Greywolf Therapeutics begins dosing of the first treatment to target the antigenic source of autoimmunity

• This is the first ever autoimmunity study to evaluate a potential functional cure that targets the antigenic source - the origin of autoimmune disease
• The Phase 1/2 study (up to 141 participants) will evaluate the safety, tolerability and efficacy of GRWD0715 in healthy volunteers and participants with axial spondyloarthritis (axSpA)
  
• GRWD0715 is an investigational small molecule designed to interrupt T-cell activation by inhibiting the peptide processing enzyme ERAP1 (Endoplasmic Reticulum Aminopeptidase 1)
  
• AxSpA has no cure and affects an estimated 0.5-1.4% of the global population - millions worldwide - leading to chronic inflammatory back pain, spinal stiffness, and significant disability if untreated
  

OXFORD, United Kingdom, Aug. 13, 2025, the clinical-stage biotech company advancing novel antigen modulation technology to guide the immune system, have successfully dosed the first healthy volunteer in their Phase 1/2 trial) evaluating GRWD0715, an oral ERAP1 inhibitor, for the treatment of axial spondyloarthritis (axSpA).

"The strong genetic association between ERAP1 and axSpA make it a very compelling primary indication for our first autoimmunity trial, and we're excited by the impact we could deliver to this underserved community," said Tom Lillie, Chief Medical Officer at Greywolf Therapeutics. "Whilst current therapies seek to suppress various inflammatory mediators produced by activated T cells, we're taking a distinctly different approach with our program and aim to target the source of disease by interrupting autoantigen presentation, preventing the damaging T-cell response from continuing."

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In people living with axSpA, the immune system mistakenly recognizes the body's own proteins as foreign and attacks healthy tissue, particularly in the spine and sacroiliac joints. In vitro models have shown that GRWD0715 modulates cell-surface antigens, removing the target antigen incorrectly recognized in axSpA patients and preventing T cells from attacking healthy tissue.

The Phase 1 component of the study will evaluate the safety and tolerability of GRWD0715 in healthy volunteers (up to 24 participants) and people living with axSpA (up to 36 participants). Findings from this part of the study will be used alongside proof-of-mechanism data to identify the biologically active dose for progression into the Phase 2 arm of the trial.

"We believe GRWD0715 represents a turning point in the treatment paradigm for autoimmune diseases like axSpA, offering the possibility of a functional cure by targeting the disease at its antigenic source," said Peter Joyce, CEO and Co-founder of Greywolf Therapeutics. "Dosing the first participant in this trial marks a major milestone for the company, testing the power of our antigen modulation approach to treat axSpA and bringing us closer to our goal of addressing significant unmet need in autoimmune diseases."

About GRWD0715

GRWD0715, a first-in-class ERAP1 inhibitor, is a selective, potent small molecule developed into an oral, once daily medicine.

ERAP1 trims antigens from bacterial and viral infections, leading to their presentation on the surface of cells and triggering an immune response to clear the threat. In axSpA, it is hypothesized that a peptide from a normal protein in the person's own cells (called a 'self-antigen') is processed via this ERAP1 trimming pathway and incorrectly recognized by the body's T cells as foreign, causing an immune reaction. In addition to Greywolf Therapeutic's preclinical data, recent scientific evidence strongly supports the role of this antigen/self-antigen presentation pathway driven by ERAP1, in the pathological stimulation of the immune system causing the inflammatory symptoms experienced by people living with axSpA.

GRWD0715 is designed to stop presentation of this self-peptide by inhibiting the ERAP1 enzyme, removing the stimulus for the immune system and the downstream inflammatory events. It has the potential to significantly reduce the symptoms experienced by people living with axSpA and halt disease progression.

About axSpA

Axial spondyloarthritis (axSpA) is a chronic immune-mediated inflammatory disease affecting mainly the spine and sacroiliac joints, causing persistent back pain and stiffness, and presenting generally before the age of 40. It affects ~0.5-1.4% of the population, with over 80% of cases in HLA-B27-positive individuals. Men and women are affected roughly equally, though forms of axSpA that cause changes in X-rays of the SI joints (radiographic axSpA) are more common in men. Symptoms may also involve hips, peripheral joints such as knees, wrists, shoulders and others, as well as extramusculoskeletal manifestations such as eyes (uveitis), skin (psoriasis), or the gut (inflammatory bowel diseases). There's no cure, but NSAIDs, biologics, tsDMARDs and non-pharmacological therapy help reduce pain, control inflammation, and maintain mobility to prevent long-term spinal damage.

About Greywolf Therapeutics

Greywolf Therapeutics is a clinical-stage biotech company advancing novel antigen modulation technology to guide the immune system. Greywolf's technology modulates antigen presentation, flicking a switch inside cells to alter their appearance to the immune system. They are progressing first-in-class antigen modulators to treat people living with autoimmune disorders, cancer and infectious diseases.

Greywolf is headquartered in Oxford, UK.

More information: www.greywolftherapeutics.com| LinkedIn

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