Coya Therapeutics (NASDAQ: COYA) is a Houston-based clinical-stage company with multiple therapeutic assets. Coya develops biologic and cell therapy treatments that modify regulatory T cell ("Treg") activity with the objective of addressing systemic inflammation in chronic complex conditions like Alzheimer's Disease. Their two most advanced therapeutic assets, COYA 301 and COYA 303, have recently achieved striking results in open-label proof-of-concept studies for Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's Disease, respectively.
| INFLAMMATION
While it gets a bad rap, inflammation is an essential defensive immune response to harmful stimuli like infection, injury, or toxins. Inflammation:
mobilizes immune cells, proteins, and growth factors to contain and eliminate threats,
isolates tissue by increasing blood flow and vascular permeability, and
brings immune resources to bear exactly where needed and coordinates a defense.
An inflammatory response is crucial for pathogen removal, wound healing, and recovery. Importantly, a reduced or weakened inflammatory response is called immunodeficiency and is characterized by increased susceptibility to infection, delayed wound healing, and an increased risk of cancers.
In contrast, an excessive or prolonged inflammatory response can lead to autoimmune diseases and drive local or wide-spread, generalized tissue damage. Inflammatory bowel disease, multiple sclerosis, tissue fibrosis, Alzheimer's Disease, ALS, and metabolic diseases have each been associated with excessive or prolonged inflammatory response.
| REGULATORY T CELLS (Tregs)
Tregs are lymphocytes (a type of white blood cell) that play a critical role in regulating the body's natural immune response. Tregs are an essential counterweight to inflammation, preventing excessive reactions that could lead to autoimmune diseases, where the immune system attacks the body's own healthy cells and tissues in a runaway response to stimulus. Healthy Tregs do this by limiting the response of pro-inflammatory immune cells to harmful stimuli. When Tregs become dysfunctional or the number of healthy Tregs is reduced, their ability to appropriately suppress the inflammatory response is weakened and this runaway inflammation can lead to autoimmune or neurodegenerative disease
| Candidates
COYA 301: Coya's "backbone" asset (COYA 301) is a low-dose of proprietary modified interleukin-2 (IL-2). IL-2 is an important endogenously-produced immune regulator (cytokine) that selectively stimulates IL-2 receptors on Tregs. While IL-2-based drugs have long been considered attractive therapeutic candidates, their development and approval has been plagued by serious adverse reactions, including hypotension, pre-renal azotemia, and pulmonary edema. Dosage and modifications to the molecule can significantly alter its selectivity, tolerability, and usefulness as a course of treatment for cancer and autoimmune patients. Importantly, data from Coya's small (n=8) proof-of-concept Phase I, open-label, feasibility study in Alzheimer's Disease suggests that subcutaneous COYA 301 is well tolerated, with no serious adverse events reported. Further, patients (who were expected to experience cognitive decline) showed no cognitive decline during the 4-month trial and this striking result was accompanied by acute expansion of Tregs and a congruent increase in Treg suppression of inflammatory cytokines.
While the etiology of Alzheimer's Disease is still hotly contested, it is widely agreed that neuroinflammation plays an important role in disease progression. The results of Coya's small Phase I feasibility study are encouraging as there are currently no approved drugs for the treatment of Alzheimer's Disease which meaningfully slow or reverse disease progression.
COYA 302: Coya's therapy for Amyotrophic Lateral Sclerosis (ALS) combines COYA 301 with complementary CTLA4-IG. CTLA4-Ig is an engineered fusion protein -- a molecule combining part of a receptor called CTLA-4 with an antibody fragment. CTLA4-Ig reduces uncontrolled inflammation by interfering with T cell stimulation which prevents the activation of pro-inflammatory macrophages. Coya posits that this combination should increase the anti-inflammatory activity of Tregs while limiting the pro-inflammatory capacity of macrophages.
ALS, also known as "Lou Gehrig's disease", is a neurodegenerative disorder affecting the motor neurons that control voluntary muscle movement. ALS causes progressive paralysis and muscle wasting that ultimately leads to death. It is a brutal and rapidly progressing disorder (most patients die within 2-5 years of symptom onset) and there are currently no approved drugs that meaningfully slow disease progression.
