UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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| Item 2.02 | Results of Operations and Financial Condition. |
On November 14, 2022, Acumen Pharmaceuticals, Inc. (the “Company”) reported financial results and business highlights for the quarter ended September 30, 2022. 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 14, 2022, 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. 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 | Earnings Press Release, dated November 14, 2022. | |
| 99.2 | Corporate Presentation, dated November 2022. | |
| 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 14, 2022 | By: | /s/ Matthew Zuga | ||||
| Matthew Zuga | ||||||
| Chief Financial Officer and Chief Business Officer | ||||||
Exhibit 99.1
Acumen Pharmaceuticals Reports Third Quarter 2022
Financial Results and Business Highlights
| • | INTERCEPT-AD, a Phase 1 clinical trial of ACU193 in patients with early Alzheimer’s disease continues to progress |
| • | Acumen anticipates completing enrollment in the first quarter of 2023 and reporting topline data from this trial in the second half of 2023 |
| • | ACU193 was granted Fast Track designation from the U.S. FDA for the treatment of early Alzheimer’s disease |
| • | Cash, cash equivalents and marketable securities of $200.2 million as of Sept. 30, 2022 expected to be sufficient to support clinical and operational goals through 2025 |
| • | Company to host conference call and webcast today at 4:30 p.m. ET |
Charlottesville, Va. and Carmel, In., Nov. 14, 2022 – Acumen Pharmaceuticals, Inc. (NASDAQ: ABOS), a clinical-stage biopharmaceutical company focused on the development of novel targeted therapeutics for Alzheimer’s disease (AD), today reported financial results for the third quarter of 2022 and provided a business update.
“During the third quarter, we remained focused on executing INTERCEPT-AD, our Phase 1 clinical trial of ACU193 in patients with early AD. We are pleased with the rate of progress in the study in the quarter, which is a testament to our team’s efforts and the therapeutic promise of ACU193. We believe that our recent receipt of Fast Track designation from the FDA also reflects the clinical potential of ACU193 and underscores the high unmet need for additional disease-modifying treatments in the Alzheimer’s patient community,” said Daniel O’Connell, President and Chief Executive Officer of Acumen. “We remain well capitalized through 2025 based on our current business plans and anticipate achieving the completion of study enrollment in INTERCEPT-AD in the first quarter of 2023 and topline results in the second half of 2023.”
Dr. Eric Siemers, M.D., Chief Medical Officer of Acumen said, “ACU193 is the first clinical-stage monoclonal antibody designed to selectively target toxic soluble amyloid beta oligomers. Many studies have shown these soluble species disrupt neuronal function and initiate the process of neurodegeneration leading to AD. Underscoring our goal to expeditiously advance ACU193, the recent publication of our clinical development plan in the Journal for Prevention of Alzheimer’s Disease details incorporation of several advancements in AD research methodology, including an adaptive Phase 2/3 trial design. Our recent Fast Track designation should also allow for close engagement with the FDA as we seek the most efficient path to develop ACU193 as a potential better and differentiated therapeutic option for patients living with AD.”
Recent Business Highlights and Anticipated Milestones
ACU193 Clinical Development
| • | INTERCEPT-AD enrollment remains ongoing. Patient screening and enrollment is continuing for INTERCEPT-AD, with 17 active clinical trial sites currently recruiting patients. |
| • | The study has progressed as planned in the protocol and blinded safety data for ACU193 are consistent with our expectations. |
| • | Acumen anticipates completing enrollment in the first quarter of 2023 and reporting topline data from this trial in the second half of 2023. |
| • | In October 2022, Fast Track designation was granted by the U.S. Food and Drug Administration (FDA) for ACU193 for the treatment of early Alzheimer’s disease. Fast Track Designation is granted to drugs being developed for the treatment of serious or life-threatening conditions where there is an unmet medical need. A drug candidate that receives Fast Track designation is eligible for more frequent communication with the FDA throughout the drug development process for the purpose of expediting the drug’s development, review, and potential approval. |
| • | In October 2022, the development rationale and clinical development plan for ACU193 was published in the Journal for Prevention of Alzheimer’s Disease (JPAD). It outlines the design of the ongoing Phase 1 INTERCEPT-AD trial for ACU193 and planned criteria for advancing to a Phase 2/3 clinical trial based on recent advancements in clinical research on Alzheimer’s disease. |
Corporate
| • | In September 2022, Derek Meisner joined Acumen as Chief Legal Officer. Mr. Meisner brings more than two decades of experience providing counsel to public and private companies across key legal and operational functions, including regulatory compliance, debt and equity financings, mergers and acquisitions, strategic partnerships, and corporate governance. Mr. Meisner previously served in a similar capacity at two other publicly-traded biotechnology companies. He also served as the General Counsel of RA Capital Management and as a Branch Chief in the Division of Enforcement of the U.S. Securities and Exchange Commission. |
Third Quarter 2022 Financial Results
| • | Cash Balance. As of September 30, 2022, cash, cash equivalents and marketable securities totaled $200.2 million, compared to cash, cash equivalents and marketable securities of $225.9 million as of December 31, 2021. The decrease in cash is related to funding ongoing operations. |
| • | Research and Development (R&D) Expenses. R&D expenses were $8.3 million for the three-month period ended September 30, 2022, compared to $1.8 million for the three-month period ended September 30, 2021. The increase in research and development expenses was primarily due to increased costs related to our ongoing clinical trial, which was initiated in 2021 and started enrolling patients in the second half of 2021, as well as nonclinical research and development activity. |
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| • | General and Administrative (G&A) Expenses. G&A expenses were $3.1 million for the three-month period ended September 30, 2022, compared to $2.1 million for the three-month period ended September 30, 2021. The increase in general and administrative expenses was primarily due to increased costs related to personnel, accounting, marketing, recruiting and travel expenses. |
| • | Loss from Operations. Losses from operations were $11.4 million for the three-month period ended September 30, 2022, compared to $3.9 million for the three-month period ended September 30, 2021. This increase was due to the increased R&D and G&A expenses over the prior year period. |
| • | Net Loss. Net loss was $10.7 million for the three-month period ended September 30, 2022, compared to $3.9 million for the three-month period ended September 30, 2021. The increase was due to the increased R&D and G&A expenses over the prior year period. |
Conference Call Details
Acumen will host a conference call and live audio webcast today, Nov. 14, 2022, at 4:30 p.m. ET.
