Speakers on a Coya Therapeutics (NASDAQ:COYA) webinar outlined the company’s scientific rationale and clinical development plans for an investigational combination immunotherapy in amyotrophic lateral sclerosis (ALS), emphasizing a shift in the field toward more targeted, biology-driven approaches.
ALS landscape and the push for targeted biology
During the discussion, presenters described an “huge need” for therapies that can more meaningfully slow or halt ALS progression—and raised the possibility that future approaches could potentially reverse some functional decline or even prevent disease, questions they said were not realistic to ask “many years ago.”
When asked why currently approved therapies tend to deliver only modest benefit and why so many ALS trials have failed, speakers suggested many prior efforts were “unfocused,” often based on broad observations of neurodegeneration rather than specific disease-driving biology. They said the field has increasingly converged on neuroinflammation as a key target, citing decades of lab work led by Stanley Appel, MD, and noting that neuroinflammation is now widely viewed as a central component of ALS pathology.
Inflammation, oxidative stress, and the role of Tregs
Appel described inflammation in ALS as involving immune system alterations, including activated macrophages releasing pro-inflammatory cytokines, and multiple T cell subtypes (including CD4 T cells such as Th1 and Th17, as well as CD8 cytotoxic T cells) that can contribute to neurodegeneration.
A central focus of the webinar was regulatory T cells (Tregs), which Appel described as neuroprotective due to their ability to suppress inflammatory responses. However, he said Tregs in ALS patients are often not suppressive “to the extent that they should be,” characterizing them as dysfunctional and unable to adequately counter neuroinflammation.
Why combine low-dose IL-2 with CTLA-4 Ig (abatacept)
Appel explained that while IL-2 can expand Tregs in animals and humans, administering IL-2 in ALS occurs within an inflammatory environment. He described lab findings suggesting activated macrophages can drive Tregs into dysfunction and “exhaustion” over several days in culture. In that context, he said the addition of CTLA-4 Ig (abatacept) was supported by in vitro data as a way to suppress inflammatory macrophage activity and help prevent Treg dysfunction.
In the proposed combination approach, IL-2 is intended to expand Tregs while abatacept suppresses macrophage-driven inflammation—an effort to address what speakers described as immune system complexity and “redundant pathways.” James Berry, MD, characterized the dual targeting as “very exciting,” noting that IL-2 alone has shown limited benefit and that the feedback loop between macrophages and Tregs may help explain why.
Small patient study and biomarker signals
Appel discussed a previously conducted study involving four ALS patients progressing at what he called an intermediate rate; one patient had a C9orf72 mutation. He said the combination was administered subcutaneously every two weeks for six months, with treatment extended beyond that period.
According to Appel, the regimen “seemed to slow progression,” and in some cases appeared to stop progression during the initial six months, though he said progression continued when followed more carefully over a longer period, albeit at a slower pace. He also reported patients “felt tremendously” about the therapy and asked to continue.
He highlighted multiple biomarker observations from the four-patient experience, including:
- Inflammation: interleukin-18 (IL-18) was suppressed in serum in 3 of 4 patients.
- Oxidative stress: oxidized LDL declined in 4 of 4 patients; 4-hydroxynonenal (4-HNE) showed similar changes, described as a lipid peroxide marker.
- Neurofilament light (NfL): two patients with elevated NfL saw levels drop, while two others did not have high NfL at baseline.
Berry emphasized that while four patients is a small sample, he views the decision to move forward as based on the “totality of the evidence,” including longstanding Treg biology, macrophage activation, and the ability to track biomarker changes alongside clinical outcomes.
ALSTARS Phase 2 design and safety commentary
Berry, identified as a principal investigator for the ALSTARS Phase 2 trial, said the randomized, placebo-controlled study is planned across close to 25 sites in the U.S. and Canada. He said the trial aims to enroll 120 people with ALS, with one-third assigned to placebo for six months. The remaining two-thirds will be split between two dosing regimens; all participants in active arms receive low-dose IL-2 five days a week in two cycles each month, while abatacept is given either once monthly or twice monthly.
Berry said the trial is designed to evaluate which regimen has an “edge,” which could include practicality, tolerability, or biomarker and clinical outcome signals. He also described a blinded extension phase in which placebo participants are re-randomized to an active regimen while maintaining blinding, allowing longer-term comparisons if clinical effects take more time to emerge.
On patient selection, Berry said inclusion criteria are designed to enroll patients earlier in disease and within a “sweet spot” where motor neurons remain to be spared and neuroinflammation may be more “rescuable,” while also ensuring enough measurable change over time to support a six-month primary endpoint.
Regarding timing, Appel said Tregs in the four-patient study were significantly elevated with enhanced suppressive function by week 4, while biomarker changes were more marked over 2 to 4 months.
On safety and tolerability, Appel said low-dose IL-2 has been “very, very safe” across many studies and that his team did not observe an increased incidence of infections in their experience. Berry added that low-dose IL-2 preferentially activates regulatory T cells, differing from high-dose IL-2 that can activate pro-inflammatory T cells. He also noted abatacept is broadly used in inflammatory diseases with significant experience, while emphasizing the need to screen for issues such as latent TB infection.
In Q&A, Berry said a slower ALSFRS-R decline typically correlates closely with improved survival, and Appel agreed while noting the need to monitor whether inflammation could increase despite therapy. The webinar host also stated the company is in discussions to create an expanded access protocol, and said FDA approval would depend on the strength of the data, noting therapies have previously been approved based on a single trial.
About Coya Therapeutics (NASDAQ:COYA)
Coya Therapeutics, Inc (NASDAQ: COYA) is a clinical‐stage biotechnology company focused on the discovery and development of first‐in‐class therapeutics for fibrotic diseases and cancer. The company’s scientific approach centers on targeting UNC-45A, a molecular chaperone implicated in the regulation of cell motility, proliferation and extracellular matrix deposition. By modulating the activity of UNC-45A, Coya aims to address underlying mechanisms of tissue fibrosis and tumor progression that currently lack effective treatments.
Coya’s pipeline is anchored by two lead programs: COY-001, a small‐molecule inhibitor in preclinical development for fibrotic disorders such as idiopathic pulmonary fibrosis and systemic sclerosis, and COY-002, which is being advanced toward the clinic for certain solid tumors.
