[Executive Summary & Recent Developments](index=1&type=section&id=1.%20Executive%20Summary%20%26%20Recent%20Developments) [Company Overview](index=1&type=section&id=1.1%20Company%20Overview) ProMIS Neurosciences Inc. is a clinical-stage biotechnology company focused on developing antibody therapies for misfolded toxic proteins in neurodegenerative diseases, including Alzheimer's, ALS, and Parkinson's disease - ProMIS Neurosciences Inc. is a clinical-stage biotechnology company focused on generating and developing antibody therapies for misfolded toxic proteins in neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease[1](index=1&type=chunk) [Key Corporate Highlights](index=1&type=section&id=1.2%20Key%20Corporate%20Highlights) ProMIS Neurosciences achieved significant progress in Q2 2025 and July, including PMN310's FDA Fast Track designation, over 50% patient enrollment in PRECISE-AD Phase 1b trial with good safety, and strengthened financial position through financing - The US FDA granted **Fast Track designation** for PMN310 in Alzheimer's disease, enhancing its potential for priority review[1](index=1&type=chunk)[2](index=2&type=chunk) - The PRECISE-AD Phase 1b Alzheimer's disease trial is on track, with **over 50% patient enrollment** and no ARIA cases or patient withdrawals observed to date, reinforcing PMN310's potentially favorable safety profile[1](index=1&type=chunk)[2](index=2&type=chunk) - Financing in July 2025 generated **$21.6 million in gross proceeds**, strengthening the financial position[1](index=1&type=chunk)[2](index=2&type=chunk) [Research & Development Programs](index=1&type=section&id=2.%20Research%20%26%20Development%20Programs) [EpiSelect™ Drug Discovery Engine](index=1&type=section&id=2.1%20EpiSelect%E2%84%A2%20Drug%20Discovery%20Engine) ProMIS's proprietary EpiSelect™ platform identifies uniquely exposed conformational epitopes on toxic misfolded proteins, generating highly selective antibodies or vaccine formulations to avoid off-target effects, successfully applied to PMN310 and candidates for α-synuclein and TDP-43 - EpiSelect™ is a computational platform used to identify uniquely exposed conformational epitopes on toxic misfolded proteins, enabling the generation of misfolding-specific antibody or vaccine formulations[3](index=3&type=chunk) - The platform generated PMN310, a clinical-stage humanized monoclonal antibody candidate, highly selective for **toxic amyloid-beta oligomers (AβO)** with no significant reactivity to amyloid-beta monomers or fibrils, thereby avoiding off-target effects and reducing the risk of ARIA (brain edema and microhemorrhages)[3](index=3&type=chunk) - Specific epitopes for α-synuclein toxic oligomers/soluble fibrils driving synucleinopathies, and for pathogenic TDP-43 in ALS/FTD, have been identified, with lead antibody candidates generated[3](index=3&type=chunk)[4](index=4&type=chunk) [Alzheimer's Disease Program (PMN310)](index=3&type=section&id=2.2%20Alzheimer's%20Disease%20Program%20(PMN310)) PMN310 is ProMIS's lead candidate for Alzheimer's disease, a humanized IgG1 antibody designed to selectively target toxic AβO, aiming to reduce ARIA risk and enhance efficacy, with significant progress in clinical trials and regulatory milestones - PMN310 is the company's lead candidate for AD, a potential best-in-class humanized monoclonal antibody designed to selectively target toxic oligomers while avoiding plaques, potentially reducing or eliminating ARIA risk and improving safety[10](index=10&type=chunk) [PRECISE-AD Phase 1b Trial Progress & Safety](index=1&type=section&id=2.2.1%20PRECISE-AD%20Phase%201b%20Trial%20Progress%20%26%20Safety) The PRECISE-AD Phase 1b Alzheimer's trial is progressing well, with over 50% patient enrollment and no ARIA cases or withdrawals reported to date, demonstrating PMN310's favorable safety profile; the DSMB recommended continuing the trial and advancing to the next dose level - As of August 12, 2025, the PRECISE-AD Phase 1b Alzheimer's disease trial has enrolled **over 50% of the planned 128 patients**[2](index=2&type=chunk)[5](index=5&type=chunk) - No amyloid-related imaging abnormalities (ARIA) cases, including brain edema or microhemorrhages, or patient withdrawals have been observed to