WALTHAM, Massachusetts, August 5, 2026
Damora Therapeutics, Inc. announced the initiation of the global Phase 1/1b CLARITY-101 clinical trial evaluating DMR-001, an investigational monoclonal antibody designed to selectively target mutant calreticulin (mutCALR) in patients with mutCALR-driven essential thrombocythemia (ET) and myelofibrosis (MF). DMR-001 is engineered as a highly potent, long-acting antibody therapy targeting both Type 1 and non-Type 1 mutCALR mutations and is designed for once-monthly subcutaneous administration. The company said the clinical trial follows receipt of health authority approval and represents the first clinical development milestone for DMR-001. In preclinical studies, the therapy demonstrated up to 30-fold greater potency and an approximately five-fold longer half-life than a reference anti-mutCALR antibody, supporting its potential as a differentiated treatment approach for patients with mutCALR-driven myeloproliferative neoplasms.
CLARITY-101 Evaluates Safety, Tolerability and Efficacy
The CLARITY-101 Phase 1/1b study is a global, open-label, multicenter clinical trial designed to evaluate the safety, tolerability and preliminary efficacy of DMR-001. The Phase 1 dose-escalation portion will begin with a 100 mg once-monthly subcutaneous dose, which is predicted to provide therapeutic exposure, and will use an adaptive Bayesian design to support cohort enrichment during dose escalation. Eligible participants include adults with a documented CALR mutation and either ET that is resistant, refractory or intolerant to at least one prior cytoreductive therapy, or MF that is resistant, refractory or intolerant to at least one JAK inhibitor. The planned Phase 1b expansion will evaluate DMR-001 in additional patient populations and treatment settings, including earlier-line disease and combination therapy. Damora Therapeutics currently expects to report the initial clinical data from CLARITY-101 beginning in mid-2027, providing the first human evidence on the investigational therapy’s safety and potential biological activity.
DMR-001 Targets the Driver of mutCALR Disease
DMR-001 is designed to selectively inhibit mutant forms of calreticulin while leaving wild-type calreticulin untouched. CALR mutations are important disease drivers in ET and MF because the abnormal protein can continuously activate the thrombopoietin receptor, promoting uncontrolled blood-cell production and contributing to thrombosis, bleeding and bone marrow fibrosis. DMR-001 was engineered to inhibit both Type 1 and non-Type 1 CALR mutations, including Type 2 mutations, which have historically presented challenges for targeted approaches. The molecule incorporates a YTE modification intended to extend its half-life and support infrequent dosing, while its Fc-null design is intended to eliminate Fc-mediated immune effector function. In head-to-head preclinical studies presented at the European Hematology Association (EHA) 2026 Congress, DMR-001 demonstrated up to 30-fold higher binding affinity for mutCALR than a reference antibody, while showing up to 26-fold greater potency against Type 2 mutations in disease-driving cell-growth assays. The therapy also demonstrated an approximately 15-day half-life in non-human primates, compared with 3.1 days for the reference antibody.
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Damora Therapeutics Advances Potential Disease-Modifying Therapy
Damora Therapeutics said mutCALR mutations occur in approximately 25% of essential thrombocythemia cases and 35% of myelofibrosis cases, representing an estimated 42,000 patients in the United States. Despite the role of mutCALR as a disease driver, there are currently no approved mutCALR-targeted therapies, leaving patients dependent largely on treatments that manage disease manifestations rather than directly addressing the underlying molecular cause. DMR-001 is being developed to potentially provide a disease-modifying treatment option through selective targeting of mutant calreticulin. However, the preclinical potency and half-life findings are not evidence of clinical efficacy, and the potential benefits and risks of DMR-001 will need to be established through human clinical trials. The initiation of CLARITY-101 marks an important transition for Damora Therapeutics as DMR-001 enters clinical development and begins testing as a potential targeted therapy for mutCALR-driven essential thrombocythemia and myelofibrosis.
Source:Damora Therapeutics press release
