[Executive Summary & Business Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Business%20Highlights) Acumen Pharmaceuticals, a clinical-stage biopharmaceutical company, provides an overview of its Alzheimer's disease therapeutics, recent operational innovations, and upcoming milestones [Company Overview](index=1&type=section&id=Company%20Overview) Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing novel therapeutics targeting toxic soluble amyloid beta oligomers (AβOs) for Alzheimer's disease. The CEO highlighted strong operational execution and the expansion of the portfolio with the Enhanced Brain Delivery (EBD) program - Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel therapeutics that target toxic soluble amyloid beta oligomers (AβOs) for the treatment of Alzheimer's disease[2](index=2&type=chunk) - CEO Daniel O'Connell emphasized **strong operational execution** and the broadening portfolio with the addition of the Enhanced Brain Delivery (EBD) program[3](index=3&type=chunk) [Recent Business Highlights](index=1&type=section&id=Recent%20Business%20Highlights) Recent highlights include presenting operational innovations in the ALTITUDE-AD Phase 2 trial, which reduced screening costs by approximately 40% using a two-step plasma pTau217 biomarker assay. The company also presented data on sabirnetug's high selectivity for toxic AβOs and announced a collaboration with JCR Pharmaceuticals for an oligomer-targeted Enhanced Brain Delivery (EBD) therapy - Operational innovations in the ALTITUDE-AD Phase 2 clinical trial, using a two-step plasma pTau217 biomarker assay, reduced total screening costs by approximately **40%** across U.S. and Canadian sites[6](index=6&type=chunk)[7](index=7&type=chunk) - Sabirnetug demonstrated **8,750-fold selectivity** for Aβ1-42 stabilized oligomers over Aβ1-40 monomers, supporting its mechanism of action and selectivity for AβOs[10](index=10&type=chunk) - In July 2025, Acumen announced a collaboration, option, and license agreement with JCR Pharmaceuticals to develop an oligomer-targeted Enhanced Brain Delivery (EBD) therapy for Alzheimer's disease[10](index=10&type=chunk) [Anticipated Milestones](index=1&type=section&id=Anticipated%20Milestones) Acumen anticipates reporting topline results for its Phase 2 ALTITUDE-AD study in late 2026 and expects a decision to advance an oligomer-targeted Enhanced Brain Delivery product candidate in early 2026, following non-clinical data - Expect to report topline results for ALTITUDE-AD, a Phase 2 study investigating sabirnetug for early Alzheimer's disease, in **late 2026**[5](index=5&type=chunk)[10](index=10&type=chunk) - Expect a decision to advance an oligomer-targeted Enhanced Brain Delivery product candidate in **early 2026**, supported by non-clinical data[5](index=5&type=chunk)[10](index=10&type=chunk) [Second Quarter 2025 Financial Results](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results) Acumen Pharmaceuticals reports a net loss increase in Q2 2025, primarily driven by higher research and development expenses, with cash reserves expected to fund operations into early 2027 [Overview of Financial Performance](index=2&type=section&id=Overview%20of%20Financial%20Performance) Acumen reported a net loss of $41.0 million for Q2 2025, an increase from $20.5 million in Q2 2024, primarily driven by higher research and development expenses. The company's cash, cash equivalents, and marketable securities totaled $166.2 million as of June 30, 2025, expected to fund operations into early 2027 | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | Change (YoY) | | :----- | :--------------------- | :--------------------- | :----------- | | Net Loss | $(40,950) | $(20,537) | $(20,413) | | Loss from Operations | $(41,750) | $(24,381) | $(17,369) | | Metric | As of June 30, 2025 (in millions) | As of March 31, 2025 (in millions) | | :----- | :-------------------------------- | :--------------------------------- | | Cash, cash equivalents and marketable securities | $166.2 | $197.9 | - Cash, cash equivalents and marketable securities of **$166.2 million** as of June 30, 2025, are expected to support current clinical and operational activities into **early 2027**[5](index=5&type=chunk)[10](index=10&type=chunk) [Operating Expenses](index=2&type=section&id=Operating%20Expenses) Research and Development (R&D) expenses significantly increased to $37.1 million in Q2 2025 from $19.5 million in Q2 2024, mainly