Acumen Pharmaceuticals Inc

Previous wording

We are a clinical-stage biopharmaceutical company developing a novel disease-modifying approach to target what we believe to be a key underlying cause of Alzheimer’s disease, or AD. Alzheimer’s disease is a progressive neurodegenerative disease of the brain that leads to loss of memory and cognitive functions and ultimately results in death. Our scientific founders pioneered research on soluble amyloid-beta oligomers, or AßOs, which are globular assemblies of the amyloid-beta, or Aß, peptide that are distinct from Aß monomers and amyloid plaques. Based on decades of research and supporting evidence, AßOs have gained increasing scientific acceptance as a primary toxin involved in the initiation and propagation of AD pathology. We are currently focused on advancing a targeted immunotherapy drug candidate, sabirnetug (ACU193), in the Phase 2 portion of a Phase 2/3 clinical trial called ALTITUDE-AD following Phase 1 results in “early AD” patients (patients with mild cognitive impairment or mild dementia due to Alzheimer’s pathology) that were first reported in July 2023. Sabirnetug is a recombinant humanized immunoglobulin gamma 2, or IgG2, monoclonal antibody, or mAb, that was designed to selectively target AßOs, has demonstrated functional and protective effects in in vitro assays, and has previously demonstrated in vivo safety and pharmacologic activity in multiple animal species, including transgenic mouse models for AD.

Current wording

We are a clinical-stage biopharmaceutical company developing a novel disease-modifying approach to target what we believe to be a key underlying cause of Alzheimer’s disease, or AD. Alzheimer’s disease is a progressive neurodegenerative disease of the brain that leads to loss of memory and cognitive functions and ultimately results in death. Our scientific founders pioneered research on soluble amyloid-beta oligomers, or AßOs, which are globular assemblies of the amyloid-beta, or Aß, peptide that are distinct from Aß monomers and amyloid plaques. Based on decades of research and supporting evidence, AßOs have gained increasing scientific acceptance as a primary toxin involved in the initiation and propagation of AD pathology. We are currently focused on advancing a targeted immunotherapy drug candidate, sabirnetug (ACU193), in Phase 2 of our ALTITUDE-AD clinical trial following the results of INTERCEPT-AD, our Phase 1 clinical trial of sabirnetug in “early AD” patients (patients with mild cognitive impairment or mild dementia due to Alzheimer’s pathology), which were first reported in July 2023. Sabirnetug is a recombinant humanized immunoglobulin gamma 2, or IgG2, monoclonal antibody, or mAb, that was designed to selectively target AßOs, has demonstrated functional and protective effects in in vitro assays, and has previously demonstrated in vivo safety and pharmacologic activity in multiple animal species, including transgenic mouse models for AD.

Previous wording

In July 2023, we announced topline results from our Phase 1 clinical trial of sabirnetug, called INTERCEPT-AD, which demonstrated that sabirnetug met the primary and secondary objectives of the study in 62 participants with early AD. Sabirnetug was well-tolerated throughout the single ascending dose, or SAD, and multiple ascending dose, or MAD, cohorts, with an overall rate of amyloid-related imaging abnormalities, or ARIA-E, of 10.4%. The incidence of 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. An analysis of change in amyloid plaque load, as measured by positron emission tomography, or PET, Centiloids, demonstrated a rapid, dose-related mean decrease at the higher dose levels studied. Statistically significant, dose-related central target engagement was observed as measured by sabirnetug-AßO complex, establishing the first target engagement assay developed that is specific to an AßO-targeting antibody. The study also demonstrated near maximal target engagement for patients receiving 25 mg/kg every two weeks or 60 mg/kg every four weeks, an important finding for dose selection in the ALTITUDE-AD study. In November 2023, we announced a number of downstream biomarkers in cerebrospinal fluid, or CSF, specific to amyloid and tau pathology and synaptic injury showed improvement in the INTERCEPT-AD MAD cohorts, further supporting a drug effect of sabirnetug on Alzheimer’s pathology. These included effects of sabirnetug on p-tau181, which reflects damage to neurons and is known to be elevated in cerebrospinal fluid, or CSF, of patients with AD, and effects of sabirnetug on neurogranin and VAMP2, markers which reflect damage to neuronal synapsis and are elevated in CSF of patients with AD.

