PART I [Business](index=7&type=section&id=Item%201.%20Business) A clinical-stage biotech firm developing therapies for neurodegenerative diseases via a proprietary computational platform - ProMIS utilizes a patented computational technology platform to discover and develop antibody therapies and vaccines for neurodegenerative diseases by **selectively targeting toxic misfolded proteins**[25](index=25&type=chunk)[26](index=26&type=chunk)[27](index=27&type=chunk) Product Pipeline Overview | Category | Product Candidate | Target Protein | Disease Indication(s) | Stage | | :--- | :--- | :--- | :--- | :--- | | **Antibody** | PMN310 | Amyloid-Beta | Alzheimer's Disease (AD) | Phase 1 | | | PMN267 | TDP-43 | Amyotrophic Lateral Sclerosis (ALS) | Pre-Clinical | | | PMN442 | Alpha-Synuclein | Multiple System Atrophy (MSA) | Pre-Clinical | | **Vaccine** | PMN440 | Alpha-Synuclein | Multiple synucleinopathies | Discovery | | | PMN311 | Amyloid-Beta | Alzheimer's Prevention | Discovery | | **Discovery** | - | Tau | FTLD, PSP, CBD | Discovery | | | - | RACK1 | ALS, HD | Discovery | | | - | DISC1+Interactome | Schizophrenia | Discovery | - The company's lead candidate, **PMN310 for Alzheimer's Disease**, initiated a **Phase 1a clinical trial** in November 2023 and a **Phase 1b study** in December 2024[56](index=56&type=chunk)[57](index=57&type=chunk)[58](index=58&type=chunk) - Key objectives for 2025 include **advancing patient enrollment for PMN310**, expanding corporate visibility, and evaluating partnership opportunities[32](index=32&type=chunk)[34](index=34&type=chunk) [Risk Factors](index=46&type=section&id=Item%201A.%20Risk%20Factors) The company faces risks from its early-stage products, need for funding, going concern uncertainty, and potential Nasdaq delisting - The company has incurred losses since inception, raising **substantial doubt about its ability to continue as a going concern** without additional financing[295](index=295&type=chunk) - The business is heavily dependent on its lead candidate, **PMN310**, which is in early clinical development in a historically challenging field[14](index=14&type=chunk)[248](index=248&type=chunk)[285](index=285&type=chunk) - As of January 3, 2025, the company was **not in compliance with Nasdaq's $1.00 minimum bid price requirement**, risking delisting[477](index=477&type=chunk) - The company **relies on third parties** for manufacturing, research, and clinical trials, posing risks of development delays[14](index=14&type=chunk)[315](index=315&type=chunk) - Management identified that the company's **internal controls over financial reporting are not effective**, which could adversely affect the business[20](index=20&type=chunk)[498](index=498&type=chunk) [Unresolved Staff Comments](index=98&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) The company has no unresolved staff comments from the Securities and Exchange Commission - There are **no unresolved staff comments**[532](index=532&type=chunk) [Cybersecurity](index=99&type=section&id=Item%201C.%20Cybersecurity) A cybersecurity program is in place with board oversight, and no material incidents have been identified to date - The company has a cybersecurity risk management program with **oversight provided by the Board's Audit Committee**[533](index=533&type=chunk)[536](index=536&type=chunk) - No cybersecurity incidents have been identified that are **reasonably likely to have a material effect** on the business[534](index=534&type=chunk) [Properties](index=99&type=section&id=Item%202.%20Properties) The company does not own or lease any material properties - The Company **does not own or lease any material properties**[537](index=537&type=chunk) [Legal Proceedings](index=99&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings - The Company is not a party to any legal proceedings expected to have a **material adverse effect** on its business[538](index=538&type=chunk) [Mine Safety Disclosures](index=99&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This section is not applicable to the company - Not applicable[539](index=539&type=chunk) PART II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=99&type=section&id=Item%205.%20Market%20for%20Registrant's%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common shares trade on Nasdaq, and no dividends are planned as funds are reinvested into operations - The company's common shares are listed on the **Nasdaq Capital Market** with 103 holders of record as of March 29, 2025[541](index=541&type=chunk)[542](index=542&type=chunk) - **No dividends have been paid** in the last five years, and none are expected in the foreseeable future[543](index=543&type=chunk)[544](index=544&type=chunk) - In July 2024, the company completed a PIPE offering, raising gross proceeds of **approximately $27.7 million**[549](index=549&type=chunk) [Reserved](index=102&type=section&id=Item%206.%20Reserved) This item is reserved [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=103&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) The operating loss increased to $16.8 million in 2024, and there is substantial doubt about the company's ability to continue as a going concern Results of Operations (Years Ended December 31) | Metric | 2024 | 2023 | Change | | :--- | :--- | :--- | :--- | | Research and development | $10,637,976 | $7,883,165 | $2,754,811 | | General and administrative | $6,189,502 | $6,379,568 | $(190,066) | | **Loss from operations** | **$(16,827,478)** | **$(14,262,733)** | **$2,564,745** | | Other income (expense) | $19,606,351 | $1,050,251 | $(18,556,100) | | **Net income (loss)** | **$2,778,873** | **$(13,212,482)** | **$(15,991,355)** | - The increase in operating loss was driven by a **$3.5 million increase in spending on the lead program, PMN310**[576](index=576&type=chunk) - Management concluded there is **substantial doubt about its ability to continue as a going concern** as cash of $13.3 million is insufficient[567](index=567&type=chunk)[588](index=588&type=chunk) Cash Flow Summary (Years Ended December 31) | Metric | 2024 | 2023 | | :--- | :--- | :--- | | Net cash used in operating activities | $(27,182,095) | $(10,843,676) | | Net cash provided by financing activities | $27,875,809 | $17,748,800 | | **Net increase in cash** | **$693,021** | **$6,722,350** | [Quantitative and Qualitative Disclosures About Market Risk](index=111&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is primarily exposed to credit and liquidity risks, while foreign currency and inflation risks are not material - The company's primary financial risks include **credit risk and significant liquidity risk**, as it relies on external financing[600](index=600&type=chunk)[601](index=601&type=chunk)[602](index=602&type=chunk) - **Foreign currency and inflation risks** are not believed to have had a material impact on financial results in 2024 or 2023[603](index=603&type=chunk)[604](index=604&type=chunk) [Financial Statements and Supplementary Data](index=200&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) The auditor's report highlights a "Going Concern Uncertainty" due to the company's history of net losses and negative cash flows - The independent auditor's report includes a **"Going Concern Uncertainty"** paragraph due to accumulated deficits and net losses[608](index=608&type=chunk) Consolidated Balance Sheet Highlights (as of Dec 31) | Metric | 2024 | 2023 | | :--- | :--- | :--- | | Cash | $13,291,167 | $12,598,146 | | Total Current Assets | $18,911,456 | $13,619,145 | | Total Current Liabilities | $2,218,425 | $9,349,662 | | Total Liabilities | $2,423,280 | $9,865,849 | | Accumulated Deficit | $(90,687,073) | $(93,465,946) | | Total Shareholders' Equity | $16,488,176 | $3,753,296 | Consolidated Statement of Operations Highlights (Year Ended Dec 31) | Metric | 2024 | 2023 | | :--- | :--- | :--- | | Total operating expenses | $16,827,478 | $14,262,733 | | Loss from operations | $(16,827,478) | $(14,262,733) | | Net income (loss) | $2,778,873 | $(13,212,482) | | Net income (loss) per share, basic | $0.11 | $(1.07) | [Changes in and Disagreements with Accountants on Accounting and Financial Disclosure](index=100&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20with%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) There were no changes in or disagreements with the company's accountants - None[745](index=745&type=chunk) [Controls and Procedures](index=100&type=section&id=Item%209A.%20Controls%20and%20Procedures) Disclosure controls were deemed ineffective due to a material weakness in internal control over financial reporting - Management concluded that **disclosure controls and procedures were not effective** as of December 31, 2024, due to a material weakness[747](index=747&type=chunk)[754](index=754&type=chunk) - A material weakness was identified related to **insufficient review controls over fair value calculations** for the PIPE Warrant Liability[753](index=753&type=chunk) - The company has initiated **remediation measures** to address the material weakness[755](index=755&type=chunk) [Other Information](index=101&type=section&id=Item%209B.%20Other%20Information) No directors or officers adopted, terminated, or modified a Rule 10b5-1 trading arrangement in Q4 2024 - No directors or officers adopted, terminated, or modified a **Rule 10b5-1 trading arrangement** during Q4 2024[758](index=758&type=chunk) [Disclosure Regarding Foreign Jurisdictions that Prevent Inspections](index=102&type=section&id=Item%209C.%20Disclosure%20Regarding%20Foreign%20Jurisdictions%20that%20Prevent%20Inspections) This section is not applicable to the company - Not applicable[759](index=759&type=chunk) PART III [Directors, Executive Officers and Corporate Governance](index=102&type=section&id=Item%2010.%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance) This information is incorporated by reference from the company's 2025 definitive proxy statement - Information for this item is **incorporated by reference** from the registrant's 2025 Proxy Statement[761](index=761&type=chunk) [Executive Compensation](index=102&type=section&id=Item%2011.%20Executive%20Compensation) This information is incorporated by reference from the company's 2025 definitive proxy statement - Information for this item is **incorporated by reference** from the registrant's 2025 Proxy Statement[765](index=765&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=102&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) This information is incorporated by reference from the company's 2025 definitive proxy statement - Information for this item is **incorporated by reference** from the registrant's 2025 Proxy Statement[766](index=766&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=102&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) This information is incorporated by reference from the company's 2025 definitive proxy statement - Information for this item is **incorporated by reference** from the registrant's 2025 Proxy Statement[767](index=767&type=chunk) [Principal Accountant Fees and Services](index=103&type=section&id=Item%2014.%20Principal%20Accounting%20Fees%20and%20Services) This information is incorporated by reference from the company's 2025 definitive proxy statement - Information for this item is **incorporated by reference** from the registrant's 2025 Proxy Statement[768](index=768&type=chunk) PART IV [Exhibits and Financial Statement Schedules](index=103&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section lists the financial statements and exhibits filed as part of the Annual Report - This item lists the financial statements and exhibits filed with the Form 10-K; **all schedules are omitted**[769](index=769&type=chunk) [Form 10-K Summary](index=103&type=section&id=Item%2016.%20Form%2010-K%20Summary) This section is not applicable - Not applicable[771](index=771&type=chunk)