due to higher manufacturing, materials, and CRO costs for the ALTITUDE-AD trial. General and Administrative (G&A) expenses slightly decreased to $4.6 million from $4.8 million due to minor reductions in insurance and recruiting costs | Expense Category | Q2 2025 (in thousands) | Q2 2024 (in thousands) | Change (YoY) | | :--------------- | :--------------------- | :--------------------- | :----------- | | Research and Development | $37,125 | $19,533 | +$17,592 | | General and Administrative | $4,625 | $4,848 | $(223) | - The increase in R&D expenses was primarily due to increased costs for manufacturing and materials, as well as CRO costs associated with the ALTITUDE-AD clinical trial[10](index=10&type=chunk) - The decrease in G&A expenses was primarily due to immaterial decreases in insurance and recruiting costs[15](index=15&type=chunk) [Product & Pipeline Information](index=3&type=section&id=Product%20%26%20Pipeline%20Information) Acumen details its lead product candidate, sabirnetug (ACU193), its ongoing Phase 2 ALTITUDE-AD study, and the Enhanced Brain Delivery (EBD) program collaboration [About Sabirnetug (ACU193)](index=3&type=section&id=About%20Sabirnetug%20(ACU193)) Sabirnetug (ACU193) is a humanized monoclonal antibody specifically designed to target soluble amyloid beta oligomers (AβOs), which are considered highly toxic and pathogenic in Alzheimer's disease. It has received Fast Track designation from the U.S. FDA for early AD treatment - Sabirnetug (ACU193) is a humanized monoclonal antibody developed for its selectivity for soluble amyloid beta oligomers (AβOs), a highly toxic and pathogenic form of Aβ[13](index=13&type=chunk) - Sabirnetug has been granted **Fast Track designation** for the treatment of early AD by the U.S. Food and Drug Administration[13](index=13&type=chunk) [About ALTITUDE-AD (Phase 2 Study)](index=3&type=section&id=About%20ALTITUDE-AD%20(Phase%202%20Study)) ALTITUDE-AD is an ongoing Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial initiated in 2024. It evaluates the efficacy and safety of sabirnetug in slowing cognitive and functional decline in 542 participants with early Alzheimer's disease across sites in the U.S., Canada, EU, and UK - ALTITUDE-AD is a Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of sabirnetug (ACU193) in slowing cognitive and functional decline[14](index=14&type=chunk) - The study has enrolled **542 individuals** with early Alzheimer's disease (mild cognitive impairment or mild dementia due to AD)[14](index=14&type=chunk) - Investigative sites are located in the United States, Canada, the European Union, and the United Kingdom[14](index=14&type=chunk)[16](index=16&type=chunk) [Enhanced Brain Delivery (EBD) Program](index=1&type=section&id=Enhanced%20Brain%20Delivery%20(EBD)%20Program) The EBD program is a collaboration with JCR Pharmaceuticals to develop an oligomer-targeted therapy for Alzheimer's disease, utilizing JCR's proprietary J-Brain Cargo® blood-brain barrier-penetrating technology combined with Acumen's AβO-targeting antibodies - Acumen is collaborating with JCR Pharmaceuticals to develop an Enhanced Brain Delivery (EBD) therapy for Alzheimer's disease[3](index=3&type=chunk)[10](index=10&type=chunk)[17](index=17&type=chunk) - The EBD program utilizes JCR's blood-brain barrier-penetrating technology (J-Brain Cargo®) combined with Acumen's AβO-selective antibodies[10](index=10&type=chunk)[17](index=17&type=chunk) [Corporate Information](index=3&type=section&id=Corporate%20Information) Acumen Pharmaceuticals provides an overview of its corporate structure, details of its Q2 2025 conference call, disclaimers regarding forward-looking statements, and investor/media contacts [About Acumen Pharmaceuticals, Inc.](index=4&type=section&id=About%20Acumen%20Pharmaceuticals%2C%20Inc.) Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company headquartered in Newton, Mass., focused on developing therapeutics targeting toxic soluble AβOs for AD. Its pipeline includes sabirnetug (ACU193) in Phase 2, a subcutaneous formulation of sabirnetug, and the EBD therapy collaboration with JCR - Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company developing a novel therapeutic that targets toxic soluble amyloid beta oligomers (AβOs) for the treatment of Alzheimer's disease[17](index=17&type=chunk) - The company is advancing its investigational product candidate, sabirnetug (ACU193), in its ongoing Phase 2 clinical trial ALTITUDE-AD and investigating a subcutaneous formulation of sabirnetug[17](index=17&type=chunk) - Acumen is also collaborating with JCR Pharmaceuticals to develop an Enhanced Brain Delivery (EBD™) therapy for Alzheimer's disease[17](index=17&type=chunk) [Conference Call Details](index=3&type=section&id=Conference%20Call%20Details) Acumen hosted a conference call and live audio webcast on August 12, 2025, at 8:00 a.m. ET to discuss the financial results and business update. An archived version of the webcast is available on the company's website - Acumen hosted a conference call and live audio webcast on **August 12, 2025, at 8:00 a.m. ET**[5](index=5&type=chunk)[11](index=11&type=chunk) - An archived version of the webcast will be available for at least **30 days** in the Investors section of the Company's website[12](index=12&type=chunk) [Forward-Looking Statements](index=4&type=section&id=Forward-Looking%20Statements) The press release contains forward-looking statements regarding Acumen's goals, expectations, financial projections, and pipeline development, which are subject to risks and uncertainties inherent in drug development and macroeconomic conditions. The company disclaims any obligation to update these statements - The press release contains forward-looking statements concerning Acumen's business, strategic and financial goals, therapeutic potential of sabirnetug, timing of ALTITUDE-AD results, and EBD technology development[18](index=18&type=chunk) - These statements are based upon current beliefs and expectations and are subject to certain factors, risks, and uncertainties inherent in the process of discovering, developing, and commercializing human therapeutics, amplified by geopolitical events and macroeconomic conditions[18](index=18&type=chunk) [Contacts](index=5&type=section&id=Contacts) Contact information for investor relations and media inquiries is provided - Investor contact: Alex Braun (abraun@acumenpharm.com)[19](index=19&type=chunk) - Media contact: AcumenPR@westwicke.com[19](index=19&type=chunk) [Financial Statements](index=6&type=section&id=Financial%20Statements) Acumen presents its balance sheets, statements of operations, and cash flows, detailing assets, liabilities, equity, and financial performance for the periods ended June 30, 2025 [Balance Sheets](index=6&type=section&id=Balance%20Sheets) The balance sheets present Acumen's assets, liabilities, and stockholders' equity as of June 30, 2025, and December 31, 2024, showing a decrease in total assets and stockholders' equity over the period | ASSETS (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Cash and cash equivalents | $36,810 | $35,627 | | Marketable securities, short-term | $106,559 | $135,930 | | Prepaid expenses and other current assets | $5,035 | $6,749 | | Total current assets | $148,404 | $178,306 | | Marketable securities, long-term | $22,797 | $59,968 | | Restricted cash | $232 | $232 | | Other assets, long-term | $464 | $486 | | Total assets | $171,897 | $238,992 | | **LIABILITIES AND STOCKHOLDERS' EQUITY** | | | | Accounts payable | $2,103 | $5,648 | | Accrued clinical trial expenses | $11,108 | $15,344 | | Accrued expenses and other current liabilities | $11,650 | $6,615 | | Total current liabilities | $24,861 | $27,607 | | Debt, long-term | $29,882 | $29,419 | | Other liabilities, long-term | $77 | $150 | | Total liabilities | $54,820 | $57,176 | | Total stockholders' equity | $117,077 | $181,816 | [Statements of Operations and Comprehensive Loss](index=7&type=section&id=Statements%20of%20Operations%20and%20Comprehensive%20Loss) The statements detail the company's operating expenses, loss from operations, and net loss for the three and six months ended June 30, 2025, and 2024, indicating a significant increase in net loss year-over-year due to higher R&D expenses | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $37,125 | $19,533 | $62,391 | $31,982 | | General and administrative | $4,625 | $4,848 | $9,729 | $10,173 | | Total operating expenses | $41,750 | $24,381 | $72,120 | $42,155 | | Loss from operations | $(41,750) | $(24,381) | $(72,120) | $(42,155) | | Interest income | $2,015 | $3,816 | $4,486 | $7,821 | | Interest expense | $(1,046) | $(1,004) | $(2,069) | $(2,004) | | Change in fair value of embedded derivatives | $(40) | $1,100 | $150 | $1,050 | | Other expense, net | $(129) | $(68) | $(193) | $(122) | | Total other income | $800 | $3,844 | $2,374 | $6,745 | | Net loss | $(40,950) | $(20,537) | $(69,746) | $(35,410) | | Unrealized gain (loss) on marketable securities | $8 | $(20) | $71 | $(476) | | Comprehensive loss | $(40,942) | $(20,557) | $(69,675) | $(35,886) | | Net loss per common share, basic and diluted | $(0.68) | $(0.34) | $(1.15) | $(0.59) | | Weighted-average shares outstanding, basic and diluted | 60,573,425 | 60,079,778 | 60,549,658 | 59,945,889 | [Statements of Cash Flows](index=8&type=section&id=Statements%20of%20Cash%20Flows) The cash flow statements show that for the six months ended June 30, 2025, net cash used in operating activities increased significantly, while net cash provided by investing activities also increased, primarily from marketable securities. Net cash used in financing activities was minimal | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Net loss | $(69,746) | $(35,410) | | Depreciation | $31 | $33 | | Stock-based compensation expense | $4,972 | $4,954 | | Amortization of premiums and accretion of discounts on marketable securities, net | $(644) | $(3,222) | | Change in fair value of embedded derivatives | $(150) | $(1,050) | | Amortization of right-of-use asset | $61 | $56 | | Realized gain on marketable securities | $(3) | $(2) | | Non-cash interest expense | $613 | $539 | | Changes in operating assets and liabilities: Prepaid expenses and other current assets | $1,714 | $(3,350) | | Other long-term assets | $18 | $(7) | | Accounts payable | $(3,545) | $2,823 | | Accrued clinical trial expenses | $(4,236) | $2,640 | | Accrued expenses and other liabilities | $4,962 | $(2,385) | | Finance lease liability | $— | $(23) | | Net cash used in operating activities | $(65,953) | $(34,404) | | Purchases of marketable securities | $(38,056) | $(57,093) | | Proceeds from maturities and sales of marketable securities | $105,316 | $85,605 | | Purchases of property and equipment | $(88) | $(16) | | Net cash provided by investing activities | $67,172 | $28,496 | | Proceeds from issuance of common stock, net of issuance costs | $— | $7,938 | | Proceeds from exercise of stock options | $37 | $— | | Payment for financing lease | $— | $(739) | | Payments for deferred offering costs | $— | $(188) | | Repurchase of common shares to pay employee withholding taxes | $(73) | $(32) | | Net cash provided by (used in) financing activities | $(36) | $6,979 | | Net change in cash and cash equivalents and restricted cash | $1,183 | $1,071 | | Cash and cash equivalents and restricted cash at the beginning of the period | $35,859 | $67,119 | | Cash and cash equivalents and restricted cash at the end of the period | $37,042 | $68,190 |

Core Viewpoint - Acumen Pharmaceuticals is advancing its clinical-stage biopharmaceutical efforts focused on developing novel therapeutics targeting toxic soluble amyloid beta oligomers (AβOs) for Alzheimer's disease treatment, with significant operational progress and financial updates reported for Q2 2025 [1][2]. Recent Highlights - The company expects to report topline results for the ALTITUDE-AD Phase 2 study investigating sabirnetug (ACU193) for early Alzheimer's disease in late 2026 [4]. - A decision to advance an oligomer-targeted Enhanced Brain Delivery (EBDTM) product candidate is anticipated in early 2026 [4]. - As of June 30, 2025, Acumen had cash, cash equivalents, and marketable securities totaling $166.2 million, projected to support operations into early 2027 [4]. Financial Results - Research and Development (R&D) expenses for Q2 2025 were $37.1 million, up from $19.5 million in Q2 2024, primarily due to increased manufacturing and clinical trial costs [10]. - General and Administrative (G&A) expenses decreased slightly to $4.6 million in Q2 2025 from $4.8 million in Q2 2024 [10]. - The net loss for Q2 2025 was $41.0 million, compared to a net loss of $20.5 million in Q2 2024 [10]. Operational Innovations - Acumen implemented a two-step screening process in the ALTITUDE-AD trial using plasma pTau217 biomarker assay testing, achieving approximately 40% reduction in total screening costs across U.S. and Canadian sites [5]. - Sabirnetug demonstrated an 8,750-fold selectivity for Aβ1-42 stabilized oligomers over Aβ1-40 monomers, supporting its mechanism of action [5]. Collaboration and Development - Acumen entered a collaboration with JCR Pharmaceuticals to develop an oligomer-targeted Enhanced Brain Delivery therapy, combining sabirnetug with JCR's blood-brain barrier-penetrating technology [5].

