ORLANDO, Fla. – Data from two studies from Forty Seven Inc. announced at the American Society of Hematology (ASH) annual meeting moved the market in a major way Monday as the company stock (NASDAQ:FTSV) soared 111% to close at $30.43, up $15.99.
The first involved updated data from its phase Ib trial evaluating magrolimab combined with azacitidine to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The second were proof-of-concept data on its all-antibody conditioning regimen for potential stem cell transplant patients. Both studies revolve around magrolimab, the company’s monoclonal anti-CD47 antibody, which triggers a “don’t eat me” signal to macrophages.
The phase Ib data show the combination of magrolimab and azacitidine is active and well-tolerated in patients with MDS and AML. The study is designed to evaluate magrolimab in combination with azacitidine in untreated patients with higher-risk MDS and untreated patients with AML, who are ineligible for induction chemotherapy. In higher-risk MDS, the overall response rate (ORR) was 92% as 12 patients achieved a complete response (CR), with 33% achieving a marrow CR and 8% achieving hematologic improvement.
In untreated AML, the ORR was 64%, with nine patients (41%) achieving a CR, three achieving a CR with complete blood count recovery (CRi) and one patient achieving a morphologic leukemia-free state (MLFS). Seven patients (32%) achieved stable disease (SD) and one patient (5%) had progressive disease.
All patients received a 1-mg/kg priming dose of magrolimab along with intrapatient dose escalation, to mitigate on-target anemia. Patients received full doses of azacitidine and a weekly magrolimab maintenance dose of 30 mg/kg.
Preclinical data from the second study show a stem-cell conditioning regimen composed of FSI-174, the company’s anti-cKIT antibody, and magrolimab significantly depleted hematopoietic stem cells (HSCs) from the bone marrow. No dose-limiting toxicities were found in the study.
The combination is designed to address stem cell transplantation issues from conditioning regimens that use chemotherapy or radiation to kill off HSCs. In addition, it’s also designed to make room for the transplanted cells, while waiving off co-morbidities such as severe infection, impaired brain development, infertility, endocrine dysfunction, secondary malignancies and organ damage that often prevent patients from receiving a transplant.
The data reveal a binding affinity in human and nonhuman primate (NHP) cKIT receptors, inducing phagocytosis and antibody-dependent cell-mediated cytotoxicity in a dose-dependent manner. FSI-174 was well-tolerated in nonhumans as a single agent. The highest dose tested, 50 mg/kg, produced no observed adverse effect level.
The combination regimen produced a high level of phagocytosis of cKIT expressing target cells while inducing a significant HSC depletion nine days after the infusion, compared to placebo. Blood cell counts remained unchanged during the study and no cytopenias were seen during the monotherapy or combination treatment.
Broadening the base of SCT-eligible patients is just one of the benefits of a successful regimen, according to Leslie Kean, director of the stem cell transplantation program Boston Children’s Hospital, and the Robert Stranahan professor of pediatrics at the Harvard Medical School. He said the regimen could possibly also be used in a range of genetic blood disorders, autoimmune diseases, leukemias and lymphomas.
Forty Seven expects to complete IND-enabling studies by year-end and begin a phase I study evaluating FSI-174 in healthy volunteers sometime in the first three months of 2020.