Core Insights - ProMIS Neurosciences is advancing its lead antibody candidate PMN310 for Alzheimer's disease (AD) through a Phase 1b clinical trial, highlighting the urgent need for improved treatment options in the AD space [1][2][3] - The company reported a net income of $2.8 million for the fiscal year 2024, a significant turnaround from a net loss of $13.2 million in 2023, primarily due to a gain on the change in fair value of warrant liabilities [7][14] - ProMIS has expanded its intellectual property portfolio with 23 newly granted or allowed patents since January 2024, strengthening its position in the neurodegenerative disease market [2][3] Alzheimer's Disease Program (PMN310) - PMN310 is a humanized IgG1 antibody targeting toxic amyloid-beta oligomers, which are believed to drive AD progression [3][4] - The Phase 1b trial (PRECISE-AD) aims to enroll approximately 100 subjects across 22 sites in the U.S., with interim results expected in the first half of 2026 and topline results anticipated by the end of 2026 [3][4] - The Phase 1a trial demonstrated that PMN310 was well-tolerated and effectively crossed the blood-brain barrier, suggesting potential for target engagement in AD patients [4] Financial Highlights - As of December 31, 2024, ProMIS had cash and cash equivalents of $13.3 million, an increase from $12.6 million in 2023 [7][11] - Research and development expenses rose to $10.6 million in 2024 from $7.9 million in 2023, reflecting costs associated with clinical trials [7][14] - The company completed a PIPE financing in Q3 2024, providing initial funding of $30.3 million and potential additional funding of $92.4 million [7] Pipeline and Future Developments - ProMIS is also advancing programs for amyotrophic lateral sclerosis (ALS) with PMN267 and multiple synucleinopathies with PMN440, showcasing a diverse pipeline in neurodegenerative diseases [2][5][6] - The company plans to present preclinical data at upcoming conferences, further demonstrating its commitment to innovation in the field [4][5][6]