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 ACU193
ACU193 is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble AßOs, which Acumen believes are the most toxic and pathogenic form of Aß, relative to Aß monomers and amyloid plaques. Soluble AßOs have been observed to be potent neurotoxins that bind to neurons, inhibit synaptic function and induce neurodegeneration. By selectively targeting toxic soluble AßOs, ACU193 aims to directly address what a growing body of evidence indicates is a primary underlying cause of the neurodegenerative process in AD. ACU193 has been granted Fast Track designation for the treatment of early Alzheimer’s disease by the U.S. Food and Drug Administration.
About INTERCEPT-AD
Approximately 62 individuals with early AD (mild cognitive impairment or mild dementia due to AD) are expected to be randomized into this double-blind, placebo-controlled, first-in-human study of ACU193.
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INTERCEPT-AD is designed to establish safety and proof of mechanism. It consists of single-ascending-dose (SAD) and multiple-ascending-dose (MAD) cohorts and is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and target engagement of intravenous doses of ACU193. The study is enrolling at multiple investigative sites located in the United States. More information can be found on www.clinicaltrials.gov, NCT identifier NCT04931459.
About Acumen Pharmaceuticals, Inc.
Acumen, headquartered in Charlottesville, VA, with clinical operations based in Carmel, IN, is a clinical stage biopharmaceutical company developing a novel disease-modifying approach to treat Alzheimer’s disease. Acumen’s scientific founders pioneered research on AßOs, which a growing body of evidence indicates are primary triggers of Alzheimer’s disease pathology. Acumen is currently focused on advancing its investigational product candidate, ACU193, a humanized monoclonal antibody that selectively targets toxic soluble AßOs in INTERCEPT-AD, a Phase 1 clinical trial involving early Alzheimer’s disease patients. 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, 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, Acumen’s ability to achieve its strategic and financial goals, including its projected use of cash, cash equivalents and marketable securities and the sufficiency of its cash resources, and the therapeutic potential of Acumen’s product candidate, ACU193, including its potential for improved safety and efficacy as compared to other monoclonal antibodies in development and expectations with respect to blinded safety data and the potential of soluble amyloid beta (Aß) species to be more effective or safer disease-modifying therapeutic targets, as well as the expectations concerning the INTERCEPT-AD trial and criteria for Acumen’s planned Phase 2/3 clinical trial, and the potential benefits of receiving Fast Track designation from the FDA. 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, 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2021, and future filings with the SEC, including Acumen’s Quarterly Report on Form 10-Q for the quarter ended and September 30, 2022. 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.
