ABSTRACT

Deka Biosciences is developing a platform of combined and targeted cytokines, called Diakines™. The lead oncology asset is a combination of wild-type interleukin-2 (IL-2) paired with a high affinity variant of Epstein Barr Viral (EBV) interleukin-10 (IL-10), targeted via coupling to a single chain variable fragment (scFv) to the epidermal growth factor (EGF) receptor, present on the surface of tumor cells. This Diakine™ is called DK210 (EGFR). High dose intravenous IL-2 induces durable responses in ~15-20% of metastatic renal cell carcinoma (RCC) and melanoma patient’s concomitant with high serum levels of proinflammatory cytokines associated with Cytokine Release Syndrome (CRS) and Vascular Leak Syndrome (VLS) which limits the therapeutic index. In addition, IL-2 treatment leads to increases in immunosuppressive regulatory T cells (Tregs). Monotherapy pegylated IL-10 induced 25% objective response rates in RCC. The therapeutic challenges of IL-2 are balanced by IL-10 because it is anti-inflammatory, activates CD8+ T cells, and suppresses IL-2 induction of Treg accumulation. Treatment of cancer patients with DK210 (EGFR) dissociates effector T/NK cell proliferation, expansion and activation from IL-2 associated CRS and VLS and limits Treg accumulation while permitting the significant induction of IFNg, IL-2Ra, IL-18, sPD-1, sPD-L1, sTIM3, sTIGIT and decreases TGFb in patients exhibiting at least stable disease and mixed responses. The primary toxicological finding is fatigue that can be ameliorated by reducing dose frequency from 3 times to 2 times per week. Targeting of the coupled cytokines to the tumor cell surface dramatically improves potency and exemplifies a paradigm shift in the use of cytokines as the Diakine™ structure enables accumulation of DK210 (EGFR) in the T cell synapse and dramatically increases T cell:tumor cell avidity resulting in enhanced T cell stimulation and recognition of tumor cells. Deka has treated a total of 31 patients with cold tumors such as microsatellite stable pancreatic ductal adenocarcinoma and colorectal carcinoma as well checkpoint relapsed non-small cell lung cancer and renal cell carcinoma inducing long term confirmed stable disease and mixed responses. Deka is further optimizing dose levels and frequency in preparation for further clinical development.

BIO

John earned his bachelor’s degree from Menlo College, an MS from Stanford University and both a MS and PhD from MD Anderson Cancer Center where he discovered that IL-10 directly activates anti-tumor CD8+ T cells. John completed post-doctoral work at DNAX Research Institute and became a Scientist at Schering Plough where he developed PEGylated IL-10 (AM0010) as an immunoncology asset. He then founded Targenics, later merged with ARMO Biosciences (briefly a publicly traded company), to clinically develop AM0010 and other immune oncology assets. ARMO Biosciences was acquired by Eli Lilly in 2018 for a $1.6B up front deal. As a founder and Senior Director of Technical Operations at ARMO, John led the manufacturing and pre-clinical research teams.

John served as the Director of Immunoncology R&D at Medimmune LLC and is the author of 28 manuscripts and 52 granted or pending patents. At Medimmune John developed diverse projects involving innate and T cell agonists, CART and other cell therapy projects and novel immunostimulatory antibody drug conjugates. John has most recently founded Deka Biosciences, the next generation cytokine company created to solve the challenges associated with harnessing the massive potential of cytokine therapy. With the challenges in developing T cell engagers and cell therapy programs, it is likely that cytokine combinations coupled with targeting modalities administered in conjunction with precision patient selection will be clear value drivers for the pharmaceutical industry for years to come.