Issue:May 2024

EXECUTIVE INTERVIEW - Coya Therapeutics: Unlocking the Power of Tregs to Combat Inflammation & Fight Neurodegenerative Diseases

Coya Therapeutics, Inc. is a Houston-based clinical-stage biotechnology company developing proprietary treatments focused on the biology and potential therapeutic advantages of regulatory T cells (Tregs) to target systemic inflammation and neuroinflammation. Dysfunctional Tregs underlie numerous conditions, including neurodegenerative, metabolic, and autoimmune diseases. Coya’s investigational product candidate pipeline leverages multiple therapeutic modalities aimed at restoring the anti-inflammatory and immunomodulatory functions of Tregs.

Drug Development & Delivery recently had a discussion with Dr. Howard Berman, Founder and CEO of Coya Therapeutics, focusing on how the company is leveraging Tregs, its investigational products and the conditions targeted, Coya’s significant partnership with Dr. Reddy’s Laboratories, and his goals throughout the next 5 years.

Q: How did you launch Coya? Can you elaborate on your background and how you started the company?

A: I earned a PhD in Neuropharmacology and have spent my career in the pharmaceutical industry. I previously worked at Novartis, Abbvie, and Eli Lilly, where I developed and harnessed skillsets in the areas of drug development and commercialization, learning all of the ropes that now serve me well at Coya. While I was at AbbVie, where I worked prior to launching Coya, my father – a brilliant triple board-certified physician – started experiencing cognitive loss. Unfortunately, the cognitive loss slowly started to increase in intensity and speed. I took him to see Dr. Stanley Appel, a renowned doctor in the area of amyotrophic lateral sclerosis (ALS) and neurological diseases. At that meeting, Dr. Appel let us know there was not a lot we could do for this condition with the current science and approved products, but asked me to meet him so he could show me what he was working on. He presented me unbelievably exciting data that illustrated that enhancing Treg function and numbers in patients could stop or slow progression in ALS patients and opened up opportunities in other neurodegenerative conditions like dementia, which afflicted my father. Dr. Appel asked me if I would be interested in moving the research initiative forward. After a conversation with my wife, I dropped everything I was doing because I knew that this was too exciting to pass up. And that’s when I launched Coya and drove it forward. Two years later, we went through an IPO and became public during the same week my father passed away. I know our company has been blessed from day one, and I attribute those blessings to my father, who has given us success and strength.

Q: How is Coya leveraging Tregs in its pipeline to treat neurodegenerative, autoimmune, and metabolic diseases?

A: Based on the work of Dr. Appel and Houston Methodist, we know Tregs are dysfunctional in neurodegenerative conditions. What we’ve discovered is that dysfunction in Tregs causes inflammation, which plays a critically important role in a patient’s decline and the pathophysiology of neurodegenerative diseases. In addition, we are also focusing on other aspects of the immune system that are compromised by neurodegenerative disease, including the innate immune system and its myeloid cells and macrophages. Our core assets are biologics that repair the Treg dysfunction but simultaneously block other pro-inflammatory pathways, ultimately resulting in synergistic approaches that may keep Tregs durably functional, active, and viable. The key discovery we have made is that inflammation is an important and central driver of these diseases and that Treg cell biology is the common denominator. That is why we are excited about this approach with our COYA 302 investigational product.

Q: Your current lead investigational products are COYA 301 and COYA 302. What specific diseases are they targeting and how far along is Coya to bringing the therapeutics to market?

A: COYA 302 is a combination biologic and our lead asset. We believe combinations are the future of treatment approaches in neurodegenerative diseases, and we’re building a pipeline and an asset around COYA 302.

COYA 302 is the combination of our proprietary low-dose interleukin-2 (COYA 301, or LD IL-2) and the immunomodulatory drug CTLA4-Ig, and we believe this combination has the potential to provide a sustained and durable effect the first series of neurodegenerative disorders we are focused on through a targeting of multiple pathways. Our research and clinical efforts have led us to believe that combination biologics using our LD IL-2 as a backbone modality could be the best way to treat neurodegenerative conditions that are inherently driven by a complexity of pathways. We believe COYA 302 represents the most clinically advanced of what we hope will be a family of combination therapies that all feature our LD IL-2.

Moreover, given its growing list of indications, we can now refer to COYA 302 as a “Pipeline in a Product.” We are developing COYA 302 for a number of indications. We’ve previously announced our objective of developing it in ALS. Why ALS? This is a disease driven by a complex set of mechanisms, including dysfunctional Treg biology. COYA 302’s combination approach is important to mitigate the underlying biology complexity and is an approach that has been lacking with other investigational agents. In March 2024, we shared new data that highlights the strong predictive value of levels of an oxidative stress biomarker (4-HNE) with the rate of disease progression and survival in 50 ALS patients from a longitudinal patient registry cohort. In a proof-of-concept study in patients with ALS, the combination of LD IL-2 and CTLA4-Ig appeared to lower 4-HNE and other proinflammatory biomarker levels and stop progression at 24 weeks, a key benchmark time point in ALS trials. We believe this is highly promising data.