Current wording

In July 2023, we announced topline results from our INTERCEPT-AD clinical trial, which demonstrated that sabirnetug met the primary and secondary objectives of the study in 62 participants with early AD. Sabirnetug was well-tolerated throughout the single ascending dose, or SAD, and multiple ascending dose, or MAD, cohorts, with an overall rate of amyloid-related imaging abnormalities, or ARIA-E, of 10.4%. The incidence of 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. An analysis of change in amyloid plaque load, as measured in Centiloids by positron emission tomography, or PET, demonstrated a rapid, dose-related mean decrease at the higher dose levels studied. Statistically significant, dose-related central target engagement was observed as measured by sabirnetug-AßO complex, establishing the first target engagement assay developed that is specific to an AßO-targeting antibody. The study also demonstrated near maximal target engagement for patients receiving 25 mg/kg every two weeks or 60 mg/kg every four weeks, an important finding for dose selection in the ALTITUDE-AD clinical trial. In November 2023, we announced a number of downstream biomarkers in cerebrospinal fluid, or CSF, specific to amyloid and tau pathology and synaptic injury showed improvement in the INTERCEPT-AD MAD cohorts, further supporting a drug effect of sabirnetug on Alzheimer’s pathology. These included effects of sabirnetug on p-tau181, which reflects damage to neurons and is known to be elevated in CSF of patients with AD, and effects of sabirnetug on neurogranin and VAMP2, markers which reflect damage to neuronal synapses and are elevated in CSF of patients with AD.

Previous wording

We 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. We intend to use the Integrated Alzheimer’s Disease Rating Scale, or iADRS, at 18 months as the primary outcome measure. Our planned doses for ALTITUDE-AD are 35 mg/kg and 50 mg/kg both dosed every four weeks, or Q4W. These dose levels and frequency were selected based on extensive pharmacokinetic, or PK, and pharmacodynamic, or PD, modeling of our Phase 1 data. Based on regulatory feedback from the European Medicines Agency, or EMA, and to enhance the probability that the EMA will consider ALTITUDE-AD as a registration-eligible study for sabirnetug, we intend to amend the ALTITUDE-AD protocol later this year to change the current Phase 2/3 study to a Phase 2 standalone study.

Current wording

We announced the dosing of the first patient in the ALTITUDE-AD clinical trial 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. We intend to use the Integrated Alzheimer’s Disease Rating Scale, or iADRS, at 18 months as the primary outcome measure. Our planned doses for ALTITUDE-AD are 35 mg/kg and 50 mg/kg both dosed every four weeks, or Q4W. These dose levels and frequency were selected based on extensive pharmacokinetic, or PK, and pharmacodynamic, or PD, modeling of our Phase 1 data. Based on regulatory feedback from the European Medicines Agency, or EMA, and to enhance the probability that the EMA will consider ALTITUDE-AD as a registration-eligible study for sabirnetug, we are in the process of amending the ALTITUDE-AD clinical trial protocol, which currently provides for a Phase 2/3 study, to a Phase 2 standalone study. The Company expects to complete enrollment in ALTITUDE-AD in the first half of 2025.

Previous wording

In November 2023, we announced a global collaboration and license agreement with Halozyme, Inc., or Halozyme, to develop a subcutaneous formulation of sabirnetug. We expect to initiate a Phase 1 trial investigating a subcutaneous dosing option of sabirnetug in mid-2024.

Current wording

In November 2023, we announced a global collaboration and license agreement with Halozyme, Inc., or Halozyme, to develop a subcutaneous formulation of sabirnetug. In July 2024, we announced that the first subject had been dosed with a subcutaneous formulation of sabirnetug in a Phase 1 PK comparison clinical trial. The clinical trial plans to compare the PK between subcutaneous and intravenous administrations of sabirnetug in healthy volunteers. Topline results from this study are expected in the first quarter of 2025.

Previous wording

We have incurred net losses and negative cash flows from operations since our inception. Our net losses were $14.9 million and $11.3 million for the three months ended March 31, 2024 and 2023, respectively. Approximately $12.4 million, or 84%, of the net loss for the three months ended March 31, 2024 was due to research and development spending. As of March 31, 2024, we had an accumulated deficit of $237.7 million and working capital of $247.4 million. Our net losses and cash flows from operations may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of nonclinical studies, clinical trials and our expenditures on other research and development activities. We expect our expenses and operating losses will increase substantially for the foreseeable future as we advance sabirnetug in clinical trials, seek to expand our product candidate portfolio through developing additional product candidates, grow our clinical, regulatory and quality capabilities, and incur additional costs associated with operating as a public company. It is likely that we will seek third-party collaborators for the future commercialization of sabirnetug or any other product candidate that is approved for marketing, sales, manufacturing and distribution. We will not generate revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for our product candidates.