date[2](index=2&type=chunk)[5](index=5&type=chunk) - In May 2025, the DSMB recommended the trial continue as planned without modifications and approved advancing from the first cohort's 5mg/kg dose to the second cohort's 10mg/kg dose[5](index=5&type=chunk) [Regulatory Milestones & Biomarker Insights](index=1&type=section&id=2.2.2%20Regulatory%20Milestones%20%26%20Biomarker%20Insights) PMN310 received FDA Fast Track designation in July 2025; studies indicate plasma pT217 or pT181 as biomarkers have three times the effect size of clinical outcome CDR-SB, suggesting higher trial power or smaller sample sizes; 6-month blinded interim results for PMN310 are expected in Q2 2026, with final topline results in Q4 2026 - In July 2025, PMN310 received **FDA Fast Track designation**[2](index=2&type=chunk)[5](index=5&type=chunk)[10](index=10&type=chunk) Biomarker vs. Clinical Outcome Effect Size Comparison | Metric | Cohen's d Effect Size | | :------------------- | :------------------- | | Plasma pT217 or pT181 | Three times that of clinical outcome CDR-SB | | Clinical Outcome CDR-SB | Baseline | - The group-level correlation between plasma pT217 or pT181 and clinical outcome CDR-SB is approximately **0.786**, with a p-value of **0.036**[12](index=12&type=chunk) - ProMIS expects to report 6-month blinded interim results for PRECISE-AD in **Q2 2026**, with topline results anticipated in **Q4 2026**[2](index=2&type=chunk)[12](index=12&type=chunk) [Alzheimer's Disease Vaccine Program (PMN311)](index=5&type=section&id=2.3%20Alzheimer's%20Disease%20Vaccine%20Program%20(PMN311)) ProMIS is advancing the development of its PMN311 Aβ vaccine program for Alzheimer's disease, based on its oligomer-targeting epitopes - ProMIS continues to advance its PMN311 Aβ vaccine program in AD, based on its oligomer-targeting epitopes[6](index=6&type=chunk) [Other Neurodegenerative Disease Programs](index=5&type=section&id=2.4%20Other%20Neurodegenerative%20Disease%20Programs) ProMIS is developing candidates for Parkinson's disease, Multiple System Atrophy, and Amyotrophic Lateral Sclerosis, with PMN442 and PMN267 ready for IND-enabling studies [Parkinson's Disease and Multiple System Atrophy (PMN442)](index=5&type=section&id=2.4.1%20Parkinson's%20Disease%20and%20Multiple%20System%20Atrophy%20(PMN442)) PMN442 is ProMIS's lead candidate for Parkinson's disease, Multiple System Atrophy, and other synucleinopathies, a humanized IgG1 antibody with selective binding and protective activity against pathogenic α-synuclein, ready for IND-enabling studies - PMN442 is ProMIS's lead candidate for PD, MSA, and other synucleinopathies, a humanized IgG1 antibody based on its selective binding and protective activity against pathogenic α-synuclein[7](index=7&type=chunk) - PMN442 is ready for **IND-enabling studies**[7](index=7&type=chunk) [Amyotrophic Lateral Sclerosis (PMN267)](index=5&type=section&id=2.4.2%20Amyotrophic%20Lateral%20Sclerosis%20(PMN267)) PMN267 is a humanized IgG1 antibody targeting toxic misfolded TDP-43, considered a potential therapeutic target for ALS, and is currently ready for IND-enabling studies - PMN267 is a humanized IgG1 antibody targeting toxic misfolded TDP-43, a potential therapeutic target for ALS[12](index=12&type=chunk) - PMN267 is ready for **IND-enabling studies**[12](index=12&type=chunk) [Financial Performance](index=5&type=section&id=3.%20Financial%20Performance) [Second Quarter 2025 Financial Highlights](index=5&type=section&id=3.1%20Second%20Quarter%202025%20Financial%20Highlights) ProMIS saw significant year-over-year increases in Q2 2025 R&D expenses and net loss, primarily due to PRECISE-AD Phase 1b trial expenditures, while raising $21.6 million in gross proceeds through multiple transactions in July 2025, substantially strengthening its cash position Key Financial Data for Q2 2025 (Year-over-Year) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :------------------- | :---------- | :---------- | :----------- | | Cash and Cash Equivalents | $4.5 million | $1.0 million | +$3.5 million | | Research and Development Expenses | $8.7 million | $1.6 million | +$7.1 million | | General and Administrative Expenses | $1.4 million | $1.1 million | +$0.3 million | | Net Loss | $(10.1) million | $(2.6) million | $(7.5) million | - The net