UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
____________________________
FORM 8-K
____________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 12, 2024
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(Exact name of Registrant as Specified in Its Charter)
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(State or Other Jurisdiction of Incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||||||
| (Address of Principal Executive Offices) | (Zip Code) | ||||
(617 ) 344-4190
(Registrant’s Telephone Number, Including Area Code)
Not Applicable
(Former Name or Former Address, if Changed Since Last Report)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||||||||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
Item 2.02 Results of Operations and Financial Condition.
On November 12, 2024, Acumen Pharmaceuticals, Inc. (the “Company”) reported financial results and business highlights for the quarter ended September 30, 2024. A copy of this press release (the “Earnings Press Release”) is furnished as Exhibit 99.1 to this Current Report on Form 8-K (this “Report”) and is incorporated by reference.
The information in this Item 2.02 of this Report (including Exhibit 99.1) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 7.01 Regulation FD Disclosure.
On November 12, 2024, the Company posted an updated corporate presentation to its website at https://investors.acumenpharm.com/news-events/presentations, which the Company may use from time to time in communications or conferences. The corporate presentation was updated to reflect the inclusion of preclinical selectivity data, the Company’s cash balance on September 30, 2024, and the projected timing for the completion of enrollment for ALTITUDE-AD. A copy of the corporate presentation is attached as Exhibit 99.2 to this Report.
The information in this Item 7.01 of this Report (including Exhibit 99.2), is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing. The Company’s submission of this Report shall not be deemed an admission as to the materiality of any information required to be disclosed solely to satisfy the requirements of Regulation FD.
Item 9.01 Financial Statements and Exhibits.
(d).Exhibits
| Exhibit No. | Description | |||||||
| 99.1 | ||||||||
| 99.2 | ||||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the Company has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Acumen Pharmaceuticals, Inc. | ||||||||
| Dated: November 12, 2024 | By: | /s/ Matthew Zuga | ||||||
Matthew Zuga Chief Financial Officer and Chief Business Officer | ||||||||
Exhibit 99.1
Acumen Pharmaceuticals Reports Third Quarter 2024 Financial Results and Business Highlights
•Expect ALTITUDE-AD, a Phase 2 study to investigate sabirnetug (ACU193) for the treatment of early Alzheimer’s disease, to complete enrollment in the first half of 2025
•Expect to announce topline results of Phase 1 study to support subcutaneous administration of sabirnetug in the first quarter of 2025
•Cash, cash equivalents and marketable securities of $258.9 million as of Sept. 30, 2024, expected to support current clinical and operational activities into the first half of 2027
•Company to host conference call and webcast today at 8:00 a.m. ET
NEWTON, Mass., Nov. 12, 2024 – Acumen Pharmaceuticals, Inc. (NASDAQ: ABOS) (“Acumen” or the “Company”), a clinical-stage biopharmaceutical company developing a novel therapeutic that targets toxic soluble amyloid beta oligomers (AβOs) for the treatment of Alzheimer’s disease (AD), today reported financial results for the third quarter of 2024 and provided a business update.
“Our team remains deeply committed to executing our plans in 2024, and I’m proud of the strides we’ve made in the third quarter. We expect enrollment completion of our Phase 2 ALTITUDE-AD study in the first half of 2025,” said Daniel O’Connell, Chief Executive Officer of Acumen. “Additionally, we anticipate topline results from our Phase 1 healthy volunteer study investigating subcutaneous sabirnetug in the first quarter of 2025. With our clinical program gaining momentum and sabirnetug’s unique selectivity for toxic amyloid beta oligomers, we are excited about the potential to offer a next-generation treatment for early Alzheimer’s disease.”
Recent Highlights
•In September 2024, the Company announced it had extended its collaboration with Lonza to enable the potential future commercial launch of sabirnetug (ACU193). The extended collaboration builds upon an existing successful relationship, in which Lonza provides drug substance manufacturing for the ALTITUDE-AD study. Under the terms of the extended agreement, Lonza will manufacture cGMP drug product of sabirnetug for the ongoing and future clinical phases and support the potential commercial launch of sabirnetug.
•In October 2024, the Company hosted a virtual investor event to provide a deep dive into the scientific rationale, Phase 1 clinical results and Phase 2 clinical plans for sabirnetug. A replay is available on the Investors section of Acumen’s website.
•In October 2024, the Company presented a late-breaking presentation featuring insights from its participant screening approach used in the ongoing Phase 2 ALTITUDE-AD clinical trial evaluating sabirnetug at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference.
•The presentation detailed the use of a validated research-use plasma phosphorylated tau 217 (pTau217) assay to screen potential participants in ALTITUDE-AD. The plasma pTau217 assay is being used as an initial screening tool to identify people who qualify for additional amyloid testing to determine eligibility for the ALTITUDE-AD trial. More details about the research are available here.
•In November 2024, the Company announced the appointment of Amy Schacterle, PhD as Chief Regulatory Officer & Head of Quality. Dr. Schacterle brings over 30 years of experience in regulatory affairs, quality assurance, and therapeutic development to Acumen, with a focus on central nervous system disorders.
Anticipated Milestones
•The Company expects ALTITUDE-AD, a Phase 2 study to investigate sabirnetug for the treatment of early Alzheimer’s disease, to complete enrollment in the first half of 2025.
•The Company expects to announce topline results of a Phase 1 study to support subcutaneous administration of sabirnetug in the first quarter of 2025.
