— Expect to Initiate Phase 1 Clinical Trial in Healthy Volunteers in First Quarter of 2020 –

MENLO PARK, CA, USA I December 09, 2019 I Forty Seven, Inc. (NASDAQ:FTSV), a clinical-stage, immuno-oncology company focused on developing therapies to activate macrophages in the fight against cancer, today announced preclinical proof-of-concept data for its novel all antibody conditioning regimen, comprised of FSI-174, its anti-cKIT antibody, and magrolimab, its anti-CD47 antibody. Preclinical studies in a non-human primate (NHP) model showed that the combination of FSI-174 and magrolimab significantly depleted hematopoietic stem cells (HSCs) from the bone marrow, with no dose limiting toxicities. The data will be presented in a poster session at the 61st American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.

“We are excited to report these preclinical data, which reflect our deep understanding of macrophage biology and our ability to build targeted antibody combinations to better facilitate phagocytosis,” said Jens-Peter Volkmer, M.D., Co-Founder and Vice President of Research and Early Development at Forty Seven. “These results demonstrate for the first time the utility of our approach in the transplant setting, and the potential of our all antibody-based conditioning regimen to successfully deplete HSCs without relying on chemotherapy or radiation. We are excited to advance FSI-174 into the clinic early next year, and to work internally and with partners to deliver a novel, non-toxic conditioning regimen for patients undergoing transplantation.”

Forty Seven’s novel all antibody condition regimen seeks to address the limitations of current stem cell transplantation (SCT) conditioning regimens, which utilize chemotherapy and/or radiation to kill HSCs and make space for transplanted cells. These regimens are highly toxic, induce immune suppression  and may require hospitalization. Numerous comorbidities are often observed, including severe infections, impaired brain development, infertility, endocrine dysfunction, secondary malignancies and organ damage. As a result, many patients are ineligible for, or choose not to undergo, SCT.

In the preclinical data presented at ASH, FSI-174 demonstrated binding affinity to both human and NHP cKIT receptors, and induced phagocytosis as well as antibody-dependent cell-mediated cytotoxicity (ADCC) in a dose-dependent manner. Additionally, FSI-174 was well-tolerated when administered to NHPs as a single agent, with no dose-limiting toxicities. The no-observed-adverse-effect level (NoAEL) was established at 50 mg/kg, the highest dose tested.

When administered together, FSI-174 and magrolimab demonstrated a synergistic benefit, promoting the highest level of phagocytosis of cKIT expressing target cells and inducing significant HSC depletion nine days after infusion compared to placebo. As expected, there were no changes in blood cell counts over the course of the study, with no cytopenias observed with either monotherapy or combination treatment. These pharmacodynamic and NHP data demonstrate the specificity and safety of FSI-174 and magrolimab, and reveal a window for SCT where the cKIT antibody is washed out, but the depletion of HSCs is sustained long enough to enable the transplantation of donor HSCs.  

“While curative for numerous diseases, SCT must be preceded by highly toxic chemotherapy or radiation that many people cannot tolerate, significantly limiting its use and leaving patients and physicians to rely on less effective options,” said Leslie S. Kean, M.D., Ph.D., Director, Stem Cell Transplantation Program, Division of Hematology/Oncology, Boston Children’s Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, and the Robert A. Stranahan Professor of Pediatrics, Harvard Medical School.  “I believe that a safe, well-tolerated conditioning regimen would substantially broaden the population eligible for SCT, potentially expanding its use for a wide range of genetic blood disorders, as well as for autoimmune diseases, leukemias and lymphomas. I look forward to seeing the combination of FSI-174 and magrolimab advance through development.”

Forty Seven expects to complete investigational new drug (IND)-enabling studies by the end of 2019, and subject to approval of the IND by the U.S. Food and Drug Administration, plans to initiate a Phase 1 clinical trial evaluating FSI-174 in healthy volunteers in the first quarter of 2020.

Investor Event and Webcast Information

Forty Seven will host an investor event on Monday, December 9, 2019, beginning at 8:00 p.m. ET in Orlando to review the data presented at ASH. The event will be webcast live and can be accessed under “Events & Presentations” in the Investors section of the Forty Seven website at www.fortyseveninc.com. A replay of the webcast will be available approximately two hours after the event and will be available for 30 days following the event.

About FSI-174 and Magrolimab

FSI-174 is a humanized monoclonal antibody targeting cKIT, which is a receptor that is highly expressed on hematopoietic stem cells. Magrolimab is a humanized monoclonal antibody targeting CD47, which is a “don’t eat me” signal to macrophages and is expressed on all cells. Magrolimab is currently being investigated in Phase 2 clinical trials to treat cancer and has established clinical efficacy in four indications, including myelodysplastic syndrome, acute myeloid leukemia, diffuse large B cell lymphoma and follicular lymphoma, with a favorable safety profile in over 400 patients treated, including some patients treated continuously for over two years. When combined, FSI-174 sends a positive signal to macrophages to target blood forming stem cells for removal as magrolimab disengages inhibitory signals that block phagocytosis. Combination of these antibodies has shown efficient removal of blood forming stem cells, allowing for transplantation in pre-clinical models.

About Forty Seven, Inc.

Forty Seven, Inc. is a clinical-stage immuno-oncology company that is developing therapies targeting cancer immune evasion pathways based on technology licensed from Stanford University. Forty Seven’s lead program, magrolimab, is a monoclonal antibody against the CD47 receptor, a “don’t eat me” signal that cancer cells commandeer to avoid being ingested by macrophages. This antibody is currently being evaluated in multiple clinical studies in patients with myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin’s lymphoma, ovarian cancer and colorectal carcinoma.

SOURCE: Forty Seven