SAN DIEGO, June 20, 2017 – eFFECTOR Therapeutics announced today it has entered into a clinical collaboration and supply agreement with Pfizer and Merck KGaA, Darmstadt, Germany, to evaluate the combination of two immuno-oncology agents in patients with microsatellite stable colorectal cancer (CRC). The companies plan to initiate a Phase 2 open-label, randomized, non-comparative study to evaluate the safety, tolerability and efficacy of eFFECTOR’s investigational small molecule MNK1/2 inhibitor, eFT508, in combination with avelumab* in microsatellite stable relapsed or refractory CRC patients. Avelumab is currently under clinical evaluation across a broad range of tumor types by the global strategic alliance between Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono, and Pfizer. The study will also include a monotherapy arm investigating eFT508 alone. Patients will be randomized 2:1 between the combination arm and the monotherapy arm.
“We believe eFT508, our lead program, is a promising new immuno-oncology drug candidate that could significantly improve patient response in combination with checkpoint inhibitors,” said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. “We are very pleased to be working with Pfizer and Merck KGaA, Darmstadt, Germany, given their demonstrated commitment to develop avelumab as a leading checkpoint inhibitor and their deep knowledge in the field of immuno-oncology.”
eFT508 and avelumab are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. eFT508 is a novel, oral immuno-oncology therapeutic that is a highly selective inhibitor of MNK1/2 kinases that mediate tumor immune evasion and are activated downstream of MEK and MAPK signaling. Avelumab is a human programmed death ligand-1 (PD-L1) blocking antibody that is designed to potentially engage both the adaptive and innate immune systems. The collaboration builds upon promising preclinical data providing a scientific rationale for combining eFT508 with checkpoint inhibitors presented at recent clinical and scientific conferences. In immunocompetent in vivo models, eFT508 induced anti-tumor immunity and immune memory as a single agent and, importantly for this collaboration, acted synergistically in combination with checkpoint inhibitors.
eFFECTOR has presented preclinical data at scientific conferences that eFT508 may play an important role in coordinately activating an anti-tumor immune response by selectively inhibiting several immuno-suppressive mechanisms while simultaneously stimulating several immunity-inducing mechanisms. Immuno-suppressive mechanisms selectively inhibited by eFT508 include PD-1, LAG3, PD-L1 and IL-10, while pro-immunity mechanisms stimulated by eFT508 include antigen presentation, dendritic cell activation, effector T-cell function and expansion of the T-cell central memory pool.
“eFFECTOR’s approach in targeting selective translation regulators is unique, and eFT508 represents a promising novel class of investigational compounds for the treatment of cancer,” said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. “Given the preclinical data already developed with eFT508 and checkpoint inhibitors, we are excited to initiate this joint clinical collaboration.”
“Colorectal cancer is a frequently diagnosed cancer and is the second most common cause of cancer death among men and women combined in the US,” said Alise Reicin, Head of Global Clinical Development at the biopharma business of Merck KGaA, Darmstadt, Germany. “New and innovative treatment strategies are desperately needed. We look forward to exploring the potential of this novel combination and the role we hope it may eventually have for improving the treatment of colorectal cancer.”
The study, which is expected to begin in the third quarter of 2017, will be conducted by eFFECTOR Therapeutics. Pfizer and Merck KGaA, Darmstadt, Germany, will share the clinical study costs with eFFECTOR. Each party will provide their respective agent for the trial.
*Avelumab is under clinical investigation for treatment of microsatellite stable colorectal cancer and has not been demonstrated to be safe and effective for this indication. There is no guarantee that avelumab will be approved for microsatellite stable colorectal cancer by any health authority worldwide.
eFT508 is a selective translation regulator and is part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. eFT508 is a highly potent and selective, oral inhibitor of MNK1 and MNK2. MNK1/2 are terminal kinases in key oncogenic signaling pathways, including KRAS-BRAF-MEK-ERK, and are activated by the mitogen dependent protein kinases (MAPK) in multiple immune cell types. MNK1 and MNK2 integrate MAPK pathway signaling at the level of mRNA translation, resulting in decreased anti-tumor immune activity due to selective upregulation of several immune checkpoint receptors and specific immunosuppressive cytokines. eFT508 selectively blocks MNK1/2 driven mRNA translation promoting anti-tumor immune response. eFT508 is currently being evaluated in a Phase 1/2 clinical trial in patients with solid tumors (NCT02605083) and in a Phase 1/2 clinical trial in patients with lymphoma (NCT02937675).
Avelumab is a human antibody specific for a protein called PD-L1, or programmed death ligand-1. Avelumab is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T-cells, exposing them to anti-tumor responses. Avelumab has been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including nine Phase III trials, and more than 5,200 patients evaluated across more than 15 different tumor types, including gastric/gastroesophageal junction, non-small cell lung cancer, renal cell carcinoma and ovarian cancer. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.
The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) metastatic Merkel cell carcinoma (mMCC) in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. Avelumab is not approved for any indication in any market outside the US.
Important Safety Information
The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with avelumab include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.
About eFFECTOR Therapeutics
eFFECTOR Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of selective translation regulators as a new class of small molecule therapeutics for cancer. The company’s investigational compounds are designed to restore translational control to halt underlying disease mechanisms while preserving healthy physiological processes. eFFECTOR’s most advanced program focuses on the development of eFT508. The company has additional selective translation regulator programs currently in discovery and development. For more information visit www.effector.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.
Heidi Chokeir, Ph.D.