Third Quarter 2024 Financial Results
•Cash Balance. As of Sept. 30, 2024, cash, cash equivalents and marketable securities totaled $258.9 million, compared to cash, cash equivalents and marketable securities of $306.1 million as of December 31, 2023. The decrease in cash is related to funding ongoing operations. Cash is expected to support current clinical and operational activities into the first half of 2027.
•Research and Development (R&D) Expenses. R&D expenses were $27.2 million for the three-month period ended Sept. 30, 2024, compared to $11.2 million for the three-month period ended Sept. 30, 2023. The increase in R&D expenses was primarily due to increased clinical trial costs related to ALTITUDE-AD and license expenses.
•General and Administrative (G&A) Expenses. G&A expenses were $5.0 million for the three-month period ended Sept. 30, 2024, compared to $4.9 million for the three-month period ended Sept. 30, 2023. The increase in G&A expenses was primarily due to increased costs related to personnel.
•Loss from Operations. Loss from operations was $32.3 million for the three-month period ended Sept. 30, 2024, compared to $16.0 million for the three-month period ended Sept. 30, 2023. This increase was due to the increased R&D and G&A expenses over the prior year period.
•Net Loss. Net loss was $29.8 million for the three-month period ended Sept. 30, 2024, compared to $13.0 million for the three-month period ended Sept. 30, 2023.
Participation in Upcoming Investor Conferences
•UBS Global Healthcare Conference, November 11-14
•Stifel 2024 Healthcare Conference, November 18-19
•7th Annual Evercore ISI HealthCONx Conference, December 3-5
Conference Call Details
Acumen will host a conference call and live audio webcast today, Nov. 12, 2024, at 8:00 a.m. ET.
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To participate in the live conference call, please register using this link. After registration, you will be informed of the dial-in numbers including PIN. Please register at least one day in advance.
The webcast audio will be available via this link.
An archived version of the webcast will be available for at least 30 days in the Investors section of the Company’s website at www.acumenpharm.com.
About Sabirnetug (ACU193)
Sabirnetug (ACU193) is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble amyloid beta oligomers (AβOs), which are a highly toxic and pathogenic form of Aβ, relative to Aβ monomers and amyloid plaques. Soluble AβOs have been observed to be potent neurotoxins that bind to neurons, inhibit synaptic function and induce neurodegeneration. By selectively targeting toxic soluble AβOs, sabirnetug aims to address the hypothesis that soluble AβOs are an early and persistent underlying cause of the neurodegenerative process in Alzheimer’s disease (AD). Sabirnetug has been granted Fast Track designation for the treatment of early AD by the U.S. Food and Drug Administration and is currently being evaluated in a Phase 2 study in patients with early AD.
About ALTITUDE-AD (Phase 2)
Initiated in 2024, 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) infusions administered once every four weeks in slowing cognitive and functional decline as compared to placebo in participants with early Alzheimer's disease. The study will enroll approximately 540 individuals with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to AD). The global study is currently enrolling at multiple investigative sites located in the United States and Canada with plans for additional sites in Europe and the UK. More information can be found on www.clinicaltrials.gov, NCT identifier NCT06335173.
About INTERCEPT-AD (Phase 1)
Completed in 2023, INTERCEPT-AD was a Phase 1, U.S.-based, multi-center, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and tolerability, and establishing clinical proof of mechanism, of sabirnetug in patients with early Alzheimer’s disease (AD). Sixty-five individuals with early AD (mild cognitive impairment or mild dementia due to AD) enrolled in this first-in-human study of sabirnetug. The INTERCEPT-AD study consisted of single-ascending-dose (SAD) and multiple-ascending-dose (MAD) cohorts. Results showed sabirnetug to be well-tolerated with a favorable overall safety profile. The trial showed amyloid plaque reduction, effects on synaptic biomarkers, low overall rates of ARIA-E, and evidence of target engagement that validated proof of mechanism. More information can be found on www.clinicaltrials.gov, NCT identifier NCT04931459.
About Acumen Pharmaceuticals, Inc.
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 (AD). Acumen’s scientific founders pioneered research on AβOs, which a growing body of evidence indicates are early and persistent triggers of Alzheimer’s disease pathology. Acumen is currently focused on advancing its investigational product candidate, sabirnetug (ACU193), a humanized monoclonal antibody that selectively targets toxic soluble AβOs, in its ongoing Phase 2 clinical trial ALTITUDE-AD (NCT06335173) in early symptomatic Alzheimer’s disease patients, following positive results in its Phase 1 trial INTERCEPT-AD. The company is headquartered in Newton, Mass. For more information, visit www.acumenpharm.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Any statement describing Acumen’s goals, expectations, financial or other projections,
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intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Words such as “believes,” “expects,” “anticipates,” “could,” “should,” “would,” “seeks,” “aims,” “plans,” “potential,” “will,” “milestone” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include statements concerning Acumen’s business, and Acumen’s ability to achieve its strategic and financial goals, including its projected use of cash, cash equivalents and marketable securities and the expected sufficiency of its cash resources into the first half of 2027, the therapeutic potential of Acumen’s product candidate, sabirnetug (ACU193), including against other antibodies, the anticipated completion date of enrollment of ALTITUDE-AD, and the anticipated timeline for results from the Phase 1 trial to support a subcutaneous dosing option of sabirnetug. These statements are based upon the current beliefs and expectations of Acumen management, and are subject to certain factors, risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing safe and effective human therapeutics. Such risks may be amplified by the impacts of geopolitical events and macroeconomic conditions, such as rising inflation and interest rates, supply disruptions and uncertainty of credit and financial markets. These and other risks concerning Acumen’s programs are described in additional detail in Acumen’s filings with the Securities and Exchange Commission (“SEC”), including in Acumen’s most recent Annual Report on Form 10-K, and in subsequent filings with the SEC. Copies of these and other documents are available from Acumen. Additional information will be made available in other filings that Acumen makes from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and Acumen expressly disclaims any obligation to update or revise any forward-looking statement, except as otherwise required by law, whether, as a result of new information, future events or otherwise.
