection site reactions, occurring in 80% of the XPro™ group compared to less than 20% in the placebo group [7] - There were no deaths or drug-related hospitalizations during the trial, indicating a favorable safety profile [7] Group 3: Future Plans - The company plans to submit for Breakthrough Therapy designation with the FDA and will present additional analyses at the Alzheimer's Association International Conference (AAIC) in July 2025 [2][10] - The company aims to engage regulatory authorities in the UK, EU, and other regions to define the path for a pivotal trial to support XPro™ approval in early AD [14]

Caregiving & Alzheimer's Disease - The speaker emphasizes the importance of person-centered care, focusing on creating joy rather than just completing tasks in caregiving [6] - The industry highlights the dignity paradox, where dignity is considered a human right but often slips away in care settings [10] - The speaker advocates for shifting the approach to care by asking what matters most to the individual, potentially making care easier and more fulfilling [10] - The industry acknowledges the challenges of Alzheimer's, including anger, accusations, paranoia, and safety concerns, not just memory loss [11] - The speaker suggests that societal stigma isolates individuals with Alzheimer's, and community support could improve their experience [11] Innovative Care Models - The report references De Hogeweyk, a village in the Netherlands, as an example of a human-centered care model where residents experience a normal life [12] - The industry notes that Daybreak, an adult day services program, provided a meaningful experience for the speaker's mother by welcoming her as a volunteer [12] Finding Joy in Unexpected Places - The speaker shares personal anecdotes, such as laughing about cutting the leg off pants, to illustrate finding joy in difficult situations [15] - The industry emphasizes embracing the present moment and finding joy in the absurdity of situations, like finding a phone in the freezer [11]

Core Insights - Blarcamesine, a drug candidate from Anavex, shows performance comparable to Aricept in treating Alzheimer's disease, indicating limited efficacy in addressing the disease's progression [1] - The underlying causes of Alzheimer's disease are linked to oxidation and nitration, with current treatments primarily targeting symptoms rather than the root causes [1] - Natural products like panax ginseng and essential oils may offer potential benefits by inhibiting oxidative stress and reversing some damage, suggesting alternative treatment avenues [1] - Anavex and Cyclo Therapeutics are highlighted as companies with promising drug candidates in the Alzheimer's space, making them recommended investment opportunities [1] Company Analysis - Anavex's long-term open label trial results are being reassessed to understand the mechanisms of action of its drug candidate, blarcamesine [1] - The company is positioned within a niche market focused on innovative treatments for Alzheimer's, which is characterized by a need for more effective solutions [1] - Cyclo Therapeutics is also mentioned as a company with potential in developing treatments that may stabilize Alzheimer's disease [1]

Core Viewpoint - Biogen's investigational Alzheimer's disease drug, BIIB080, has received fast track designation from the FDA, which may expedite its development and review process [1][2]. Group 1: Fast Track Designation Benefits - Fast track designation aims to facilitate the development and expedite the review of drugs addressing serious conditions and unmet medical needs [2]. - The designation allows for rolling review, enabling Biogen to submit completed sections of its regulatory filing for BIIB080 as they become available, potentially speeding up the review process [2]. Group 2: BIIB080 Overview - BIIB080 is an investigational antisense oligonucleotide therapy targeting tau protein, which is linked to neurodegeneration and cognitive decline in Alzheimer's disease [5][6]. - The drug is currently being evaluated in the phase II CELIA study for early-stage Alzheimer's, with patient enrollment recently completed and data expected next year [5][6]. - Previous phase Ib study data indicated that BIIB080 treatment resulted in dose-dependent reductions in tau protein levels in cerebrospinal fluid and decreased tau buildup in the brain, along with positive trends in cognitive and functional measures [6]. Group 3: Partnership and Market Context - BIIB080 is developed in partnership with Ionis Pharmaceuticals, from which Biogen licensed exclusive global rights in December 2019, with Ionis eligible for royalties on potential sales [7]. - In the Alzheimer's drug market, two FDA-approved drugs, Leqembi and Kisunla, are currently available, both targeting amyloid beta plaque accumulation, a primary cause of cognitive decline [8][9].

