ABOS - Acumen: A First In Targeting May Lead To Improvement For Early AD Patients

2023-07-18 08:34:40 ET

Summary

• Positive topline results released from phase 1 INTERCEPT-AD study, which used ACU193 for the treatment of patients with early AD.
• The global market for Alzheimer's disease treatments is expected to rise past $13 billion by 2030.
• There was statistically significant amyloid plaque reduction observed with higher doses of ACU193 in the phase 1 INTERCEPT-AD study; statistically significant plaque reduction observed with a p-value of p=0.01.
• Unique approach in treating early Alzheimer's Disease patients, which is ACU193 as being the first clinical-stage amyloid beta oligomer [A?O]-targeting antibody for this population.

Acumen Pharmaceuticals (ABOS) has made some good progress lately as it relates to its drug, known as ACU193, which is being developed to treat patients with early-stage Alzheimer's Disease [AD]. The use of this drug candidate was being advanced in a phase 1 study, whereby positive topline results were released. The higher doses tested, which were 60 mg/kg every 4 weeks [Q4W] and 25 mg/kg every 2 weeks [Q2W] of ACU193, is whereby there was a statistically significant amyloid plaque reduction observed. The safety profile of this drug with respect to this early data is ideal, because it was noted that there were no drug-related serious adverse events [SAEs]. Why I believe that further gains might be possible here is because this positive topline data allows for a few other catalysts to come into play.

For starters, full results are going to be released at future medical congress. A second catalyst is that these findings are going to be submitted for publication in a peer-reviewed clinical journal. Thus, when these are published in a prestigious medical journal, that might cause the stock price to trade higher. A third catalyst might be the eventual initiation of a phase 2/3 study. That's because Acumen intends to meet with the FDA to discuss a timeline of being able to advance a phase 2/3 study, whereby ACU193 will be used to treat patients with early AD. The uniqueness of this biotech is that it is the first to be targeting amyloid beta oligomers [A?Os] for this disease. Such a selective approach with targeting soluble amyloid beta oligomers with ACU193 may not only lead to an improved treatment option for early AD patients, but also a safer alternative.

Positive Topline Data Shows Statistically Significant Amyloid Plaque Reduction

As I stated above, Acumen Pharmaceuticals reported positive topline results from its phase 1 INTERCEPT-AD study, which used ACU193 for the treatment of patients with early Alzheimer's Disease [AD]. Such positive data was presented at the Alzheimer's Association International Conference [AAIC] 2023, which took place in Amsterdam from July 16 - 20 of 2023. Alzheimer's Disease [AD] is a brain disorder whereby memory and thinking skills are destroyed. When that happens, patients also have issues with being able to carry out very simple tasks. Thus, mental functioning declines over time. A decline in mental function occurs when cells on the brain die off. It is believed that the disease might start about 10 years before the first symptoms appear. Not only that, but it also most commonly affects people who are over the age of 65. It is a very large market opportunity for sure, thus any company that can successfully get a drug to market for AD, might be able to reap the benefits. The global market for Alzheimer's disease treatments is expected to rise past $13 billion by 2030 . With respect to this indication though, it is not just about whether or not regulatory approval is ultimately received, but if Medicare or other insurers cover it. That's because insurers are hesitant to cover the cost of a treatment that does not show great improvement in being able to help this patient population [That is to significantly slow the decline of cognitive function].

The phase 1 study, whereby positive topline results were released was from INTERCEPT-AD . This was a randomized, double-blind, placebo controlled study that was evaluating the use of ACU193 for the treatment of patients with early AD. It was noted that about 65 patients with early AD [mild cognitive impairment or mild dementia due to AD] were enrolled into this particular study. The major positive development that was achieved in this study was that higher doses of ACU193, were able to show a statistically significant reduction of amyloid plaque load. Such a reduction was determined by amyloid PET scan, which is a diagnostic Alzheimer's test to evaluate cognitive impairment caused by amyloid plaques in these early AD patients. The doses of ACU193 used to achieve such amyloid plaque reduction were as follows:

• 60 mg/kg Q4W [once a month dosing]
• 25 mg/kg Q2W [once every 2-weeks dosing]

Thus, the ultimate conclusion was that proof of mechanism of ACU193, as a first clinical-stage amyloid beta oligomer targeting antibody. There was a statistically significant amyloid plaque reduction observed with higher doses of 25% [60 mg/kg Q4W cohort at day 63] and 20% reduction [25 mg/kg Q2W cohort at day 70]. Such statistical significance of amyloid plaque reduction was achieved with a p-value of p=0.01.

Despite only being a phase 1 data, this was of importance to prove the capability of ACU193 to reduce amyloid plaque levels. Why is that? That's because it is the first clinical-stage amyloid beta oligomer targeting antibody used for this AD patient population. To understand this, it is important to understand where a lot of studying is going for developing AD drugs. A lot of companies are only targeting certain types. For instance, in AD patients, there are five dominant pools of Amyloid Beta species and they are as follows:

• A? monomers
• A? oligomers [A?Os]
• Protofibrils
• Fibrils
• Amyloid Plaques

Historically, the focus has been on developing AD drugs that target either amyloid plaques and AB monomers. Acumen Pharma doesn't want to be another company targeting amyloid plaques or A? monomers, thus it believes that by targeting soluble A?Os, it has a unique treatment approach. This is evidenced with it having the first A?O targeting antibody ACU193 in the clinic. Thus, by specifically targeting soluble A?Os, which are the most toxic form of A?, it believes it can do better to help early AD patients. Not only was good target engagement shown with ACU193 for these patients, but it was also noted that there were no drug-related serious adverse events either.