CONTACTS:
Investors:
Alex Braun
abraun@acumenpharm.com
Media: AcumenPR@westwicke.com
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Acumen Pharmaceuticals, Inc.
Condensed Balance Sheets
(in thousands, except share and per share data)
| September 30, 2024 | December 31, 2023 | ||||||||||
| (unaudited) | |||||||||||
| ASSETS | |||||||||||
| Current assets | |||||||||||
| Cash and cash equivalents | $ | 33,184 | $ | 66,886 | |||||||
| Marketable securities, short-term | 167,159 | 176,636 | |||||||||
| Prepaid expenses and other current assets | 7,289 | 3,093 | |||||||||
| Total current assets | 207,632 | 246,615 | |||||||||
| Marketable securities, long-term | 58,552 | 62,553 | |||||||||
| Right-of-use asset | 296 | 381 | |||||||||
| Restricted cash | 236 | 233 | |||||||||
| Property and equipment, net | 89 | 122 | |||||||||
| Other assets | 170 | 221 | |||||||||
| Total assets | $ | 266,975 | $ | 310,125 | |||||||
| LIABILITIES AND STOCKHOLDERS’ EQUITY | |||||||||||
| Current liabilities | |||||||||||
| Accounts payable | $ | 2,342 | $ | 1,379 | |||||||
| Accrued clinical trial expenses | 12,517 | 4,387 | |||||||||
| Accrued expenses and other current liabilities | 4,926 | 6,339 | |||||||||
| Finance lease liability, short-term | — | 756 | |||||||||
| Operating lease liability, short-term | 129 | 110 | |||||||||
| Total current liabilities | 19,914 | 12,971 | |||||||||
| Operating lease liability, long-term | 185 | 284 | |||||||||
| Debt, long-term | 29,674 | 29,897 | |||||||||
| Total liabilities | 49,773 | 43,152 | |||||||||
| Commitments and contingencies | |||||||||||
| Stockholders’ equity | |||||||||||
| Preferred stock, $0.0001 par value; 10,000,000 shares authorized and no shares issued and outstanding as of September 30, 2024 and December 31, 2023 | — | — | |||||||||
| Common stock, $0.0001 par value; 300,000,000 shares authorized as of September 30, 2024 and December 31, 2023; 60,079,778 and 57,910,461 shares issued and outstanding as of September 30, 2024 and December 31, 2023 | 6 | 6 | |||||||||
| Additional paid-in capital | 504,651 | 489,453 | |||||||||
| Accumulated deficit | (287,973) | (222,798) | |||||||||
| Accumulated other comprehensive income | 518 | 312 | |||||||||
| Total stockholders’ equity | 217,202 | 266,973 | |||||||||
| Total liabilities and stockholders’ equity | $ | 266,975 | $ | 310,125 | |||||||
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Acumen Pharmaceuticals, Inc.
Condensed Statements of Operations and Comprehensive Loss
(in thousands, except share and per share data)
(unaudited)
| Three Months Ended September 30, | Nine Months Ended September 30, | ||||||||||||||||||||||
| 2024 | 2023 | 2024 | 2023 | ||||||||||||||||||||
| Operating expenses | |||||||||||||||||||||||
| Research and development | $ | 27,247 | $ | 11,179 | $ | 59,229 | $ | 29,025 | |||||||||||||||
| General and administrative | 5,018 | 4,860 | 15,191 | 13,627 | |||||||||||||||||||
| Total operating expenses | 32,265 | 16,039 | 74,420 | 42,652 | |||||||||||||||||||
| Loss from operations | (32,265) | (16,039) | (74,420) | (42,652) | |||||||||||||||||||
| Other income (expense) | |||||||||||||||||||||||
| Interest income | 3,504 | 3,124 | 11,325 | 6,840 | |||||||||||||||||||
| Interest expense | (1,027) | — | (3,031) | — | |||||||||||||||||||
| Change in fair value of embedded derivatives | (10) | — | 1,040 | — | |||||||||||||||||||
| Other income (expense), net | 33 | (42) | (89) | (62) | |||||||||||||||||||
| Total other income | 2,500 | 3,082 | 9,245 | 6,778 | |||||||||||||||||||
| Net loss | (29,765) | (12,957) | (65,175) | (35,874) | |||||||||||||||||||
| Other comprehensive gain (loss) | |||||||||||||||||||||||
| Unrealized gain on marketable securities | 682 | 137 | 206 | 242 | |||||||||||||||||||
| Comprehensive loss | $ | (29,083) | $ | (12,820) | $ | (64,969) | $ | (35,632) | |||||||||||||||
| Net loss per common share, basic and diluted | $ | (0.50) | $ | (0.24) | $ | (1.09) | $ | (0.79) | |||||||||||||||
| Weighted-average shares outstanding, basic and diluted | 60,079,778 | 54,229,630 | 59,990,844 | 45,474,953 | |||||||||||||||||||
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Acumen Pharmaceuticals, Inc.