While there is a genetic component in a fraction of ALS cases, roughly 90% of cases are sporadic with no clear genetic etiology. Neuroinflammation driven by glial cells like microglia and astrocytes is increasingly recognized as a driver of motor neuron damage and symptom progression in ALS. Autopsies show significant activation of microglia and astrocytes in the spinal cord of ALS patients. These glial cells release inflammatory cytokines, free radicals, and other toxic molecules that cause oxidative stress and cellular dysfunction. This creates a neurotoxic environment that amplifies neuronal injury and drives symptom progression.
Coya recently reported data from a small (n=4) proof-of-concept Phase I, open-label, feasibility study in ALS. This study included patients with well documented (typical) disease progression prior to treatment. Over a 48-week trial period, patients received subcutaneous injections of COYA 302 -- during the trial period, disease progression did not continue at its expected clip (-1.1 points/month), with mean symptom scores reduced by only 1.5 points over a 4-month period. Importantly, these results were consistent with increased population of Tregs and decreased macrophage-mediated oxidative stress. A remarkable (while statistically insignificant) finding, is that COYA 302 was effective in patients with sporadic (n=3) and familial (inherited, n=1) ALS. If these results are borne out in a larger trial, they would tell a compelling story about neuroinflammation as a critical factor in disease progression that is at least partially independent of ALS type.
| Select Leadership
Howard Berman, Ph.D. (Chief Executive Officer + Chairman): Nearly two decades of biopharma and healthcare experience, including a proven track record building relationships with KOLs while holding key leadership roles at pharmaceutical giants. Technical leader with broader-than-average competencies, including advanced scientific training (Ph.D., Neuroscience and Pharmacology), training in intellectual property management (Technology Transfer Officer, MD Anderson), and over a decade supporting business development via medical affairs (AbbVie, Eli Lilly).
Fred Grossman, D.O., FAPA (President and Chief Medical Officer): Seasoned executive leader (former Eli Lilly, Johnson & Johnson, Bristol Myers Squibb, Sunovion) in drug development, with decades of experiencing in clinical-stage asset development and numerous successful CNS drugs on market. Board-Certified in Psychiatry and a Fellow of the American Psychiatric Association and was a Fellow at the National Institutes of Health (NIH).
David Snyder, MBA (Chief Financial Officer and Chief Operating Officer): Proven CFO of publicly companies (25+ years), including 15 years as CFO at various therapeutics companies. Coya gets bonus points for Mr. Snyder's dual appointments -- perhaps easily overlooked, this shows a willingness to wear multiple hats and stay lean that is so useful when developing drugs in a choppy market.
Arun Swaminathan, Ph.D. (Chief Business Development Officer): Key stakeholder in partnerships and deals worth billions of dollars, including $6B worth of deals over a ~3 year period (Alteogen, 2018-2021). Advanced technical training (Ph.D., Pharmaceutical Sciences).
Michelle Frazier, Ph.D. (Senior Vice President, Regulatory Affairs): Advanced scientific training (Ph.D., Cell Biology). 20+ years of regulatory experience, including 7 years at the Federal Drug Administration (FDA). During her time with the FDA, Dr. Frazier reviewed 60+ novel molecular entities, oversaw multiple biologic license applications (BLAs), and was recognize multiple times for her leadership and excellence. After her time with the FDA, led regulatory strategy for multiple multiple candidates that received FDA approval.
To learn more about Coya's leadership and board of directors, visit their website.
| MARKET
Trends: Alzheimer’s Disease and Amyotrophic Lateral Sclerosis are debilitating complex disorders with few available treatment options.