Also, given our research and clinical findings in a proof-of-concept trial that showed LD IL-2 alone was able to improve cognitive function in Alzheimer’s Disease (AD) patients after four months of treatment, we recently expanded our pipeline with COYA 302 into Parkinson’s disease (PD), Frontotemporal disease (FTD), and AD. While this monotherapy data is clearly encouraging, we believe that treating PD, FTD, and AD patients with our combination therapy of COYA 302, may offer an even better approach in these patient populations, given what we believe are similar underlying multiple, complex pathways. In the fall of 2023, we completed enrollment of a Phase 2 investigator-initiated trial evaluating LD IL-2 in AD. The results from that trial, expected during the summer of 2024, are expected to serve as the basis for the design of a future trial with COYA 302 in AD patients. Additionally, we anticipate filing an IND in the second half of 2024 to evaluate COYA 302 in patients with FTD and initiating that trial shortly thereafter. Topline data from this Phase 2 trial in FTD is expected in 2025.

Thus, one can see why we now refer to COYA 302 as a “Pipeline in a Product.” ALS is our lead indication, but many other larger neurodegenerative patient populations also stand to benefit given the common disease pathways involved.

Q: What makes your pipeline different from other biotech companies looking to combat these diseases?

A: Many biotechs are focused on one neurodegenerative disease, one target, one mechanism, one drug. We believe that is not the correct paradigm nor correct way to target these diseases, as they are complex diseases and not driven by one pathway.

We are moving into the regime of combination approaches and combination biologics, just like the general biotech market has done in cancer, HIV, and viral disease treatment. These combination approaches have transformed the way these diseases are currently treated and have pushed life expectancy out for many years. It’s not different in neurodegenerative conditions, in our opinion. Moreover, other companies that are now correctly targeting inflammation as a key pathway driver in neurodegenerative disease are focused on targeting one pathway, which is probably not going to be sufficient, again in our opinion. We are targeting the top of the pyramid of the adaptive immune system, the Tregs, as well as targeting the innate immune system, which is another critically important component of the immune system. By addressing both of these pathways simultaneously, there is the potential to have a disease-modifying treatment that can stop the disease from progressing, whether that be in ALS, PD, FTD, or AD.

Q: What is the significance of Coya’s partnership with Dr. Reddy’s Laboratories for COYA 302?

A: First, this partnership further validates our approach, the science, the IP, and the commercial opportunity we see with our potential combination therapy platform. Dr. Reddy’s Laboratories (DRL) is an independent multi-billion dollar company that did its own deep due diligence and believes in our approach, which is validating.

Second, the partnership is great for ALS patients who are waiting for a more effective treatment for this devastating neurodegenerative disease. Coya and DRL are working seamlessly with our respective strengths to advance COYA 302 as efficiently as possible in ALS.

Third, the partnership strengthens COYA’s balance sheet in the short-term and potentially in the mid-term and long-term through this non-dilutive deal worth a potential $700M+. Importantly, DRL received licensing rights only in the ALS indication in the US, Canada, the EU, and the UK, meaning Coya retains the rights to the ALS indication in some key territories (like Japan), as well as all other indications. This provides us with the optionality to execute additional non-dilutive agreements for COYA 302 that can further strengthen the balance sheet.

We executed this deal in a tough biotech environment in 2023, and – when combined with all the clinical and regulatory milestones we achieved in 2023 – demonstrates that we are a company that can execute with an eye on creating value for patients and our shareholders alike.

We are now nearly six months into our partnership with DRL, and we are proud to have the company by our side in our joint effort to bring COYA 302 forward for patients suffering from ALS.

Q: Coya recently licensed intellectual property rights from the University of Nebraska Medical Center for the use of next-generation immune modulatory biologics in combination with COYA 301 to enhance and strengthen Tregs in inflammatory disease. How will Coya utilize this license, and what makes it important?

A: We strongly believe COYA 301 will serve as a backbone for future combination approaches. Similar to COYA 302, there are many other mechanisms that have synergistic potential with LD IL-2. Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is one of them. The preclinical data generated to date by the experts at the University of Nebraska is compelling, as Treg function and numbers are significantly enhanced from the combination of LD IL-2 and GM-CSF, which sets up for applications in many neurodegenerative diseases like PD. This partnership also gives us access to one of the leading experts in the field, and we fully plan to leverage that relationship to advance this combination. Through this partnership, we have the opportunity to enhance our pipeline and potentially enter into strategic partnerships with companies currently developing/manufacturing GM-CSF, providing us additional opportunities for business development deals as well.

Q: What developments do you expect for Coya in the coming five years?

A: There is the near-term, mid-term, and long-term, and I consider five years long-term.

Our near-term objective is to file the IND for COYA 302 in ALS and subsequently initiate the Phase 2 clinical trial in 2024.

Over the mid-term, we expect to have the data readout from that Phase 2 ALS trial with COYA 302 toward the end of 2025 and hope to present a case to the FDA that our drug is safe and efficacious in patients suffering from ALS.

In parallel with the Phase 2 ALS trial, we expect to conduct a Phase 2 trial in patients with FTD and share data from that trial in 2025, also. That data will guide our next steps, including the potential initiation of a subsequent registrational study in FTD, assuming the Phase 2 data supports continued development. The FTD indication also brings additional potential partnership opportunities for us.

We also anticipate advancing COYA 302 in PD and AD in parallel with our ALS and FTD development activities. Moreover, we expect to advance the other assets in our pipeline, including our exosome-based programs that may be ideal for multiple partnering opportunities.