Damora launches trial testing novel antibody therapy for rare blood cancers
Phase 1/1b study to evaluate DMR-001 for CALR-driven myelofibrosis and ET
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The global CLARITY-101 trial will evaluate the safety and optimal dosage of DMR-001 in adults with CALR-mutated myelofibrosis or essential thrombocythemia. (Photo from iStock)
Damora Therapeutics has launched a global Phase 1/1b clinical trial testing DMR-001, an experimental antibody therapy, in adults with myelofibrosis driven by CALR gene mutations.
DMR-001 specifically targets mutant calreticulin (mutCALR). This abnormal protein continuously activates signals that drive excessive blood cell production and bone marrow scarring, and is a known disease driver in some people with myelofibrosis.
CLARITY-101 will assess DMR-001’s safety, tolerability, and preliminary efficacy, and identify a recommended dose for further clinical development. The therapy is designed as a monthly under-the-skin (subcutaneous) injection, and Damora expects to report initial trial data in mid-2027.
The trial will also enroll people with essential thrombocythemia (ET), a blood cancer characterized by overproduction of platelets (small cell fragments involved in blood clotting) and driven by CALR mutations.
Targeted approach for CALR-driven blood cancers
“We’re excited to announce the initiation of our first clinical trial of DMR-001, a potentially best-in-class mutCALR-targeted therapy,” Becker Hewes, MD, chief medical officer of Damora Therapeutics, said in a company press release. “In preclinical studies, DMR-001 showed a differentiated profile that we believe can translate into deeper, more durable disease control with the simplicity and convenience of a once-monthly subcutaneous injection.
“The achievement of this important clinical milestone furthers Damora’s commitment to solving important medical needs in hematology, beginning with DMR-001’s potential to redefine treatment for the tens of thousands of patients living with mutCALR-driven myeloproliferative neoplasms,” Hewes added.
Myelofibrosis and ET belong to a group of blood cancers called myeloproliferative neoplasms, in which the bone marrow produces an excessive number of blood cells.
According to Damora, CALR mutations are a primary driver of disease in about 35% of myelofibrosis cases and 25% of ET cases, representing an estimated 42,000 people in the U.S. alone.
These mutations cause cells to produce an abnormal version of the calreticulin protein. Mutant CALR binds to and continuously activates the thrombopoietin receptor (TpoR), which normally helps regulate the production of platelets. Persistent activation can lead to abnormal blood cell growth, an increased risk of clotting or bleeding, and, in myelofibrosis, scarring of the bone marrow.
DMR-001 is designed to block the interaction between mutant CALR and TpoR without targeting normal (wild-type) calreticulin. No therapies specifically targeting mutant CALR are currently approved, according to the company.
“Targeting the root cause of mutCALR-driven disease is one of the most exciting frontiers in myeloproliferative neoplasms today and has the potential to be the first disease modifying treatment for patients with this disease,” said David Ross, MD, PhD, associate professor of hematology at Flinders Medical Centre in Adelaide, South Australia, and an investigator in the CLARITY-101 study. “DMR-001’s broad activity and convenient administration makes it a potentially compelling new therapy for patients with ET and [myelofibrosis].”
Trial design and patient eligibility
The open-label, multicenter CLARITY-101 trial includes both dose-escalation and dose-expansion phases. Open-label means both participants and researchers know that DMR-001 is being administered.
Eligible participants include adults with a documented CALR mutation who have ET that is resistant or refractory to at least one previous cytoreductive therapy — treatments that reduce excess blood cell production — or who could not tolerate such treatment. Adults with a documented CALR mutation and myelofibrosis must have disease that is resistant or refractory to at least one JAK inhibitor, a type of treatment that helps control abnormal blood cell production and disease-related symptoms, or must have been unable to tolerate such treatment.
The initial Phase 1 dose-escalation portion aims to rapidly identify a recommended dose for further clinical testing. During this part of the trial, DMR-001 will be given at a starting dose of 100 mg once monthly by subcutaneous injection. Damora said this dose is predicted to fall within the range needed to achieve therapeutic exposure.
The study will use an adaptive Bayesian design, which allows information collected as the trial progresses to guide enrollment into particular dose groups.
The Phase 1b dose-expansion portion will assess the safety and efficacy of DMR-001 in additional patient populations and treatment settings, including earlier stages of treatment and in combination with other therapies.
Preclinical findings support monthly dosing
DMR-001 was designed to recognize several forms of mutant CALR, including type 1 and type 2 mutations. According to Damora, type 2 mutations have historically been more difficult to target.
In preclinical studies presented at the European Hematology Association 2026 Congress, DMR-001 showed up to a 30-fold higher binding affinity for mutant CALR than a reference anti-mutCALR antibody. It was also up to 26 times more potent at suppressing disease-driving cell growth in type 2 mutCALR, according to Damora.
The antibody was engineered to stay in the body longer. In nonhuman primates, DMR-001 demonstrated a half-life — the time required for a drug’s concentration to decrease by half — of about 15 days, compared with 3.1 days for a reference antibody. This supports Damora’s planned monthly dosing schedule, or potentially longer intervals.
DMR-001 has what is known as an Fc-null design to prevent the antibody from triggering unwanted immune reactions after binding its target. The company said this feature is intended to support the therapy’s favorable safety profile.
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