The positive topline results was a huge achievement in showing that targeting A?Os for early AD patients is a good approach. However, I believe it also establishes a few catalysts for investors to look forward to as well. The first catalyst is that full results of the phase 1 INTERCEPT-AD study are going to be released at a future medical congress meeting. A second catalyst is that these positive topline results from this early-stage study, using ACU193 for the treatment of patients with early AD, are going to be sent for publication in a peer-reviewed medical journal. I believe that if this approach of targeting soluble A?Os for early AD patients is published in a prestigious medical journal, then it could be another event that may cause the stock price to trade higher. The third and final catalyst to come from this, would be the initiation of a phase 2/3 study for this program. I believe that once such a study is initiated it could be another catalyst that investors could look forward to.

Potential Competitors For The Treatment Of Patients with Alzheimer's Disease

There are a few possible competitors that Acumen might have to deal with, even if it does ultimately get ACU193 past all clinical stage trials and ultimately receives regulatory approvals. For instance, Biogen ( BIIB ) and Eisai ( OTCPK:ESAIY ) received FDA approval of LEQEMBI as a disease-modifying treatment for AD. What is to be noted is that this drug is an immunoglobulin gamma 1 [IgG1] monoclonal antibody directed against targeting:

• Protofibril
• Insoluble forms of A? - which are "Fibrils" and "Amyloid Plaques"

Where ACU193 can differentiate itself is that it has a unique approach in being the only to target A? oligomers [A?Os]. It remains to be seen if this drug with such an alternate approach reduces the progression of AD by a greater margin, but it is good to see such innovation in being able to develop a drug targeting these patients with an entirely different approach. A problem for Acumen is that it has a tough hill to climb and it largely depends upon what happens in phase 2/3 and possibly later testing. It has to be shown that this alternate approach, targeting A? oligomers [A?Os], is at least as effective or superior compared to other approaches out there. For instance, Eli Lilly just reported results from a 1,700 patient study, whereby donanemab was able to reduce progression of AD by 35% . This is pretty good, especially compared to Biogen's and Eisai's LEQEMBI, where AD progression was reduced by 27%. Donanemab is designed to specifically target the plaques of AD patients. Thus, between LEQEMBI and donanemab, each in their own has a different mechanism of action. Acumen Pharmaceuticals is hoping to take an entirely different approach in specifically targeting A?Os. Ultimately, the hope is that later testing proves that this drug can reduce AD progression by greater than what was achieved with LEQEMBI and donanemab, which was 27% and 35% respectively.

Financials

According to the 10-Q SEC Filing , Acumen Pharmaceuticals had cash, cash equivalents and marketable securities of $183.8 million as of March 31, 2023. It stated in its filing that it believes it has enough cash on hand to fund its operations through 2025. However, I believe that a cash raise may be imminent. For starters, moving on towards phase 2/3 clinical testing is going to be costly. Secondly, the biotech's stock traded higher by as much as $11.31 per share on the back of the release of the positive topline results from the phase 1 INTERCEPT-AD study. When a biotech trades higher by such a percentage, management typically takes advantage of this. Thus, despite the guidance given to be able to fund itself through 2025, it may possibly choose to raise cash immediately.

Risks To Business

There are several risks that investors should be aware of before investing in Acumen Pharmaceuticals. The first risk to consider would be with respect to the use of ACU193 in treating patients with early AD. That's because even though Acumen was able to prove rapid, dose-related, statistically significant amyloid plaque reduction in this phase 1 INTERCEPT-AD study, there is no guarantee a similar outcome will be achieved in a phase 2/3 study. Even then, there is no assurance that the reduction of amyloid plaque observed will result in reduced progression of AD. A second risk to consider would then be with respect to competition, as I highlighted above.

Even if Acumen does get through all clinical testing successfully with ACU193, along with regulatory approvals, it may have to go up against a few other approved AD drugs. For instance, LEQEMBI has been approved by the FDA for AD and donanemab may also be approved for it as well [Decision of donanemab filing in AD expected before end of 2023]. Thus, Acumen must either get equivalent or greater reduction in progression of AD compared to these other drugs, if intends to compete well in this sector. A third risk to consider would be with respect to the financials I highlighted above. That is, with positive data causing the stock price to trade much higher, it is quite possible that management could take advantage of it. Thus, a cash raise may be done almost immediately, if the company believes that it will need the cash for phase 2/3 testing.

Conclusion

With positive topline results from the phase 1 INTERCEPT-AD study, using ACU193 for the treatment of patients with early Alzheimer's Disease [AD], it can press on to speak with the FDA to establish a plan for phase 2/3 testing. What separates Acumen Pharmaceuticals from other companies producing a drug for AD, is that it is taking on an entirely unique approach. That would be the targeting of amyloid beta oligomers [A?Os] in these early AD patients. It remains to be seen if such an approach delivers in late-stage clinical testing, but at least Acumen is striving to succeed in a new area for AD clinical development. With the positive topline results released from the phase 1 INTERCEPT-AD study, there are a few catalysts that investors can look forward to, as I stated above. These would be publication of peer-reviewed medical journal of released INTERCEPT-AD study data, phase 2/3 study initiation of ACU193 for the treatment of early AD patients and full results from the phase 1 study at an upcoming medical conference.

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