Company Overview - Acumen Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing a novel therapeutic targeting toxic soluble amyloid beta oligomers for Alzheimer's disease treatment [3] - The company is advancing its investigational product candidate, sabirnetug (ACU193), a humanized monoclonal antibody, currently in Phase 2 clinical trial ALTITUDE-AD for early symptomatic Alzheimer's disease patients [3] - Acumen's scientific founders have pioneered research on amyloid beta oligomers, which are recognized as early triggers of Alzheimer's disease pathology [3] Recent Developments - Acumen Pharmaceuticals will report its second quarter 2025 financial results on August 12, 2025, and will host a conference call and live audio webcast at 8:00 a.m. ET for a business and financial update [1] - The company is also investigating a subcutaneous formulation of sabirnetug using Halozyme's ENHANZE® drug delivery technology [3] - Acumen is collaborating with JCR Pharmaceuticals to develop an Enhanced Brain Delivery therapy for Alzheimer's disease utilizing a transferrin-receptor-targeting technology [3]

Core Insights - Acumen Pharmaceuticals has reported a 40% reduction in clinical trial screening costs through the implementation of a blood-based pTau217 screening assay in its Phase 2 ALTITUDE-AD study for early Alzheimer's disease [1][3][4] - The company’s investigational product, sabirnetug, has demonstrated superior selectivity for soluble amyloid beta oligomers (AβOs) compared to other treatments, indicating a differentiated mechanism of action [5][6] Company Overview - Acumen Pharmaceuticals is focused on developing therapies targeting toxic soluble amyloid beta oligomers (AβOs) for Alzheimer's disease, with its lead candidate being sabirnetug (ACU193) [10] - The company has received Fast Track designation from the U.S. FDA for sabirnetug, which is currently in a Phase 2 clinical trial [7][10] Clinical Trial Details - The ALTITUDE-AD trial is a multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of sabirnetug in slowing cognitive decline in early Alzheimer's disease patients [9] - The trial has enrolled 542 participants across the U.S., Canada, the EU, and the UK, with a focus on improving patient-centric and cost-effective trial execution strategies [9][2] Screening Process Efficiency - The two-step screening process using plasma pTau217 biomarker testing resulted in 48% of participants meeting the threshold for confirmatory testing, with 81% of those passing the initial screening meeting amyloid positivity eligibility [4][3] - This innovative approach has led to strong enrollment rates and reduced the need for unnecessary amyloid PET scans and lumbar punctures [4][3] Mechanism of Action - Sabirnetug targets soluble AβOs, which are believed to be a significant factor in the neurodegenerative process of Alzheimer's disease, potentially slowing neurodegeneration and preventing synapse loss [5][7] - The product has shown an 8,750-fold selectivity for Aβ1-42 stabilized oligomers over Aβ1-40 monomers, highlighting its targeted action [6]

Core Viewpoint - Acumen Pharmaceuticals has entered into a collaboration with JCR Pharmaceuticals to develop an Enhanced Brain Delivery therapy targeting amyloid beta oligomers for Alzheimer's disease treatment [1][2][3] Company Overview - Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing therapies targeting toxic soluble amyloid beta oligomers (AβOs) for Alzheimer's disease [1][13] - The lead program, sabirnetug (ACU193), is a humanized monoclonal antibody that selectively targets AβOs, which are linked to neurodegeneration in Alzheimer's disease [4][11] Collaboration Details - The collaboration aims to combine Acumen's AβO-targeted antibody expertise with JCR's blood-brain barrier-penetrating technology, J-Brain Cargo, to enhance therapeutic delivery to the brain [2][7] - Acumen has an exclusive option to develop up to two candidates from this collaboration, with preclinical data expected in early 2026 [7][10] Technology Insights - J-Brain Cargo technology utilizes receptor-mediated transcytosis to deliver drugs to the central nervous system, applicable to various therapeutic modalities [3][14] - JCR's technology has previously led to an approved therapy in Japan, demonstrating its efficacy and safety profile [3][14] Clinical Trials - Acumen is currently conducting the ALTITUDE-AD Phase 2 clinical trial, which has enrolled 542 patients with early Alzheimer's disease, with topline results expected in late 2026 [5][12] - The Phase 1 INTERCEPT-AD trial showed that sabirnetug was well-tolerated and demonstrated significant amyloid plaque reduction compared to placebo [4][5] Financial Terms - Under the collaboration agreement, JCR will receive an upfront payment and may earn additional payments based on development milestones and royalties from future sales [10]