Condensed Statements of Cash Flows
(in thousands)
(unaudited)
| Nine Months Ended September 30, | |||||||||||
| 2024 | 2023 | ||||||||||
| Cash flows from operating activities | |||||||||||
| Net loss | $ | (65,175) | $ | (35,874) | |||||||
| Adjustments to reconcile net loss to net cash used in operating activities: | |||||||||||
| Depreciation | 49 | 42 | |||||||||
| Stock-based compensation expense | 7,292 | 4,511 | |||||||||
| Amortization of premiums and accretion of discounts on marketable securities, net | (4,599) | (1,344) | |||||||||
| Change in fair value of embedded derivatives | (1,040) | — | |||||||||
| Amortization of right-of-use asset | 85 | 103 | |||||||||
| Realized gains on marketable securities | (97) | — | |||||||||
| Non-cash interest expense | 823 | — | |||||||||
| Other non-cash expense | 230 | — | |||||||||
| Changes in operating assets and liabilities: | |||||||||||
| Prepaid expenses and other current assets | (4,196) | (436) | |||||||||
| Other assets | 51 | (38) | |||||||||
| Accounts payable | 963 | (278) | |||||||||
| Accrued clinical trial expenses | 8,130 | (1,151) | |||||||||
| Accrued expenses and other current liabilities | (1,413) | (182) | |||||||||
| Finance lease liability | (23) | — | |||||||||
| Operating lease liability | (80) | (103) | |||||||||
| Net cash used in operating activities | (59,000) | (34,750) | |||||||||
| Cash flows from investing activities | |||||||||||
| Purchases of marketable securities | (155,631) | (178,857) | |||||||||
| Proceeds from maturities and sales of marketable securities | 174,011 | 55,997 | |||||||||
| Proceeds from sale of property and equipment | — | 3 | |||||||||
| Purchases of property and equipment | (16) | (7) | |||||||||
| Net cash provided by (used in) investing activities | 18,364 | (122,864) | |||||||||
| Cash flows from financing activities | |||||||||||
| Proceeds from issuance of common stock, net of issuance costs | 7,938 | 122,294 | |||||||||
| Proceeds from exercise of stock options | — | 325 | |||||||||
| Payment for financing lease | (739) | — | |||||||||
| Payments for deferred offering costs | (230) | — | |||||||||
| Repurchase of common shares to pay employee withholding taxes | (32) | — | |||||||||
| Net cash provided by financing activities | 6,937 | 122,619 | |||||||||
| Net change in cash and cash equivalents and restricted cash | (33,699) | (34,995) | |||||||||
| Cash and cash equivalents and restricted cash at the beginning of the period | 67,119 | 130,101 | |||||||||
| Cash and cash equivalents and restricted cash at the end of the period | $ | 33,420 | $ | 95,106 | |||||||
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Corporate Presentation November 2024 1
Forward-Looking Statements 2 This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Any statement describing Acumen’s goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Words such as “believes,” “expects,” “anticipates,” “could,” “would,” “seeks,” “aims,” “plans,” “potential,” “will” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include statements concerning Acumen’s business, and Acumen’s ability to achieve its strategic and financial goals, including its projected use of cash, cash equivalents and marketable securities and the expected sufficiency of its cash resources into the first half of 2027, the therapeutic potential of Acumen’s product candidate, sabirnetug (ACU193), including against other antibodies, the anticipated timeline for announcing the top-line results from our Phase 1 trial of a subcutaneous dosing option of ACU193, and the anticipated timeline for the completion of enrollment of our Phase 2 ALTITUDE-AD trial. These statements are based upon the current beliefs and expectations of Acumen management, and are subject to certain factors, risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing safe and effective human therapeutics. Such risks may be amplified by the impacts of the COVID-19 pandemic. These and other risks concerning Acumen’s programs are described in additional detail in Acumen’s filings with the Securities and Exchange Commission (“SEC”), including in Acumen’s most recent Annual Report Form 10-K and future filings and reports by Acumen. Copies of these and other documents are available from Acumen. Additional information will be made available in other filings that Acumen makes from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and Acumen expressly disclaims any obligation to update or revise any forward-looking statement, except as otherwise required by law, whether, as a result of new information, future events or otherwise. In this presentation, references to cash also include cash equivalents.