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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, 2022 | December 31, 2021 | |||||||
| (unaudited) | ||||||||
| ASSETS |
||||||||
| Current assets |
||||||||
| Cash and cash equivalents |
$ | 157,540 | $ | 122,162 | ||||
| Marketable securities, short-term |
42,654 | 72,075 | ||||||
| Prepaid expenses and other current assets |
2,366 | 4,424 | ||||||
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|
|
|||||
| Total current assets |
202,560 | 198,661 | ||||||
| Marketable securities, long-term |
— | 31,619 | ||||||
| Property and equipment, net |
142 | 36 | ||||||
| Deferred offering costs |
337 | — | ||||||
| Right-of-use asset |
133 | — | ||||||
| Other assets |
92 | 14 | ||||||
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|||||
| Total assets |
$ | 203,264 | $ | 230,330 | ||||
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| LIABILITIES AND STOCKHOLDERS’ EQUITY |
||||||||
| Current liabilities |
||||||||
| Accounts payable |
$ | 2,084 | $ | 1,088 | ||||
| Accrued expenses and other current liabilities |
4,396 | 4,059 | ||||||
| Operating lease liability, current portion |
133 | — | ||||||
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|
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|||||
| Total current liabilities |
6,613 | 5,147 | ||||||
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|
|||||
| Total liabilities |
6,613 | 5,147 | ||||||
| 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, 2022 and December 31, 2021 |
— | — | ||||||
| Common stock, $0.0001 par value; 300,000,000 shares authorized and 40,503,124 and 40,473,270 shares issued and outstanding as of September 30, 2022 and December 31, 2021, respectively |
4 | 4 | ||||||
| Additional paid-in capital |
355,173 | 352,981 | ||||||
| Accumulated deficit |
(157,561 | ) | (127,571 | ) | ||||
| Accumulated other comprehensive loss |
(965 | ) | (231 | ) | ||||
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|||||
| Total stockholders’ equity |
196,651 | 225,183 | ||||||
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| Total liabilities and stockholders’ equity |
$ | 203,264 | $ | 230,330 | ||||
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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, | |||||||||||||||
| 2022 | 2021 | 2022 | 2021 | |||||||||||||
| Operating expenses |
||||||||||||||||
| Research and development |
$ | 8,309 | $ | 1,800 | $ | 21,615 | $ | 6,632 | ||||||||
| General and administrative |
3,062 | 2,135 | 9,374 | 4,537 | ||||||||||||
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| Total operating expenses |
11,371 | 3,935 | 30,989 | 11,169 | ||||||||||||
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| Loss from operations |
(11,371 | ) | (3,935 | ) | (30,989 | ) | (11,169 | ) | ||||||||
| Other income (expense) |
||||||||||||||||
| Change in fair value of preferred stock tranche rights liability and preferred stock warrant Liability |
— | — | — | (81,157 | ) | |||||||||||
| Interest income, net |
663 | 14 | 1,000 | 22 | ||||||||||||
| Other income, net |
(2 | ) | 19 | (1 | ) | 47 | ||||||||||
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| Total other income (expense) |
661 | 33 | 999 | (81,088 | ) | |||||||||||
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| Net loss |
(10,710 | ) | (3,902 | ) | (29,990 | ) | (92,257 | ) | ||||||||
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| Other comprehensive loss |
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| Unrealized loss on marketable securities |
— | (28 | ) | (734 | ) | (28 | ) | |||||||||
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| Comprehensive loss |
$ | (10,710 | ) | $ | (3,930 | ) | $ | (30,724 | ) | $ | (92,285 | ) | ||||
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| Net loss per common share, basic and diluted |
$ | (0.26 | ) | $ | (0.10 | ) | $ | (0.74 | ) | $ | (7.00 | ) | ||||
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| Weighted-average shares outstanding, basic and diluted |
40,502,860 | 38,266,593 | 40,491,181 | 13,177,983 | ||||||||||||
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Acumen Pharmaceuticals, Inc.
Condensed Statements of Cash Flows
(in thousands)
(unaudited)
| Nine Months Ended September 30, | ||||||||
| 2022 | 2021 | |||||||
| Cash flows from operating activities |
||||||||
| Net loss |
$ | (29,990 | ) | $ | (92,257 | ) | ||
| Adjustments to reconcile net loss to net cash used in operating activities: |
||||||||
| Depreciation |
20 | 1 | ||||||
| Change in fair value of preferred stock tranche rights liability and preferred stock warrant liability |
— | 81,157 | ||||||
| Stock-based compensation expense |
2,173 | 557 | ||||||
| Amortization of premiums and accretion of discounts on marketable securities, net |
575 | (6 | ) | |||||
| Amortization of right-of-use asset |
