Acumen Pharmaceuticals : ADPD 2024 CSF Biomarker Presentation

Sabirnetug (ACU193) Lowers CSF Neurogranin & pTau181 Levels in INTERCEPT-AD Study in Early AD

Erika N Cline, PhD

Acumen Pharmaceuticals

AD/PD

Lisbon, Portugal

March 8, 2024

Disclosures

Dr. Cline is an employee and shareholder at Acumen Pharmaceuticals.

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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, sabirnetug, 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.

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Acknowledgements

Participants and their Study Partners

• We acknowledge with gratitude the individuals who enrolled in the 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), Nida Laurin (Clinical Endpoints), Sanjiv Sharma (CenExel), Gustavo Alva (Hoag Memorial Hospital Presbyterian) and Maria Johnson (ACMR)

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Sabirnetug (ACU193) is a Monoclonal Antibody that is Highly Selective for Soluble Amyloid β Oligomers, a Synaptotoxic Form of Amyloid β

Amyloid β oligomers (AβOs):

• Impair synaptic function1

• Induce tau hyperphosphorylation2

• Contribute to impairment of memory & cognition3

1. Lacor et al., 2004 & 2007; Townsend et al., 2006; Batista et al., 2018

2. De Felice et al., 2008; Zempel et al., 2010

3. Clearly et al., 2005; Poling et al., 2008; Cline et al., 2019

Sabirnetug-AβO

Complex

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INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 Study in Early

AD Patients

PART A:

COHORT 4:

≥ 1wk 60 mg/kg Sabirnetug

SINGLE-ASCENDING DOSE (SAD)

n = 8 per cohort (32 total)

COHORT 3:

or Placebo

6:2 per cohort			≥ 1wk
					COHORT 2:
		≥ 1wk		10 mg/kg Sabirnetug
					or Placebo
	COHORT 1:
	2 mg/kg Sabirnetug
	or Placebo
						≥ 1wk
PART B:
MULTIPLE-ASCENDING DOSE (MAD)	COHORT 5:
n = 10 per cohort (30 total)	10 mg/kg Sabirnetug
3 administrations of drug or PBO	or Placebo (Q4W)
8:2 per cohort

Q2W: Dosing every two weeks; Q4W: Dosing every four weeks.

PBO: placebo

25 mg/kg Sabirnetug or Placebo

• 1wk

≥ 1wk

			COHORT 7:
	≥ 1wk		25 mg/kg Sabirnetug
COHORT 6:			or Placebo (Q2W)
60mg

60 mg/kg Sabirnetug or Placebo (Q4W)

CSF was collected for biomarker analysis:

1. Pre-dosing
2. Post-dosing(7-21 days after last dose)

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Key CSF Biomarkers Associated with AD Pathology were Assessed

Amyloid Pathology:

Aβ 40

Aβ 42

Amyloid plaque

Aβ oligomer

Tau Pathology: pTau181 pTau217

Synaptic Injury:	Neuronal Injury:
Neurogranin	Total tau

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.

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Sabirnetug-Associated Changes in CSF Aβ and Synaptic Biomarkers Indicate Downstream Pharmacology After 3 Doses

Aβ 42/40 Ratio

Normalization AD progression

Neurogranin

AD progression Normalization

Amyloid pathology	Synaptic injury
				•	Aβ assays: Lumipulse
•	n = 8 subjects/treated group; 6 subjects in pooled placebo (PBO)	•	Neurogranin: ELISA
•	p-values from unpaired, 2-sided Student's t test

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Sabirnetug-Associated Changes in CSF Tau Proteoforms are Consistent with Downstream Pharmacology After 3 Doses

pTau181

AD progression Normalization

pTau217

AD progression Normalization

tTau

AD progression Normalization

Tau pathology			Neuronal injury
					•	All assays: Lumipulse
•	n = 8 subjects/treated group; 6 subjects in pooled placebo (PBO)	•	pTau217: ADx prototype
•	p-values from unpaired, 2-sided Student's t test

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CSF Biomarker Responses to Sabirnetug Are Dose & Duration Dependent

Neurogranin

p-value = 0.007

Pearson r = -0.423

tTau

p-value = 0.005

Pearson r = -0.439

pTau181

p-value = 0.001

Pearson r = -0.504

AD progression Normalization

•	LP = lumbar puncture	•	Neurogranin: ELISA
•	n = 40 subjects	•	Tau assays: Lumipulse

• p-valuesfrom Pearson's correlation test

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