Semafore Pharmaceuticals Reports Encouraging Phase I Data at ASH for Novel PI3K/mTOR Pathway Inhibitor
Company also announces plans to expand ongoing Phase I studies into B-cell malignancies
INDIANAPOLIS--(BUSINESS WIRE)--Dec 8, 2009 - Semafore Pharmaceuticals today reported encouraging data from a Phase I dose-escalation trial of SF1126 in patients with relapsed and refractory myeloma. SF1126 is a novel small molecule inhibitor of phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), two key members of the PI3K signaling pathway that is vital to several essential biological processes, such as cell proliferation and survival. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. Data were presented during the 51st American Society of Hematology (ASH) Annual Meeting in New Orleans, LA.
“The data from this trial demonstrates that SF1126 suppresses the pathway in tumor cells at well-tolerated doses,” said Principal Investigator, Sagar Lonial, MD, Associate Professor of Medicine, at the Winship Cancer Institute of Emory University. “We are encouraged by these preliminary results which support a dose level to move into follow-on combination studies.”
"Both the Multiple Myeloma Research Foundation (MMRF), through its Biotech Investment Award program (LEAD), and the Multiple Myeloma Research Consortium (MMRC) are proud to have contributed to this trial as it aligns with our commitment to expand the portfolio of treatment options for multiple myeloma patients - especially those aimed at effectively treating patients who have suffered a relapse," said Kathy Giusti, Founder and Chief Executive Officer of the MMRF and MMRC, and a myeloma patient.
The study is evaluating SF1126 administered as a 1.5 hour intravenous infusion given twice a week for four weeks on a 28 day cycle. To date, a total of 8 patients have been treated with escalating doses ranging from 90 to 1110 mg/m2 for a median of one (1) cycle. Patients had previously received a median of eight (8) prior treatment regimens.
Drug-related adverse events have been of Grade 1 or 2 severity and manageable. The most frequently occurring adverse events were nausea, allergic reaction, and vomiting. The maximum tolerated dose (MTD) has not yet been determined.
Pharmacodynamic analyses using serial bone marrow samples demonstrate substantial reductions in biomarkers of PI3K pathway activity in marrow plasma cells. Pharmacokinetic analyses indicate that the maximal concentration and exposure of SF1126 increased with doses at 140 mg/m2 or higher, achieving exposures demonstrated to be efficacious in animal xenograft models of multiple myeloma.
Of the 8 patients receiving SF1126, one patient achieved stable disease as evidenced by urinary protein stabilization following a rapid rise prior to study initiation. Completion of the study at the current dose (1110 mg/m2) and planning for a future trial combining SF1126 with other active agents in myeloma is currently ongoing.
Semafore Pharmaceuticals also announced today that the company has received capital commitments from existing shareholders to allow the company to expand ongoing Phase I studies into B-cell malignancies, such as non-Hodgkins lymphoma (NHL) and chronic lymphocytic leukemia (CLL). While PI3K is among the most frequently activated signaling pathways in cancer, patients with B-cell malignancies have not been treated to date with SF1126 despite promising preclinical data that provides a rationale to explore its therapeutic activity.
Semafore Pharmaceuticals' lead product candidate, SF1126, inhibits both the phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), two key members of the PI3K signaling pathway that is vital to several essential biological processes, such as cell proliferation and survival. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy.
In view of the fact that mTOR can be activated in a PI3K-independent manner, dual PI3K-mTOR inhibitors, such as SF1126, are expected to offer a therapeutic advantage. As a prodrug that is administered in an inactive form, SF1126 is also unique among clinical stage, dual PI3K-mTOR inhibitors. Once administered, SF1126 targets specific transmembrane cell adhesion proteins known as integrins that are expressed in new tumor vasculature and within the tumor compartment. Because of the targeted design of SF1126, there is a markedly lower chance of inhibiting PI3K and mTOR in healthy, non-cancerous cells which reduces the potential for side-effects. In preclinical studies, SF1126 has shown attractive pharmacokinetic and pharmacodynamic properties and compelling efficacy in xenograft models, both as a single agent and in combination with other therapies.
Data from an ongoing Phase I clinical trial of SF1126 in patients with solid tumors recently presented at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated selective inhibition of the PI3K pathway in tumor tissue but not in normal skin tissue. Notably, there were no clinically significant changes in glucose or insulin levels reported at biologically active doses. Upon completion of single agent Phase I trials, Semafore Pharmaceuticals expects to initiate combination trials in the near future.
About Semafore Pharmaceuticals, Inc.
Founded in 2000, Semafore Pharmaceuticals is a clinical-stage biotechnology company dedicated to the discovery and development of novel small molecule signal transduction inhibitors targeting the phosphoinositide-3-kinase (PI3K) pathway for the treatment of cancer and other serious diseases. The PI3K signaling pathway is vital to several biological processes, such as cell proliferation and survival, and is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. For more information see the company's web site at www.semaforepharma.com
Contact: Michael D. Becker, 215-493-5674
Acting Chief Executive Officer, Semafore Pharmaceuticals
President and Chief Executive Officer, MD Becker Partners LLC
Posted: December 2009