Greywolf Therapeutics has dosed the first healthy volunteer in a Phase 1/2 trial of its oral ERAP1 inhibitor, GRWD0715, for axial spondyloarthritis (axSpA). The study (NCT07047703) will enroll up to 141 participants and assess safety, tolerability, and efficacy in both healthy volunteers and individuals with axSpA.
This trial marks Greywolf’s first foray into autoimmunity and represents a novel approach to treating the disease. Rather than suppressing inflammatory mediators produced by activated T-cells, GRWD0715 aims to block the underlying antigenic source driving the autoimmune response. By inhibiting ERAP1, a peptide-processing enzyme, the drug prevents the presentation of self-antigens that trigger T-cell attacks on healthy tissue, specifically within the spine and sacroiliac joints.
This strategy of targeting the root cause of the autoimmune reaction differentiates Greywolf from competitors focused on downstream inflammatory cascades. The company’s preclinical data suggest that modulating antigen presentation via ERAP1 inhibition could offer a “functional cure” for axSpA, a chronic condition affecting an estimated 0.5–1.4% of the global population. The current standard of care focuses on symptom management using NSAIDs, biologics, and tsDMARDs, leaving a significant unmet need for disease-modifying therapies.
The Phase 1 portion of the trial will determine the safety and tolerability of GRWD0715 in both healthy volunteers and axSpA patients. This data, combined with proof-of-mechanism findings, will inform dose selection for the subsequent Phase 2 efficacy assessment. The study will also shed light on the clinical translatability of ERAP1 inhibition, a mechanism with strong genetic links to axSpA but limited clinical validation to date.
Several questions remain as the trial progresses. Will the in vitro efficacy of GRWD0715 translate into clinically meaningful improvements in axSpA symptoms and disease progression? What will the long-term safety profile of ERAP1 inhibition look like, given its role in broader immune function? How will payers view a novel mechanism of action compared to existing therapies, particularly given the potential for disease modification versus symptom control?
The outcome of this trial could have broad implications for the autoimmunity field. If successful, GRWD0715 could validate antigen modulation as a viable therapeutic strategy, potentially opening new avenues for drug development in other autoimmune conditions. It could also reshape the treatment landscape for axSpA, offering patients a potential pathway to disease remission rather than ongoing symptom management. The trial’s progress and data readouts will be closely watched by investors, pharmaceutical companies, and clinicians alike.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
