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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 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
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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 (Early AD) $ ACU193: First, Alzheimer's Experienced Phase 1 Clinical Scientific Strong Clinical-Stage Represents an Consensus Leadership Trial in Early AD Balance Sheet: Monoclonal Enormous Market Supports Comprised
of Patients Ongoing ~$210M in cash Antibody (mAb) to Proof of Driven by High Amyloid-Beta Industry Leaders at 30-Jun-22 Selectively Target with AD Drug Mechanism Unmet Need and Oligomers (A Os) July 2021 IPO A Os and has Discovery, Target
Engagement Recent Scientific as the Most toxic ~$184M Gross Promising Pre- and Regulatory form of A and a Development, and Safety Data RA Capital Clinical Evidence Momentum Novel Target for Regulatory Topline Results Deep Track Supporting its
Expected Effective AD Expertise from Eli Sands Capital Differentiation Lilly & Co. 1H 2023 Treatment PBM Capital 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 AD (RCT) Topline results (Proof of Mechanism) following full database lock expected in 1H 2023 Safety / ARIA-E PK Target engagement Trial enrollment on-going at 15
active sites, 2 additional sites selected for potential activation Strong cash position has provided us the ability to expand study footprint to support recruitment and complete follow-up period (Cohort 7 Day 168) prior to read out
Complete trial results anticipated for presentation at major Alzheimer's meeting in 1H 2023 Phase 2/3 Ready' Activities Chronic GLP toxicity testing ongoing New drug substance production process and drug
product formulation being finalized Developing Phase 2/3 study for ACU193; design and planning for FDA End of Phase 2 meeting 5
AD, Amyloid & Abeta Oligomers
Alzheimer's Pathophysiology Build-up of amyloid-beta (A ) is
believed to lead to neurodegeneration and dementia Previous and current anti-amyloid and related drug targets have attempted to intervene secretase Amyloid (A ) Inhibitors Anti-monomer A mAb Amyloid plaque A monomers
Anti-amyloid plaque mAb A fibrils BACE inhibitors A oligomers Anti-A Symptomatic and oligomer mAb neuroprotective treatments Tau destabilization Tau directed treatments Data indicate that soluble amyloid oligomers
(A Os) are the most toxic species and should be preferentially targeted for removal. 7
What is an A Oligomer? A Os may consist of 2 to >200
A peptides. Figure 1. A Os composed of 3 (a) and 18 (b) A peptides are depicted below. (b) (a) ____________________ Sources: 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 . 8
Scientific Evidence Supports Anti-A O Hypothesis Predominant forms
of A in AD: A monomers (non-toxic), A Os, A fibrils, and amyloid plaques A Oligomers A monomers 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 phosphorylation of Abeta and may induce toxicity due to Inflammatory A fibrils responses microglial and astrocytic Growing understanding of disease mechanisms indicate that A Os are
the activation 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 only approved antibody product for AD and three late stage products all preferentially target amyloid plaques with only limited effects on A Os. Acumen's drug candidate ACU193 targets A Os. 9
ACU193 Positioning Relative to Late-stage and Approved
Anti-A /plaque mAbs crenezumab bapineuzumab* solanezumab IgG4, Ph3 stop, API 1H22 IgG1, Ph3, stop IgG1, Ph3 stop, A4, DIAN A oligomers A protofibrils ACU193 lecanemab donanemab* gantenerumab* aducanumab* IgG2m4, Ph1 IgG1 IgG1 IgG1
IgG1 AAP filed 2Q22 Ph2 positive Ph3 4Q22 Approved (AAP), Filing AAP 2Q22 CMS CED Ph3 3Q22 Ph3 1H23 commercial stop ACU193's high selectivity for A Os combined with an expected lack of ARIA-related safety concerns is anticipated to
provide superior cognitive 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. 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 EXPEDITION 3 EMERGE ENGAGE BAN2401 donanemab Measured Outcome** (Phase 3) (Phase 3) (Phase 3) (Phase 2) (Phase 2) ADAS-cog -11%
-27% -12% -47% -39% -15% -40% -18% N.A. -23% ADCS-ADL -15% -23% 2% -26% -23% CDR-SB MMSE -13% -15% 3% N.A. -21% -11% N.A. N.A. N.A. -32% 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: 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 AB MONOMERS AMYLOID PLAQUES solanezumab aducanumab aducanumab lecanemab donanemab EXPEDITION 3 EMERGE ENGAGE BAN2401 (Phase 2) (Phase 3) (Phase 3) (Phase 3) (Phase 2)
PC Treated PC Low High PC Low High PC High PC Treated 0.2% 0.1% 2.2% 26.1% 34.4% 3.0% 25.6% 35.7% 0.8% 9.9% 0.8% 27.5% ARIA-E ApoE 4 carriers 1.9% 29.8% 42.5% 2.4% 28.7% 41.8% 1.2% 14.6% 3.6% 44.0% ApoE 4 non- 2.9% 18.1% 17.9% 4.3% 17.5%
27.7% 0.0% 8.0% carriers 10.3% 32.8% 41.2% 9.8% 30.7% 40.3% N.A. 8.0% 38.9% 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 ARIAs 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 12 product candidates.
ACU193's High Selectivity for toxic A Os, 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 A fibrils A monomers A oligomers
safety concerns ACU193 untested TM Aduhelm Biogen lecanemab Eisai / Biogen gantenerumab Roche Lilly donanemab untested
solanezumab* Lilly crenezumab* Roche / Genentech bapineuzumab* Pfizer / Janssen ____________________ *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..
ACU193: Our differentiated approach
Target Product Profile: ACU193 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 amyloid plaques. ACU193 is an IgG2m4 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 Effective as
stand-alone therapy or potentially in combination with other symptomatic, anti-inflammatory, and/or tau directed therapies 15
ACU193: Extensive 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 IgG2m4 subclass lacks inflammatory effector function
signaling (C1q, Fc R1, Fc RIII) Microhemorrhage studies show no increased risk of SAFETY microhemeorrhage 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
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 selective binding to A Os is preserved even in the presence of a large excess of A monomer which is
present in brain - limited target distraction. 17 % Percent Control A Os binding (RLUs)
SELECTIVITY ACU193 has a greater preference for A Os than other
mAbs Comparison of A species-mAb complex signals across SEC fractions Synthetic A Os SEC ACU193 binds to a wide range of oligomeric species of A that are differentiated from those bound by hu266 (solanezumab) or hu3D6
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 A (green) AD Hippocampus AD Hippocampus ACU193/A Os species ThioS/amyloid plaque 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. 19
SELECTIVITY PHARMACOLOGY A Os Bind to Neurons and are Toxic; mouse
analogue of ACU193 prevents toxicity After binding to neurons, A Os 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 A O mediated Ca2+ hippocampal LTP ex vivo elevation in cell cultures Control A (50 nM) 42 A (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 underlying memory loss in AD and prevents A O 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 Morris Water Maze Open Field 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
A Os in Transgenic Mice in Dose Dependent Manner ACU193 engages target A Os in transgenic mouse brain (tg2576) in dose dependent manner. Ability to push doses higher in patient clinical trials may provide increased target coverage.
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 For more information on the INTERCEPT-AD trial, see https://clinicaltrials.gov/ct2/show/NCT04931459.