BioXcel Therapeutics Announces Addition of Merck KGaA & Pfizer to Clinical Collaboration With Nektar  

BioXcel Therapeutics, Inc. recently announced the addition of Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the US and Canada, and Pfizer Inc. to its Nektar Therapeutics clinical collaboration to evaluate a novel triple combination therapy in pancreatic cancer.

The collaboration now includes avelumab, BXCL701, and NKTR-214 as a potential combination therapy for pancreatic cancer. Avelumab is a human anti-programmed death ligand (PD-L1) co-developed and co-commercialized by Merck KGaA Darmstadt, Germany, and Pfizer. BXCL701 is an orally available systemic innate-immune activator that inhibits dipeptidyl peptidase (DPP) 8/9 and FAP developed by BTI. NKTR-214 is a CD122-biased agonist developed by Nektar. BTI is a clinical stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology.

Under the collaboration, BTI will be responsible for initiating and managing the clinical program, with Merck KGaA, Darmstadt, Germany, and Pfizer supplying avelumab and Nektar supplying NKTR-214. BTI and Nektar will equally share all development costs. The primary objectives of the study are to evaluate safety and efficacy of the triple combination of BXCL701, NKTR-214 and avelumab for the treatment of patients with pancreatic cancer. Additionally, correlative immune activation markers will be evaluated in blood and tumor tissue.

“We are excited to welcome Merck KGaA, Darmstadt, Germany, and Pfizer as partners for the development of this novel triple combination regimen with Nektar,” said Vimal Mehta, Chief Executive Officer of BTI. “We believe that the expansion of this clinical collaboration provides clear evidence of industry enthusiasm toward BXCL701. We look forward to working closely with Merck KGaA, Darmstadt, Germany, and Pfizer as well as Nektar to leverage their clinical and regulatory expertise as we establish the development plan for the triple combination in pancreatic cancer.”

“We believe it is essential to target multiple dimensions of the immune system in parallel to address the multi-faceted etiologies underlying cancer cell growth in difficult-to-treat tumors such as pancreatic cancer,” said Jonathan Zalevsky, Chief Scientific Officer of Nektar Therapeutics. “This experimental triple combination regimen of BXCL701, NKTR-214 and avelumab is designed to leverage multiple mechanisms of action to better fight pancreatic cancer while potentially generating long-term cancer immunity. We’re pleased to be working with BTI as well as Merck KGaA, Darmstadt, Germany, and Pfizer on this program.”

BXCL701 is an orally available systemic innate-immune activator with dual mechanisms of action. It has demonstrated single agent activity in melanoma, with an established safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting Fibroblast Activation Protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other immuno-oncology agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. BXCL701’s primary mechanism of action has recently been highlighted in multiple peer reviewed journals, providing an important validation of the scientific rationale behind BXCL701.

NKTR-214 preferentially binds to the CD122 receptor on the surface of cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment. NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models. Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via 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.