# EDGAR Filing Document

**Accession Number:** 0001576885
**File Stem:** 0001193125-23-021525
**Filing Date:** 2023-2
**Character Count:** 35460
**Document Hash:** c25bdc3572262efcc6881a0ce64df9fd
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001193125-23-021525.hdr.sgml**: 20230201

**ACCESSION NUMBER**: 0001193125-23-021525

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 48

**CONFORMED PERIOD OF REPORT**: 20230201

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20230201

**DATE AS OF CHANGE**: 20230201

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Acumen Pharmaceuticals, Inc.
- **CENTRAL INDEX KEY:** 0001576885
- **STANDARD INDUSTRIAL CLASSIFICATION:** BIOLOGICAL PRODUCTS (NO DIAGNOSTIC SUBSTANCES) [2836]
- **IRS NUMBER:** 364108129
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-40551
- **FILM NUMBER:** 23576731

**BUSINESS ADDRESS:**
- **STREET 1:** 427 PARK ST.
- **CITY:** CHARLOTTESVILLE
- **STATE:** VA
- **ZIP:** 22902
- **BUSINESS PHONE:** 925-368-8508

**MAIL ADDRESS:**
- **STREET 1:** 427 PARK ST.
- **CITY:** CHARLOTTESVILLE
- **STATE:** VA
- **ZIP:** 22902

?xml version="1.0" encoding="utf-8" ? 8-K

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### UNITED STATES

### SECURITIES AND EXCHANGE COMMISSION

#### WASHINGTON, D.C. 20549

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### FORM 8-K

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#### CURRENT REPORT

#### Pursuant to Section 13 or 15(d)

#### of the Securities Exchange Act of 1934

#### Date of Report (Date of earliest event reported): February 1, 2023

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## Acumen Pharmaceuticals, Inc.

#### (Exact name of Registrant as Specified in Its Charter)

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| | | |
|:---|:---|:---|
| **Delaware** | **001-40551** | **36-4108129** |
| **(State or Other Jurisdiction**<br> **of Incorporation)** | **(Commission**<br> **File Number)** | **(IRS Employer**<br> **Identification No.)** |

---

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| | |
|:---|:---|
| **427 Park St.,**<br> **Charlottesville, Virginia** | **22902** |
| **(Address of Principal Executive Offices)** | **(Zip Code)** |

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(434) 297-1000

#### (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:

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| | | |
|:---|:---|:---|
| **Title of each class** | **Trading<br>Symbol(s)** | **Name of each exchange**<br> **on which registered** |
| Common Stock, $0.0001 par value | ABOS | The Nasdaq Global Select Market |

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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 ☒

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. ☐

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|:---|:---|
| **Item 7.01** | **Regulation FD Disclosure.**  |

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On February 1, 2023, the Acumen Pharmaceuticals, Inc. (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 99.1 to this Report.

The information in this Item 7.01 of this Report (including Exhibit 99.1), 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.

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|:---|:---|
| **Item 8.01** | **Other Events.**  |

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The Company's updated corporate presentation provides updates with respect to INTERCEPT-AD, the Company's Phase 1 clinical trial of ACU193 in patients with early Alzheimer's disease. The corporate presentation notes that the Company expects to complete enrollment in INTERCEPT-AD in the first quarter of 2023 and anticipates reporting topline data from this trial in the third quarter of 2023. The corporate presentation also notes that as of January 31, 2023, a total of 52 subjects have been randomized and dosed in Cohorts 1 through 6 of the clinical trial. Cohort 6 is fully enrolled, with planned doses of 60 mg/kg of ACU193 every four weeks.

In addition, the updated corporate presentation notes that on January 30, 2023, the Company submitted a protocol amendment to the U.S. Food and Drug Administration with respect to Cohort 7 of the clinical trial to reduce the dosage plan to 25 mg/kg every two weeks (updated from 60 mg/kg every two weeks). The proposed change was based in part on a blinded review of preliminary pharmacokinetic data, inclusive of plasma and cerebrospinal fluid levels, which indicated a dose of 60 mg/kg every two weeks should not be needed to attain central target engagement, and preliminary safety data, inclusive of two asymptomatic cases of ARIA-E (one in Cohort 4 after a single 60 mg/kg dose and one in Cohort 5 after a third 10 mg/kg dose).

#### Cautionary Note on Forward-Looking Statements
This Current Report contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Any statement describing the Company'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 "expects," "anticipates," "plans," "potential" 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 the Company's plans with respect to completion of enrollment in its INTERCEPT-AD Phase 1 clinical trial and its expectations with regards to the timing of reporting topline data, the Company's proposed protocol amendment, the Company's expectations with respect to the therapeutic dose range of the Company's product candidate, ACU193, and the therapeutic potential of ACU193, including its safety profile, potential for improved safety (including expected rate of ARIA) and efficacy, as well as the expectations concerning the INTERCEPT-AD trial. These statements are based upon the current beliefs and expectations of the Company's 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, 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.