loss was primarily attributable to increased expenditures for the PMN310 PRECISE-AD Phase 1b trial[13](index=13&type=chunk) - In July 2025, ProMIS obtained **$21.6 million in gross proceeds** through a registered direct offering, private placement, and warrant exercises[2](index=2&type=chunk)[13](index=13&type=chunk) [Consolidated Balance Sheets](index=8&type=section&id=3.2%20Consolidated%20Balance%20Sheets) As of June 30, 2025, ProMIS's total assets and cash balance significantly decreased from December 31, 2024, while total liabilities substantially increased, resulting in a negative total shareholders' (deficit) equity, reflecting changes in financial position due to clinical trial investments and operating losses Selected Consolidated Balance Sheet Items (As of June 30, 2025 vs. December 31, 2024) | Item | June 30, 2025 | December 31, 2024 | Change | | :--------------------------- | :------------ | :----------- | :------- | | Cash | $4,510,119 | $13,291,167 | $(8,781,048) | | Total Current Assets | $9,509,496 | $18,911,456 | $(9,401,960) | | Total Current Liabilities | $9,824,087 | $2,218,425 | +$7,605,662 | | Total Liabilities | $9,892,074 | $2,423,280 | +$7,468,794 | | Accumulated Deficit | $(108,152,005) | $(90,687,073) | $(17,464,932) | | Total Shareholders' (Deficit) Equity | $(382,578) | $16,488,176 | $(16,870,754) | [Consolidated Statements of Operations](index=9&type=section&id=3.3%20Consolidated%20Statements%20of%20Operations) In Q2 and H1 2025, ProMIS's R&D and total operating expenses significantly increased year-over-year, leading to a substantial expansion in net loss and net loss per share, primarily reflecting increased investment in clinical trials Selected Consolidated Statements of Operations Items (Q2 2025 vs. Q2 2024) | Item | Q2 2025 | Q2 2024 | YoY Change | | :--------------------------- | :---------- | :---------- | :----------- | | Research and Development Expenses | $8,749,784 | $1,625,821 | +$7,123,963 | | General and Administrative Expenses | $1,434,877 | $1,087,885 | +$346,992 | | Total Operating Expenses | $10,184,661 | $2,713,706 | +$7,470,955 | | Net Loss | $(10,117,029) | $(2,623,657) | $(7,493,372) | | Net Loss Per Share (Basic and Diluted) | $(0.29) | $(0.13) | $(0.16) | Selected Consolidated Statements of Operations Items (Six Months Ended June 30, 2025 vs. Six Months Ended June 30, 2024) | Item | H1 2025 | H1 2024 | YoY Change | | :--------------------------- | :---------- | :---------- | :----------- | | Research and Development Expenses | $14,214,034 | $3,749,599 | +$10,464,435 | | General and Administrative Expenses | $3,430,723 | $2,640,758 | +$789,965 | | Total Operating Expenses | $17,644,757 | $6,390,357 | +$11,254,400 | | Net Loss | $(17,464,932) | $(6,258,745) | $(11,206,187) | | Net Loss Per Share (Basic and Diluted) | $(0.50) | $(0.32) | $(0.18) | [Company and Product Information](index=5&type=section&id=4.%20Company%20and%20Product%20Information) [About ProMIS Neurosciences Inc.](index=5&type=section&id=4.1%20About%20ProMIS%20Neurosciences%20Inc.) ProMIS Neurosciences is a clinical-stage biotechnology company dedicated to discovering and developing therapeutic antibodies and vaccines targeting toxic oligomers in neurodegenerative and other misfolded protein diseases, utilizing its proprietary EpiSelect™ target discovery engine to identify disease-specific epitopes - ProMIS Neurosciences is a clinical-stage biotechnology company focused on discovering and developing therapeutic antibodies and vaccines targeting toxic oligomers in neurodegenerative and other misfolded protein diseases[9](index=9&type=chunk) - The company's proprietary target discovery engine, EpiSelect™, has been shown to predict novel disease-specific epitopes (DSEs) on the surface of misfolded protein molecules that cause neurodegenerative and other misfolded protein diseases, including AD, ALS, FTD, MSA, and PD[9](index=9&type=chunk) [About PMN310](index=5&type=section&id=4.2%20About%20PMN310) PMN310 is ProMIS's lead candidate for Alzheimer's disease, a potential best-in-class humanized monoclonal antibody designed to selectively target toxic oligomers while avoiding plaques, potentially reducing or eliminating ARIA risk and improving safety; PMN310 received FDA Fast Track designation in July 2025 - PMN310 is the company's lead candidate for AD, a potential best-in-class humanized monoclonal antibody designed to selectively target toxic oligomers while avoiding plaques, potentially reducing or eliminating ARIA risk and improving safety[10](index=10&type=chunk) - PMN310 received **FDA Fast Track designation** in July 2025[10](index=10&type=chunk) [Forward-Looking Statements](index=5&type=section&id=5.