Heads up for Saul & ZioPharm followers

As I go through competing CART alliances and partnerships, I add my findings to a growing comparative matrix. I noticed under the heading “OTHER TREATMENTS UNDER DEVELOPMENT”, I had checked off three items for ZioPharm, i.e., CAR - Chimeric Antigen Receptor/allogeneic; Neoantigen recognition for solid tumors; and Checkpoint inhibitor.

Here are my reference notes (source: ZIOP FY 2016 10k):

• We plan to leverage the synergy between the platforms to accelerate an immuno-oncology pipeline and programs for the development of allogeneic CAR + T and/or NK (natural killer) cells that can be used as off-the-shelf, or OTS, therapies. For example, NK cells do not have endogenous TCRs (T Cell Receptors), so do not require genetic editing to eliminate TCRs, and may be used as an OTS therapy. Further, cytokines such as IL- 12 are “fuel” for NK cells. In addition to developing T cells, we expect to initiate an investigator led trial of OTS primary NK cells for AML after completing regulatory review during 2017. We have additional interest in OTS products such as the development of an allogeneic CAR + T therapy.

My comment: Competitors are fully aware of the Pfizer/Cellectis allogeneic approach (i.e., a single healthy donor who can potentially supply T-cells that can treat thousands of patients), and some like ZioPharm are jumping into the fray.

• Only a minority of tumor antigens are on the surface and thus can be targeted by CARs, while most tumor-derived antigens are within the cell and will likely need to be targeted by TCRs. Therefore, we are developing approaches to target solid tumors using T cells genetically modified with the SB system to express TCRs for recognition of neoantigens. An update was provided in publication (Molecular Therapy (2016); 24(6), 1078–1089) and further pre-clinical information regarding the targeting of solid tumors was presented at the annual meeting of ASH in December 2016. On January 10, 2017, the Company announced the signing of a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for the development of adoptive cell transfer (ACT)-based immunotherapies genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express T cell receptors (TCRs) for the treatment of solid tumors.

My comment: ZIOP and others are jumping on the neoantigen research bandwagon after taking notice of Dr. Steven Rosenberg’s efforts at the National Cancer Institute, which I reported in my 4/3/2017 CART macro view post here.

• In addition to Ad-RTS-IL-12 + veledimex as monotherapy, we have undertaken pre-clinical studies that suggest we may be able to combine this viral-based immunotherapy with an immune checkpoint inhibitor, or iCPI, to improve the anti-tumor effect for glioblastoma (GBM). These pre-clinical data were presented at the 2016 Annual Meeting of the American Society of Gene and Cell Therapy, or ASGCT, in May, and we believe the data will lend support to the first-in-human application of combining Ad-RTS-IL-12 + veledimex with an iCPI for investigational treatment of GBM.

My comment: As mentioned in my 4/13/17 big pharma post, recently, Merck KGaB in collaboration with Pfizer successfully delivered a checkpoint inhibitor avelumab to the marketplace. Merck KGaB brings this valuable knowledge and experience to its partnership with ZioPharm and Intrexon. I believe Merck KGaA with a broad in-house diverse base will follow Pfizer’s example, alliances rather than acquisitions.

The CART race continues fast and furious. With so much happening, I try to glean what I consider significant developments and events. For sure I’ll miss a large number, so please chime in and contribute your findings.

Back to the “deep dive”!