Financial Data and Key Metrics Changes - The company reported a net loss of $34 million or $0.86 per basic and diluted share for the year ended December 31, 2024, compared to a net loss of $25.8 million or $0.86 per basic and diluted share for 2023 [23] - Cash and cash equivalents as of December 31, 2024, were approximately $25 million, with total obligated grant funds remaining from the NIA at $50 million [20] - Research and development expenses increased to $41.7 million for the year ended December 31, 2024, from $37.2 million in 2023, primarily due to higher costs associated with completing two Phase II trials [21] Business Line Data and Key Metrics Changes - The company decided to conclude its Phase II dry AMD study before completion, reallocating resources entirely to Alzheimer's and DLB programs [11][19] - The decision to conclude the dry AMD study was based on prioritizing the success of the Alzheimer's and DLB programs, despite showing potential efficacy in dry AMD [12][13] Market Data and Key Metrics Changes - The company is actively pursuing partnerships for funding and development in the Alzheimer's and DLB space, indicating strong interest from biotech and pharma players [15] - The company has received a 6-month grace period to regain compliance with NASDAQ's minimum bid requirement, needing to maintain a stock price above $1 for 10 consecutive days before September 8, 2025 [24] Company Strategy and Development Direction - The focus remains on advancing zervimesine for Alzheimer's disease and dementia with Lewy bodies, with plans to submit final study documents to the FDA for two different end of Phase II meetings [9][10] - The company is preparing for Phase III readiness and has developed a novel chemical process for zervimesine manufacturing, with provisional patent applications filed [17][18] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in regaining NASDAQ compliance and highlighted upcoming milestones that could drive stock value [24] - The company is committed to addressing financing challenges while aiming to deliver multiple clinical milestones and create long-term shareholder value [60] Other Important Information - The company has built strong relationships with potential partners and is evaluating all options for financing clinical development efforts [15][16] - The publication process for SHIMMER data is underway, with expectations for release in the coming months [37] Q&A Session Summary Question: Thoughts on tau cutoff threshold for Phase II FDA meeting - Management plans to enrich participants in the next study for those with lower tau, similar to the SHINE study, but has not finalized the specific cutoff [29][30] Question: Feedback from investigative physicians on SHIMMER data - Management received excellent feedback from KOLs and payers, indicating a strong need for zervimesine and appreciation for its safety profile [35] Question: Competitive landscape in DLB and potential approvability - Management is confident that neuropsychiatric symptoms will be of interest to physicians and the FDA, with a focus on determining appropriate outcome measures for studies [49][50] Question: Outlook for accelerated approval in Europe vs. the US - The company plans to follow a traditional pathway for Phase III studies, as the accelerated approval process has been complex and not necessarily easier in Europe [52][53] Question: NIH funding outlook and potential for new grants - The company has a remaining balance of $50 million from NIH funding, which is expected to support ongoing trials, but anticipates lower probability for new grant funding as it progresses to Phase III [54][56]

Core Insights - Acumen Pharmaceuticals is advancing sabirnetug (ACU193), a humanized monoclonal antibody targeting soluble amyloid beta oligomers (AβOs) for Alzheimer's disease treatment [6][8] - Upcoming scientific presentations at major conferences will focus on the implementation of a plasma pTau217 assay and the effects of sabirnetug on synaptic biomarkers in Alzheimer's disease [1][2] Company Overview - Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company headquartered in Newton, Massachusetts, focusing on therapies for Alzheimer's disease [8] - The company has received Fast Track designation from the U.S. FDA for sabirnetug, which is currently in a Phase 2 clinical trial [6][8] Clinical Trials - The ALTITUDE-AD study is a Phase 2, multi-center, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of sabirnetug in early Alzheimer's disease patients [7] - Approximately 540 individuals with early Alzheimer's disease are being enrolled in the ALTITUDE-AD study, which is ongoing across multiple sites in the U.S., Canada, UK, and EU [7] Upcoming Presentations - Acumen will present findings at the International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders in Vienna from April 1-5, 2025, and at the American Academy of Neurology Annual Meeting in San Diego from April 5-9, 2025 [1][2] - Oral presentations will include the use of plasma pTau217 screening in the ALTITUDE-AD study, while poster presentations will cover various methodologies related to AβOs and synaptic biomarkers [2][3]