%20Forward-Looking%20Statements) [Forward-Looking Statements](index=5&type=section&id=5.1%20Forward-Looking%20Statements) This press release contains forward-looking statements regarding future events, expectations, and projections, including clinical trial results, pipeline progress, and financial outlook; these statements are based on management's current expectations, assumptions, and estimates, but are subject to known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially from forward-looking information, particularly that preclinical or early clinical results may not be indicative, and regarding the company's ability to continue as a going concern - This press release contains forward-looking information regarding the company's Phase 1b study in AD patients and expected results (including interim results in **H1 2026** and topline results by **end of 2026**), potential benefits of PMN310, pipeline progress, timing of IND-enabling studies, future financial results, and ability to continue as a going concern[11](index=11&type=chunk)[14](index=14&type=chunk) - Forward-looking information is necessarily based on a number of opinions, assumptions, and estimates that, while considered reasonable by the company as of the date of the press release, are subject to known and unknown risks, uncertainties, and other factors that may cause the actual results, level of activity, performance, or achievements to be materially different from those expressed or implied by such forward-looking information[14](index=14&type=chunk) - Important factors that could cause actual results to differ materially from forward-looking information include that preclinical or early clinical results may not be indicative, the company's ability to fund its operations and continue as a going concern, and its accumulated deficit and expectation of ongoing losses[14](index=14&type=chunk) [Contact Information](index=7&type=section&id=6.%20Contact%20Information) [Contact Information](index=7&type=section&id=6.1%20Contact%20Information) This section provides contact details for ProMIS Neurosciences, including the company website, media inquiries email, and investor relations contact - Company Website: **www.promisneurosciences.com**[15](index=15&type=chunk) - Media Inquiries: **info@promisneurosciences.com**[15](index=15&type=chunk) - Investor Relations Contact: **Kaytee Bock Zafereo (katherine.bock@promisneurosciences.com)**[15](index=15&type=chunk)

Core Insights - ProMIS Neurosciences has received Fast Track designation from the U.S. FDA for its Alzheimer's disease treatment candidate PMN310, enhancing its potential for priority review [2][11] - The PRECISE-AD Phase 1b trial for PMN310 is progressing well, with over 50% of the planned 128 patients enrolled, no cases of amyloid-related imaging abnormalities (ARIA) reported, and no patient dropouts [2][9] - The company has strengthened its financial position by raising approximately $21.6 million in gross proceeds in July 2025 [2][14] Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing antibody therapeutics targeting toxic misfolded proteins associated with neurodegenerative diseases, including Alzheimer's disease, ALS, and Parkinson's disease [10] - The company's proprietary platform, EpiSelect™, is designed to identify conformational epitopes on toxic misfolded proteins, enabling the generation of selective therapeutic antibodies [4][10] Clinical Development - PMN310 is a humanized IgG1 monoclonal antibody specifically targeting toxic amyloid-beta oligomers (AβO), which are believed to be a major driver of Alzheimer's disease [5][11] - The PRECISE-AD trial is a randomized, double-blind, placebo-controlled study aimed at evaluating the safety, tolerability, and pharmacokinetics of PMN310, with interim results expected in Q2 2026 and final results in Q4 2026 [12][9] Financial Performance - As of June 30, 2025, ProMIS reported cash and cash equivalents of $4.5 million, an increase from $1.0 million a year earlier [14] - Research and development expenses for Q2 2025 were $8.7 million, significantly higher than $1.6 million in the same period of 2024, primarily due to costs associated with the PRECISE-AD trial [14][20] - The net loss for Q2 2025 was $10.1 million, compared to a net loss of $2.6 million in Q2 2024, reflecting increased clinical trial expenditures [14][20]

