DUBLIN – Immatics Biotechnologies GmbH is pocketing $54 million up front and could earn up to $1.65 billion more in development, regulatory and commercial milestones from a three-product immuno-oncology research collaboration and license agreement with Genmab A/S. The two companies will pool their respective capabilities in cancer target discovery, T-cell receptor (TCR) engineering and antibody engineering to develop bispecific protein-based therapeutics that will target both intracellular tumor-associated peptides (Tumaps) and T cells.

The initial phase of the deal involves three cancer targets discovered by Immatics. Genmab has an option to license up to two more targets, while Immatics will received tiered royalties, up to a double-digit percentage of net product sales.

Immatics is not disclosing the nature of the targets, but Immatics CEO Carsten Reinhardt noted that the present progress with chimeric antigen receptor T-cell (CAR T) therapies is limited to extracellular antigens expressed on lymphocytes. CAR T developers have so far struggled to extend the same success into solid tumors.

"The market clearly lacks solid tumor targets," Reinhardt told BioWorld. Tu maps, which are recognized when bound to a human leukocyte antigen (HLA), have the potential to expand significantly the target universe that can be addressed – with either adoptive cell therapies or protein-based drugs.

At first glance, the present deal seems to map closely to the pact Tuebingen, Germany-based Immatics entered with Amgen Inc., of Thousand Oaks, Calif., in January 2017, even if the financial terms are somewhat better this time round. The Amgen agreement involved $30 million up front and more than $500 million in per-product milestones. (See BioWorld Today, Jan. 10, 2017.)

"In principle, it's similar," Reinhardt told BioWorld. "It builds on the increasing appetite of big pharma and big biotech for new targets." Immatics claims to be a world leader in the identification and characterization HLA-bound Tumaps that are uniquely expressed on cancer cells – avoiding cross-recognition of epitopes on healthy tissues is crucial to the safety of that approach.

From a commercial standpoint, there is, however, one big difference between the present deal and the earlier pact. "With Genmab, we have certain co-promotion rights," he said. "That was very important for us." It will give the company an opportunity to build more value in the long term.

The deal with Copenhagen, Denmark-based Genmab is also distinctive from a technological standpoint. The drug candidates that emerge from the initial research phase could either be engineered T-cell receptors (TCRs) linked to a T-cell recognition moiety or bispecific antibodies that recognize the same tumor target and the CD3 T-cell antigen. "We are able to generate T-cell receptors – they are able to generate antibody binders," Reinhardt said.

Each firm will work on lead compounds independently, and Genmab will make the final call on which molecules will be selected as candidate drugs, depending on their performance and pharmacokinetic profiles. With Amgen, Immatics is working on engineered TCRs linked to a T-cell recognition element only.

In addition to its TCR engineering expertise, Immatics also has capabilities in adoptive cell therapy, again based on the high-affinity recognition of Tumaps. Having the two capabilities under one roof represents a significant level of ambition. Oxford, U.K., firms Immunocore Ltd. and Adaptimmune Therapeutics plc share a common history in Avidex Ltd. (and later Medigene AG) but have pursued separate development paths – Immunocore majors in the development of TCR-based therapeutics, while Adaptimmune is developing cell-based therapies that recognize novel antigens. Planegg, Germany-based Medigene, which acquired Avidex and later spun out its offspring, is itself pursuing adoptive cell therapies, again based on TCR engineering expertise.

Immatics has no plans to spin off one or other of its technology platforms. "Our investors clearly decided we want to stay as one company," Reinhardt said.

In addition to its partnered programs, Immatics also has an in-house pipeline, which includes three adoptive cell therapy programs that are currently under open INDs. IMA-101 is in a phase I trial for advanced solid tumors. IMA-201 is undergoing a phase I trial in patients with advanced solid tumors, with an emphasis on head and neck cancer and non-small-cell lung cancer. Details of the third program, IMA-202, have not been disclosed. All three are part of a clinical collaboration between Immatics' Houston-based subsidiary, Immatics US, and MD Anderson Cancer Center in Houston. (See BioWorld Today, Aug. 27, 2015.)

Shares in Genmab (Copenhagen:GEN) closed Thursday at DKK1,082.50 ($169.65), a gain of 2.6 percent on the previous close. Immatics remains privately held.

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