XPro Program for Alzheimer's Disease - XPro1595 is designed to selectively inhibit soluble TNF to treat neurologic disease, with Phase 1b study demonstrating safety and dose-dependent reduction in inflammatory cytokines in cerebrospinal fluid (CSF)[34] - A Phase 2 study of XPro1595 in early Alzheimer's patients with biomarkers of inflammation used an enriched population (n=100) with amyloid and ≥ 2 biomarkers of inflammation, showing a beneficial signal across multiple measures[42, 57] - In the Safety Analysis Set (SAF) population (n=206) for the Phase 2 study, 51% were female, and 95.1% were white[39] - In the mITT population (n=200), 75% were Amyloid-beta (Aβ) positive[39] - The most common Treatment Emergent Adverse Event (TEAE) in the XPro1595 group was Injection Site Reaction (ISR), occurring in 52.5% of patients[54] - The company plans to validate the enriched population in a fully powered trial and anticipates an end-of-Phase 2 meeting with the FDA in Q4 2025[56, 59] CORDStrom Program for RDEB - CORDStrom is an investigational disease-modifying treatment for recessive dystrophic epidermolysis bullosa (RDEB), a rare genetic disease affecting an estimated 4000 people in the US, UK, and EU, representing a > $1B peak sales opportunity[64] - A Phase 2 trial of CORDStrom in 30 pediatric patients with RDEB showed beneficial effects with respect to Itch Man Scale, iscorEB clinician score, skin score, and QOL, with no CORDStrom-related serious adverse events reported[66] - The company plans to compile and file a BLA in the US & MAA in UK/EU in 1H 2026[77] INKmune Program for Cancer - INKmune is an off-the-shelf NK cell therapy candidate designed to convert patient's resting NK cells into cancer-killing memory-like NK cells[78] - An INKmune® mCRPC Phase I/II Trial is ongoing, with safety endpoints met and evidence of in-vivo NK cell activation and regression of some tumor lesions by PSMA-PET[80]

Core Insights - Voyager Therapeutics is expanding its Alzheimer's disease franchise with a new program targeting apolipoprotein E (APOE), specifically modulating the expression of the high-risk APOE4 variant while delivering the protective APOE2 variant [1][5][6] - The TRACER capsid platform is utilized for intravenous delivery, allowing the bifunctional payload to effectively cross the blood-brain barrier and target relevant brain regions [2][4] - The company aims to leverage its expertise in Alzheimer's biology to advance multiple therapeutic targets, including tau, amyloid, and APOE, to improve patient outcomes [3][5] Company Overview - Voyager Therapeutics is a biotechnology firm focused on using human genetics to treat neurological diseases, with a pipeline that includes programs for Alzheimer's disease, Friedreich's ataxia, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) [5][7] - The company's Alzheimer's disease franchise now includes four wholly-owned assets, including the anti-tau antibody VY7523 and gene therapies targeting tau, amyloid, and APOE [3][5][6] Research and Development - Preclinical studies demonstrated that a single intravenous injection of the TRACER capsid significantly reduced endogenous APOE4 levels while increasing APOE2 expression in relevant brain regions [2][6] - VY7523 is currently in a multiple ascending dose clinical trial, with initial tau PET data expected in the second half of 2026 [6] - VY1706, a tau silencing gene therapy, has shown up to 73% knockdown of tau mRNA in non-human primates and is advancing towards IND in 2026 [6] Technology Platform - The TRACER capsid discovery platform enables rapid identification of novel AAV capsids for gene therapy, facilitating effective delivery across the central nervous system [4][7] - The platform has been validated in cross-species preclinical studies, demonstrating widespread payload expression in the CNS at low doses [4][7]

Core Insights - INmune Bio Inc. is experiencing a significant decline in stock price, trading down 59% at $2.14, with a session volume of 23.2 million shares compared to an average of 1.45 million shares [1][5] - The company announced results from its Phase 2 MINDFuL trial for XPro, a selective soluble TNF inhibitor aimed at early Alzheimer's Disease, which showed cognitive benefits in a specific subpopulation despite not meeting the primary endpoint in the modified intent-to-treat population [2][4] Trial Results - The MINDFuL trial enrolled 208 participants, with the primary endpoint being the change in cognition over 6 months measured by the Early Mild Alzheimer's Cognitive Composite (EMACC) [3] - Although the primary endpoint was not met in the mITT group, significant benefits were observed in a subpopulation of patients with two or more biomarkers of inflammation [4] - Key findings indicated a cognitive benefit for XPro over placebo on the primary endpoint EMACC (effect size: 0.27) and a behavioral benefit on the Neuropsychiatric Inventory (effect size: -0.24) [5] Future Plans - The company plans to file for Breakthrough Therapy Designation with the FDA and schedule an End-of-Phase 2 meeting in Q4 2025 to discuss the path for a pivotal trial to support XPro's approval in early Alzheimer's Disease [5] - INmune Bio announced a registered direct offering of 3 million shares at $6.30 per share, aiming for approximately $19 million in gross proceeds to be used for working capital and general corporate purposes [4][5]