Core Insights - ProMIS Neurosciences Inc. is advancing its Phase 1b clinical trial, PRECISE-AD, for PMN310, a therapeutic candidate targeting toxic oligomers in Alzheimer's Disease (AD) [2][6] - The company has received Fast Track designation from the FDA for PMN310, indicating its potential to address unmet medical needs in AD [2][10] - The ongoing trial has enrolled over 50% of the planned 128 patients, reflecting a swift enrollment process [2][7] Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing therapeutic antibodies for neurodegenerative diseases, including AD, ALS, and PD [8] - The company's proprietary platform, EpiSelect, identifies toxic misfolded proteins, enabling the design of selective therapeutic antibodies [3][8] Clinical Trial Details - The PRECISE-AD trial is a randomized, double-blind, placebo-controlled study assessing the safety, tolerability, and pharmacokinetics of PMN310 at multiple ascending doses [7] - The trial aims to evaluate the effects of PMN310 on biomarkers associated with AD pathology and clinical outcomes, with a primary focus on safety [6][7] - Interim data from the trial is expected to be reported in Q2 2026, with topline results anticipated by Q4 2026 [2][10] Presentation and Conference Participation - ProMIS Neurosciences will present its findings at the Alzheimer's Association International Conference 2025, highlighting the PRECISE-AD trial and the EpiSelect platform [1][4] - Key presentations will include discussions on the design and validation of the EpiSelect platform and the ongoing clinical trial [4][5]

Core Points - ProMIS Neurosciences, Inc. has announced a private investment in public equity (PIPE) financing, raising approximately $2.4 million through the issuance of warrants, with total gross proceeds expected to reach $9.2 million when including additional funds from existing warrant exercises [1][3] - The warrants have an exercise price of $1.25 per share, are immediately exercisable, and will expire five years from the date of issuance [2] - Proceeds from the PIPE financing will be utilized to advance the clinical development of PMN310, the company's lead therapeutic candidate, as well as for working capital and general corporate expenses [4] Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing therapeutic antibodies targeting toxic misfolded proteins associated with neurodegenerative diseases, including Alzheimer's disease, ALS, and Parkinson's disease [7] - The company employs a proprietary target discovery engine, EpiSelect™, to identify Disease Specific Epitopes (DSEs) on misfolded proteins, which are implicated in various neurodegenerative conditions [7]

Core Viewpoint - ProMIS Neurosciences Inc. has raised $0.8 million through the issuance of pre-funded warrants to an existing healthcare-focused institutional investor, aimed at advancing its clinical development of therapeutic antibodies for neurodegenerative diseases [1][3]. Group 1: Financial Details - The company issued pre-funded warrants to purchase 984,736 common shares at a price of $0.8124 per share, with a nominal exercise price of $0.0001 per share [2]. - The gross proceeds from this offering are expected to be approximately $0.8 million before deducting offering expenses [3]. - The closing of the offering is anticipated to occur around July 24, 2025, subject to customary closing conditions [2][3]. Group 2: Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing therapeutic antibodies targeting toxic misfolded proteins associated with neurodegenerative diseases such as Alzheimer's disease, ALS, and Parkinson's disease [1][6]. - The company utilizes its proprietary target discovery engine, EpiSelect™, to identify Disease Specific Epitopes (DSEs) on misfolded proteins [6].

