-- 5F9 Well Tolerated with Clinical Activity as Monotherapy and in Combination with Azacitidine --
-- CR Rate of 55% and ORR of 100% Observed in Patients with Higher-Risk MDS --
-- CR/CRi Rate of 50% and ORR of 64% Observed in Patients with Untreated AML Who Are Ineligible for Induction Chemotherapy --
-- Received FDA Feedback Suggesting Single Arm Pivotal Trial May Support Registration of 5F9 in Combination with Azacitidine in Higher-Risk MDS --
-- Forty Seven to Host Investor Event and Webcast at 6:30 p.m. CT --
MENLO PARK, Calif., June 03, 2019 (GLOBE NEWSWIRE) -- Forty Seven, Inc., a clinical-stage, immuno-oncology company focused on developing therapies to activate macrophages in the fight against cancer, today announced updated initial data from its Phase 1b clinical trial evaluating 5F9 as a monotherapy and in combination with azacitidine for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The data, which have matured since the abstract submission and now include additional patients and longer-term follow-up, will be presented in a poster discussion session at the 2019 ASCO Annual Meeting in Chicago, Illinois.
“These new data for 5F9 show encouraging clinical activity in a broad population of patients with MDS and AML, who may be unfit for existing therapeutic options or at higher risk for developing rapidly-advancing disease,” said David Sallman, M.D., H. Lee Moffit Cancer Center and Research Institute, an investigator for the clinical trial. “Despite an evolving treatment landscape, physicians continue to seek new therapies for MDS and AML that can be used safely to help patients more rapidly achieve durable responses. I am excited to see meaningful clinical activity in a majority of patients treated with 5F9 in combination with azacitidine, with a median time to response of under two months. These results confirm our preclinical data demonstrating synergy between 5F9 and azacitidine, and warrant the further exploration of this combination in patients with MDS and AML.”
“We are extremely pleased by the tolerability and clinical activity observed for 5F9 in combination with azacitidine to date, which validates the approach of combining 5F9 with other therapeutic agents that induce prophagocytic ‘eat me’ signals on tumor cells. This supports our belief in the potential of 5F9 as an immune checkpoint inhibitor,” said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of Forty Seven, Inc. “In particular, we are encouraged to see activity in patients with MDS, a disease characterized by significant morbidity, such as the need for frequent blood transfusions, and which can progress to AML. Despite advances in the treatment of hematologic cancers, the standard of care for MDS has not changed in over a decade, and existing agents demonstrate objective activity in only a limited fraction of treated patients. As a result, many MDS patients receive only supportive care, and there is a clear and compelling need for new, disease-modifying options. Following recent engagement with the U.S. Food and Drug Administration (FDA), we believe a single arm pivotal trial may serve as the basis for a biologics license application for 5F9 in combination with azacitidine in higher-risk MDS, and we are working hard to finalize the design of our potentially registration-enabling study, while continuing to enroll expansion cohorts in our ongoing study in MDS and AML.”
Data from the Ongoing Phase 1b Clinical Trial
Forty Seven’s Phase 1b trial, which is being funded in part by the California Institute for Regenerative Medicine (CIRM), is designed to evaluate 5F9 as a monotherapy in patients with relapsed or refractory (r/r) MDS or AML, and 5F9 in combination with azacitidine in higher-risk MDS patients and untreated, induction chemotherapy-ineligible AML patients. All patients received a 1 mg/kg priming dose of 5F9, coupled with intrapatient dose escalation, to mitigate on-target anemia. Patients in the combination cohort were then treated with full doses of azacitidine and a 5F9 maintenance dose of 30 mg/kg once weekly.
As of the data cutoff of May 10, 2019, 46 patients had been treated in the Phase 1b portion of the trial, including 10 r/r MDS or AML patients who received monotherapy 5F9, and 36 untreated higher-risk MDS patients or untreated AML patients ineligible for induction chemotherapy, who received 5F9 in combination with azacitidine.
Preliminary Safety Data
As of the data cutoff, 5F9 was well-tolerated both as a monotherapy and in combination with azacitidine, with no evidence of increased toxicities compared to azacitidine alone. Adverse events (AEs) were consistent with what has been previously seen with 5F9, and no significant cytopenias or autoimmune-related AEs were observed in patients treated with monotherapy 5F9. Overall, the most commonly reported treatment-related AEs were expected CD47-mechanism-based effects on red blood cells, which led to a temporary and reversible anemia, and many patients in the combination cohort experienced a hemoglobin improvement over the course of their treatment with a decrease in transfusions. Importantly, no treatment-related infections were observed, and only one patient out of 36 treated with the combination experienced neutropenic fever (3%). No deaths were observed in the first 60 days on combination treatment. Only one patient out of 46 (2%) discontinued treatment due to a treatment-related AE.
