Inhibiting the immune checkpoint protein PD-1 to fight tumors is the premise of a number of profitable immuno-oncology medication, together with Merck’s Keytruda. However these medication are identified to boost the danger of some autoimmune ailments, similar to colitis.
Startup Pandion Therapeutics is taking that threat and turning it into a chance—creating medication that activate PD-1 as a substitute of inhibiting it within the hopes of addressing a number of autoimmune ailments. It offered preclinical knowledge on a number of of these medication on the digital assembly of the Federation of Scientific Immunology Societies (FOCIS).
One of many medication, dubbed PT001, was engineered to selectively activate PD-1 within the intestine. In a preclinical examine, Pandion demonstrated that PT001 activated PD-1 there with out blocking the conventional receptor. In animal fashions of graft-versus-host illness, the drug extended survival, in response to the presentation (PDF).
Pandion, a 2018 Fierce 15 choice, raised $80 million in April of this 12 months to drive its lead candidate, PT-101 for ulcerative colitis, by means of medical trials.
Pandion’s specialty is “modular” drug design, an engineering course of it makes use of to tether therapeutics to tissue-targeted molecules. PT-101 combines interleukin-2 with a protein designed to increase disease-fighting T cells with out activating different immune cells that trigger irritation.
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PT-001 is a PD-1 agonist tethered to a gut-targeted molecule Pandion calls MAdCAM. The corporate is creating the drug to deal with autoimmune ailments of the gastrointestinal tract and liver.
Throughout FOCIS, Pandion unveiled particulars about different preclinical applications within the works. The corporate created an IL-2 drug that’s tethered to a kidney-targeted molecule. It’s now investigating the method to deal with inflammatory circumstances of the kidney, it mentioned.
It additionally created a PD-1 activator that’s tethered to the pores and skin. In an animal mannequin of vitiligo, that drug decreased the skin-lightening results of the illness with out affecting regular immune cells, the corporate mentioned.