What role is Cognition Therapeutics playing in the space of neurodegenerative diseases, and Alzheimer’s in particular?

We are focused on age-related neurodegenerative disorders, specifically Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and dry age-related macular degeneration. Having been around for the launch of intravitreal injections as a standard course of therapy, it is exciting to consider an oral drug that reaches the back of the eye – and both eyes simultaneously. Presently, we are conducting three trials with two more in the planning stages, all with the help of our CRO partners. Innovation needs a lot of capital and we have secured $170 million of non-dilutive funding from the NIA (National Institute on Aging), which we have used to advance into multiple Phase 2 trials.

It is fair to say we are a scientific leader in the field of age-related neurodegeneration.

In terms of our programs, we have a unique and well-validated approach. Many of the therapeutics on the market and in development for neurodegeneration conditions are monoclonal antibodies. One challenge is that very little of these drugs, sometimes only 0.01% of the drug, actually gets across the blood-brain barrier. Our candidate, CT1812 is an oral small molecule that has a high degree of blood-brain barrier penetration and a high degree of selectivity for its target, the sigma-2 receptor. This receptor regulates several processes - a cleanup mechanism if you will - that get damaged in Alzheimer's disease. We believe that our lead drug can normalize these processes so neurons can rid themselves of the toxins and regain function.

We have plenty of preclinical evidence from animal models and in vitro studies in human tissue, and now data from human trials on brain volume, biomarkers, and early cognitive results supporting that CT1812 has an impact on Alzheimer's disease by modifying the underlying disease processes. Importantly, it appears to have an effect on both diseases characterized by amyloid beta oligomers and alpha-synuclein oligomers. In addition, CT1812 is being studied in dry AMD, where it is posited to protect retinal pigment epithelial (RPE) cells, which are responsible for maintaining photoreceptor health. 

What is the selection process behind choosing clinical trial patients in order to ensure diversity?

While we want to enroll people in our trials that are representative of patients with the disease, this can prove difficult for many reasons. Many of our studies are done at large academic centers that have certain diagnostics, such as PET scans, that are required for diagnosis but not readily available throughout the country. Protocols may require that patients fit certain criteria such as amyloid level or score within a specific range on cognitive tests. Patients also need to have a caregiver who is willing and able to assist them to attend regular clinic visits. That said, we and our CRO partners are committed to improving access to our studies by translating our clinical trial information into multiple languages and providing transportation assistance.

How close are you to finding efficacious treatments for Alzheimer’s, dementia and other age-related cognitive diseases that are impacting the lives of tens of millions around the world?

Advancements are being made and we are closer now to unlocking cures and preventing the decline of brain function than we ever have been before. Recently, Eisai presented data on its monoclonal antibody, lecanemab, which was approved by the FDA in January. This drug also targets a soluble form of amyloid beta – protofibrils – and showed a 27% reduction in disease progression. It is unquestionably an important advance, but there are challenges, namely the need for patients to live near and be able to travel to infusion centers for bi-monthly treatments. 

Our lead drug, CT1812 works on a similar form of amyloid beta as lecanemab– soluble oligomers – and prevents them from binding to the neuron thus damaging synapses. Because CT1812 is an oral, small-molecule drug, when it reaches the market, we believe it could provide an important treatment option for people regardless of where they live. Further, since it works by a different mechanism, we believe it may be complementary to monoclonal antibody therapies. 

Drug development, as you know, is a painstaking process. We have shown positive results in a number of patient trials to date, but the first real meaningful evidence of cognitive impact will come from our ongoing SHINE study in 140 mild-to-moderate AD patients over six months.  In the first cohort of patients evaluated, we observed a 3-point difference in cognition. This difference was seen in a small group of patients so it was not statistically significant, but if it proves out in the full patient set, it could be clinically significant. Notably, this was the same degree of symptomatic improvement that previous Alzheimer's drugs used for approval. 

What are the main objectives you would like to achieve in the next five years for Cognition Therapeutics?

We have a number of important clinical trials we are running that we expect to conclude and read out in the next five years. We are running a study called SEQUEL - an eight-week trial where we are analyzing the pattern of theta waves, which are brain waves often associated with executive function and memory formation, with the goal of showing that they are normalized after using our drug. SHINE, which I mentioned earlier, should complete this year with data in 2024. Our SHIMMER study in patients with dementia with Lewy bodies should also have data in 2024. And our largest and most ambitious program yet – a 540-patient study of patients with early Alzheimer’s disease is expected to start enrollment this year and could yield important insights within this period.   

Of course, we are also planning for the next stages of development. We are working on our plan to advance to Phase 3.  Hopefully, we will see other disease-modifying drugs approved or in development – and perhaps we will evaluate combinations of these drugs and CT1812 in the future. All the signals to date show that we are impacting the underlying drivers of neurodegenerative disease, but there is only one way to move on to approval: complete the studies and evaluate the data.