Alzheimer's Disease: Numerous FDA-approved drugs are available for managing symptoms of Alzheimer's Disease. Cholinesterase inhibitors, which prevent the breakdown of acetylcholine (critical for creating and maintaining neural connections) are commonly prescribed (e.g., Donepezil, Galantamine, Rivastigmine) and reasonably well tolerated, but do not offer sustained improvements to quality of life, nor slow the progression of disease. NMDA antagonists (e.g., Memantine) work by regulating the excitatory neurotransmitter glutamate which can lead to cell death when significantly elevated (Glutamate-mediated neurotoxicity is thought to play a role in disease progression) and can be prescribed in combination with cholinesterase inhibitors. Unfortunately, like cholinesterase inhibitors, NMDA-antagonists fall far short of meaningfully improving patient outcomes. Recent advances in monoclonal antibody development have led to the development of Aducanumab (FDA Accelerated Approval) and Lecanemab (FDA Approved). Both drugs work by targeting amyloid beta plaques (a hallmark of Alzheimer's Disease) and, while these drugs do appear to reduce amyloid plaques and perhaps even slightly slow disease progression (both drugs are still quite new), they also have a pretty nasty safety profile, with brain bleeds, brain shrinking and even death reported. This is perhaps due to the non-specific action of the antibody on other amyloids (some of which are critical for normal brain function). Hopes that a subcutaneous injection of Lecanemab would be better tolerated (and not cause brain bleeding) were dashed when Eisai recently released additional data -- the efficacy and the safety profile were found to be similar to the original route of administration. While these drugs represent a step forward, they are poorly tolerated and do not stop or reverse disease progression Numerous private and public companies have candidates in development or in the clinic. Eli Lilly's recent Phase III trial suggests that their drug, donanemab, may be able to slow disease progression in ~1/3 of patients. This is fine, but it's about the same as Lecanemab. Eli Lilly may wax poetic about their drug being better tolerated, but this drug is still just a moderate improvement on existing standard of care -- it is not a breakthrough. Amyotrophic Lateral Sclerosis: The FDA has approved several drugs for ALS that may prolong life, slow decline, or manage symptoms. However, like Alzheimer's Disease, there is no available treatment that stops or reverses ALS progression. While ALS is not as prevalent as Alzheimer's Disease, the 5,000 new cases of ALS each year constitute an annual economic burden of roughly $1B. Like Alzheimer's, treating ALS is entirely about managing quality of life, not stopping or reversing progression. Earlier this year, Amylyx raked in >$90M in sales over two quarters for their ALS drug, Relyvrio, which looks like it may slow disease progression by ~10 months.
Value: Coya's listed shares (NASDAQ:COYA) are trading at $4.65 USD (as of market close 10/30/23) and there are currently 9,947,915 shares outstanding (as of 08/03/23) and cash or cash equivalents of $13.1M USD (as of 06/30/23). Assuming continued quarterly operating expenses of ~$3M, COYA should have runway through the end of Q2 2024, though non-dilutive financing from drug development partnerships could significantly extend runway as they await trials results in H1 2024.
Risks: Aside from the typical clinical, regulatory and manufacturing risks facing clinical-stage therapeutics companies, we observe the following specific risks for Coya Therapeutics:
There's not enough data yet. IL-2 drugs have notoriously bad safety profiles and the small investigator-initiated trials, while very exciting, are insufficient for assessing tolerability -- additional data in 2024 will tell us more. If they can get through safety trials and see similar efficacy in Phase II, both drugs have the potential to be home runs.
While they have kept the belt tight as an organization ($3M/quarter for a public drug development company is very lean), they may need to raise capital in H1 to keep the dream alive. Both assets in Phase I could be attractive focal points for collaboration or acquisition and, given the enormous interest large pharmaceutical companies have in both ALS and Alzheimer's Disease, this may be a viable path forward. Thankfully Coya's executive team is flush with partnership experience.
To stay up to date with Coya Therapeutics, visit their website.
The above opinion is for information purposes only and is not intended to be investment advice. Always seek a licensed professional for investment advice.
Integra Consulting has been retained by Coya Therapeutics (NASDAQ:COYA) ("COYA") as a consultant from July 3, 2023 to January 3, 2024, and pursuant to such, COYA has agreed to pay Integra a monthly cash retainer of $7,500 USD.