Current wording

We have incurred net losses and negative cash flows from operations since our inception. Our net losses were $35.4 million and $22.9 million for the six months ended June 30, 2024 and 2023, respectively. Approximately $32.0 million, or 90%, of the net loss for the six months ended June 30, 2024 was due to research and development spending. As of June 30, 2024, we had an accumulated deficit of $258.2 million and working capital of $251.5 million. Our net losses and cash flows from operations may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of nonclinical studies, clinical trials and our expenditures on other research and development activities. We expect our expenses and operating losses will increase substantially for the foreseeable future as we advance sabirnetug in clinical trials, seek to expand our product candidate portfolio through developing additional product candidates, grow our clinical, regulatory and quality capabilities, and incur additional costs associated with operating as a public company. It is likely that we will seek third-party collaborators for the future commercialization of sabirnetug or any other product candidate that is approved for marketing, sales, manufacturing and distribution. We will not generate revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for our product candidates.

Previous wording

As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of public or private equity offerings and debt financings or other sources, such as potential collaboration agreements, strategic alliances and licensing arrangements. We may be unable to raise additional funds or enter into such other agreements or arrangements when needed on acceptable terms, or at all. In addition, global economic conditions may impact our ability to raise additional funds, and we may be impacted by disruptions to, and volatility in, the credit and financial markets in the U.S. and worldwide, rising inflation and supply disruptions, the ongoing conflicts between Russia and Ukraine and Israel and Hamas and related sanctions, and otherwise. If these conditions persist and deepen, we could experience an inability to access additional capital, or our liquidity could otherwise be impacted. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs and/or future commercialization efforts. Our failure to raise capital or enter into such agreements as, and when needed, could have a material adverse effect on our business, results of operations and financial condition.

Current wording

As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of public or private equity offerings and debt financings or other sources, such as potential collaboration agreements, strategic alliances and licensing arrangements. We may be unable to raise additional funds or enter into such other agreements or arrangements when needed on acceptable terms, or at all. In addition, global economic conditions may impact our ability to raise additional funds, and we may be impacted by disruptions to, and volatility in, the credit and financial markets in the U.S. and worldwide, fluctuations in inflation and supply disruptions, the ongoing conflicts between Russia and Ukraine and Israel and Hamas and related sanctions, and otherwise. If these conditions persist and deepen, we could experience an inability to access additional capital, or our liquidity could otherwise be impacted. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs and/or future commercialization efforts. Our failure to raise capital or enter into such agreements as, and when needed, could have a material adverse effect on our business, results of operations and financial condition.

Previous wording

As of March 31, 2024, we had cash and cash equivalents andmarketable securities totaling $296.6 million, which amount includes the first tranche of $30.0 million that we received under the Loan Agreement with K2HV. Based on our current operating plan, we expect that our existing cash and cash equivalents and marketable securities will be sufficient to enable us to fund our oper ating expenses and capital expenditure requirements into the first half of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect, including based on our decision to initiate other clinical trials or programs. See “—Liquidity and Capital Resources.”

Current wording

As of June 30, 2024, we had cash and cash equivalents andmarketable securities totaling $281.4 million, which amount includes the first tranche of $30.0 million that we received under the Loan Agreement with K2HV. Based on our current operating plan, we expect that our existing cash and cash equivalents and marketable securities will be sufficient to enable us to fund our oper ating expenses and capital expenditure requirements into the first half of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect, including based on our decision to initiate other clinical trials or programs. See “—Liquidity and Capital Resources.”

Previous wording

As we currently only have one product candidate, sabirnetug, in development, we do not separately track expenses by program. Further, we have historically relied primarily on consultants for research and development activities; our internal research and development personnel costs currently represent approximately 29% of our total research and development expenses. Our research and development expenses increased substantially since initiating the clinical trial program for sabirnetug in 2021. We expect that our research and development expenses will continue to increase substantially in connection with our continued clinical development activities for sabirnetug.

Current wording

As we currently only have one product candidate, sabirnetug, in development, we do not separately track expenses by program. Further, we have historically relied primarily on consultants for research and development activities; our internal research and development personnel costs currently represent approximately 22% of our total research and development expenses. Our research and development expenses increased substantially since initiating the clinical trial program for sabirnetug in 2021. We expect that our research and development expenses will continue to increase substantially in connection with our continued clinical development activities for sabirnetug.

Previous wording

We expect that our general and administrative expenses will increase as our organization and headcount needed in the future grows to support continued research and development activities and potential commercialization of our product candidates. These increases will likely include increased costs related to the hiring of additional personnel and fees to outside consultants, attorneys and accountants, among other expenses. Additionally, we expect to continue to incur significant expenses associated with being a public company, including costs of additional personnel, accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with exchange listing and Securities and Exchange Commission, or SEC, requirements, director and officer insurance costs, and investor and public relations costs.