100 | — | ||||||
| Changes in operating assets and liabilities: |
||||||||
| Prepaid expenses and other current assets |
2,058 | (4,297 | ) | |||||
| Other assets |
(78 | ) | (13 | ) | ||||
| Accounts payable |
996 | (149 | ) | |||||
| Operating lease liability |
(100 | ) | — | |||||
| Accrued expenses and other current liabilities |
296 | 685 | ||||||
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| Net cash used in operating activities |
(23,950 | ) | (14,322 | ) | ||||
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| Cash flows from investing activities |
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| Purchases of marketable securities |
(12,129 | ) | (94,095 | ) | ||||
| Proceeds from maturities and sales of marketable securities |
71,860 | — | ||||||
| Purchases of property and equipment |
(126 | ) | (14 | ) | ||||
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| Net cash provided by (used in) investing activities |
59,605 | (94,109 | ) | |||||
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| Cash flows from financing activities |
||||||||
| Proceeds from issuance of Series B milestone shares, net of issuance costs |
— | 30,031 | ||||||
| Proceeds from exercise of Series A-1 warrant |
— | 1,250 | ||||||
| Proceeds from exercise of common stock warrants |
— | 614 | ||||||
| Payments for deferred offering costs |
(296 | ) | 168,559 | |||||
| Proceeds from the exercise of stock options |
19 | 2 | ||||||
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| Net cash provided by (used in) financing activities |
(277 | ) | 200,456 | |||||
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| Net change in cash and cash equivalents |
35,378 | 92,025 | ||||||
| Cash and cash equivalents at the beginning of the period |
122,162 | 43,777 | ||||||
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| Cash and cash equivalents at the end of the period |
$ | 157,540 | $ | 135,802 | ||||
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| Supplemental disclosure of noncash investing and financing activities |
||||||||
| Right-of-use asset obtained in exchange for operating lease liabilities |
$ | 233 | $ | — | ||||
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| Deferred offering costs in accrued expenses and other current liabilities |
$ | 41 | $ | — | ||||
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| Conversion of convertible preferred stock into common stock upon initial public offering |
$ | — | $ | 174,504 | ||||
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| Reclassification of preferred stock tranche rights liability upon share issuance |
$ | — | $ | 81,190 | ||||
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| Reclassification of warrant liability upon exercise of preferred stock warrant |
$ | — | $ | 5,380 | ||||
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Exhibit 99.2 Corporate Presentation November 2022
Forward-Looking Statements 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, Acumen’s ability to achieve its strategic and financial goals, including its projected use of cash, cash equivalents and marketable securities and the sufficiency of its cash resources, and the therapeutic potential of Acumen’s product candidate, ACU193, including its potential for improved safety and efficacy as compared to other monoclonal antibodies in development, as well as the expectations concerning the INTERCEPT-AD trial and Acumen’s planned Phase 2/3 clinical trial, including the expected timing of initiation, enrollment and reporting data, and risks and uncertainties relating to the progression and duration of the COVID-19 pandemic and responsive measures thereto and related effects on Acumen. 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 Form 10-K for the year ended December 31, 2021, Acumen’s Form 10-Q for the quarter ended September 30, 2022, 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. 2
Advancing a Potential Best-/First-In-Class Antibody Product for Early Alzheimer’s disease (AD) $ Scientific Experienced Strong Phase 1 Clinical Alzheimer’s ACU193: First, Represents an Consensus Clinical-Stage Leadership Team Balance Sheet: Trial in Early AD Enormous Market Supports Amyloid- Monoclonal Comprised of ~$200M in cash Patients Ongoing Proof of Driven by High Beta Oligomers Antibody (mAb) to Industry Leaders at 30-Sep-22 (AβOs) as the and several with Mechanism Unmet Need and Selectively Target July 2021 IPO Most Toxic Form AD clinical Drug, Target Recent Scientific AβOs with ~$184M Gross and Regulatory of Aβ and a Novel Promising Pre- Development, and Engagement RA Capital Momentum Target for Effective Clinical Evidence Regulatory Safety Data Deep Track Topline Results AD Treatment Supporting its Expertise from Eli Sands Capital Expected Differentiation Lilly & Co. PBM Capital 2H 2023 We believe that Acumen has the organizational expertise and fiscal resources to advance ACU193 through 2025. 3