Positive Phase 1 clinical trial results presented in 2H 2023 3 Advancing a Next Generation Antibody Targeting Toxic Amyloid Beta Oligomers (AβOs) for Early Alzheimer’s Disease (AD) Large market in need of additional treatment options Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs Experienced leadership team with extensive AD drug development experience Strong balance sheet supporting clinical development plans for sabirnetug Phase 2 (IV) enrollment completion expected 1H25; Phase 1 (subcutaneous) TLR expected in 1Q25 $
Early AD Patient Population Represents Significant and Growing Market 4 STAGES AND CHARACTERISTICS OF AD PROGRESSION Severe DementiaModerate DementiaMild Dementia Mild Cognitive Impairment (MCI) Preclinical AD ~5 Million* ~2 Million* Early Alzheimer’s Disease in the U.S. Cognitive Decline Behavioral and Psychological Complications Functional Decline *Alzheimer's Association Growing Market Higher prevalence due to aging population More diagnosed cases driven by improved ability to diagnose in earlier stages of AD More treated cases due to availability of treatment options and favorable shifts around adoption
AD, Amyloid & Abeta Oligomers
6 Amyloid Beta Oligomers (AβOs) in Alzheimer’s Disease Pathology
Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease Disrupted Ca2+ homeostasis Demuro et al, 2005 De Felice et al, 2007 Alberdi et al, 2010 Wang et al, 2018 ChAT loss Heinitz et al, 2006 Nunes-Tavares et al, 2012 Inhibition of axonal transport Pigino et al, 2009 Poon et al, 2009 Decker et al, 2010 Oxidative stress Longo et al, 2000 Sponne et al, 2003 Tabner et al, 2005 De Felice et al, 2007 ER stress Resende et al, 2008 Nishitsuji et al, 2009 Insulin resistance Zhao et al, 2008 Zhao et al, 2009 Ma et al, 2009 De Felice et al, 2009 Impact on astrocytes/microglia Hu et al, 1998 Jimenez et al, 2008 Sondag et al, 2009 Tomiyama et al, 2010 Aberrant Tau phosphorylation De Felice et al, 2008 Ma et al, 2009 Tomiyama et al, 2010 Zempel et al, 2010 Bloom, 2014 Forny-Germano et al, 2020 Wakeman et al, 2022 Darricau et al, 2023 Selective neuron death Lambert et al, 1998 Kim et al, 2003 Florent et al, 2006 Ryan et al, 2009 Lee et al, 2017 Komura, 2019 Plasticity dysfunction Lambert et al, 1998 Walsh et al, 2002 Wang et al, 2002 Townsend et al, 2006 Yasumoto et al, 2019 Synapse deterioration Zhao et al, 2006 Lacor et al, 2007 Shankar et al, 2007 Wu et al, 2010 Brito-Moreira et al, 2017 Actor-Engel et al, 2021 Sackmann & Hallbeck, 2020 Limegrover et al, 2021 Receptor Redistribution Snyder et al, 2005 Roselli et al, 2005 Lacor et al, 2007 Zhao et al, 2008 • Soluble Aβ forms appear early in the course of disease pathophysiology • Consequences of soluble Aβ oligomer production include synapse dysfunction and loss, tau hyperphosphorylation, immune cell activation and functional impairment • Reduced neuronal toxicity and intervention at the synaptic level may prevent irreversible neuronal cell death • Production of toxic soluble Aβ persists after plaque removal Aberrant Tau Phosphorylation Selective Neuron Death Oxidative & ER Stress Insulin Resistance ChAT Loss Synaptic Deterioration Plasticity Dysfunction Receptor Redistribution Impact on Astrocytes/Microglia Disrupted Ca2+ homeostasis Inhibition of Axonal Transport Supported by extensive literature:
8 AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AOs species Sabirnetug is Highly Selective for AβOs Versus Aβ Plaques Sabirnetug Thioflavin S Sabirnetug staining in human AD brain slices Adapted from Krafft et al. 2022
9 Amyloid Plaques are Surrounded by a Halo of AβOs Transgenic mouse model of AD Sabirnetug targets AβOs that form halos of soluble aggregates around dense core of plaques Sabirnetug binding to soluble AβOs Sabirnetug Plaque (ThioS) Spires-Jones et al. 2016 AOs (AW7) Plaque (ThioS) AD brain tissue Lab of William Klein, NU, 2017
Sabirnetug: Potential Next Generation Immunotherapy for Early AD 10 • Humanized, affinity matured mAb developed to target toxic Aβ oligomers • IgG2 subclass mAb with reduced effector function Designed for Improved Efficacy & Safety Large Pharma Collaboration Encouraging FDA Interactions • FDA Fast Track designation for the treatment of early Alzheimer’s disease • FDA End of Phase 2 meeting in 4Q 2023 • Discovered in collaboration with Merck & Co. Acumen holds exclusive program rights with no future financial or other obligations due to Merck Positive Phase 1 in AD • Successful Phase 1 exclusively in early AD patients • Phase 2 initiated in 2Q24 with ~540 participants • Expect to complete Phase 2 enrollment in 1H25
11 • Aβ monomers are ~7000x fold higher concentration than AβOs in AD CSF • Higher affinity for monomeric Aβ will reduce functional selectivity due to high monomer levels • Sabirnetug has much lower affinity than other mAbs for Aβ monomers Sabirnetug was Developed to Selectively Target AβOs High selectivity for AβOs versus monomeric Aβ H ig h e r b in d in g a ff in it y Internal data, 2024
