Coya Therapeutics On Developing A Combination Biologic

By Tyler Menichiello, contributing editor

Complex diseases demand complex treatment solutions, and in cases like neurodegenerative diseases, which are driven by a variety of different biological factors and pathways, “one target may not be sufficient,” says Coya Therapeutics’ executive chairman, Howard Berman, Ph.D. That’s why Coya’s lead candidate, COYA 302, is a combination biologic that combines low-dose interleukin-2 with abatacept to modulate regulatory T-cell (T-reg) responses in the hopes of treating a variety of neurodegenerative conditions.

COYA 302 is currently preparing for an upcoming Phase 2 study for the treatment of ALS, but the company is working to develop it for other neurodegenerative conditions such as frontotemporal dementia (FTD), as well as Alzheimer’s and (eventually) Parkinson’s. I had the chance to meet with Dr. Berman to learn about Coya’s approach to developing this combination biologic and the challenges that multi-targeted therapeutics present.

The Sum Of Its Parts

COYA 302 is a therapy that combines two different biologics — low-dose interleukin-2 (IL-2) and abatacept, or CTLA-4 Ig (cytotoxic T-lymphocyte-associated protein 4). IL-2 is a cytokine that, at a low dose, specifically and selectively upregulates T-reg activity to elicit an anti-inflammatory response in the immune system, and CTLA-4 Ig works to suppress effector T-cell and macrophage activity.

“By giving the two drugs together, you may have a significant, synergistic impact in slowing this inflammatory cascade,” Berman explains.

This idea of targeting multiple cascades and pathways to mitigate inflammation is similar to the combination approach seen in oncology, he says. “We’re doing the same approach with neurodegeneration.” This idea makes sense: by targeting multiple pathways to lessen inflammation, it should effectively slow or stop the progression of these conditions. At least, that’s what Berman and his team at Coya believe.

This idea of multi-targeted treatment strategy for neurodegenerative diseases is not unique to Coya. In fact, it’s one that is showing increasing promise. However, leveraging combination biologics is not a trivial matter, Berman tells me. It requires regulatory feedback and alignment with the FDA and other agencies. The non-clinical work involves testing the individual components as well as the combination to illustrate safety for each, which is what Coya has done for COYA 302.

Strategic Partnerships For Multiple Indications

“Smaller companies need to be innovative,” Berman says about funding and developing candidates for different indications. It’s a fine balance of staying focused while also being flexible. “If you become distracted, you lose focus and you waste money,” he says.

In the interest of staying focused and flexible, Coya is developing COYA 302 for multiple indications through external partnerships in the form of non-dilutive funding and investment. For example, Coya partnered with Dr. Reddy’s Laboratories for its ALS indication (Dr. Reddy’s is funding the entire COYA 302 ALS program), a decision that was an “obvious choice,” Berman says, because Coya in-licensed the abatacept biosimilar from Dr. Reddy’s. Coya is also partnering with the Alzheimer Drug Discovery Foundation, which has invested $5 million to run the subsequent trial for the FTD indication.

Coya recently announced Phase 2 data of low-dose IL-2 for Alzheimer’s, and Berman says they will explore strategic partnerships and other collaborations in this indication as well as in Parkinson’s Disease.

“We’ll never start an indication or start trials unless we’re fully committed and have the resources and budgets to do so,” he says.

I think that as COYA 302 continues to move through clinical development — and hopefully with continued positive results — it may increase clinical interest in multi-targeted approaches to neurodegenerative diseases. As the industry’s toolbox expands, and as we learn more about the underlying causes of these complex diseases, I’m hopeful that such combination approaches, and specifically multi-targeted biologics, will continue to grow in popularity and efficacy, one day making these devastating diseases a thing of the past.