Reverse engineering localized antibodies that protect organs by mimicking tumors
CEO: Anthony Coyle
CSO: Jo Viney
Based: Cambridge, Massachusetts
Clinical focus: Immune-related conditions such as inflammatory bowel disease, type 1 diabetes, and autoimmune liver, kidney and skin diseases.
The scoop: One of the most recalcitrant aspects of cancer has been the tumor’s frustrating ability to avoid surveillance and attack from the body’s immune system. Understanding and overcoming those defensive measures has become the raison d’etre for other members of this year’s class of Fierce 15, as well as plenty of those who came before. But what if those very frustrations could be turned on their heads and used to help cloak and protect organs from autoimmune diseases, where T cells are doing their jobs a little too well?
That’s exactly what Pandion Therapeutics hopes to do, by translating those insights into tissue-specific antibodies that mimic the molecules that regulate and disarm the immune system, but only on a local scale, to avoid the risks of standard immunosuppressive drugs. The company recently identified its lead candidate, and after a $58 million infusion of venture capital in January, it plans to enter the clinic by the end of next year.
What makes Pandion fierce: This startup is thinking big to go small. Taking radical flight from the traditional approach of suppressing the entire immune system, Pandion aims to confine its drugs’ effects to a single tissue type—and, it expects, produce a smaller set of side effects.
Its founders have moved into a smaller venue as well: Before Pandion, CEO Anthony Coyle had been chief scientific officer of Pfizer’s Centers for Therapeutic Innovation since 2010 and before that, global head of respiratory, inflammation and autoimmunity research at MedImmune. Meanwhile, CSO Jo Viney helped lead Biogen’s immunology research and drug discovery efforts as VP and senior VP, respectively.
“We felt it was a great idea to combine our experiences and our understanding of drug discovery, and to bring that experience together to do something big and different,” Coyle said. “We felt the best place to do that was in a startup.”
“The real draw for me," Viney added, "was to take this radical idea and very nimbly come at it from all different angles—to really explore the different tissues and different molecules, and be able to pivot quickly in those decisions to advance the program and test our concepts."
Pandion is taking a modular approach to drug development, aiming for a bi-specific antibody platform that can apply broadly across a wide variety of inflammatory disorders, including transplantation.
The company’s antibodies aren’t bi-specific in the traditional sense either, where each upper arm of the Y-shaped protein would bind to a different antigen. Instead, the tail of the Y is designed to lock into a specific tissue or organ site—such as the liver, kidney or skin—affected by inflammatory disease.
After studding the tissue with these antibodies, the top half of the antibody—the arms of the Y—forms a “protect me” signal coat. That coat inhibits activated T cells and activates regulatory T cells, and Pandion believes it will disguise the organ from the immune system and help bring immune reactions into proper balance.
The modular approach also applies to the company culture. Coyle and Viney have focused on building and mentoring a diverse team of thinkers. “We have the slow, 24-hour decision makers, we have people who like to ponder, people who are inquisitive, people who are careful,” Viney said.
“We've really tried, with our small team, to get at least one of each of those phenotypes,” she said. The idea is that tapping a variety of thinking styles can head off the groupthink and regression-to-the-mean decision making that can crop up at larger companies, she said. “We've made some perhaps-not-conventional hires in people we wanted to bring in under our umbrella, because we felt that they had potential, and we're certainly very pleased.”
“We've already seen tremendous growth in some of those more junior-level scientists,” who are just starting to understand how close their lab work is coming to the real world and real patients, Viney said. Right now, Pandion is starting to hire its first clinicians and manufacturing specialists while pursuing partnerships with pharma companies and patient organizations.
But when it comes to the end goal, the company has its feet set firmly on the ground: “We're making really innovative molecules, but let’s make sure we're making molecules that don't run into challenges,” Coyle said.
“Having been part of Big Pharma, where we both came from, we both want to make sure that we make molecules that look like drugs,” he said. The company has no plans to get cute with delivery methods, for example—they intend to let the tissue-specific binding sites do the work for them.
“We don't want to create molecules that we appreciate later on, but you can't manufacture them, or you can't administer them properly by the subcutaneous route of administration,” he said.
Investors: Polaris Partners, Roche Venture Fund and Versant Ventures