PD-1 as a Therapeutic Target

PD-1 is a receptor naturally expressed on activated T cells. When stimulated, PD-1 acts as a brake and checkpoint on the immune response. PD-1 is an important control node for the development of self-tolerance to prevent the immune system from attacking a host’s own cells indiscriminately. For example, patients with cancer who receive PD-1 antagonists, or inhibitors, can frequently develop autoimmune-like side effects arising from this treatment.

PD-1 Agonists

Pandion’s approach is to agonize, or activate, PD-1 to attenuate an inappropriate immune response in autoimmune diseases. We identified novel antibodies which can selectively activate the PD-1 receptor, without blocking the natural PD-1 ligands PD-L1 and PD-L2, and without risk of antagonism. Our PD-1 agonists can be used in systemic as well as tissue-tethered formats.

We have demonstrated promising preclinical results with both systemic and  tissue tethered formats of our PD-1 agonists in animal models of various autoimmune diseases. These include global tissue and organ inflammation models for systemic and gut-tethered PD-1 agonists as well as vitiligo, dermatitis and psoriasis models for skin-tethered PD-1 agonists.

 


PT627

PT627 is our systemically-acting PD-1 agonist product candidate. It contains a PD-1 agonist effector module that does not interfere with PD-1’s natural ligands on a fully-human IgG1 backbone.

We initiated investigational new drug (IND)-enabling studies of PT627 and expect to file an IND application in 2022.

PT001

PT001 is a bifunctional molecule, consisting of our PD-1 agonist with a MAdCAM tether. MAdCAM is constitutively expressed in the gastrointestinal tract and is a critical receptor for the trafficking of immune cells into gut tissue. Pandion’s MAdCAM tether is a proprietary antibody designed to localize the PD-1 agonist to the gut, but not interfere with MAdCAM’s function. PT001 has the potential to increase concentration and effect of a PD-1 agonist to the gut as an approach to treat gut-restricted autoimmune diseases.

We plan to initiate IND-enabling studies with PT001 in the first half of 2021.

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