Acumen Business Strategy: 2022-2025 → Rapidly advance ACU193 through clinical development in patients with early AD; → Evaluate combination approaches to complement our core ACU193 monotherapy strategy; → Selectively explore potential of ACU193 for other diseases; → Expand our product portfolio by in-licensing and/or developing additional candidates and/or alternative formulations for, or derivatives of, ACU193; and → Optimize value of ACU193 and future drug candidates in major markets. 4
INTERCEPT-AD Trial Update – 3Q 2022 • INTERCEPT-AD: Phase 1 clinical trial of ACU193 in patients with early Alzheimer’s disease (AD) (RCT) → Trial enrollment ongoing at 17 active sites ▪ Enrollment completion expected in 1Q 2023 → Topline results (proof-of-mechanism) following full database lock expected in 2H 2023 ▪ Safety / ARIA-E ▪ PK ▪ Target engagement • Phase 2/3 ‘Ready’ Activities → Chronic GLP toxicity study in-life phase completed; final study report expected in 1Q 2023 → Well-positioned to efficiently scale manufacturing to have sufficient drug supply to meet the requirements of our current development plan → Confirmation of ACU193’s IgG2 antibody subclass; maintain expectation that reduced effector function should favorably influence ACU193 safety outcomes 5
AD, Amyloid & Abeta Oligomers
Alzheimer’s Pathophysiology Build-up of amyloid-beta (Ab) is believed to lead to neurodegeneration and dementia Previous and current anti-amyloid and related drug targets have attempted to intervene g secretase Amyloid β (Aβ) Inhibitors Anti- Ab monomer mAb Amyloid plaque Aβ monomers Anti-amyloid plaque mAb Aβ fibrils BACE inhibitors Aβ oligomers Anti-Ab Symptomatic and oligomer mAb neuroprotective treatments Tau destabilization Tau directed treatments Data indicate that soluble amyloid β oligomers (AbOs) are the most toxic species and should be preferentially targeted for removal. 7
What is an Aβ Oligomer? AbOs May Consist of 2 to >200 Ab Peptides Figure 1. AbOs composed of 3 (a) and 18 (b) Ab peptides are depicted below. (a) (b) ____________________ Source: Kelley et al. J Chem Physics 2008. Quaternary structures of Aβ oligomers, protofibrils, and fibrils Figure 2. Atomic force microscopy images of representative steps of amyloid aggregation: (A) oligomers; (B) protofibrils; (C) mature fibrils. Scan size 1.0 µm. Z range (A) 8.0 nm; (B) 15 nm; (C) 20 nm. ____________________ Source: Relini et al. Biomolecules 2014. 8
Scientific Evidence Supports AβO Hypothesis Predominant forms of Ab in AD: Ab monomers (non-toxic), AbOs, Ab fibrils, and amyloid plaques Aβ monomers Aβ oligomers AβOs bind to neurons, impair synaptic function, contribute to Amyloid plaque impairment of memory and cognition, and plaques serve induce tau hyper phos- as a reservoir phorylation of Abeta and may induce toxicity due to Inflammatory Aβ fibrils responses microglial and astrocytic activation Growing understanding of disease mechanisms indicate that AβOs are the most toxic Aβ species and have the potential to be an ideal target for effective AD therapy ____________________ Sources: Adopted From: Selkoe, Hardy EMBO Molecular Medicine, 2016 Cline, Journal of Alzheimer’s Disease, 2018 The only approved antibody product for AD and several late stage products preferentially target amyloid plaques with only limited effects on AβOs. Acumen’s drug candidate ACU193 targets AbOs. 9
ACU193 Positioning Relative to Late-Stage and Approved Anti-Ab/Plaque mAbs bapineuzumab* solanezumab crenezumab IgG1, Ph3 stop IgG1, Ph3 stop, A4, DIAN negative IgG4, Ph3 stop, API negative Aβ oligomers Aβ protofibrils ACU193 aducanumab* lecanemab donanemab* gantenerumab* IgG2, Ph1 IgG1 IgG1 IgG1 IgG1 1 1 AAP filed, PDUFA Jan-2023 Approved (AAP ), Ph2 positive Ph3 4Q22 1 Ph3 positive 3Q22 CMS CED Filing AAP 4Q22 commercial stop Ph3 1H23 ACU193’s high selectivity for AβOs combined with an expected lack of ARIA-related safety concerns is anticipated to provide better safety and efficacy compared to anti-plaque mAbs * IgG1 monoclonal antibodies that bind amyloid plaque are associated with high rates of ARIA-E. See e.g., Plotkin, Neurobiology of Disease, 2020. • There have been no head-to-head clinical trials between any of the product candidates listed above. Study designs and protocols for each product candidate were different, and results may not be comparable between product candidates. 1 AAP: Accelerated approval 10