Core Insights - ProMIS Neurosciences Inc. is advancing its antibody therapeutics and vaccines targeting toxic misfolded proteins for neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) [1][9] - The company plans to present its findings at the 2025 Alzheimer's and Parkinson's Disease International Conference in Vienna, Austria, from April 1-4, 2025 [1][2] Research and Development - ProMIS has developed a computational modeling platform that aids in creating next-generation antibodies and targeted vaccines for neurodegenerative diseases [2] - Preclinical data suggests that vaccination with platform-derived epitopes and selective antibody targeting of misfolded toxic aggregates of TDP-43 may be a safe and effective treatment method [2] - The company identified four different conformational B cell epitopes of amyloid-beta oligomers (AβOs) through computational modeling, which are crucial in the development of an Alzheimer's vaccine [3] Preclinical Study Results - Immunization with a single conformational epitope, peptide 301, showed maximal reactivity against AD brain oligomers [4] - Vaccination against pathogenic species of alpha-synuclein (ASyn) demonstrated potential protection against synucleinopathies, preserving normal ASyn function while minimizing off-target effects [4][5] - The study on TDP-43 revealed that selective targeting of misfolded toxic aggregates could be a promising approach for treating diseases associated with TDP-43 proteinopathy [6][7] Product Information - PMN310 is a humanized monoclonal antibody designed to selectively target soluble amyloid-beta oligomers, which are believed to be the most toxic form of Aβ [8] - PMN310 has completed a Phase 1a clinical study and is currently in a Phase 1b clinical trial involving Alzheimer's disease patients [9]

CAMBRIDGE, Massachusetts, March 24, 2025 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Inc. (NASDAQ:PMN), a clinical-stage biotechnology company focused on the generation and development of antibody therapeutics and vaccines targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today announced plans to deliver virtual oral presentations at the 2025 Alzheimer's and Parkison's Disease (AD/PD) Interna ...

