Acumen Pharmaceuticals : CTAD Symposium Presentation 2023

INTERCEPT-AD phase 1 insights and findings

from the investigation of ACU193, a

monoclonal antibody targeting soluble Aβ

oligomers

Clinical Trials on Alzheimer's Disease

Boston, Massachusetts

October 27, 2023

INTERCEPT-AD phase 1 insights and findings from the investigation of ACU193, a monoclonal antibody targeting soluble Aβ oligomers

Chair: Diana Kerwin, Kerwin Medical Center, Dallas, TX

Determination of target engagement at various doses of ACU193 in INTERCEPT-AD

Mirjam Trame, Certara, Boston, MA

Reduction in amyloid plaque load at higher doses of ACU193 in INTERCEPT-AD

Eric Siemers, Acumen Pharmaceuticals, Inc, Charlottesville, VA

Characteristics of participants in INTERCEPT-AD who did or did not develop ARIA with ACU193

Stephen Salloway, Alpert Medical School of Brown University, Providence, RI

2

Acknowledgements

Participants and their Study Partners

• We acknowledge with thanks the individuals who enrolled in INTERCEPT-AD trial as well as their family, study partners, and friends who supported them.

Site Staff and Study Team Members

• We would also like to acknowledge the site staff, CRO, and all study team members who were vital to the successful completion of this trial.

Site Investigators

• Kimball Johnson (iResearch Atlanta), Diana Kerwin (Kerwin Research Center), Jeffrey Norton (Charter Research), Mohammad Reza Bolouri (Alzheimer's Memory Center), Alida Reinoso (Columbus Clinical Services), Shirley Valdez-Arroyo (Santos Research Center), Eric Carbonell (Combined Research), David Weisman (Abington Neurological), Alexander White (Progressive Medical Research), Beth Safirstein (MD Clinical), Lawrence Honig (Columbia University Hospital), Nelson Berrios (Clinical Trial Network), Steve Sitar (Orange County Research Institute), Nidia Laurin (Clinical Endpoints), Sanjiv Sharma (CenExel), Gustavo Alva (Hoag Memorial Hospital Presbyterian) and Maria Johnson (ACMR)

Determination of Target Engagement at Various

Doses of ACU193 in INTERCEPT-AD

Mirjam N Trame, PharmD, PhD

Vice President, Certara Drug Development Solutions

Clinical Trials on Alzheimer's Disease

Boston, Massachusetts

October 27, 2023

© Copyright 2020 Certara, L.P. All rights reserved.

4

4

Disclosure

• Dr. Trame is an employee of Certara and consulting for Acumen Pharmaceuticals.

© Copyright 2020 Certara, L.P. All rights reserved.

5

5

Forward Looking Statement

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," "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; the safety, tolerability, pharmacokinetics, target engagement and other clinical measures associated with Acumen's product candidate, ACU193, including its performance against other antibodies. 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, including Acumen's most recent Quarterly Report on Form 10-Q. 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.

© Copyright 2020 Certara, L.P. All rights reserved.

6

6

INTERCEPT-AD Phase 1 Study

© Copyright 2020 Certara, L.P. All rights reserved.	7
7

Target Engagement: Measuring ACU193-AβO Complex in CSF

MSD S-Plex (Turbo) Immunoassay

ACU193-AβO	AβO selective detection
Complex
	(anti-AβΟ mAb)

Only drug/AβO complex is measurable

ACU193 drug specific capture

(anti-ACU193 idiotype mAb)

Novel assay configuration tailored to selectively detect ACU193-AβO complex in CSF as direct measure of target engagement

© Copyright 2020 Certara, L.P. All rights reserved.

8

Clear ACU193 Concentration Target-Engagement Profile in the CSF

• Clear concentration- response profile in CSF
• These lumbar samples were taken while drug levels were falling, so they represent the lowest target engagement levels
  (something like "trough levels"); within dosing interval target engagement will be higher
• These results motivated the development of a PK/PD model for ACU193 effect on target engagement in the CSF

Predicted EC50

Predicted Emax

Red dashed line: predicted Emax from PKPD model; green dashed line: predicted EC50 from PKPD model

© Copyright 2020 Certara, L.P. All rights reserved.

9

PK/PD Model for ACU193 Target Engagement

• CSF concentrations defined by a two-compartment model, then linked to target engagement in the CSF and Amyloid PET Centiloid reduction using a Michaelis-Menten (Emax) model

Serum	CSF	CSF Target	∙ []
(Periphery)	Engagement, AU/mL	= [] + 50
		Change in Centiloids,
Elimination		PET

© Copyright 2020 Certara, L.P. All rights reserved.

10