The field of immuno-oncology rests upon the basic principle that a patient’s own immune system can be harnessed to find and destroy cancer cells. The question now is can we do the reverse: Can aspects of the tumor microenvironment be replicated to shut down autoimmune and other inflammatory disorders at a tissue-specific level?
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Pandion Therapeutics plans to find out. The Cambridge, Massachusetts-based startup exited stealth mode on Thursday with a $58 million Series A round, jointly led by Polaris Partners, Versant Ventures, and Roche Venture Fund. SR One and BioInnovation Capital also chipped-in.
Following a popular VC trend of late, the company has a platform designed to generate many drug candidates for a variety of indications. They will take the form of bispecific antibodies, a therapeutic modality that is well-established with more than 60 molecules currently in clinical trials and one drug, Amgen’s Blincyto, already approved.
While monoclonal antibodies are designed to bind one protein, bispecific antibodies have two arms that can simultaneously engage two separate molecules. Four out of every five bispecifics are being developed as anti-cancer drugs. Pandion’s novel twist – and intellectual property – covers the use of bispecifics as a localized barrier that protects healthy tissue from an autoimmune assault.
In many ways, the immune system is like a seesaw. It needs to find a balance between eliminating pathogens and would-be cancer cells, while still tolerating normal tissue — be it heart or lung or skin.
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In autoimmune diseases, the immune system overreacts. It begins targeting healthy tissue. In Type 1 diabetes, insulin-producing cells in the pancreas are destroyed; in irritable bowel disease (IBD) it’s the lining of the intestines.
Conversely, the immune system can be too lax, allowing lethal tumor cells to grow. This often the result of cancers’ ability to develop tools for evading immune detection. One common trick is to augment the tissue around it, creating a protective ‘bubble’ known as the tumor microenvironment.
Which brings us to Pandion’s approach. Instead of beating down the entire immune system to protect a specific organ or tissue, the company wants to create something more akin to a tumor microenvironment. Bispecific antibodies will be used to specifically shield a given tissue or organ. Picture a person breaking up a fight with both arms extended in either direction.
That’s where the two arms of the antibody come into play, Coyle said.
“The technology that we’ve developed is really based on building, I think, some really exciting new bispecific antibodies. Part of those antibodies will allow the therapeutic to localize at the site of inflammation. The other side of the bispecific will then be able to interact with inflammatory cells — with immune cells that are present and are recruited to sites of inflammation,” Coyle described in a phone interview. “By doing so, the fundamental concept there is to really restore normal immune homeostasis.”
The idea came about through some extensive brainstorming between Polaris Partner Alan Crane, Pandion Chief Scientific Officer Jo Viney, and Coyle. The latter two are both pharmacologist/immunologists. Coyle previously headed Pfizer’s Centers for Therapeutic Innovation (CTI), while Viney held senior drug discovery and immunology roles at Biogen and, before that, Amgen. While neither has true startup experience, they have advanced a total of 22 products into the clinic, with multiple products on the market and in late-stage clinical trials.
“I think we’ve brought our understanding of what a therapeutic has to look like to be a good viable drug,” Coyle said, noting that their experience is an integral part of Pandion’s business model. “We’re building-in some of [therapeutic] characteristics to ensure that very early on, as we build our new bispecifics, that we have the end in mind — that we are building molecules that can move from candidates to IND and into the clinic.”
The Series A will be used to advance both the platform and several preclinical drug programs. Coyle said the early targets are IBD and autoimmune liver disease. From there, inflammatory kidney disorders and type 1 diabetes could be in the cross-hairs. Of note, the approach could also theoretically be applied to prevent organ rejection in transplant patients.
There’s no shortage of targets and the field is, in some ways, trailing behind. Oncologists have drugs to help expose cancer cells to the immune system. Immunologists need therapies that can selectively ‘hide’ healthy tissue from dysfunctional immune systems.
But it’s a case of one step at a time. The company is less than one-year-old and has a dozen employees — though Coyle expects the headcount to double in next 12-18 months.
Photo: freedigitalphotos user Salvatore Vuono
