DUBLIN – Immatics Biotechnologies GmbH is banking $50 million up front and could earn up to $550 million more in per-product milestones from an adoptive cell therapy deal in solid tumor indications with Glaxosmithkline plc, which initially involves two autologous cell therapies engineered to express T-cell receptors (TCRs) that bind novel cancer targets. Immatics would receive royalties on sales of any approved therapies.
The deal is reminiscent of the pact Tuebingen, Germany-based Immatics entered with Celgene Corp. (now part of New-York-based Bristol-Myers Squibb Co.) less than six months ago, in which it banked $75 million up front and is in line for milestone payments of up to $505 million per product. In that three-program deal, the German firm retained certain co-development rights. This time round, it has been less explicit about potential co-development rights, but they are also an option in the present deal. So, too, is the possibility of employing Immatic’s allogeneic gammadelta T-cell therapy platform. “In principle, every program can be an allogeneic program,” Immatics Chief Medical Officer Carsten Reinhardt told BioWorld.
The agreement follows a similar course to other pacts Immatics has entered, on the strength of its target discovery capabilities. CAR T-cell therapies and T-cell-targeting bispecific molecules, such as Bites (bispecific T-cell engagers), have been successfully deployed in hematological cancer indications, but the approach has been less successful in solid tumor indications because of the scarcity of surface-expressed antigens that are unique to the cancerous cells. “That’s the real issue,” Reinhardt said. “The really good targets are all intracellular. That’s something people have started to recognize and understand.”
Immatics’ high-throughput Xpresident platform combines mRNA sequencing and mass spectrometry to identify human leukocyte antigen-presented peptide antigens that are expressed on cancer cells but absent from healthy cells. The company can quantify the level of expression of a given target, which can be an important factor in determining its immunogenicity. “It’s a very sophisticated method, based on our 20-year experience in mass spectrometry,” Reinhardt said.
London-based GSK and Immatics are not disclosing the targets they are pursuing at this point, but the programs are de novo initiatives, which arose from discussions between the two firms. They are some way from the clinic, therefore. “I would say a typical time frame from nominating a target to having a final TCR candidate is in the 24-30-month range,” Reinhardt said. GSK has an option to include additional programs in the alliance, which would trigger further option, milestone and royalty payments.
The present deal continues a recent positive run for companies engaged in TCR-based cell therapies. Earlier this month, Oxford, U.K.-based Adaptimmune plc netted $89.8 million in a rights issue launched on the back of promising, if preliminary, clinical data in four solid-tumor indications it released in January. In the same week, the same firm also received $50 million upfront from a potential $897.5 million co-development deal on TCR-based and CAR T-cell therapies with Tokyo-based Astellas Pharma Inc. Also in January, London-based startup Ervaxx Ltd. entered a collaboration with the University of Cardiff in Wales to develop a ‘universal’ T-cell receptor, which may have application in multiple solid tumor indications.
For Immatics, the deal is further validation of its strategic shift to adoptive cell therapy, which was enabled by entering an alliance in 2015 with the MD Anderson Cancer Center in Houston and establishing a U.S. subsidiary. It still has two additional active alliances, with Genmab A/S, of Copenhagen, Denmark, and Amgen Inc., of Thousand Oaks, Calif., which marry its target discovery capabilities to their respective Duobody and Bite bispecific antibody platforms. “They are proceeding according to plan,” Reinhardt said. The company also has longstanding alliances with Martinsried, Germany-based Morphosys AG and Basel, Switzerland-based Roche Holding AG. Immatics is, at this point, fully loaded in terms of deals. “There is no real need for us to do another partnership in the next 12 to 18 months or so,” he said. The company is funded well into 2021 at this point.
Immatics also has several internal MD Anderson-partnered programs in phase I/II trials in solid tumor indications. IMA-201 targets melanoma-associated antigen 4 (MageA4) and MageA8; IMA-202 targets MageA1; IMA-203 targets Prame (preferentially expressed antigen in melanoma); and IMA-204 targets Col6A3 exon 6. It has yet to release data from any of those studies. IMA-101, which comprises unmodified autologous T cells that are selected ex vivo for their specificity to defined cancer targets and then primed in the presence of interleukin-21, has generated clinical data, but it is no longer a core program, Reinhardt said. It was developed as proof of principle of its cell manufacturing process.