12 Aducanumab Sabirnetug 1×10 -10 1×10 -9 1×10 -8 1×10 -7 1×10 -6 1×10 -5 Sabirnetug vs Aducanumab A ff in it y - K D ( M ) Aβ1-40 monomer Aβ oligomers 8750x 79.6x Sabirnetug is more selective for AβOs than aducanumab Sabirnetug is Highly Selective for Aβ Oligomers H ig h e r b in d in g a ff in it y Internal data, 2024 Lecanemab Sabirnetug 1×10 -10 1×10 -9 1×10 -8 1×10 -7 1×10 -6 1×10 -5 Sabirnetug vs Lecanemab A ff in it y - K D ( M ) Aβ1-40 monomer Aβ oligomers 8750x 222x Sabirnetug is more selective for AβOs than lecanemab Relative selectivity for AβO versus monomeric Aβ measured with SPR
Sabirnetug: Value Proposition 13 The Alzheimer’s disease market is at a key inflection point with recent and expected approvals paving a new path for the treatment of AD … … and sabirnetug is well-positioned to emerge as a potential next generation treatment of choice. Market will likely remain consolidated with A therapies emerging as the primary treatment option over the next few years Stakeholders are encouraged about the advancements in the AD treatment landscape and are working together to enable broader patient access With potential clinical and safety benefits conferred by AO selectivity, sabirnetug has the opportunity to be a treatment of choice in the broader early AD population
Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Q2W: Dosing every two weeks; Q4W: Dosing every four weeks. PART A: SINGLE-ASCENDING DOSE n = 8 per cohort (32 total) 6:2 per cohort PART B: MULTIPLE-ASCENDING DOSE n = 10 per cohort (30 total) 3 administrations of drug or PBO 8:2 per cohort COHORT 1: 2 mg/kg Sabirnetug or Placebo 2mg COHORT 2: 10 mg/kg Sabirnetug or Placebo 10mg COHORT 3: 25 mg/kg Sabirnetug or Placebo 25mg COHORT 4: 60 mg/kg Sabirnetug or Placebo 60mg COHORT 5: 10 mg/kg Sabirnetug or Placebo (Q4W) 10mg COHORT 6: 60 mg/kg Sabirnetug or Placebo (Q4W) 60mg COHORT 7: 25 mg/kg Sabirnetug or Placebo (Q2W)* ≥ 1wk ≥ 1wk ≥ 1wk ≥ 1wk ≥ 1wk ≥ 1wk 25mg ≥ 1wk INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD Patients 15
Sabirnetug drug specific capture (anti-sabirnetug idiotype mAb) 16 Target Engagement Assessed by Measuring Sabirnetug-AO Complex in CSF AO selective detection (anti-A mAb) Only Sabirnetug-AO complex is measurable • Novel assay configuration tailored to selectively detect sabirnetug-AβO complex in CSF as direct measure of target engagement • Translated for clinical use from a preclinical assay developed by Merck that showed sabirnetug engages target AβOs in transgenic mouse brain (tg2576) in dose dependent manner MSD S-Plex (Turbo) Immunoassay TARGET ENGAGEMENT
Target Engagement of Sabirnetug with AβOs is Dose Proportional 17 Single Dose Cohorts Multiple Dose Cohorts* 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg 0 10 20 30 ACU193 IV Infusion Dose C S F A C U 1 9 3 -A β O li g o m e r C o m p le x ( A U /m L ) a t V is it 8 ( D a y 2 1 ) *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar infarct). TARGET ENGAGEMENT p = 0.001 p = 0.03 p = 0.0007No Significant Differences
Doses Approaching Maximal Target Engagement Support Sabirnetug AO Mechanism and Helped Guide Dose Selection for Next Study Phase 18 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Emax: 22.71 AU/mL Complex EC50: 136 ng/mL sabirnetug *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar infarct). 0 600 1200 1800 0 10 20 30 CSF [ACU193] (ng/mL) A C U 1 9 3 -A β O C o m p le x ( A U /m L ) SAD 2 mg/kg SAD 10 mg/kg SAD 25 mg/kg SAD 60 mg/kg MAD 10 mg/kg Q4W MAD 60 mg/kg Q4W MAD 25 mg/kg Q2W Sabirnetug- AO Complex Target Engagement TARGET ENGAGEMENT
Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Reductions in Plaque Load After Three Doses at 63 or 70 days 19 Plaque load based on florbetapir PET 0 15 30 45 60 75 0 25 50 75 100 125 25 mg/kg Q2W MAD Days C e n ti lo id s 20 21 22 23 24 25 26 27 0 15 30 45 60 75 0 25 50 75 100 125 60 mg/kg Q4W MAD Days C e n ti lo id s 28 29 30 31 32 33 34 35 25 mg/kg Q2W MAD 60 mg/kg Q4W MAD Mean reduction in amyloid plaque ∆ (absolute value, centiloids) 13.7 ∆ (%, centiloids) 20.6% Mean reduction in amyloid plaque ∆ (absolute value, centiloids) 18.1 ∆ (%, centiloids) 25.6% PLAQUE REDUCTION
Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque at Similar Rate and Magnitude to Lecanemab at Comparable Timepoints 6% slowing of cognitive decline 8% slowing of cognitive decline -2% slowing of cognitive decline 22% slowing of cognitive decline 27% slowing of cognitive decline 23% slowing of cognitive decline 29% slowing of cognitive decline E ff ic a cy a ch ie v e d Mean reduction in amyloid plaque (centiloids)* Acumen Pharmaceuticals, data on file; van Dyck (2023), NEJM (amyloid PET reduction estimated from graphs). *There have been no head-to-head clinical trials between the product candidates listed above. Study designs and protocols for each product candidate were different, and as a result, results may not be comparable between product candidates. 20 PLAQUE REDUCTION
Sabirnetug Serum Exposure is Dose Proportional Without Accumulation 21 Single Dose Cohorts Multiple Dose Cohorts PHARMACOKINETICS Estimated serum terminal T1/2 of 5-7 days
Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional 22 Single Dose Cohorts Multiple Dose Cohorts* *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar infarct). PHARMACOKINETICS
