Welcome to your Cell Therapy Deal Review for the month of September. Aduro Biotech went the way of Juno and Kite and bought an antibody discovery platform. Intrexon and ZIOPHARM entered into an agreement to develop a novel Treg-based immunotherapy for GvHD. Kite Pharma expanded its relationship with the Netherlands Cancer Institute to develop novel TCRs. Ontario-based Sernova secured rights to a cell source for its diabetes technology.
As cell-based immunotherapy innovators seek to broaden the horizons of their respective platforms, they have been on the hunt for new technologies and capabilities to bring in-house. In 2015, Juno Therapeutics (JUNO) and Kite Pharma (KITE) secured deals to purchase X-BODY and T Cell Factory, respectively. Kite’s purchase gave it capabilities to generate novel T cell receptors (TCRs), while Juno’s purchase provided a portfolio of antibodies and engineering capabilities to produce new CAR products.
Aduro Biotech (ADRO), which already has a diverse platform of interesting technologies to deploy, has made itself even more competitive now with the purchase of BioNovion, which, similar to X-BODY, is an antibody discovery and development company. Assets acquired by Aduro include antibody candidates in preclinical development that inhibit known checkpoint pathways (PD1, CTLA-4) and other, novel immune pathways. BioNovion’s portfolio also includes five bi-specific antibody candidates being developed, at the preclinical stage, along with Genmab, and an “APRIL” (proliferation-inducing ligand) antagonist targeted to B-cell lymphomas. All this for €29 million upfront – a great deal indeed!
Next generation cell-based immunotherapies are being engineered in novel ways to supplement their activity. One of these engineering tools is the introduction of transgenes encoding cytokines, an approach that is being investigated by OncoSec Medical (ONSC) and ZIOPHARM (ZIOP) with IL-12 in a variety of cancer types. Intrexon (XON) and ZIOPHARM have now teamed up to create a first-in-class engineered T regulatory (Treg) cell that is engineered to express IL-2. The technology will be deployed to temper graft-versus-host disease (GvHD) in patients following hematopoietic stem cell transplantation, which remains a significant source of mortality for patients requiring reconstitution of the bone marrow compartment. Tregs will be engineered using Intrexon’s RheoSwitchTM technology, such that they conditionally express IL-2, under the control of an inducible promoter.
Another interesting new technology to come out of this partnership is microbes for oral administration (ActoBioticsTM) that therapeutically express IL-2. Microbes will be put into pill form and given orally to patients to help temper some of the GI symptoms associated with GvHD.
Kite Pharma (KITE) has formed close ties with the Netherlands since its acquisition of T Cell Factory in March of 2015, which is now Kite Pharma EU, based in Amsterdam. T Cell Factory’s technology, called GENEratorTM, was based on the work of Dr. Ton Schumacher, an investigator at the Netherlands Cancer Institute. Dr. Schumacher stayed on with the company as Chief Scientific Officer. KITE announced that it expanded its collaboration with the Netherlands Cancer Institute to gain access to a number of novel TCR gene sequences targeted to solid tumours. Kite and Adaptimmune are the current industry leaders in TCR technology.
Caladrius Biosciences (CLDS) has a unique approach for the treatment of type 1 diabetes (T1D). The company formed a strategic collaboration with Sanford Research to investigate the use of Treg cells for treating recent-onset T1D in adolescents. Sanford Research, which will pay for the Phase 2 Trutina study, hopes to enroll 111 subjects across 12 to 15 sites in the United States. Caladrius’ CLBS03 is an autologous product derived from a patient’s blood. Following a blood draw, Treg cells are isolated, expanded, and then infused back into the patient. The primary endpoint in the study is C peptide levels compared to placebo at 52 weeks. CLBS03 was previously shown to be safe for administration in humans in a Phase 1 dose-escalating study in 14 adult patients with established T1D, conducted at the University of California, San Francisco (UCSF) and Yale.
Ontario-based Sernova (SVA) completed a licensing deal with the University Health Network (UHN) to gain exclusive worldwide rights for the production of glucose-responsive cells from pluripotent stem cells. The intellectual property behind the technology is that of Dr. Cristina Nostro. Sernova’s Cell PouchTM technology, which is currently being investigated in T1D patients in a phase 1/2 study, at the University of Alberta, provides a vascularized reservoir within which to transplant therapeutic cells.
Semma Therapeutics, a company spawned from the work of Dr. Doug Melton, at the Harvard Stem Cell Institute, is also after a cure for T1D using cells. Earlier this year, Melton and his team published research showing they were able to produce terminally differentiated, functioning beta cells from induced pluripotent stem cells. Industry now has commercially viable sources (pluripotent) of glucose-responsive cells. However, the remaining challenge will be solving immune-isolation to prevent graft rejection following transplant.