Damora Therapeutics has initiated the global Phase 1/1b CLARITY-101 clinical trial evaluating DMR-001, an investigational monoclonal antibody designed to selectively target mutant calreticulin (mutCALR), following regulatory approval to begin the study. The trial will assess the therapy in patients with mutCALR-driven Essential Thrombocythemia (ET) and myelofibrosis (MF), two myeloproliferative neoplasms with significant unmet medical needs.

The CLARITY-101 study is an open-label, multicentre, dose-escalation and dose-expansion trial designed to evaluate the safety, tolerability and preliminary efficacy of DMR-001. The Phase 1 portion aims to establish the recommended dose for future development, while the subsequent Phase 1b expansion will further investigate the therapy across additional patient populations, including earlier lines of treatment and combination therapy settings.

DMR-001 is administered as a once-monthly subcutaneous injection, beginning with a starting dose of 100 mg. The study employs an adaptive Bayesian design that allows flexible cohort expansion during dose escalation. Eligible participants include adults with confirmed CALR-mutated essential thrombocythemia who are resistant, refractory or intolerant to at least one prior cytoreductive therapy, as well as patients with CALR-mutated myelofibrosis who have failed or are intolerant to at least one JAK inhibitor.

Becker Hewes, MD, Chief Medical Officer of Damora Therapeutics, said the initiation of the company's first clinical study marks a significant milestone in developing a potentially best-in-class therapy for patients with mutCALR-driven diseases. He noted that preclinical findings demonstrated a differentiated profile that could potentially deliver deeper and longer-lasting disease control while offering the convenience of once-monthly subcutaneous administration. According to the company, the programme reflects its commitment to developing disease-modifying therapies for patients with myeloproliferative neoplasms.

David Ross, MD, PhD, Associate Professor of Haematology at Flinders Medical Centre in Adelaide and an investigator in the CLARITY-101 trial, described targeting mutant CALR as one of the most promising advances in the treatment of myeloproliferative neoplasms. He said DMR-001's broad activity against CALR mutations and its convenient dosing schedule could make it a valuable therapeutic option for patients with essential thrombocythemia and myelofibrosis.

DMR-001 has been engineered to selectively bind mutant forms of calreticulin while sparing the normal wild-type protein, thereby aiming to minimise off-target effects. CALR mutations produce an abnormal protein that continuously activates the thrombopoietin receptor (TpoR), leading to uncontrolled blood cell production, increased risks of clotting and bleeding, and progressive bone marrow scarring. By interrupting this interaction, DMR-001 seeks to address the underlying biological driver of disease rather than simply managing symptoms.

The investigational therapy has also been designed to inhibit both Type 1 and Type 2 CALR mutations, including mutation subtypes that have historically been difficult to target. A YTE modification extends the antibody's half-life to support prolonged target engagement and infrequent dosing, while its Fc-null design eliminates Fc-mediated immune activity to potentially improve safety.

Preclinical data presented at the European Hematology Association (EHA) 2026 Congress demonstrated encouraging performance for DMR-001. In comparative laboratory studies, the therapy exhibited up to 30-fold higher binding affinity to mutant CALR than a reference anti-mutCALR antibody. Against Type 2 CALR mutations, DMR-001 showed up to 26-fold greater potency in inhibiting disease-driving cell growth. Studies in non-human primates also demonstrated an approximately five-fold longer half-life than the comparator antibody, supporting a dosing interval of four weeks or longer.

Damora Therapeutics expects to report initial clinical data from the CLARITY-101 trial beginning in mid-2027.

CALR mutations account for approximately 25 percent of essential thrombocythemia cases and 35 percent of myelofibrosis cases, representing an estimated 42,000 patients in the United States alone. Despite their role as primary disease drivers, there are currently no approved therapies specifically targeting mutant CALR, with existing treatments largely focused on symptom management rather than altering disease progression. Through DMR-001, Damora aims to advance a new class of targeted biologics capable of addressing the root cause of these blood disorders and improving long-term patient outcomes.