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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
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 (A Os) as the and Several with Mechanism Unmet Need and Selectively Target July 2021 IPO Recent Scientific Most
Toxic Form AD Clinical Drug, Target A Os with ~$184M Gross and Regulatory of A 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
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
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 (A O) 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
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
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 (A ) Inhibitors Anti- Ab monomer mAb Amyloid plaque A monomers
Anti-amyloid plaque mAb A fibrils BACE inhibitors A oligomers Anti-Ab Symptomatic and oligomer mAb neuroprotective treatments Tau destabilization Tau directed treatments Data indicate that soluble amyloid oligomers (AbOs) are the
most toxic species and should be preferentially targeted for removal. 8
Scientific Evidence Supports A O Hypothesis Predominant forms of Ab
in AD: Ab monomers (non-toxic), AbOs, Ab fibrils, and amyloid plaques A monomers A oligomers A Os 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 A fibrils responses microglial and astrocytic activation Growing understanding of disease mechanisms indicate that A Os are the most toxic
A 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 A Os. Acumen's drug candidate ACU193 targets AbOs. 9
What is an A 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 A 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 m. Z range (A) 8.0 nm; (B) 15 nm; (C) 20 nm. ____________________ Source: Relini et al. Biomolecules 2014.
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
Anti-Plaque mAbs Demonstrate Dose-Related ARIAs That Will Likely Limit
Their Use Percent of ARIA Events for Anti-A /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 4 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 4 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 A 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 A , i.e. A monomers and A Os. 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 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 A oligomers A 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 A Os 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
ACU193's High Selectivity for Toxic A Os, 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 A fibrils A monomers A oligomers Low rate of ARIA ACU193 untested
Expected TM Aduhelm Biogen lecanemab Eisai / Biogen Roche gantenerumab donanemab Lilly untested
solanezumab* Lilly Roche / Genentech crenezumab* Pfizer / Janssen bapineuzumab* ____________________ *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
ACU193: Our Differentiated Approach
ACU193 Target Product Profile: Best-in-Class, 1st Line, Anti-A O,
Disease- Modifying Immunotherapy for Early AD DRUG: ACU193 is a humanized, affinity-matured, mAb with high selectivity for toxic A Os vs. A 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 A Os is expected to provide superior cognitive efficacy and improved PROPOSITION: safety and tolerability relative to non-selective anti-A /plaque mAbs, including: Slowing the decline of memory
and cognition in Early AD Decreasing A O 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
ACU193: Extensive Pre-Clinical Data Package Supporting Development
Nanomolar affinity for A Os, >500-fold greater selectivity for A Os over A monomer, with limited or no discernable binding to vascular amyloid or dense core amyloid plaques SELECTIVITY Binds broad range of endogenous
A Os present in transgenic mice and human AD samples (binds dimers to mid-sized molecular weight A Os) 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 (Fc R 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
SELECTIVITY ACU193 is the First mAb Developed to Selectively Target
A Os Highly selective for A oligomers versus A monomers ACU193 Selectivity in presence of ACU193 Selectivity 5 M monomeric A Log [Competing Antigen] M ACU193 Log M Even in the presence of a large excess of
A monomer, Binding of ACU193 to A Os >500x binding of ACU193 to A Os is unchanged binding to A monomer ACU193 selectivity for binding to A Os is preserved even in the presence of a large excess of A monomers
- such as what is present in the brain, thus limiting target distraction.' 18
SELECTIVITY ACU193 Has a Greater Preference for AbOs Than Other mAbs
Comparison of A 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
SELECTIVITY ACU193 is Highly Selective for A Os Versus A
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
A plaque in human AD brain tissue. ____________________ Sources: E. Cline et al. CTAD 2019. 20
SELECTIVITY PHARMACOLOGY A Os 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 A O inhibition of ACU3B3 prevents