Damora Therapeutics Starts Global Phase 1/1b Trial of DMR-001 for Blood Cancer Patients with CALR Mutations

First Patient Trial Begins for Investigational Therapy Targeting mutCALR-Driven Blood Disorders

Damora Therapeutics has announced the start of its global Phase 1/1b CLARITY-101 clinical trial evaluating DMR-001, an investigational monoclonal antibody therapy designed for patients with mutant calreticulin (mutCALR)-driven blood disorders.

The study begins after receiving approval from health authorities and will evaluate DMR-001 in patients living with essential thrombocythemia (ET) and myelofibrosis (MF) caused by CALR mutations.

The company believes this marks an important milestone as DMR-001 becomes its first therapy to enter clinical testing.

Company Aims to Target the Root Cause of Disease

According to Damora Therapeutics, DMR-001 has been developed to directly target mutant calreticulin, one of the main causes of disease in certain patients with ET and MF.

Unlike current treatment options that mainly help control symptoms, DMR-001 is designed to block the disease-driving protein while leaving healthy calreticulin unaffected.

The company hopes this targeted approach may provide deeper and longer-lasting disease control while reducing unwanted side effects.

Monthly Injection Could Improve Convenience

Another feature of DMR-001 is its dosing schedule.

The investigational therapy is designed to be given as a once-monthly injection under the skin.

Damora believes this could offer a simpler and more convenient treatment option compared to therapies that require more frequent dosing.

Chief Medical Officer Dr. Becker Hewes said preclinical studies showed encouraging results and supported the decision to move DMR-001 into human clinical trials.

Doctors See Strong Potential for Patients

Dr. David Ross, Associate Professor of Haematology at Flinders Medical Centre in Australia and an investigator in the CLARITY-101 study, said targeting the underlying cause of mutCALR-driven disease could become one of the biggest advances in treating myeloproliferative neoplasms.

According to him, DMR-001 has the potential to become the first disease-modifying treatment specifically developed for patients with these CALR-driven diseases.

He also noted that its broad activity and convenient monthly administration could make it an attractive treatment option for people living with ET and MF.

How the CLARITY-101 Trial Is Designed

CLARITY-101 is a global, open-label, multi-center Phase 1/1b clinical study.

The trial will evaluate:

• Safety
• Tolerability
• Preliminary effectiveness

The first part of the study focuses on dose escalation to identify the most appropriate dose for future development.

Patients will begin treatment with a 100 mg monthly subcutaneous injection.

Researchers are also using an adaptive Bayesian study design, allowing adjustments as more clinical data become available during the trial.

Who Can Join the Study?

The Phase 1 portion of the study includes adults who have a confirmed CALR mutation.

Eligible participants include:

• Patients with essential thrombocythemia who are resistant, intolerant, or no longer responding to at least one previous cytoreductive therapy.
• Patients with myelofibrosis who are resistant, intolerant, or no longer responding to at least one JAK inhibitor.

Later stages of the study will expand into additional patient groups and evaluate DMR-001 both as a standalone treatment and in combination with other therapies.

Damora expects to report initial clinical data beginning in mid-2027.

How DMR-001 Works

DMR-001 is designed to selectively block mutant calreticulin proteins that drive disease in ET and MF.

CALR mutations produce an abnormal protein that continuously activates the thrombopoietin receptor (TpoR), leading to excessive blood cell production, increased risks of blood clots and bleeding, and progressive bone marrow scarring.

DMR-001 blocks this abnormal interaction while leaving normal calreticulin proteins untouched.

The treatment has also been engineered with several additional features designed to improve its performance.

These include:

• Activity against both Type 1 and Type 2 CALR mutations.
• A YTE modification that extends the medicine's half-life.
• An Fc-null design intended to reduce immune-related side effects.

Preclinical Studies Show Promising Results

Data presented at the European Hematology Association (EHA) 2026 Congress highlighted encouraging laboratory findings for DMR-001.

According to Damora, the investigational therapy demonstrated:

• Up to 30 times stronger binding to mutant CALR compared with a reference antibody.
• Up to 26 times greater potency against Type 2 CALR mutations, which are generally more difficult to treat.
• Approximately five times longer half-life in non-human primates compared with a reference antibody.

These findings support the company's goal of once-every-four-week dosing.

Understanding CALR-Driven Blood Disorders

CALR mutations are responsible for around:

• 25% of essential thrombocythemia cases.
• 35% of myelofibrosis cases.

In the United States alone, these mutations affect an estimated 42,000 patients.

The abnormal CALR protein continuously stimulates blood cell growth, leading to complications such as:

• Blood clots
• Bleeding
• Bone marrow fibrosis
• Fatigue
• Headaches
• Difficulty concentrating
• Pain in the hands and feet

Currently, there are no approved therapies that directly target CALR mutations.

Most available treatments focus on managing symptoms rather than treating the underlying cause of the disease.

About Damora Therapeutics

Damora Therapeutics is a biotechnology company focused on developing new biologic medicines for blood disorders.

The company's research is centered on creating disease-modifying therapies for patients with mutant CALR-driven myeloproliferative neoplasms, including essential thrombocythemia and myelofibrosis, where significant unmet medical needs remain.