Current wording

We expect that our general and administrative expenses will increase as our organization and headcount needed in the future grow to support continued research and development activities and potential commercialization of our product candidate. These increases will likely include increased costs related to the hiring of additional personnel and fees to outside consultants, attorneys and accountants, among other expenses. Additionally, we expect to continue to incur significant expenses associated with being a public company, including costs of additional personnel, accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with exchange listing and Securities and Exchange Commission, or SEC, requirements, director and officer insurance costs, and investor and public relations costs.

Previous wording

Research and development expenses were $12.4 million and $8.7 million for the three months ended March 31, 2024 and 2023, respectively. The $3.7 million increase in research anddevelopment expenses was primarily due to $1.2 million for higher personnel costs, which included a $0.4 million increase for non-cash stock compensation expenses, a $1.1 million increase for manufacturing and materials costs, a $0.8 million increase related to services provided by research and development contractors and consultants and $0.4 for other clinical trial expenses and $0.3 million for CRO costs; partially offset by a $0.1 million decrease in license expense. CRO costs increased slightly for the three months ended March 31, 2024 as compared to the three months ended March 31, 2023 primarily due to the costs incurred associated with the ALTITUDE-AD study, for which we announced the dosing of the first patient in May 2024 and the conclusion of our INTERCEPT-AD clinical trial, which was initiated in 2021 with topline results announced in July 2023.

Current wording

Research and development expenses were $32.0 million and $17.8 million for the six months ended June 30, 2024 and 2023, respectively. The $14.2 million increase in research and development expenses was primarily due to a $6.2 million increase in CRO costs associated with the ALTITUDE-AD clinical trial, for which we announced the dosing of the first patient in May 2024. Additionally, we incurred$2.6 million for higher personnel costs, which included a $0.8 million increase for non-cash stock compensation expenses, as well as increases in the following: $1.4 million for license agreement expenses, $1.3 million for manufacturing and materials costs, $1.0 million for other clinical trial expenses, $0.9 million related to services provided by research and development contractors and consultants, $0.5 million for shipping and packaging of our drug products and an overall $0.3 million increase in other contract research expenses.

Previous wording

General and administrative expenses were $5.3 million and $4.4 million for the three months ended March 31, 2024 and 2023, respectively. The $0.9 million increase was primarily due to an increase of $1.0 million in personnel costs, including a $0.7 million increase for non-cash stock compensation expenses, which was partially offset by a decrease of $0.1 million for insurance expense.

Current wording

General and administrative expenses were $10.2 million and $8.8 million for the six months ended June 30, 2024 and 2023, respectively. The $1.4 million increase was primarily due to an increase of $1.7 million in personnel costs, including a $1.2 million increase for non-cash stock compensation expenses, which was partially offset by a decrease of $0.3 million for insurance expense.

Previous wording

Other income was $2.9 million and $1.8 million for the three months ended March 31, 2024 and 2023, respectively. The$1.1 million increase was primarily attributable to a$2.2 million increase in interest income on our portfolio of marketable securities due to both higher interest rates and increased investment in marketable securities following our July 2023 public offering, which raised net proceeds of $121.9 million and our borrowings of $30.0 million upon the closing of our Loan Agreement in November 2023. The increased interest income was partially offset by an increase in interest expense of$1.0 million related to our Loan Agreement, as well as a $0.1 million increase in the fair value of the embedded derivatives that are bifurcated from the term loan under the Loan Agreement, and a $0.1 million increase in other expense, net.

Current wording

Other income was $6.7 million and $3.7 million for the six months ended June 30, 2024 and 2023, respectively. The $3.0 million increase was primarily attributable to a $4.1 million increase in interest income on our portfolio of marketable securities due to both higher interest rates and increased investment in marketable securities following our July 2023 public offering, which raised net proceeds of $121.9 million, and our borrowings of $30.0 million upon the closing of our Loan Agreement in November 2023, as well as increased income of $1.1 million due to a decrease in the fair value of the embedded derivatives that are bifurcated from the term loan under the Loan Agreement. The increased income was partially offset by an increase in interest expense of $2.0 million related to our Loan Agreement, as well as a $0.1 million increase in other expense, net.

Previous wording

On March 27, 2024, we filed a shelf registration statement on Form S-3, or the 2024 Registration Statement. Pursuant to the 2024 Registration Statement, we may offer and sell securities having an aggregate public offering price of up to $200 million.

Current wording

On March 27, 2024, we filed a shelf registration statement on Form S-3, or the 2024 Registration Statement. Pursuant to the 2024 Registration Statement, we may offer and sell securities having an aggregate public offering price of up to $200.0 million.

