Coya Therapeutics Publishes ALS Study in Frontiers in Neurology

Coya Therapeutics, Inc. has revealed promising findings from a Phase 1 clinical trial that examined the effects of a combination therapy on Amyotrophic Lateral Sclerosis (ALS) patients. The study was detailed in a peer-reviewed manuscript titled, “A Phase 1 Proof-of-Concept Study Evaluating Safety, Tolerability, and Biological Marker Responses with Combination Therapy of CTLA4-Ig and Interleukin-2 in Amyotrophic Lateral Sclerosis,” published in the journal Frontiers in Neurology.

The trial explored the safety and efficacy of combining CTLA4-Ig Fusion Protein (CTLA4-Ig) and Low Dose Interleukin-2 (LD IL-2) in ALS patients. The participants, who were previously experiencing a decline of -1.1 points per month on the ALSFRS-R scale, showed a promising change at the end of the six-month treatment period, with the mean rate of change shifting to +0.04 points per month. This is significant, as ALS normally progresses rapidly, leading to severe disability and death often within three to five years after diagnosis.

The study was led by Dr. Stanley Appel from the Houston Methodist Research Institute. Four participants, including three with sporadic ALS and one with mutant C9ORF72-mediated ALS, were administered subcutaneous injections of LD IL-2 every day for five consecutive days every two weeks, alongside bi-weekly CTLA4-Ig injections over a 48-week period. The treatment aimed to enhance the function of regulatory T cells (Tregs) and reduce inflammation.

Key outcomes from the study indicated that the therapy was well-tolerated among patients, with no serious adverse events reported. Notably, there was a significant increase in Treg suppressive function at weeks 16, 24, and 48, which reverted to baseline levels six weeks after the final treatment cycle. Clinical progression, as measured by the ALSFRS-R scale, remained relatively stable during the first 24 weeks of treatment. Although individual responses varied, the average rate of change over the entire 48-week period was -0.13 points per month, demonstrating slower disease progression.

Biological markers such as 4-HNE (a lipid peroxide), ox-LDL (oxidized low-density lipoprotein), IL-18 (an inflammatory cytokine), and Nf-L (a marker of neuronal damage) were assessed. Participants generally showed a declining trend in these markers, correlating with the stable clinical progression observed during the treatment.

Coya’s CEO, Dr. Howard H. Berman, highlighted the significance of these findings, noting that the combination therapy could potentially offer a new therapeutic pathway for ALS patients, who currently have very limited treatment options. The company plans to continue the development of its ALS program and is preparing for an Investigational New Drug Application (IND) with the FDA for a larger, randomized, double-blind, placebo-controlled study slated for June 2024.

The investigational product, COYA 302, incorporates a dual immunomodulatory mechanism combining proprietary low dose IL-2 and CTLA4-Ig. This combination aims to boost the anti-inflammatory function of Tregs while suppressing inflammation from activated monocytes and macrophages.

This initial study sets the groundwork for further exploration of COYA 302’s potential benefits in treating ALS and possibly other neurodegenerative conditions. The upcoming larger-scale trials will be crucial in confirming these early promising results and could lead to significant advancements in the management of ALS, offering hope to those afflicted by this devastating disease.