Positive Signals and Proof of Concept From Recent Phase 2-3 Anti-Amyloid mAb AD Studies Percent Slowing of Cognitive/Functional Decline* solanezumab aducanumab aducanumab lecanemab lecanemab EXPEDITION 3 EMERGE ENGAGE donanemab BAN2401 Clarity-AD + Measured Outcome** (Phase 3) (Phase 3) (Phase 3) (Phase 2) (Phase 2) (Phase 3) (p<0.01) ADAS-cog -11% -27% -12% -39% -47% (p<0.01) -15% -40% -18% -23% N.A. ADCS-ADL -15% -23% 2% -23% -26% -27% CDR-SB (p<0.01) MMSE -13% -15% 3% -21% N.A. (p<0.01) -11% N.A. N.A. -32% N.A. iADRS * Percent Slowing = P[1- [(endpoint score-baseline score)active/(endpoint score-baseline score)placebo]]*100%*(-1) ** ADAS-cog: Alzheimer's Disease Assessment Scale – Cognitive Subscale ADCS-ADL: Alzheimer's Disease Cooperative Study – Activities of Daily Living CDR-SB: Clinical Dementia Rating – Sum of Boxes MMSE: Mini-Mental State Examination iADRS: Integrated Alzheimer's Disease Rating Scale Note: ENGAGE Post-Protocol Version 4 – at least 14 doses of 10 mg/kg, High Dose cohort achieved 27% improvement on CDR-SB compared to placebo We're looking for a biological foothold against Alzheimer's that we can build on. And so, these effects are small, but I think ++ they are meaningful, and I hope they're the beginning of a process that we can add to.” - Stephen Salloway, MD of Brown University ____________________ + Source: Eisai/Biogen press release September 28, 2022. ++Source: Wall Street Journal, Biogen Details Case for Controversial Alzheimer's Drug, published December 5, 2019. See e.g., Plotkin, Neurobiology of Disease, 2020. There have been no head-to-head clinical trials between any of the product candidates listed above. Study designs and protocols for each product candidate were different, and results may not be comparable between product candidates. 11
Anti-Plaque mAbs Demonstrate Dose-Related ARIAs That Will Likely Limit Their Use Percent of ARIA Events for Anti-Aβ/plaque mAbs* TARGETING TARGETING TARGETING AB MONOMERS AMYLOID PLAQUES PROTOFIBRILS solanezumab aducanumab aducanumab lecanemab lecanemab donanemab EXPEDITION 3 EMERGE ENGAGE BAN2401 BAN2401 (Phase 2) + (Phase 3) (Phase 3) (Phase 3) (Phase 2) (Phase 3) PC Treated PC Low High PC Low High PC Treated PC High PC Treated 0.2% 0.1% 2.2% 26.1% 34.4% 3.0% 25.6% 35.7% 0.8% 27.5% 0.8% 9.9% 1.7% 12.5% ARIA-E ApoE ε4 carriers 1.9% 29.8% 42.5% 2.4% 28.7% 41.8% 3.6% 44.0% 1.2% 14.6% N.A. N.A. ApoE ε4 non- 2.9% 18.1% 17.9% 4.3% 17.5% 27.7% 0.0% 8.0% N.A. N.A. carriers 10.3% 32.8% 41.2% 9.8% 30.7% 40.3% 8.0% 38.9% N.A. 9.3% 21.5% Any ARIA E or H * PC = Placebo, Low = Low Dose; High = High Dose Shows the absence of ARIA after treatment with antibodies targeting Aβ monomers (solanezumab) in comparison to the increasing presence of ARIA after treatment at increasing dose levels with antibodies targeting amyloid plaques (aducanumab, BAN2401, and donanemab), indicate that ARIA results from the removal of amyloid plaques around blood vessels and likely does not result from treatment with antibodies that target other species of Aβ, i.e. Aβ monomers and AβOs. ARIA-E represents a dose limiting adverse effect for mAbs with amyloid plaque binding. We believe antibodies that avoid ARIA should be safer and more feasible to administer, possibly at higher doses. There have been no head-to-head clinical trials between any of the product candidates listed above. Study designs and protocols for each product candidate were different, and results may not be comparable between product candidates. 12 + Source: Eisai/Biogen press release September 28, 2022 12
ACU193’s High Selectivity for Toxic AβOs, Combined With its Expected Lack of ARIA- Related Safety Concerns, is Anticipated to Provide Superior Efficacy Compared to Peers + TARGET SELECTIVITY SAFETY PROFILE Lack of ARIA-related Company Asset Amyloid plaque Aβ fibrils Aβ monomers Aβ oligomers safety concerns ACU193û untested Expected û ✓ TM Biogen Aduhelm ✓û✓ ✓û Eisai / Biogen lecanemab û ✓û✓ ✓ gantenerumab Roche ✓û✓ ✓û donanemab Lilly untested ûûû ✓ solanezumab* Lilly û ûû✓ ✓ Roche / Genentech crenezumab* ✓ ✓ ✓✓✓ bapineuzumab* Pfizer / Janssenû ✓ ✓✓✓ ____________________ *Phase 3 discontinued for primary AD indication. + There have been no head-to-head trials between any of the product candidates listed above. Study designs and protocols for each product candidate were different, and results may not be comparable between product candidates.. 13
ACU193: Our Differentiated Approach
ACU193 Target Product Profile: Best-in-Class, 1st Line, Anti-AβO, Disease- Modifying Immunotherapy for Early AD DRUG: ACU193 is a humanized, affinity-matured, mAb with high selectivity for toxic AβOs vs. Aβ monomers (>500x) and limited to no binding to amyloid plaques. ACU193 is an IgG2 subclass mAb which lacks inflammatory effector functions of other IgG subclasses. POPULATION: Early AD - Mild Cognitive Impairment and Mild Dementia due to AD (amyloid positive by PET) DOSING: IV infusion every 4 weeks DURATION: Chronic therapy for duration of Early AD VALUE Selectivity for toxic AβOs is expected to provide superior cognitive efficacy and improved PROPOSITION: safety and tolerability relative to non-selective anti-Aβ/plaque mAbs, including: • Slowing the decline of memory and cognition in Early AD • Decreasing AβO induced synaptic and neuronal network toxicity • Slowing disease progression and downstream effects on tau, neurodegeneration, and neuro- inflammation • With expected low rate of ARIA • Potentially effective as stand-alone therapy or in combination with other symptomatic, anti-inflammatory, and/or tau directed therapies 15