Preliminary Clinical Activity Data
As of the data cutoff, 35 patients were evaluable for response assessment, including 25 patients with untreated higher-risk MDS or AML who were treated with 5F9 and azacitidine (11 patients with higher-risk MDS and 14 patients with untreated AML) and 10 patients with r/r MDS or AML who were treated with monotherapy 5F9.
- In higher-risk MDS, the overall response rate (ORR) for the combination was 100%, with six patients (55%) achieving a complete response (CR), four patients (36%) achieving a marrow CR and one patient (9%) achieving hematologic improvement.
- In untreated AML, the ORR for the combination was 64%, with five patients (36%) achieving a CR, two patients (14%) achieving a complete response with incomplete blood count recovery (CRi), and two patients (14%) achieving a morphologic leukemia-free state (MLFS). Additionally, five patients (36%) achieved stable disease (SD).
- In r/r MDS or AML treated with monotherapy 5F9, the ORR was 10%, consisting of one patient who achieved a MLFS. Additionally, seven patients (70%) achieved SD.
- The median time to response among MDS and AML patients treated with the combination was 1.9 months.
- Six patients (30% of responders) receiving the combination who had an objective response have experienced deepening responses over time resulting in complete remissions. Five patients (25% of responders) have also successfully received allogeneic stem cell transplants.
- Historical response rates for single-agent azacitidine, show CR rates of approximately 15-20% in higher-risk MDS and untreated AML patients, with initial responses generally occurring after 4-6 months in most patients who respond.1
1 Azacitidine US package insert, Al-Ali et al., 2012; Dombretet al., 2015; Fenauxet al., 2010; Silverman et al., 2002
Clinical Development Plans for 5F9 in MDS and AML
Based on the favorable safety profile and encouraging clinical activity observed in this Phase 1b clinical trial to-date, expansion cohorts have been initiated in patients with both higher-risk MDS and untreated AML with 5F9 in combination with azacitidine.
Additionally, based on feedback from a Type B meeting with the FDA in May 2019, Forty Seven believes that data from a single arm pivotal study evaluating durability, CRs and partial responses may be sufficient to support the registration of 5F9 in combination with azacitidine in patients with untreated, higher-risk MDS. The Company is currently finalizing the operational components of the proposed registrational study, including details on trial design and chemistry, manufacturing and controls (CMC), and will provide a detailed update in the second half of 2019.
In August 2015, the FDA granted orphan drug designation to 5F9 for the treatment of AML.
Investor Event and Webcast Information
Forty Seven will host an investor event on Monday, June 3, 2019 beginning at 6:30 p.m. CT (7:30 p.m. ET) in Chicago to review the initial clinical data presented at ASCO. 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.
5F9 is a monoclonal antibody against CD47 that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don't eat me" signal used by cancer cells to avoid being ingested by macrophages. Forty Seven, Inc. is initially developing 5F9, an investigational medicine, for the treatment of patients with solid tumors, acute myeloid leukemia, non-Hodgkin's lymphoma and colorectal cancer. 5F9 has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma, two forms of B-cell non-Hodgkin's lymphoma, and Orphan Drug designation by the U.S. Food and Drug Administration and European Medicines Agency for the treatment of acute myeloid leukemia.
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, 5F9, 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 solid tumors, myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin’s lymphoma, ovarian cancer and colorectal carcinoma.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," “potential,” “believe” and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those related to the potential of 5F9 as a monotherapy and in combination with azacitidine for the treatment of MDS and AML; the potential of 5F9 as a tolerable treatment option for patients with MDS and AML as a monotherapy and in combination; the effectiveness of the Company’s dosing strategy to mitigate on-target anemia; the overall advancement of 5F9 in clinical trials; the likelihood of receiving FDA approval for 5F9 in combination with azacitidine for the treatment of patients with MDS, the sufficiency of the Company’s single arm pivotal trial design and results from such trial for FDA approval; and Forty Seven’s plans to continue development of 5F9 as a monotherapy and in combination with azacitidine. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. The product candidates that Forty Seven develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all. In addition, clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release. Such product candidates may not be beneficial to patients or successfully commercialized. The failure to meet expectations with respect to any of the foregoing matters may have a negative effect on Forty Seven's stock price. Additional information concerning these and other risk factors affecting Forty Seven's business can be found in Forty Seven's periodic filings with the Securities and Exchange Commission at www.sec.gov. These forward-looking statements are not guarantees of future performance and speak only as of the date hereof, and, except as required by law, Forty Seven disclaims any obligation to update these forward-looking statements to reflect future events or circumstances.
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