Acumen Pharmaceuticals, Inc. (NASDAQ:ABOS) is a clinical-stage biopharmaceutical company developing a novel disease-modifying approach to target what it believes to be a key underlying cause of Alzheimer's disease (AD). The company's lead product candidate, sabirnetug, has demonstrated promising results in early clinical trials, positioning it as a potential best-in-class treatment option for the substantial early AD patient population.

Business Overview

Acumen was founded in 1996 and was previously party to an exclusive license and research collaboration with Merck & Co., Inc. in 2003. The company acquired the exclusive rights to sabirnetug from Merck in 2011 following Merck's strategic decision to focus its AD development efforts on a different product candidate. Since 2018, Acumen has devoted substantially all of its efforts to advancing sabirnetug through clinical development.

Sabirnetug is a recombinant humanized immunoglobulin gamma 2 (IgG2) monoclonal antibody (mAb) that was designed to selectively target soluble amyloid-beta oligomers (AßOs), which are believed to be a primary toxin involved in the initiation and propagation of AD pathology. The company's scientific founders pioneered research on AßOs, and Acumen is leveraging this expertise to develop a targeted immunotherapy approach.

In July 2023, Acumen announced topline results from its Phase 1 clinical trial of sabirnetug, called INTERCEPT-AD. The trial enrolled 65 patients with "early AD" (mild cognitive impairment or mild dementia due to Alzheimer's pathology), with 62 participants receiving at least one dose of the study drug. The results demonstrated that sabirnetug met the primary and secondary objectives of the study, with the drug being well-tolerated throughout the single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. Importantly, the incidence of amyloid-related imaging abnormalities (ARIA-E) was dose dependent, with a rate of 7% for patients given 10 mg/kg or 25 mg/kg and 21% for patients given 60 mg/kg.

The INTERCEPT-AD study also showed statistically significant, dose-related central target engagement as measured by sabirnetug-AßO complex, establishing the first target engagement assay developed that is specific to an AßO-targeting antibody. Additionally, downstream biomarkers in cerebrospinal fluid (CSF) specific to amyloid and tau pathology and synaptic injury showed improvement in the MAD cohorts, further supporting a drug effect of sabirnetug on Alzheimer's pathology.

Acumen announced the dosing of the first patient in the ALTITUDE-AD study in May 2024. ALTITUDE-AD is a randomized, double-blind, placebo-controlled, three-arm study designed to evaluate the clinical efficacy, safety, and tolerability of sabirnetug, with up to 180 participants per arm for a total of up to 540 participants with mild cognitive impairment or mild dementia due to AD. The company plans to use the Integrated Alzheimer's Disease Rating Scale (iADRS) at 18 months as the primary outcome measure.

Financial Overview

For the fiscal year ended December 31, 2023, Acumen reported an annual net loss of $52.4 million and no revenue, as the company has not yet commercialized any products. The company's annual operating cash flow was -$43.1 million, and its annual free cash flow was -$43.1 million.

In the first quarter of 2024, Acumen reported a net loss of $14.9 million, with research and development expenses of $12.4 million and general and administrative expenses of $5.3 million. The company's cash and cash equivalents and marketable securities totaled $296.6 million as of March 31, 2024, which the company expects will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2027.

Acumen has funded its operations primarily through the sale of its convertible preferred stock and common stock, the issuance of notes, entry into a term loan facility, grant revenue, and, during its collaboration with Merck, certain payments received under the collaboration agreement. In November 2023, the company announced a global collaboration and license agreement with Halozyme, Inc. to develop a subcutaneous formulation of sabirnetug, which the company plans to initiate a Phase 1 trial for in mid-2024.

Risks and Challenges

As a clinical-stage biopharmaceutical company, Acumen faces several risks and challenges common to the industry, including the uncertainty of whether its intellectual property will develop into successful commercial products, the ability to obtain necessary regulatory approvals, and the ability to secure additional funding for its operations and future development activities.

Specifically, the company's success will depend on the continued development and potential commercialization of sabirnetug. While the INTERCEPT-AD study demonstrated promising results, there is no guarantee that the ALTITUDE-AD study or any future clinical trials will be successful or that sabirnetug will receive regulatory approval. Additionally, the company may face competition from other Alzheimer's therapies, such as lecanemab and potentially donanemab, which could impact the commercial potential of sabirnetug.

Guidance and Outlook

Acumen has not provided specific financial guidance for the full year 2024. However, the company has stated that it expects its existing cash and cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2027.

The company remains focused on efficiently and thoughtfully advancing the clinical development of sabirnetug, with the ALTITUDE-AD study as its top priority. Acumen is also working to initiate a Phase 1 study in healthy subjects for a subcutaneous formulation of sabirnetug in mid-2024, which could provide additional flexibility and convenience for patients and caregivers.

Conclusion

Acumen Pharmaceuticals is a promising clinical-stage biopharmaceutical company developing a novel disease-modifying approach to Alzheimer's disease. The company's lead product candidate, sabirnetug, has demonstrated encouraging results in early clinical trials, positioning it as a potential best-in-class treatment option for the substantial early AD patient population.

With a strong financial position and a clear focus on advancing sabirnetug through clinical development, Acumen is well-positioned to capitalize on the significant unmet need in the Alzheimer's disease market. As the company continues to execute on its strategic priorities, investors will be closely watching the progress of the ALTITUDE-AD study and the development of the subcutaneous formulation of sabirnetug.