ACU193: Extensive Data Package Supporting Development — Nanomolar affinity for AβOs, >500-fold greater selectivity for AβOs over Aβ monomer, with limited or no discernable binding to vascular amyloid or dense core amyloid plaques SELECTIVITY — Binds broad range of endogenous AβOs present in transgenic mice and human AD samples (binds dimers to mid-sized molecular weight AβOs) — Dose-dependent effects in multiple in vitro neuroprotection assays PHARMACOLOGY — Positive memory and behavioral effects in multiple in vivo transgenic mouse models for AD — Brain penetration and biodistribution demonstrated in multiple species PK/PD — Performs like other peripherally administered CNS mAbs — IgG2 subclass lacks inflammatory effector function signaling (FcγR binding) — Nonclinical microhemorrhage studies show no SAFETY increased risk of microhemorrhage — GLP studies demonstrated acceptable safety margin for clinical dosing plans ACU193 is a promising immunotherapy for early AD expected to provide meaningful cognitive and functional benefits, slow disease progression, and offer an attractive safety profile. 16
SELECTIVITY ACU193 is the First mAb Developed to Selectively Target AβOs Highly selective for Aβ oligomers versus Aβ monomers ACU193 Selectivity in presence of ACU193 Selectivity 5μM monomeric Aβ Log [Competing Antigen] μM ACU193 Log μM Even in the presence of a large excess of Aβ monomer, Binding of ACU193 to AβOs >500x binding of ACU193 to AβOs is unchanged binding to Aβ monomer ACU193 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.’ 17
SELECTIVITY ACU193 Has a Greater Preference for AbOs Than Other mAbs Comparison of Aβ species-mAb complex signals across SEC fractions ACU193 binds to a wide range of oligomeric species of Ab that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab). 18
SELECTIVITY ACU193 is Highly Selective for AβOs Versus Aβ Plaques ACU193 staining in human AD brain slices ACU193 (red) binds non-Thioflavin S positive Ab (green) AD Hippocampus AD Hippocampus ThioS/amyloid plaque ACU193/AbOs species ACU193 has little or no binding to thioflavin S positive fibrillar Aβ plaque in human AD brain tissue. ____________________ Sources: E. Cline et al. CTAD 2019. 19
SELECTIVITY PHARMACOLOGY AβOs Bind to Neurons and are Toxic; Mouse Analogue of ACU193 Prevents Toxicity After binding to neurons, AbOs disrupt Long Term Potentiation (LTP) and cause pathologic increases in intracellular calcium that is destructive to cells. ACU3B3 prevents AβO inhibition of ACU3B3 prevents AβO mediated Ca2+ hippocampal LTP ex vivo elevation in cell cultures Control Aβ (50 nM) 42 Aβ (50 nM) + 42 ACU3B3 (100 pM) Note: (1) ACU3B3 is the mouse monoclonal antibody precursor to and equivalent of humanized ACU193 ACU3B3 prevents changes in aberrant neuronal activity thought to underlie memory loss in AD and prevents AbO mediated disruption of calcium homeostasis in neuronal cultures. 20
SELECTIVITY PHARMACOLOGY Treatment of a Transgenic Mouse Model of AD Results in Behavioral Improvements Murine parent version of ACU193 (ACU3B3) was used to treat younger mice with depositing plaque or older mice with abundant plaque MWM swim speed Open field total abnormality distance measurement, (**p<0.02). APP-Veh vs. APP-3B3, *p=0.029. Deficits in younger (5-7 months) transgenic mice are Deficits in older (9-10 months) transgenic mice are markedly reduced with treatment markedly reduced with treatment 21
SELECTIVITY PHARMACOLOGY PK/PD ACU193 Enters the CNS and Binds to AbOs in Transgenic Mice in Dose Dependent Manner ACU193 engages target AβOs in transgenic mouse brain (tg2576) in dose dependent manner. Ability to administer higher doses in patient clinical trials may provide increased target coverage. 22
Clinical Development Plans
(ACU-001) INTERCEPT-AD Trial: Phase 1 Overview TRIAL Randomized Placebo Controlled Phase 1 DESIGN: • Part A : Single-Ascending Doses • Part B : Multiple-Ascending Doses ENROLLMENT Early AD CRITERIA: • Mild Cognitive Impairment and Mild Dementia due to AD (amyloid positive by PET) TRIAL Proof of Mechanism (PoM) OBJECTIVES: — Safety and tolerability — Pharmacokinetics — Target engagement — Biomarkers; cognition (exploratory) For more information on the INTERCEPT-AD trial, see https://clinicaltrials.gov/ct2/show/NCT04931459. 24
