Patients with essential thrombocythemia, myelofibrosis and other myeloproliferative neoplasms need new, safe and effective options. Our pipeline of therapies targeting LSD1 in various cancers and other bone marrow diseases reflects this immense need.
*Investigator Sponsored Trial
A promising product candidate for the treatment of MPNs
We are developing our internally discovered lead product candidate, bomedemstat, for the treatment of myeloproliferative neoplasms (MPNs), a family of related, chronic cancers of the bone marrow. Bomedemstat is an orally available, small molecule, inhibitor of LSD1. Currently, bomedemstat is being tested in clinical studies as a potentially disease-modifying monotherapy for essential thrombocythemia (ET), myelofibrosis (MF), and polycythemia vera (PV). Bomedemstat has also been studied in patients with acute myeloid leukemia (AML) and preclinically in various solid tumor models, where it has shown activity in combination with other agents.
ET is a rare blood cancer resulting from the overproduction of platelets which increases the risk of blood clots and bleeding. It is one of the MPN family of rare bone marrow diseases, and affects approximately 80,000 – 100,000 patients in the U.S. There is a significant unmet need for new ET therapies that can effectively reduce patient platelet levels without general bone marrow suppression, while slowing the progression of the underlying disease. By normalizing elevated platelets, the primary clinical feature of ET, we believe bomedemstat can address an unmet need in the 20% of the high risk ET patients who are intolerant or resistant to hydroxyurea, the current standard-of-care for those patients with ET at greatest risk for blood clots.
Our preliminary data from the ongoing Phase 2 study demonstrates bomedemstat is well-tolerated and a significant proportion of patients have achieved a normal platelet count within the first eight weeks of treatment. We are continuing to enroll patients in this trial and expect to complete enrollment in 2021.
Bomedemstat has received Orphan Drug and Fast Track Designations for ET from the FDA. For more information about our current clinical trials investigating bomedemstat for ET, visit our patients page.
MF is a progressive cancer in which the bone marrow is gradually replaced by fibrous, scar-like tissue. There is a significant unmet need for a disease-modifying therapy. Bomedemstat has shown such activity in pre-clinical models. The need is greatest in patients with MF whose disease is not adequately managed with current JAK inhibitors, the current standard of care. Our Phase 2 clinical data in MF demonstrated bomedemstat was well-tolerated and resulted in improvements in patient symptoms, reductions in spleen volume and reduction in mutant allele frequency (MAF). We have recently completed enrollment in a Phase 2 clinical trials of bomedemstat monotherapy in patients with advanced MF.
We expect to support an investigator-sponsored Phase 2 clinical trial of bomedemstat in combination with ruxolitinib for the treatment of patients with MF. This trial will include both patients with MF who have not received any prior treatment, as well as those currently receiving ruxolitinib, but not achieving adequate symptom control or spleen volume reduction. We plan to have discussions with the U.S. Food and Drug Administration (FDA) about the endpoints and control arm for a Phase 3 pivotal program in MF.
Bomedemstat has received Orphan Drug and Fast Track Designations for MF from the FDA in addition to Orphan Drug and PRIME Designations from the EMA. For more information about our current clinical trials investigating bomedemstat for myelofibrosis, visit our patients page.
LSD1 inhibition modulates the proliferation of malignant blood cells and therefore represents a viable therapeutic approach to treating PV, an MPN characterized by the excessive production of red blood cells. While there are some available treatments for PV, namely phlebotomy for low-risk patients and hydroxyurea or ruxolitinib for high-risk patients, there are no disease-modifying therapies for the disease. Bomedemstat represents a novel therapeutic option for this patient population. An ongoing investigator-sponsored trial is evaluating bomedemstat in PV patients who have failed at least one standard therapy. For more information about our investigator-sponsored trial investigating bomedemstat for PV visit clinicaltrials.gov.
Academic studies have demonstrated that inhibition of LSD1 can induce the production of fetal hemoglobin, which normally shuts off shortly after birth. Fetal hemoglobin can compensate for defects in adult hemoglobin that contribute to the development of sickle cell disease and thalassemia. The goal of this program is to develop novel inhibitors of LSD1 to provide levels of fetal hemoglobin which, based on published academic research, may reduce or eliminate the symptoms, morbidity and mortality from these hemoglobinopathies. We are currently conducting lead optimization and preclinical studies for this program.
LSD1 can also act as a scaffold where other epigenetic enzymes such as histone deacetylase 1 and DNMT1 can attach to LSD1 thereby adding distinct epigenetic regulation. Therefore, the loss of the LSD1 protein through degradation has a broader range of effects than inhibiting its enzymatic activity alone. We are currently engaged in lead discovery of a series of small molecules designed to target LSD1 for degradation by harnessing normal cellular processes.