Core Insights - ProMIS Neurosciences Inc. is set to present preclinical data on computationally-derived vaccines targeting neurodegenerative diseases at the AAN Annual Meeting in April 2025 [1][2] Group 1: Company Overview - ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing antibody therapeutics and vaccines for neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) [9] - The company utilizes a proprietary computational discovery platform, ProMIS™, to identify Disease Specific Epitopes on misfolded proteins [9] - PMN310, the lead product candidate, is a humanized monoclonal antibody designed to selectively bind toxic soluble amyloid-beta oligomers, which are believed to be a primary cause of neurodegeneration in AD [7][8] Group 2: Research and Development - The preclinical studies demonstrated that immunization with a single conformational epitope, peptide 301, resulted in maximal reactivity against AD brain oligomers [4] - The company is exploring a novel approach to vaccine design that targets misfolded toxic proteins, aiming to induce a specific immune response against amyloid-beta oligomers for AD and pathogenic alpha-synuclein for MSA [2][5] - Results indicated that vaccination with conformational B cell epitopes produced high-affinity antibodies with selectivity for pathogenic alpha-synuclein, preserving normal protein function [6] Group 3: Upcoming Presentations - ProMIS Neurosciences will present two key studies at the AAN Annual Meeting: - The first study focuses on optimizing Alzheimer's vaccine configuration to target toxic amyloid-beta oligomers, presented by Dr. Johanne Kaplan on April 9, 2025 [3] - The second study discusses the rational design of a vaccine for synucleinopathies, presented by Dr. Johanne Kaplan on April 8, 2025 [5]

Company Overview - ProMIS Neurosciences, Inc. is a clinical-stage biotechnology company focused on developing antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) [3] - The company utilizes a proprietary target discovery engine, ProMIS™, which employs a thermodynamic, computational discovery platform to identify Disease Specific Epitopes on misfolded proteins [3] Product Development - The lead product candidate, PMN310, is a humanized monoclonal antibody designed to selectively bind toxic Aβ oligomers, which are implicated in the progression of Alzheimer's disease, while avoiding binding to plaque or monomers [3] - PMN310 has successfully completed a Phase 1a clinical study and is currently in a Phase 1b clinical trial involving Alzheimer's disease patients [3] Upcoming Events - Neil Warma, the CEO of ProMIS Neurosciences, will participate in a fireside chat at the 37th Annual Roth Conference on March 18, 2025, at 8:00 a.m. PT in Dana Point, CA [1] - A live webcast of the event will be available on the company's website for at least 30 days following the event [2]

Rapid Enrollment and Dosing of First Patients Encouraging and Underscores Unmet Need for Better Treatment Options for Alzheimer’s Disease Six-month Interim Results Expected in 1H 2026 with Topline Results Anticipated in 2H 2026 CAMBRIDGE, Massachusetts, Feb. 25, 2025 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Inc. (Nasdaq: PMN), a clinical-stage biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as A ...

Rapid Enrollment and Dosing of First Patients Encouraging and Underscores Unmet Need for Better Treatment Options for Alzheimer's Disease   Six-month Interim Results Expected in 1H 2026 with Topline Results Anticipated in 2H 2026 CAMBRIDGE, Massachusetts, Feb. 25, 2025 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Inc. (NASDAQ:PMN), a clinical-stage biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as A ...

CAMBRIDGE, Massachusetts, Jan. 29, 2025 (GLOBE NEWSWIRE) -- ProMIS Neurosciences, Inc. (NASDAQ:PMN), a clinical-stage biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today announced that Neil Warma, Chief Executive Officer of ProMIS Neurosciences, will participate in a fireside chat at the Guggenheim ...

CAMBRIDGE, Massachusetts, Jan. 13, 2025 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Inc. (NASDAQ:PMN) (ProMIS), a clinical-stage biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today announced that its Chief Executive Officer, Neil Warma, issued the following letter to the Company's shareholders. Dear ...