Importance of Key Fluid Biomarkers Associated with AD Pathology 23 Tau Pathology: pTau181 pTau217 Neuronal Injury: Total tau Synaptic Injury: Neurogranin VAMP2 Amyloid Pathology: A 42/40 Astrocytic Activation: GFAP • Biomarkers from cerebrospinal fluid and plasma capture neuronal, synaptic, and axonal injury and reflect the cumulative outcome of different pathological substrates in AD1 • Evidence suggests that biomarkers are likely to be better predictors of the underlying pathology of AD than imaging alone2 • After just three administrations of sabirnetug, patients with early AD demonstrated improvements in biomarkers associated with AD pathology 1. Tarawneh, R. Biomarkers: Our Path Towards a Cure for Alzheimer Disease. Biomarker Insights Volume 15: 1–15. 2020; 2. Blennow K, Zetterberg H. The Past and the Future of Alzheimer's Disease Fluid Biomarkers. J Alzheimers Dis. 2018;62(3):1125-1140. A oligomer Amyloid plaque
Consistent Improvement in CSF Amyloid, Tau and Synaptic Biomarkers Indicate Downstream Pharmacology of Sabirnetug After Only Three Doses 24 CSF BIOMARKERS pTau181 NeurograninA 42/40 Ratio VAMP2 Tau pathologyAmyloid pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo (PBO); p-values from unpaired, 2-sided Student’s t test
Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W 25 M A D P B O 10 m g/k g Q 4W 25 m g/k g Q 2W 60 m g/k g Q 4W -100 -50 0 50 100 150 P la s m a G F A P (% c h a n g e f ro m b a s e li n e ) M A D P B O 10 m g/k g Q 4W 25 m g/k g Q 2W 60 m g/k g Q 4W -50 0 50 100 P la s m a p T a u 1 8 1 (% c h a n g e f ro m b a s e li n e ) M A D P B O 10 m g/k g Q 4W 25 m g/k g Q 2W 60 m g/k g Q 4W -100 -50 0 50 100 150 P la s m a p T a u 2 1 7 (% c h a n g e f ro m b a s e li n e ) 1 -6 w k p o st -d o si n g • Plasma measurements of glial fibrillary acidic protein (GFAP), pTau181, and pTau217 in 10 mg/kg Q4W & 60 mg/kg Q4W groups were lower than placebo • More impact to fluid biomarkers was observed with longer dosing duration o The 25 mg/kg Q2W cohort differed in dose and sample timing, with drug on board for less time than the 10 mg/kg & 60 mg/kg Q4W cohorts PLASMA BIOMARKERS pTau181GFAP pTau217 A D P ro g re ssio n N o rm a liz a tio n n = 8 subjects/treated group; 6 subjects in pooled placebo (PBO); p-values from unpaired, 2-sided Student’s t test
Sabirnetug Demonstrates Potential for Best-in-Class Safety Compelling Overall Safety Profile, with Low Incidence of ARIA-E 26 SAFETY ✓ Limited incidence of ARIA-E • 10 mg/kg Q4W: 1 asymptomatic case • 25 mg/kg Q2W: 1 asymptomatic case • 60 mg/kg Q4W: 2 asymptomatic cases; 1 symptomatic case ✓ No ARIA-E observed in ApoE4 homozygotes (n=6), despite comprising 13% of study • Differentiated from other antibodies that have ARIA-E rates ~30% to ~40% in participants who are E4-homozygotes ✓ Broad therapeutic index with convenient monthly dosing • Safety profile may support attractive benefit/risk option for large portion of patients 5 0 Total ARIA-E cases, or ~10% Cases of ARIA-E in ApoE4 homozygotes N=6 0 Deaths, SAEs Related to Study Drug INTERCEPT-AD Phase 1 Safety Data
Potential for Differentiated Efficacy Potential for Differentiated Safety INTERCEPT-AD Phase 1 Data Support Potential for Sabirnetug to Offer Best-in-Class Efficacy and Safety 27 ✓ Compelling safety profile with low incidence of ARIA-E ✓ Absence of ARIA-E observed in ApoE4 homozygotes ✓ Broad therapeutic index with convenient monthly dosing ✓ First mAb to demonstrate selective target engagement of AβOs (most toxic form of Aβ) ✓ Rapid, significant plaque reduction comparable to the current market front-runners at similar timepoints ✓ Improvement of AD biomarkers in CSF and plasma are a strong indication of downstream effects Key Takeaways from INTERCEPT-AD
Clinical Development Plans & Strategic Considerations
R a n d o m iz a ti o n 1 :1 :1 Sabirnetug 35mg/kg Q4W (n ~180) Sabirnetug 50mg/kg Q4W (n ~180) Placebo Q4W (n ~180) Primary Endpoint Change in iADRS1 at 18 months Secondary Endpoints1 CDR-SB, ADAS-Cog13, ADCS-ADL, AD biomarkers Open label extension Objective: To evaluate the clinical efficacy, safety and tolerability of sabirnetug Patient population: ~540 participants with early AD (MCI or mild dementia due to early AD) ALTITUDE-AD Study Currently Enrolling 1. iADRS: Integrated Alzheimer's Disease Rating Scale; CDR-SB: Clinical Dementia Rating – Sum of Boxes; ADAS-cog: Alzheimer's Disease Assessment Scale – Cognitive Subscale; ADCS-ADL: Alzheimer's Disease Cooperative Study – Activities of Daily Living 29
30© Copyright 2020 Certara, L.P. All rights reserved. Simulated CSF Target Engagement at Steady-State for ALTITUDE-AD Doses CSF target engagement was simulated at a candidate list of doses given Q4W at steady-state • Notable diminishing differentiation as dose increases • Doses were selected with peak- trough variation in mind: select doses based on trough (end of dosing interval) CSF engagement upper dose: 50 mg/kg Q4W lower dose: 35 mg/kg Q4W Ph2 Dosing Strategy (ALTITUDE-AD) TIME 30
