Core Viewpoint - The research on Alzheimer's disease (AD) has shifted focus from the traditional view of amyloid-beta (Aβ) accumulation and tau protein tangles as the primary causes of dementia, highlighting the role of dysfunctional microglia and chronic neuroinflammation in disease progression [2][3]. Group 1: Research Findings - Recent studies indicate that abnormal protein deposition is a pathological feature of AD rather than its causative mechanism, emphasizing the harmful effects of these proteins on disease progression [2]. - The study published by Xu Peisheng's team at the University of South Carolina introduces a ceria nanocluster-based therapy that targets activated microglia and reduces Aβ deposition [3][4]. Group 2: Innovative Treatment Approach - The developed brain-targeted ceria nanoparticles (T-CeNP) effectively penetrate the blood-brain barrier (BBB) and alleviate neuroinflammation while reducing Aβ accumulation [4][6]. - T-CeNP operates through a triple-function mechanism: it crosses the BBB via RAGE-targeting peptides, regulates pathological processes by enhancing microglial phagocytosis of Aβ, and exhibits multi-pathway synergistic effects in AD mouse models [6][7]. Group 3: Implications for Future Research - The study's findings suggest that T-CeNP can effectively block the pathological cascade of Alzheimer's disease by modulating the neuroinflammatory microenvironment and amyloid metabolism, providing a new paradigm for multi-target therapies in neurodegenerative diseases [9].

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for Q1 2025 was approximately $9.7 million, compared to approximately $11 million for the same period in 2024, indicating an improvement [26] - Research and development expenses totaled approximately $7.6 million for Q1 2025, down from approximately $8.7 million in Q1 2024 [26] - General and administrative expenses remained stable at approximately $2.3 million for both Q1 2025 and Q1 2024 [26] - As of March 31, 2025, the company had cash and cash equivalents of approximately $19.3 million, which is expected to fund operations through Q3 2025 [27] Business Line Data and Key Metrics Changes - The company is preparing to report top-line results from the MINDFUL phase two trial in early Alzheimer's disease, expected in mid to late June 2025 [6][27] - The market opportunity for EXPAREL in early Alzheimer's disease has increased to nearly 70% of early AD patients, up from the previously estimated 40% [7][8] - The safety profile of EXPAREL remains excellent, with no reports of adverse events in the ongoing trial [9] Market Data and Key Metrics Changes - The approval of mecanumab in the EU and UK excludes patients with two copies of the APOE4 gene, creating an unmet need for EXPAREL therapy in this subgroup [10][11] - The evolving biomarker landscape in Alzheimer's disease, particularly the significance of p-tau217, is expected to enhance the company's market position [12] Company Strategy and Development Direction - The company is focused on targeting neuroinflammation in Alzheimer's disease, positioning itself as a leader in this area [81][82] - Plans for the Kordstrom program include filing a Biologics License Application (BLA) in 2026 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB) [17][24] - The company aims to transition manufacturing processes to optimize production for both Kordstrom and Inkmune, ensuring cost-effectiveness and regulatory compliance [24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming MINDFUL trial results, believing they will significantly impact the treatment landscape for early Alzheimer's disease [16][81] - The company is optimistic about the regulatory environment for rare disease treatments, particularly following recent FDA comments [18][24] Other Important Information - The company has successfully transitioned its drug supply logistics for Inkmune to a US-based contractor, Cryoport, to ensure trial completion [21] - The company is also preparing for an IND submission for Kordstrom in the US, with manufacturing of a new batch of products using US-approved cord donors starting soon [73] Q&A Session Summary Question: Can you walk us through the next steps for the program assuming a positive readout in June? - Management indicated that they would defer specific timelines until after the FDA meeting, aiming to move quickly to open sites and enroll patients [32][33] Question: Can you comment on the FDA review team for your program? - Management believes that the FDA has remained on track and that the review team is stable, although they cannot predict future outcomes [36] Question: How do you think investors will react if EMAC hits but CDR is equivocal? - Management emphasized that EMAC is the primary driver for cognitive changes, and they expect correlations with CDR, which is a more blunt instrument [46][49] Question: Are APOE4 patients inherently inflammatory? - Management confirmed that APOE4 carriers tend to have earlier onset and faster progression of Alzheimer's disease, indicating a link to inflammation [62] Question: Are you still on track to initiate the twelve-month open-label trial for Cordstrom mid this year? - Management confirmed they are following FDA guidance and expect to submit an IND late this year, with plans for a follow-on trial in the US [73][74]

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for Q1 2025 was approximately $9.7 million, compared to approximately $11 million for the same period in 2024, indicating an improvement [27] - Research and development expenses totaled approximately $7.6 million for Q1 2025, down from approximately $8.7 million in Q1 2024 [27] - General and administrative expenses remained stable at approximately $2.3 million for both Q1 2025 and Q1 2024 [27] - As of March 31, 2025, the company had cash and cash equivalents of approximately $19.3 million, sufficient to fund operations through Q3 2025 [28] Business Line Data and Key Metrics Changes - The company is preparing to report top-line results from the MINDFUL trial, a Phase 2 trial in early Alzheimer's disease, expected in mid to late June 2025 [5][16] - The market opportunity for EXPAREL in early Alzheimer's disease patients has increased to nearly 70%, up from the previously estimated 40% [6][8] - The safety profile of EXPAREL remains strong, with no reports of adverse events in the MINDFUL trial [9] Market Data and Key Metrics Changes - The approval of mecanumab in the EU and UK excludes patients with two copies of the APOE4 gene, creating an unmet need for EXPAREL therapy in this subgroup [10][11] - The evolving biomarker landscape in Alzheimer's disease, particularly the significance of p-tau217, is expected to enhance the company's market position [12] Company Strategy and Development Direction - The company aims to position itself as a leader in targeting immune dysfunction that drives neuroinflammation in Alzheimer's disease [81][82] - Plans to file a Biologics License Application (BLA) for Cordstrom in 2026, with ongoing development for Inkmune in prostate cancer [17][29] - The company is focused on transitioning manufacturing processes to meet regulatory requirements and maximize production efficiency [25] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in reporting results that could change the care of patients with early Alzheimer's disease, highlighting substantial share ownership by management as alignment with investor interests [16][80] - The company anticipates an end-of-Phase 2 meeting with the FDA in Q4 2026 to discuss the design of a Phase 3 trial [29] Other Important Information - The company has successfully transitioned its drug supply logistics for Inkmune to a US contractor, ensuring readiness for trial completion [21] - The FDA has indicated a willingness to expedite the approval process for rare disease treatments, which bodes well for Cordstrom [18] Q&A Session Summary Question: What are the next steps for the program assuming a positive readout in June? - Management indicated that they would defer specific timelines until after the results and discussions with the FDA [35] Question: Can you comment on the turnover at the FDA and the receptivity at the ADPD conference? - Management believes the FDA remains on track and noted positive feedback from the ADPD conference regarding their approach to measuring cognition [39][44] Question: How many APOE homozygous patients are in the trial? - The trial includes approximately 9% of APOE homozygous patients, which is consistent with other studies [53] Question: What is the expected reduction in CDR for the trial? - Management expressed confidence in their power calculations based on previous studies, suggesting they are well-positioned to achieve statistically significant results [62] Question: Are you still on track to initiate the open-label trial for Cordstrom? - The company is following FDA guidance and expects to submit an IND later this year, with plans for a follow-on trial in the US [73]