Welcome to your Cell Therapy Deal Review for the month of March. Cellectis continues to differentiate through a collaboration with MabQuest. PCT formed a partnership with Japanese conglomerate Hitachi. Kite partnered with Roche’s Genentech on a program for lymphoma.
Cellectis (CLLS) has already separated itself from the pack with UCART19, a universal CAR product targeting CD19 that just entered the clinic. The recent deal the company did with MabQuest, which gives it access to a novel class of PD-1 antagonists, gives it another competitive edge. Cell-based immunotherapy developers are competing aggressively in the solid tumor space, and all the leading companies have forged partnerships with Pharma to investigate synergistic effects of checkpoint inhibitors in combination with engineered T cells. Though, the mechanism of these checkpoint inhibitors is the same across the board: use antibodies to directly block either PD-1 or PD-L1, which, upon engaging one another, suppresses release of IL-2 and T cell proliferation. Interestingly, MabQuest’s checkpoint inhibitors, while working on PD-1, do not impact the PD-1-PD-L1 interaction. Cellectis is planning on completing clinical studies combining these new antibody candidates and its UCART technology.
Last year Nikon executed a deal with Lonza that provided it access to Lonza’s manufacturing technology, factory blueprint and consulting services, to put in place manufacturing capability in Japan. Caladrius’ (CLDS) subsidiary, PCT, another leading contract manufacturer, followed suit this past month and did a deal with Hitachi Chemical. Similar to Nikon, Hitachi (also a Japanese conglomerate) will get access to manufacturing technology and know-how to build out a cell manufacturing footprint. A trend we’ve been following closely here on Signals is Japan’s aggressive positioning in the regenerative medicine space through deals and acquisitions. Other deals of recent note are FujiFilm’s acquisition of CDI and Astellas’ determined takeover of Ocata Therapeutics.
On the topic of checkpoint inhibitors, Kite Pharma (KITE) partnered up with Genentech, a subsidiary of Roche, to investigate Genentech’s atezolizumab in combination with KTE-C19 in patients with refractory/aggressive non-Hodgkin lymphoma. Kite expects to launch a Phase 1b/2 of the combination this year. KTE-C19 is currently being evaluated in a number of pivotal studies investigating the product in a variety of lymphomas.
Argos Therapeutics (ARGS), which is in late clinical development with a dendritic cell (DC)-based immunotherapy for metastatic renal cell carcinoma, announced plans to raise $60 million to fund its operations until 2017. The funds will get the company through to the second quarter of 2017, at which time the final results of the company’s pivotal ADAPT study in renal cell carcinoma will be disclosed.
Despite successive iterations of DC-based immunotherapies over the years, industry has struggled to demonstrate solid efficacy using this cell type. The first DC therapies were created by pulsing a single protein with a patient’s own tumor cells in hopes of eliciting an immune response targeted to a single neo-antigen (a protein surface marker unique to a cancer cell or over-expressed by a cancer cell). This approach has largely been discarded because it fails to address the heterogeneity inherent to tumour cells. Later iterations have used tumour lysate (the liquid inside tumour cells) to “prime” dendritic cells against cancer proteins or nucleic acids.
More recently, the standard has been to prime dendritic cells against whole, live tumour cells, by taking small samples of patients’ tumours, digesting them enzymatically into single-cell suspension, and mixing them with DCs. This is the approach that Northwest Biotherapeutics is taking, which is developing a DC therapy for glioblastoma. The direction of the DC field will be heavily influenced by the results of these two pivotal studies.