Core Insights - ProMIS Neurosciences Inc. has received Fast Track designation from the FDA for its lead therapeutic candidate PMN310, aimed at treating Alzheimer's disease [1][2][3] - The Fast Track designation is intended to expedite the development of therapies addressing serious conditions and unmet medical needs, allowing for enhanced engagement with the FDA [2] - PMN310 is designed to selectively target toxic forms of amyloid-beta, potentially reducing serious side effects associated with current Alzheimer's treatments [3][5] Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing therapeutic antibodies for neurodegenerative diseases, including Alzheimer's disease, ALS, and Parkinson's disease [7] - The company utilizes its proprietary EpiSelect™ technology to identify Disease Specific Epitopes (DSEs) on misfolded proteins, which are implicated in neurodegenerative diseases [7] Clinical Trials - The ongoing PRECISE-AD Phase 1b trial is evaluating PMN310 in early Alzheimer's patients, focusing on safety, tolerability, pharmacokinetics, and biomarkers [3][6] - Interim biomarker and safety data from the trial are expected to be reported in Q2 2026, with final results anticipated in Q4 2026 [3][6] - The trial is designed to provide insights into the effects of PMN310 on biomarkers and clinical outcomes, with a particular emphasis on assessing the risk of ARIA [6] Market Context - Alzheimer's disease affects over 6 million people in the U.S. and is a leading cause of death and disability among older adults, highlighting the urgent need for safer and more effective treatment options [4] - PMN310 aims to offer a differentiated approach by selectively targeting toxic oligomers, potentially leading to improved efficacy and reduced side effects compared to existing therapies [5]

Core Insights - The FDA has granted Fast Track designation to PMN310, a therapeutic candidate by ProMIS Neurosciences for Alzheimer's disease, highlighting its potential to address an unmet medical need [1][2][3] - PMN310 is designed to selectively target toxic oligomers of amyloid-beta, potentially reducing side effects associated with current treatments [3][5] - The ongoing PRECISE-AD Phase 1b trial is evaluating PMN310's safety, tolerability, and pharmacokinetics, with interim results expected in Q2 2026 [3][6] Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing therapeutic antibodies for neurodegenerative diseases, including Alzheimer's, ALS, and Parkinson's [1][7] - The company utilizes its proprietary EpiSelect™ technology to identify Disease Specific Epitopes (DSEs) on misfolded proteins [7][8] Industry Context - Alzheimer's disease affects over 6 million people in the U.S. and is a leading cause of death and disability among older adults, indicating a significant need for effective treatments [4] - The Fast Track program by the FDA aims to expedite the development of therapies for serious conditions, which is crucial for addressing the urgent need for safer and more targeted Alzheimer's treatments [2][4]

Summary of ProMIS Neurosciences (PMN) FY Conference Call Company Overview - **Company**: ProMIS Neurosciences (PMN) - **Industry**: Biotechnology, focusing on neurodegenerative disorders, particularly Alzheimer's disease [1][4] Key Points and Arguments Alzheimer's Disease Opportunity - Alzheimer's disease is a significant global epidemic, especially with the aging population in developed countries [4] - There is a substantial unmet medical need in Alzheimer's treatment, with millions of patients suffering [7] - Current market products, donanemab and lecanemab, are generating revenue but are underperforming expectations [7] - Existing treatments show modest efficacy and significant side effects, particularly ARIA (amyloid-related imaging abnormalities) [8][9] ProMIS's Approach - ProMIS aims to develop differentiated therapeutics that address the underlying pathology of Alzheimer's disease [6] - The company is focused on creating antibodies that improve efficacy while reducing side effects, particularly ARIA [10][18] - The Episelect platform allows ProMIS to selectively target harmful misfolded proteins, avoiding non-pathogenic forms [21][24] ARIA and Its Impact - ARIA occurs in 15-30% of patients treated with current anti-amyloid drugs, leading to significant concerns regarding treatment [13][15] - The presence of ARIA affects physician prescribing habits and overall treatment uptake [14][16] - ProMIS believes it can develop antibodies that minimize ARIA risk while maintaining efficacy [18][41] PMN310 Development - PMN310 is currently in Phase 1b