Sabirnetug (ACU193) Overview - Sabirnetug (ACU193) is a monoclonal antibody (mAb) highly selective for toxic Amyloid Beta Oligomers (AβOs) for early Alzheimer's Disease (AD)[4, 9] - Phase 2 (IV) topline results expected in late 2026[5] - Acumen believes it has the expertise and resources to advance sabirnetug into early 2027[99] Alzheimer's Disease Market and Sabirnetug's Potential - Early AD patient population represents a significant and growing market, with approximately 5 million early Alzheimer's Disease cases in the U S[6, 7] - Sabirnetug has the opportunity to be a treatment of choice in the large early AD population due to potential clinical and safety benefits conferred by AO selectivity[37] - Sabirnetug is well-positioned to emerge as a potential next-generation treatment of choice, with recent approvals paving a new path for the treatment of AD[36] Clinical Trial Results and Development - INTERCEPT-AD Phase 1 data support the potential for Sabirnetug to offer next-generation efficacy and safety[73] - Phase 2 ALTITUDE-AD study enrollment completed in March 2025, with topline results expected in late 2026[19, 101] - Topline results announced in March 2025 show systemic exposure supports further clinical development of the subcutaneous formulation[85, 101] Sabirnetug's Selectivity and Target Engagement - Sabirnetug demonstrates high selectivity for AβOs versus monomeric Aβ, with 8750x higher binding affinity for Aβ oligomers compared to Aβ1-40 monomer[20, 25] - Nearly all Sabirnetug-treated patients in high-dose MAD cohorts showed reductions in plaque load after three doses at 63 or 70 days[49] - Mean reduction in amyloid plaque was 137 centiloids (206%) in the 25 mg/kg Q2W MAD cohort and 181 centiloids (256%) in the 60 mg/kg Q4W MAD cohort[50] Safety Profile - The Phase 1 trial showed a compelling overall safety profile, with a low incidence of ARIA-E, approximately 10% of total ARIA-E cases[72]

Financial Data and Key Metrics Changes - The cash position as of March 31 was $115.8 million with no debt [10] - Cash utilized in operating activities during the quarter was $5.9 million [10] - General and administrative expenses decreased to $2.6 million from $2.9 million year-over-year [11] - Research and development expenses increased slightly to $9.9 million from $9.7 million year-over-year [11] - The net loss for the quarter was reported at $11.2 million or $0.13 per share [11] Business Line Data and Key Metrics Changes - The company continues to focus on noninvasive targeted upstream precision compounds, particularly for Alzheimer's disease and schizophrenia [4] - Blacaramazine for Alzheimer's disease showed significant clinical benefits over three years of treatment [5] - Enrollment in the Phase II clinical study of ANAVEX 371 for schizophrenia was successfully completed with 71 participants [6][7] Market Data and Key Metrics Changes - The company is actively engaging with potential partners for the distribution of blacaramazine in Europe [27] - Discussions with CROs are ongoing to establish a sales force for potential drug launch [27] Company Strategy and Development Direction - The company aims to advance precision medicine compounds with a focus on scalable treatment alternatives for Alzheimer's and schizophrenia [13] - The strategy includes preparing for potential drug launches in various international markets, including Europe, Canada, and Australia [32][34] Management's Comments on Operating Environment and Future Outlook - Management expects feedback from the EMA regarding Alzheimer's treatment submission by the end of the year or early next quarter [15] - The focus remains on the safety and biomarker effects of the schizophrenia trial, addressing significant unmet needs in treatment [17][18] Other Important Information - The company has expanded its scientific advisory board with the appointment of experts in Alzheimer's disease [8] - The advantages of oral blacaramazine include timely access to treatment without logistical barriers, benefiting both patients and caregivers [46][49] Q&A Session Summary Question: Timeline for EMA feedback on Alzheimer's treatment - Management expects feedback by the end of the year or early next quarter, with no interim updates provided [15] Question: Key inflection points for 2025 - The focus is on the Phase II study in schizophrenia, particularly on safety and biomarker effects [17] Question: Details on the schizophrenia trial duration - The trial consists of two parts, with Part B lasting 28 days [23] Question: Pre-launch activities for blacaramazine in Europe - The company is in discussions with potential partners and CROs to ensure readiness for distribution [27] Question: Countries that might piggyback on European approval - Other regions include South America, Africa, the Middle East, and parts of Asia [31] Question: Parallel discussions with regulatory bodies - The company plans to initiate discussions with Canadian and Australian authorities in parallel with European feedback [34] Question: Revenue timeline post-approval - Revenue could potentially be realized in the March quarter, depending on logistical factors [41] Question: Drug manufacturing and launch inventory - The drug is manufactured by a major US manufacturer, and the company has a large launch inventory [42]