Pandion Therapeutics Inc.'s deal with Astellas Pharma Inc. brings as much as $45 million in up-front money and payments related to research and preclinical activities, with potentially more than $750 million in development and commercial milestone rewards to come, plus royalties if products reach the market.
Cambridge, Mass.-based Pandion and Astellas, of Tokyo, will work on locally acting immunomodulators for autoimmune diseases of the pancreas, first focusing on type 1 diabetes (T1D). The effort combines Pandion's modular biologics and functional immunology expertise with Astellas' pharmaceutical oomph. Pandion will be responsible for design and discovery of bispecific drug candidates based on the firm's modular immune effector and tissue tether platform, and Astellas will handle preclinical, clinical and commercialization activities for selected prospects.
"Certainly, there were other parties that we were in discussion with and continue to be in discussion with, and we have been actively discussing potential partnerships to focus on other tissue types for other manifestations of autoimmune diseases," Pandion CEO Rahul Kakkar told BioWorld. "To their credit, of all the technologies Astellas has available to them internally and within the biotech world through partnering, they chose our platform as in alignment with their vision" of how to address difficult-to-treat conditions in the space, he said. "That was very powerful."
The arrangement will speed up Pandion's R&D efforts and build upon an existing collaboration with the JDRF T1D Fund. Since T1D involves the autoimmune destruction of the patient's own pancreas, Pandion is designing targeted immune effectors designed to directly address the problem. The firm uses bispecific antibodies with targeting fragments that bind to specific tissues at inflammatory disease locations, coupled with effector molecules that modulate immune activity to restore immune homeostasis. "One end is an immune modulator, a compound which retrains the immune system toward a balance of recognizing self and not self," Kakkar said. "The other end of that scaffold is a targeting moiety which goes to a specific tissue," and Pandion has programs in gut, liver, skin and kidney as well as pancreas.
Two-year progress brisk
In September of last year, Seattle-based Just Biotherapeutics Inc. and Pandion signed an agreement for the development and cGMP clinical manufacturing by Just of Pandion's lead program, PT-101, a systemically active variant of interleukin-2 (IL-2), called an IL-2 mutein, bound for the clinic in the first half of next year. Kakkar pointed to a "broad swath of autoimmune diseases that various companies are going into" using such an approach, including inflammatory bowel disease (IBD), graft-vs.-host disease, lupus and more. "We believe, and obviously others believe, that this class of drugs is going to be a very large, multi-indication drug class," he said. Pandion has chosen IBD, in keeping with the philosophy of attacking indications "in which anti-cytokine therapies or their oral follow-on molecules are showing good but imperfect disease coverage."
Kakkar mentioned the phase IIIb Varsity trial in moderately to severely active ulcerative colitis, published last month in The New England Journal of Medicine, saying the results "highlight the unmet need of a problem that we are trying to address." In that experiment, 769 patients underwent randomization and received at least one dose of vedolizumab (Entyvio, Takeda Pharmaceutical Co. Ltd.; 383 patients) or adalimumab (Humira, Abbvie Inc.; 386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15; p=0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; p<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years. Researchers concluded that vedolizumab proved superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission.
Behind PT-101, the company has PD-1 agonist PT-627 in its pipeline – the best analogy to which is a quiver full of arrows, Kakkar said. "Each arrow tip is an effector molecule that retrains the immune system in some way. We can deploy those either in systemically active molecules, where they are delivered subcutaneously and they act systemically to dampen down the immune signals of a given autoimmune diseases, or tethered in this bispecific format to home directly with a tissue of interest, as we are doing with Astellas in pancreas with T1D."
Kakkar called the present an "interesting and exciting time of our growth. It's not common for a company to be able to say that in two years we've been able to go from concept to a lead asset moving into the clinic, a novel platform with functional bispecific biologics in active preclinical testing, and a collaboration to bring intensive focus [on] a very important disease."
At the start of last year, Pandion scored $58 million in a series A financing co-led by Polaris Partners, Versant Ventures and Roche Venture Fund. SR One and Bioinnovation Capital participated in the round. Research into bispecifics generally continues apace after the success of Thousand Oaks, Calif.-based Blincyto (blinatumomab), the first to emerge from CD19-directed CD3 T-cell engager antibody platform developed by Rockville, Md.-based Micromet Inc. Last month, Amphivena Therapeutics Inc., of South San Francisco, closed on a $62 million series C that will allow the company to continue its study of selective myeloid-derived suppressor cell removal in hematologic and solid cancers and to advance its lead candidate, AMV-564, a bivalent, bispecific engager of T cells in a phase I trial for treating patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. (See BioWorld, Feb. 9, 2015, Jan. 19, 2018, and Sept. 25, 2019.)