trials (PRECISE AD) with interim results expected in the first half of next year [45][51] - The study involves 100 patients with early Alzheimer's disease, measuring biomarkers, safety, and clinical signals [48][49] - The interim analysis will focus on ARIA incidents, with expectations that PMN310 will show no ARIA liability [53] Pipeline and Future Prospects - ProMIS is also developing PMN267 for ALS and PMN440 for synucleinopathies, with a focus on selectively targeting misfolded proteins [55][59] - The company is exploring a vaccine approach for Alzheimer's that could allow individuals to produce their own PMN310 [62][63] - The potential for PMN310 to become a blockbuster drug exists if it can deliver improved efficacy without ARIA [42] Other Important Content - The discussion highlighted the importance of understanding protein misfolding and the need for targeted therapies in neurodegenerative diseases [22][27] - ProMIS's unique approach to targeting toxic oligomers while avoiding plaque and beneficial monomers sets it apart from competitors [30][31] - The company is optimistic about its ability to deliver a safer and more effective treatment for Alzheimer's, which could significantly impact patient compliance and treatment outcomes [42][43]

Core Viewpoint - ProMIS Neurosciences Inc. is actively engaged in the development of therapeutic antibodies targeting toxic oligomers linked to neurodegenerative diseases, with a focus on Alzheimer's Disease, ALS, and MSA [1][3]. Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company based in Cambridge, Massachusetts, and Toronto, Ontario, specializing in the discovery and development of therapeutic antibodies for misfolded protein diseases [3]. - The company utilizes its proprietary target discovery engine, EpiSelect™, to identify Disease Specific Epitopes (DSEs) on misfolded proteins associated with various neurodegenerative diseases [3]. Product Development - PMN310 is the lead product candidate for Alzheimer's Disease, designed as a humanized monoclonal antibody that selectively targets toxic oligomers while avoiding plaque, potentially enhancing safety and efficacy compared to other therapies [4]. - The PRECISE-AD trial is a Phase 1b clinical study initiated to evaluate the safety, tolerability, and pharmacokinetics of PMN310 in patients with Mild Cognitive Impairment and mild Alzheimer's Disease [5]. - The trial aims to assess the effects of PMN310 on biomarkers related to Alzheimer's pathology and clinical outcomes, with a primary focus on safety and reduced risk of ARIA due to its non-plaque binding nature [5].

PART I: FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (unaudited)](index=7&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(unaudited)) Unaudited Q1 2025 financials show a widened net loss and decreased cash, raising substantial doubt about its going concern status Condensed Consolidated Balance Sheet Data | Balance Sheet Items | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash | $8,364,301 | $13,291,167 | | Total Current Assets | $13,646,671 | $18,911,456 | | Total Assets | $13,646,671 | $18,911,456 | | Total Current Liabilities | $4,056,248 | $2,218,425 | | Total Liabilities | $4,174,940 | $2,423,280 | | Total Shareholders' Equity | $9,471,731 | $16,488,176 | Condensed Consolidated Statements of Operations Data | Operations Items | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $5,464,250 | $2,123,778 | | General and administrative | $1,995,845 | $1,552,873 | | Loss from operations | $(7,460,095) | $(3,676,651) | | Net Loss | $(7,347,903) | $(3,635,088) | | Net loss per share, basic and diluted | $(0.21) | $(0.19) | Condensed Consolidated Statements of Cash Flows Data | Cash Flow Items | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(4,926,866) | $(10,291,447) | | Net cash provided by financing activities | $0 | $190,274 | | Net decrease in cash | $(4,926,866) | $(10,101,173) | | Cash at end of period | $8,364,301 | $2,496,973 | - The company has a history of net losses, an **accumulated deficit of $98.0 million** as of March 31, 2025, and **negative operating cash flows of $4.9 million** for the quarter, raising substantial doubt about its ability to continue as a going concern[29](index=29&type=chunk)[30](index=30&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=33&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The company's net loss widened due to increased R&D for its lead candidate PMN310, with current cash deemed insufficient - The company's lead product candidate is **PMN310**, a monoclonal antibody for Alzheimer's