Imago BioSciences Advances Myelofibrosis Trials, With Phase IIb Prelim Readout Imminent
Imago BioSciences will announce preliminary results from its Phase IIb clinical trial for myelofibrosis (MF) at the 25th European Hematology Association (EHA) Annual Congress that begins June 12, 2020 and has an ongoing study for a Phase IIb trial targeting essential thrombocythemia (ET). In July, Imago expects to close a $26 million second tranche and recently hired a medical affairs and chief business officer and added a member of the board.
Imago’s lead compound, bomedemstat (IMG-7289), is a small molecule lysine-specific demethylase-1 (LSD1, also known as KDM1A) inhibitor for the treatment of myelofibrosis. That enzyme is vital for blood cells maturation, and is a key differentiator for cancer stem/progenitor cells – particularly neoplastic bone marrow cells.
“Myelofibrosis is the disease we first started treating. It’s characterized by the obliteration of the bone marrow,” Hugh Rienhoff, Jr., M.D., CEO, told BioSpace. MF is considered a surrogate biomarker for acute myeloid leukemia (AML).
When Imago presents its Phase IIb clinical trial data for MF in a few days, it will demonstrate bomedemstat’s potential as a once-daily oral monotherapy for intermediate-2 and high-risk patients who are resistant to, intolerant of, or otherwise ineligible for Jakafi® (ruxolitinib), the Janus Kinase (JAK) inhibitor that is the standard of care today.
“There is clear clinical activity against the symptoms, which we think is most important,” Rienhoff said. “Most patients hve spleen volume reduction and decreases in blast counts, and bomedemstat is extremely well-tolerated. We’ve given six times the dose for typical MF patients with no dose-limiting toxicity.”
Bomedemstat has FDA Orphan Drug and Fast Track Designation for the treatment of MF and ET, and Orphan Drug Designation for treatment of acute myeloid leukemia. Assuming its continued success in those programs, “We’re planning to go all the way through to commercialization,” Rienhoff said. “We’ll have to do another financing next year for a PIII study on MF, though.”
The goal is launch that trial the first half of 2021 when they have FDA clarity and still have a year’s cash.
The company currently recruiting for a Phase IIa study targeting ET.
“This is a quiet bone marrow cancer than can linger for years,” Rienhoff said in a January statement announcing its Fast Track designation by the FDA. This is a bone marrow disease associated with high platelet counts and potentially catastrophic vascular complications.
In a subset of patients, the excess of platelets leads to bleeding and clotting including strokes and infarctions, each having a significant impact on these patients. With only one FDA approved therapy – one that does not increase overall survival – patients are in desperate need of new options. In clinical studies, bomedemstat shows it inhibits the enzyme LSD1, thus preventing excess platelet and neutrophil production.
Imago BioSciences focuses on understanding the signaling process and exploiting transcriptional regulators to alter gene express in blood cells to produce clinical benefits. To that end, the company also has a Phase IIa trial underway for polycythemia vera and completed a Phase IIb trials in progress using bomedemstat as a combination therapy for AML.
Imago scientists speculate that bomedemstat also may be administered alongside ruxolitinib to provide a clinical benefit to patients with a sub-optimal response to ruxolitinib. The therapeutic also may have the potential as a treatment option in sickle cell disease and thalassemia intermedia, based upon the LSD1 enzymes’s ability to induce fetal hemoglobin production.
Non-clinical studies showing robust in vivo anti-tumor efficacy across a range of myeloid malignancies as a single agent and in combination with other chemotherapeutic agents. Currently, Imago has several other studies in preclinical development that will require additional funding to advance.
“We envision a cross-over financing the first half of 2021,” Rienhoff said.
This progress is despite the COVID-19 pandemic, which slowed clinical trial enrollment globally and cause many trials to suspend activities.
“We had five country studies underway for multiple indications,” Rienhoff said. “It will take Italy a while to be up and running, and in the UK it’s hard to say.”
But studies are enrolling in the U.S. and Germany for both myelofibrosis and essential thrombocytopenia.
The enrollment in one trial and ongoing work in another is possible for several reasons.
“Hematologists aren’t very involved in COVID-19 care,” he explained, “and clinical trials are very important to university hospitals. They are referral centers from community physicians, so there is pent-up demand to do something for MF patients, who are frail, but not acutely ill.”