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|:---|:---|
| **Item 9.01** | **Financial Statements and Exhibits.**  |

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#### (d). Exhibits

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| | |
|:---|:---|
| **Exhibit**<br> **No.** | **Description** |
| 99.1 | [Corporate Presentation, dated February 2023.](d453609dex991.htm) |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |

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#### 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.

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| | | |
|:---|:---|:---|
|  | **Acumen Pharmaceuticals, Inc.** | **Acumen Pharmaceuticals, Inc.** |
| Dated: February 1, 2023 | By: | /s/ Matthew Zuga |
|  |  | Matthew Zuga |
|  |  | *Chief Financial Officer and Chief Business Officer* |

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## Exhibit 99.1

![](g453609ex99_1p1g1.jpg)

Exhibit 99.1 Corporate Presentation February 2023 1

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![](g453609ex99_1p2g1.jpg)

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 safety profile, potential for improved safety (including expected rates of ARIA) 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

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![](g453609ex99_1p3g1.jpg)

Advancing a Potential Best-/First-In-Class Antibody Product for Early Alzheimer's disease (AD) $ Alzheimer's Scientific Experienced Strong Phase 1 Clinical 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 Beta Oligomers Proof of Driven by High Antibody (mAb) to Industry Leaders at 30-Sep-22 (AβOs) as the and Several with Mechanism Unmet Need and Selectively Target July 2021 IPO Recent Scientific Most Toxic Form AD Clinical Drug, Target 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 AD Treatment Topline Results Supporting its Expertise from Eli Sands Capital Lilly & Co. Expected Differentiation PBM Capital Q3 2023 We believe that Acumen has the organizational expertise and fiscal resources to advance ACU193 through 2025 and multiple clinical milestones. 3

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![](g453609ex99_1p4g1.jpg)

Acumen Business Strategy: 2023 - 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

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![](g453609ex99_1p5g1.jpg)

INTERCEPT-AD Trial Update – February 2023 • INTERCEPT-AD: Phase 1 clinical trial of ACU193 in patients with early Alzheimer's disease (AD) (RCT) → Topline results, safety and clinical proof-of-mechanism following full database lock expected in Q3 2023 → Enrollment expected to be complete in Q1 2023 ▪ As of Jan. 31, a total of 52 subjects have been randomized and dosed in Cohorts 1 through 6 → Cohort 7 dose level amended to 25 mg/kg every two weeks (Q2W) from 60 mg/kg Q2W prior to start ▪ Preliminary, blinded plasma pharmacokinetic (PK) data demonstrated higher-than-expected ACU193 exposures at all dose levels ▪ Preliminary Cohort 3 (SAD 25 mg/kg) dose results in Day 21 cerebrospinal fluid (CSF) ACU193 levels in excess of reported soluble amyloid beta oligomer (AβO) levels ▪ Two blinded observations of asymptomatic ARIA-E factored into decision to amend Cohort 7 dose; one in Cohort 4 (after single 60 mg/kg dose) and one in Cohort 5 (after third 10 mg/kg dose) ▪ Cohort 6 is fully enrolled with planned dose (60 mg/kg every four weeks (Q4W)) Safety profile to date remains supportive of targeting soluble amyloid beta oligomers and, combined with the selectivity of ACU193, is expected to offer a favorable benefit-to-risk ratio for patients with early AD. 5

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![](g453609ex99_1p6g1.jpg)

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 ≥ 1wk 10mg or Placebo ≥ 1wk COHORT 1: 2 mg/kg ACU193 COHORT 7: 2mg or Placebo 25mg 25 mg/kg ACU193 ≥ 1wk or Placebo (Q2W)\* ≥ 1wk 60mg COHORT 6: PART B: 60 mg/kg ACU193 MULTIPLE- or Placebo (Q4W) ASCENDING DOSE COHORT 5: n = 10 per cohort (30 total) 10 mg/kg ACU193 10mg 3 administrations of drug or or Placebo (Q4W) Q2W: Dosing every two weeks; Q4W: Dosing every four weeks. placebo; 8:2 per cohort \* On January 30, 2023, Acumen submitted a protocol amendment to FDA to reduce the dose in Cohort 7 to 25 mg/kg Q2W from 60 mg/kg Q2W. This was based on a blinded review of preliminary pharmacokinetic data, inclusive of plasma and CSF levels, that indicate a dose of 60 mg/kg Q2W should not be needed to attain central target engagement, and preliminary safety data, inclusive of two asymptomatic cases of ARIA-E. While ACU193 is early in clinical development, the incidence of ARIA-E to date is consistent with our previous expectations regarding the safety profile of ACU193. The dose of ACU193 in Cohort 6 (60 mg/kg Q4W) has been maintained as planned. 6