Core Insights - Acumen Pharmaceuticals is set to present new findings at the Alzheimer's Association International Conference (AAIC®) 2025, focusing on cost savings from using pTau217 as a screening tool in its Phase 2 ALTITUDE-AD trial of sabirnetug for Alzheimer's disease [1][2] - The company emphasizes the significance of combining biomarker-driven screening with targeted therapeutics to enhance clinical trial designs and drug development for Alzheimer's disease [2] Company Overview - Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company developing sabirnetug (ACU193), a humanized monoclonal antibody targeting soluble amyloid beta oligomers (AβOs), which are linked to Alzheimer's disease [3][5] - Sabirnetug has received Fast Track designation from the U.S. FDA for treating early Alzheimer's disease and is currently in a Phase 2 study [3][7] ALTITUDE-AD Trial - The ALTITUDE-AD trial, initiated in 2024, is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sabirnetug in slowing cognitive decline in early Alzheimer's disease patients [4] - The trial has enrolled 542 participants across multiple sites in the U.S., Canada, the EU, and the UK [4] Presentation Details - Acumen's presentations at AAIC will cover the cost savings analysis of pTau217 in the ALTITUDE-AD trial and the selectivity of sabirnetug for Aβ oligomers compared to other treatments like lecanemab and aducanumab [2][6]

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]

Summary of Acumen Pharmaceuticals (ABOS) Conference Call Company Overview - **Company**: Acumen Pharmaceuticals - **Focus**: Development of new treatment options for Alzheimer's disease, specifically targeting amyloid beta oligomers with their main program, sabrutinib [2][3] Key Points and Arguments - **Mechanism of Action**: - Sabrutinib is a monoclonal antibody selectively targeting amyloid beta oligomers, which are considered the most toxic species in Alzheimer's pathology [2] - The approach aims to neutralize the toxic effects of oligomers, which disrupt neuronal function and lead to Alzheimer's symptoms [2][3] - **Phase I Study (INTERCEPT AD)**: - Conducted exclusively in early Alzheimer's patients to assess safety, pharmacokinetics, and tolerability [4] - Results showed a favorable safety profile with a lower incidence of ARIA (Amyloid Related Imaging Abnormalities) compared to plaque-directed antibodies [5][12] - Demonstrated robust target engagement with a novel assay showing a dose-response relationship [5][6] - Imaging results indicated a 20-25% reduction in amyloid PET signal at high doses, comparable to other agents like Leukembi [6] - Biomarker assessments showed significant signals in CSF and plasma, indicating engagement with the target [7][8] - **Cognitive Impact**: - The study was not powered to detect cognitive benefits, and no significant clinical effects were observed [10][11] - Future studies, particularly the Phase II ALPITUDE AD study, are expected to provide more insights into cognitive outcomes over an 18-month period [11][14] - **Safety Profile**: - The incidence of ARIA was low, with only five cases reported, and none in the high-risk APOE4 homozygous population [12][13] - The mechanism of action is believed to contribute to a better safety profile by targeting soluble aggregates rather than plaque-bound amyloid [12][13] - **Future Studies**: - The ALPITUDE AD study aims to enroll 540 patients across multiple sites and is designed to assess the long-term effects of treatment [18][19] - The study's rapid enrollment reflects increased awareness and willingness to participate in Alzheimer's research [19] Competitive Landscape - The Alzheimer's treatment market is evolving, with several approved agents facing limitations, indicating room for improvement [22][24] - There is interest in enhancing drug delivery to the brain, potentially through combination therapies with other mechanisms of action [24][25][28] Additional Insights - Acumen is exploring subcutaneous formulations of sabrutinib alongside intravenous options, which could provide flexibility for patients and physicians [26][27] - Combination strategies with other therapeutic modalities are being considered to enhance treatment efficacy [28] This summary encapsulates the key discussions and findings from the conference call, highlighting Acumen Pharmaceuticals' strategic focus on Alzheimer's treatment and the promising results from their ongoing studies.