disease, which entered a **Phase 1b clinical trial** (PRECISE-AD) in December 2024[95](index=95&type=chunk)[100](index=100&type=chunk) Results of Operations Comparison | Item | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | Change | | :--- | :--- | :--- | :--- | | Research and development | $5,464,250 | $2,123,778 | $3,340,472 | | General and administrative | $1,995,845 | $1,552,873 | $442,972 | | **Net loss** | **$(7,347,903)** | **$(3,635,088)** | **$(3,712,815)** | - **R&D expenses increased by $3.3 million (157%)** in Q1 2025 compared to Q1 2024, mainly due to a $3.2 million increase in costs for the PMN310 phase 1b trial[121](index=121&type=chunk) - **General and administrative expenses increased by $0.4 million (29%)**, largely due to $0.5 million in severance costs recognized in Q1 2025[122](index=122&type=chunk) - The company's **cash of $8.4 million** as of March 31, 2025, is **insufficient to fund operations for the next 12 months**, raising substantial doubt about its ability to continue as a going concern[100](index=100&type=chunk)[131](index=131&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=45&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exposed to credit, liquidity, and inflation risks, with liquidity being a significant concern for the pre-revenue entity - The company's primary financial risks are **credit risk, liquidity risk, and market risk**[142](index=142&type=chunk) - **Liquidity risk is a major concern**, as the company is pre-revenue and relies on external fundraising to support its operations and meet commitments[146](index=146&type=chunk) - **Inflation is not considered to have had a material impact** on the company's financial condition or results for the three months ended March 31, 2025[147](index=147&type=chunk) [Item 4. Controls and Procedures](index=47&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls were ineffective as of March 31, 2025, due to an unremediated material weakness - Management concluded that **disclosure controls and procedures were not effective** as of March 31, 2025, due to a material weakness in internal control over financial reporting[149](index=149&type=chunk) - The material weakness relates to the failure to design **sufficient review controls over certain fair value calculations**, including the July 2024 PIPE Warrant Liability[150](index=150&type=chunk) - **Remediation measures are underway**, but the material weakness was not yet remediated as of the report date[151](index=151&type=chunk)[152](index=152&type=chunk) PART II: OTHER INFORMATION [Item 1. Legal Proceedings](index=48&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material litigation or legal proceedings - As of the report date, the company is **not involved in any material legal proceedings**[155](index=155&type=chunk) [Item 1A. Risk Factors](index=48&type=section&id=Item%201A.%20Risk%20Factors) Key risks include a history of losses, going concern uncertainty, and a material weakness in internal financial controls - The company has **incurred losses since inception** and anticipates continued losses, raising substantial doubt about its ability to continue as a going concern[157](index=157&type=chunk) - **Failure to obtain necessary additional financing** could force the company to delay, limit, reduce, or terminate its development programs and commercialization efforts[157](index=157&type=chunk)[160](index=160&type=chunk) - A **material weakness in internal control over financial reporting** has been identified, which could adversely affect investor confidence and the company's ability to report financial results accurately and timely[161](index=161&type=chunk)[162](index=162&type=chunk) [Item 2. Unregistered Sales of Equity Securities, Use of Proceeds and Issuer Purchases of Equity Securities](index=50&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%2C%20Use%20of%20Proceeds%20and%20Issuer%20Purchases%20of%20Equity%20Securities) No unregistered sales of equity securities, use of proceeds, or issuer purchases occurred during the period - No unregistered sales of equity securities or issuer purchases were made during the period[165](index=165&type=chunk) [Item 6. Exhibits](index=52&type=section&id=Item%206.%20Exhibits) This section lists filed exhibits, including agreement amendments, officer certifications, and interactive data files - Exhibits filed include an amendment to the Collaborative Research Agreement with the University of British Columbia, **CEO and CFO certifications** pursuant to Sarbanes-Oxley Sections 302 and 906, and Inline XBRL documents[170](index=170&type=chunk)