INTERCEPT-AD a Randomized Placebo Controlled Phase 1 in Early AD patients 60mg COHORT 4: ≥ 1wk 60 mg/kg ACU193 PART A: or Placebo SINGLE- COHORT 3: ASCENDING DOSE 25mg ≥ 1wk 25 mg/kg ACU193 n = 8 per cohort (32 total) or Placebo COHORT 2: ≥ 1wk 10 mg/kg ACU193 10mg or Placebo ≥ 1wk COHORT 1: 2 mg/kg ACU193 60mg COHORT 7: 2mg or Placebo ≥ 4wk 60 mg/kg ACU193 or Placebo (Q2W) ≥ 1wk 60mg COHORT 6: PART B: 60 mg/kg ACU193 or Placebo (Q4W) MULTIPLE- ASCENDING DOSE COHORT 5: 10 mg/kg ACU193 n = 10 per cohort (30 total) 10mg or Placebo (Q4W) Q2W: Dosing every two weeks; Q4W: Dosing every four weeks. 25
Phase 1 Objectives: Proof of Mechanism – Ability to Move to Phase 2/3 1. SAFETY AND TOLERABILITY • Assessment of ARIA-E • Absence of problematic immunogenicity PROOF OF MECHANISM 2. PHARMACOKINETICS Requirements for Phase 2/3 • Peripheral and Central ✓ Acceptable safety and 3. EVIDENCE OF TARGET ENGAGEMENT tolerability • CSF level of ACU193: AbO complexes (bound) ✓ Show ACU193 gets across the blood brain barrier and into 4. FLUID BIOMARKER EFFECTS central compartment • Phospho-tau, Neurofilament light, et. al. ✓ Target engagement 5. CLINICAL MEASURES (exploratory) • Assessment of clinical cognitive measures, computerized tests (Cogstate Ltd.) 6. MRI EFFECTS (exploratory) • Potential improvements in cerebral blood flow shown with MRI ASL pulse sequence Topline results anticipated in 2H 2023: primary outcomes safety/ARIA-E, PK and target engagement. Detailed study results anticipated to be presented at an Alzheimer’s medical meeting. 26
Cogstate computerized test battery (exploratory) Test Domains tested Time (minutes) International shopping list test Immediate recall 5 (immediate) Cogstate brief battery Attention, working memory, 15 learning International shopping list test (delayed) Delayed recall 1 Groton maze learning test Executive function 7 International digit-symbol substitution test Processing speed 3 Total = 31 Frequency of administration and sensitivity of battery offers improved possibility to observe effects. 27
Arterial Spin Labelling (ASL) as an MRI Measure of Cerebral Blood Flow • Mild cognitive impairment patients show hypoperfusion in parietal cortex, precuneus, posterior cingulate cortex and medial temporal lobe • AD patients show global hypoperfusion, but especially cingulate, precuneus, parietal lobes and inferior frontal regions • Perfusion correlates with several neuropsychological tests • Hypoperfusion can be improved in middle and posterior cingulate cortex with cholinesterase inhibitors and was associated with improvement in ADAS-cog scores 28
ACU193 Development Summary Þ Differentiated profile: Nonclinical data consistent with toxicity of Ab oligomers and selective binding of ACU193 to Ab oligomers Þ Enrollment in a Phase1 study assessing safety, PK, and target engagement is ongoing Þ Although unlikely with this small sample size, the possibility of improvement in cognitive scales, computerized cognitive testing, and cerebral blood flow will also be assessed as exploratory outcomes in the Phase 1 study Þ Anticipate next clinical study, with success in Phase 1, starting as Phase 2 study with potential to expand to Phase 3 registration study based on interim expansion analysis 29
Business Considerations
Acumen Leadership Team Experienced in AD/Neuro Drug Development ERIC SIEMERS, MD JANICE HITCHCOCK, PHD MATT ZUGA DANIEL O'CONNELL Chief Medical Officer VP, Regulatory Affairs Chief Financial Officer & President & CEO Chief Business Officer RUSSELL BARTON ROBERT DEAN, MD, PHD LIEAN SCHENK SIEW TIN GAN Chief Operating Officer Sr. Development Advisor VP, Head of CMC Head of Clinical Operations JASNA JERECIC, PHD DEREK MEISNER, JD Analytical Methods Chief Legal Officer Leader, Research Scientist Acumen team has decades of experience in Alzheimer’s drug discovery and development. 31
ACU193 IP & Market Exclusivity • Exclusive, perpetual, irrevocable, worldwide, royalty-free license from Merck to its Amyloid Derived Diffusible Ligand (ADDL) IP including, issued ACU193 patents • ACU193 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 ACU193 as a novel biologic drug ✓ US provides 12 years market exclusivity for novel biologics ✓ Europe provides 10 years of market exclusivity for novel biologics 32
Acumen is Well Capitalized, With Expected Cash Runway Through 2025 STATUS/ MILESTONES EXPECTED TIMING ~$200M Initiated Ph1 clinical trial INTERCEPT-AD ✓ Cash, cash equivalents and marketable securities as of September 30, 2022 INTERCEPT-AD enrollment complete 1Q 2023 Proof-of-mechanism topline results 2H 2023 We believe that Acumen has the organizational expertise and cash and marketable securities on hand to advance ACU193 through 2025. 33
ABOS: Key Takeaways Massive unmet need in AD, recent favorable trends and cumulative learnings position field for future successes Upcoming sector catalysts 2H22 - 1H23 Differentiated product candidate targeting toxic AbOs Experienced AD drug development team Blue chip investors, very strong balance sheet and cash $ runway with multiple milestones through 2025 Value-inflection clinical data 2H 2023 34
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