Sabirnetug Subcutaneous Formulation Under Development in Collaboration with Halozyme Potential to Broaden Patient Access and Increase Treatment Convenience • Announced partnership with Halozyme in November 2023 to develop subcutaneous dosing option for sabirnetug • Halozyme’s drug delivery technology, ENHANZE®, is commercially validated in eight approved therapies available in 100+ countries, with >800,000 patients treated • Current sabirnetug potential target product profile inclusive of no more than single weekly injection Phase 1 bioavailability study ongoing to compare the pharmacokinetics of subcutaneous form of sabirnetug to the IV form 31
Population: Ongoing Phase 1 Subcutaneous Healthy Volunteer Study Topline Results Expected in Q1 2025 Output: IV dose (1/month) (n = 12) • Safety • Subcutaneous bioavailability • Information on flat dosing Subcutaneous dose (1/week) (n = 16) • Healthy volunteers • Age matched to AD population in sabirnetug Phase 1 (INTERCEPT-AD) study
Acumen Leadership Team Experienced in AD/Neuro Drug Development Acumen team has decades of experience in Alzheimer’s drug discovery and development JANICE HITCHCOCK, PHD VP, Regulatory Affairs PAUL SHUGHRUE, PHD VP, Research & Strategy JASNA JERECIC, PHD Analytical Methods Leader, Research Scientist ERIC SIEMERS, MD Chief Medical Officer MATT ZUGA Chief Financial Officer & Chief Business Officer RUSSELL BARTON Chief Operating Officer DANIEL O'CONNELL Chief Executive Officer LIEAN SCHENK VP, Head of CMC SIEW TIN GAN Head of Clinical Operations 33 DEREK MEISNER, JD Chief Legal Officer JULIE BOCKENSTETTE Executive Vice President, Head of HR JAMES DOHERTY, PHD President & Chief Development Officer AMY SCHACTERLE, PHD Chief Regulatory Officer & Head of Quality
Sabirnetug IP & Market Exclusivity • Exclusive, perpetual, irrevocable, worldwide, royalty-free license from Merck to its Amyloid Derived Diffusible Ligand (ADDL) IP including issued sabirnetug patents • Sabirnetug Global IP estate: ✓ Issued patents in 19 countries ✓ Composition of matter patents and methods of use run into July 2031 ✓ Patent term extensions may be available, 3-5 years depending on jurisdiction • Biologics market exclusivity is expected for sabirnetug as a novel biologic drug ✓ US provides 12 years market exclusivity for novel biologics ✓ Europe provides 10 years of market exclusivity for novel biologics 34
Milestones Achieved in 2024 and Anticipated in 2025 ~$259M Cash, cash equivalents and marketable securities as of Sept. 30, 2024 35 MILESTONES STATUS/ EXPECTED TIMING Initiation of ALTITUDE-AD Phase 2 trial ✓ Initiation of Phase 1 subcutaneous trial ✓ Expected Phase 1 subcutaneous topline results 1Q25 Expected completion of enrollment of ALTITUDE-AD 1H25 We believe that Acumen has the expertise and resources to advance sabirnetug into the first half of 2027
Summary 36 ✓ Significant and growing Alzheimer's population in need of additional treatment options ✓ Sabirnetug demonstrates high selectivity for toxic AβOs in AD patients ✓ Positive Phase 1 data strengthen potential for sabirnetug to offer best-in-class efficacy and safety ✓ Phase 2 IV study and Phase 1 subcutaneous study ongoing Key Takeaways Next Steps Anticipate Phase 1 subcutaneous healthy volunteer topline results in Q1 2025 Anticipate completion of enrollment in Phase 2 ALTITUDE-AD study in H1 2025
Appendix www.acumenpharm.com 37
Highly selective for Aβ oligomers versus Aβ monomers Even in the presence of a large excess of Aβ monomer, binding of sabirnetug to AβOs is unchanged Binding of sabirnetug to AβOs >500x binding to Aβ monomer Log [Competing Antigen] μM Sabirnetug Selectivity Sabirnetug Selectivity in presence of 5μM monomeric Aβ ACU193 Log μM Sabirnetug is the First mAb Developed to Selectively Target AβOs Sabirnetug selective for binding to AβOs is preserved even in the presence of a large excess of Aβ monomers – such as what is present in the brain, thus limiting ‘target distraction’ 38
39 Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ Broad AβO size distribution recognized by sabirnetug in human AD brain Sabirnetug dose dependently binds to AβOs in brain tissue from Tg2576 mice Data from lab of William Klein, NU, 2018 Merck internal data, 2011 0 0.2 0.4 0.6 0.8 1 1.2 1101001000 R e la ti v e A β O Im m u n o re a ct iv it y w it h S a b ir n e tu g Molecular Weight (kDa) ~3-8 mers~18-100 mers
1. Prevention of hippocampal LTP impairment Functional Consequences of AβO Clearance: Restoring Plasticity 40 • Aβ at 50 nM markedly reduced HFS-induced LTP in wildtype slices • Pre-treatment with ACU3B3 oligomer-selective antibody prevented Aβ1-42-induced LTP deficits Time course of LTP induction From manuscript in prep; data collected by lab of Gerhard Rammes, University of Regensburg, Max-Planck Institute of Psychiatry, Germany
Functional Consequences Following ACU3B3 Treatment 41 • ACU3B3 (murine oligomer selective antibody) treatment prior to plaque pathology leads to reduced amyloid deposition in J20 Tg model (5-7 months) • Treatment effects are less prominent in aged animals (16-23 months) • Evidence of synaptic recovery in advanced stages of pathology in contrast to minor effects on plaque deposition From manuscript in prep; data collected by lab of Jorge Palop, Gladstone Institute 2. Reduced amyloid deposition and increased spine density