Financial Performance - The company reported a net loss of $28.8 million for the three months ended March 31, 2025, compared to a net loss of $14.9 million for the same period in 2024, representing a 94% increase in losses [126]. - The company has an accumulated deficit of $353.9 million as of March 31, 2025, reflecting ongoing financial challenges [116]. - Net cash used in operating activities increased by $16.2 million to $34.1 million for the three months ended March 31, 2025, compared to $17.9 million for the same period in 2024 [138]. - Interest income decreased by 38% to $2.5 million for the three months ended March 31, 2025, compared to $4.0 million in 2024 [126]. - Net cash provided by financing activities was immaterial and decreased by $7.1 million from $7.1 million in the same period of 2024, primarily due to the issuance of common stock [141]. Research and Development - Research and development expenses increased to $25.3 million for the three months ended March 31, 2025, up from $12.4 million in 2024, marking a 103% increase primarily due to costs associated with the ALTITUDE-AD clinical trial [127]. - The ALTITUDE-AD clinical trial for sabirnetug is designed to evaluate clinical efficacy with up to 540 participants, and top-line results are expected in late 2026 [110]. - The company expects expenses to increase significantly as it continues research and development and seeks marketing approval for product candidates [142]. - The company plans to seek third-party collaborators for the future commercialization of sabirnetug or any other approved product candidates [116]. Cash and Funding - The company has cash and cash equivalents of $197.9 million as of March 31, 2025, which is expected to fund operations into early 2027 [118]. - The company had cash and cash equivalents and marketable securities totaling $197.9 million as of March 31, 2025, expected to fund operations into early 2027 [135]. - The company entered into a loan agreement providing a term loan facility of up to $50 million, of which $30 million has been drawn down [114]. - The company anticipates that existing cash and marketable securities may be exhausted sooner than expected if additional clinical trials or programs are initiated [143]. - The company expects to incur additional costs associated with operating as a public company and ongoing research and development activities, indicating a need for substantial additional funding [142]. - The company may need to raise additional funds sooner than anticipated if it chooses to expand more rapidly than currently planned [143]. Operational Expenses - General and administrative expenses slightly decreased to $5.1 million for the three months ended March 31, 2025, from $5.3 million in 2024 [128]. - Cash provided by investing activities was $28.7 million for the three months ended March 31, 2025, an increase of $37.9 million from cash used in investing activities of $9.2 million in the same period of 2024 [139]. - The company issued 2,068,246 shares of common stock under the ATM in January 2024 for net proceeds of $7.9 million, or $3.84 per share [134]. Company Classification - The company is classified as a smaller reporting company, with the market value of shares held by non-affiliates being less than $700 million [152].

Financial Performance Highlights - P&C premium production increased by 70% to approximately $318 million[5] - Total revenue increased by 27% to approximately $63 million[5] - Beat Capital contributed over $20 million of revenue, up approximately 40%[5] Cirrata (Insurance Distribution) - Premium placed increased 156% to $231 million[9] - Total revenue increased 129% to $41 million year-over-year[9] - Adjusted EBITDA was $12 million with a margin of 29%[9] - Adjusted EBITDA to shareholders was $7 million with a margin of 17%[9] - Net loss of $(2) million with a margin of (4)%[9] Everspan (Specialty P&C Program Insurer) - Gross Written Premium (GPW) was $87 million, a decrease of 10% compared to Q1 2024[12] - 67% of Q1 2025 GPW is E&S lines[12] - Loss ratio was 66.9% compared to 75.7% for Q1 2024[12] - Combined ratio was 102.1% compared to 98.4% for Q1 2024[12]