Previous wording

We have a sales agreement, or, as amended, the Sales Agreement, with BofA Securities, Inc., Stifel, Nicolaus & Company, Incorporated, and BTIG, LLC, as sales agents, pursuant to which we may issue and sell shares of our common stock for an aggregate offering price of up to $50 million under an at-the-market offering program, or ATM, which is included in the $200 million of securities that were registered for sale pursuant to a registration statement on Form S-3 filed in 2022. Pursuant to the Sales Agreement, we will pay the sales agents a commission rate of up to 3.0% of the gross proceeds from the sale of any shares of our common stock. We are not obligated to make any sales of shares of our common stock under the ATM.

Current wording

We have a sales agreement, or, as amended, the Sales Agreement, with BofA Securities, Inc., Stifel, Nicolaus & Company, Incorporated and BTIG, LLC as sales agents, pursuant to which we may issue and sell shares of our common stock for an aggregate offering price of up to $50.0 million under an at-the-market offering program, or ATM, which is included in the $200.0 million of securities that were registered for sale pursuant to a registration statement on Form S-3 filed in 2022. Pursuant to the Sales Agreement, we will pay the sales agents a commission rate of up to 3.0% of the gross proceeds from the sale of any shares of our common stock. We are not obligated to make any sales of shares of our common stock under the ATM.

Previous wording

As of March 31, 2024, we had cash and cash equivalents andmarketable securities totaling $296.6 million. Ouravailable-for-sale marketable securities mature over the next 2 years. Based on our current operating plan, we expect that our existing cash and cash equivalents and marketable securities will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into the first half of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect, including based on our decision to initiate other clinical trials or programs.

Current wording

As of June 30, 2024, we had cash and cash equivalents andmarketable securities totaling $281.4 million. Ouravailable-for-sale marketable securities mature over the next 15 months. Based on our current operating plan, we expect that our existing cash and cash equivalents and marketable securities will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into the first half of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect, including based on our decision to initiate other clinical trials or programs.

Previous wording

Net cash used in operating activities increased by $7.7 million to $17.9 million for the three months ended March 31, 2024 from $10.2 million for the three months ended March 31, 2023. Increased net loss of $3.6 million for the three months ended March 31, 2024, adjusted for non-cash expenses including stock-based compensation of $1.1 million, non-cash interest of $0.3 million and change in fair value of embedded derivatives of $0.1 million, which were offset by non-cash income for amortization and accretion on marketable securities of $1.4 million, was responsible for $3.6 million of the increase in cash used as compared to the prior period. Working capital changes also resulted in an increased use of cash of $4.1 million and included increases in cash used for accrued clinical trial expenses of $4.5 million and accrued expenses and other current liabilities of $3.5 million, both of which were primarily due to our increased research and development accruals for our ALTITUDE-AD study; which were partially offset by increases in cash provided by accounts payable of $2.6 million, prepaid expenses and other current assets of $0.7 million, and operating lease liabilities of $0.6 million.

Current wording

Net cash used in operating activities increased by $12.6 million to $34.4 million for the six months ended June 30, 2024 from $21.8 million for the six months ended June 30, 2023. The primary reason for this was an increase in net loss of $12.5 million for the six months ended June 30, 2024. When adjusted for increases in non-cash expenses including stock-based compensation of $2.0 million and non-cash interest of $0.5 million, which were offset by increases in non-cash income for amortization and accretion on marketable securities of $2.6 million and change in fair value of embedded derivatives of $1.0 million, our net loss for the six months ended June 30, 2024 was responsible for a $13.6 million increase in cash used as compared to the six months ended June 30, 2023. Working capital changes offset the adjusted net loss, providing $1.0 million of cash for operating activities, which included an increase in cash provided by accrued clinical trial expenses of

Previous wording

Cash provided by financing activities was $7.1 million for the three months ended March 31, 2024, including $7.9 million of net proceeds from the issuance of our common stock under our ATM, partially offset by a payment of $0.7 million under a finance lease agreement for certain computer equipment for our ALTITUDE-AD clinical trial and $0.1 million of deferred offering costs related to our 2024 Registration Statement.

Current wording

Cash provided by financing activities during the six months ended June 30, 2024 of $7.0 million increased by $7.1 million from cash used in financing activities of $0.1 million during the six months ended June 30, 2023, primarily due to $7.9 million of net proceeds from the issuance of our common stock under our ATM, which was partially offset by a payment of $0.7 million under a finance lease agreement for certain computer equipment for our ALTITUDE-AD clinical trial and a $0.1 million increase in deferred offering costs related to our 2024 Registration Statement.