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![](g453609ex99_1p7g1.jpg)

AD, Amyloid & Abeta Oligomers

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![](g453609ex99_1p8g1.jpg)

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. 8

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![](g453609ex99_1p9g1.jpg)

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 two approved antibody products for AD and several late-stage products target amyloid plaques with only limited effects on AβOs. Acumen's drug candidate ACU193 targets AbOs. 9

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![](g453609ex99_1p10g1.jpg)

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. 10

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![](g453609ex99_1p11g1.jpg)

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) ADAS-cog -11% -27% -12% -39% -47% -26% -15% -40% -18% -23% N.A. -37% ADCS-ADL -15% -23% 2% -23% -26% -27% CDR-SB MMSE -13% -15% 3% -21% N.A. N.A. -11% N.A. N.A. -32% N.A. 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

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![](g453609ex99_1p12g1.jpg)

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% 12.6% 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% 2.3% 15.8% ApoE ε4 non- 2.9% 18.1% 17.9% 4.3% 17.5% 27.7% 0.0% 8.0% 0.3% 5.4% carriers 10.3% 32.8% 41.2% 9.8% 30.7% 40.3% 8.0% 38.9% N.A. 9.5% 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

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![](g453609ex99_1p13g1.jpg)

ACU193 Positioning Relative to Late-Stage and Approved Anti-Ab/Plaque mAbs bapineuzumab\* solanezumab crenezumab IgG1, Ph3 stop, A4, DIAN negative IgG1, Ph3 stop IgG4, Ph3 stop, API negative Aβ oligomers Aβ protofibrils ACU193 aducanumab\* lecanemab donanemab\* gantenerumab\* IgG2, Ph1 IgG1 IgG1 IgG1 IgG1 1 1 Approved (AAP) Jan-2023 Approved (AAP), Ph2 positive Ph3 negative 4Q22 1 Ph3 positive 3Q22 CMS CED Filing AAP 4Q22 commercial stop Ph3 1H23 ACU193's high selectivity for AβOs combined with an expected low rate of ARIA 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 13

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![](g453609ex99_1p14g1.jpg)

ACU193's High Selectivity for Toxic AβOs, Combined With its Expected Low Rate of ARIA, is Anticipated to Provide Superior Efficacy Compared to Peers + TARGET SELECTIVITY SAFETY PROFILE Company Asset Amyloid plaque Aβ fibrils Aβ monomers Aβ oligomers Low rate of ARIA ACU193 û untested Expected û ✓ TM Aduhelm Biogen ✓û✓ ✓û lecanemab Eisai / Biogenû ✓û✓ ✓ Roche gantenerumab ✓✓û✓û donanemab Lilly untested ûû û ✓ solanezumab\* Lilly ûûû✓ ✓ Roche / Genentech crenezumab\* ✓✓ ✓✓✓ Pfizer / Janssen bapineuzumab\*û ✓ ✓✓✓ ____________________ \*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.. 14

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![](g453609ex99_1p15g1.jpg)

ACU193: Our Differentiated Approach

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![](g453609ex99_1p16g1.jpg)

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 16

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![](g453609ex99_1p17g1.jpg)

ACU193: Extensive Pre-Clinical 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. 17

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![](g453609ex99_1p18g1.jpg)

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 selectivity 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.' 18

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![](g453609ex99_1p19g1.jpg)

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). 19

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![](g453609ex99_1p20g1.jpg)

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. 20

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![](g453609ex99_1p21g1.jpg)

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. 21

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![](g453609ex99_1p22g1.jpg)

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 22

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![](g453609ex99_1p23g1.jpg)

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. 23

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![](g453609ex99_1p24g1.jpg)

Clinical Development Plans

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![](g453609ex99_1p25g1.jpg)

(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. 25

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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 Q3 2023: primary outcomes safety/ARIA-E, PK and target engagement. Detailed study results anticipated to be presented at an Alzheimer's medical meeting. 26

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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

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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

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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 an ongoing Phase 1 study assessing safety, PK, and target engagement is expected to be complete in Q1 2023 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

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Business Considerations

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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 Biomarkers and Analytical Operations Methods JASNA JERECIC, PHD DEREK MEISNER, JD JULIE BOCKENSTETTE Analytical Methods Chief Legal Officer Executive Vice President, Leader, Research Scientist Head of HR Acumen team has decades of experience in Alzheimer's drug discovery and development. 31

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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

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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 Q1 2023 Proof-of-mechanism topline results Q3 2023 We believe that Acumen has the organizational expertise and cash and marketable securities on hand to advance ACU193 through 2025. 33

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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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Thank You