With lessons learned from Vor, Siddhartha Mukherjee takes a different route to target solid tumors with startup Myeloid
Siddhartha Mukherjee is a busy man these days.
The Pulitzer Prize-winning author, Columbia professor, oncologist, hematologist and leading cancer researcher in 2016 launched Vor, a Cambridge, MA-based startup focused on a new cancer treatment in which cell surface antigens such as CD33 are removed from hematopoietic stem cells. They can then unleash a CAR-T therapy — made from T cells in a patient’s blood and genetically engineered to hunt for the antigens — to treat cancer using the body’s own immune system without attacking healthy cells that would’ve shared those antigens.
Now, Mukherjee is adding a new startup to his plate, still focused on treating cancer using the immune system. But this time, his focus is on types of cancers that have demonstrated they can’t be cured by the CAR-T cell technology he prioritizes at Vor.
This startup, also based in Cambridge, is called Myeloid Therapeutics, named for the specific cells which play a critical role in a new therapy founded by Mukherjee and renowned biochemist Ronald Vale. The two are backed by over $50 million in Series A funding from around the biopharma industry, led by Newpath Partners out of Boston.
Mukherjee told Endpoints News in an interview that using myeloid cells to target cancers — mostly those in solid tumors — has the potential to meet an “enormous” unmet medical need.
“Most solid cancers such as ovarian cancer or colorectal cancer or esophageal cancer for whatever reason are not amenable to CAR-T cell therapy or to so-called checkpoint inhibitor therapies, which activated T cells against these cancers,” he said. “We now know a lot about why, and that’s because when you look at these cancers, even after you treat them with these (therapies), you find that they form a kind of shell and resistance shell around the cancer … which exclude T cells from entering the tumor.”
It’s almost like the shell on the outside of a Star Wars battleship, Mukherjee said.
This is where myeloid cells come into play. Unlike T cells, myeloid cells are actually “intrinsically designed” to penetrate solid cancer tumors, he said, as if they have a free pass to invade the mass and survey what’s happening inside of it.
Mukherjee and Vale discovered that they could genetically engineer receptors in the myeloid cells to not only penetrate a tumor, but to recognize the tumor and be activated by the tumor itself. In other words, the technology bridges the gap between the human body’s innate immune system, which can generally scan the body for viruses and the like, and the immune system’s capacity to recognize and later attack cancer cells.
Thus became Myeloid Thereapeutics.
“Those were the two crucial insights that drove this company and the therapies that this company is producing,” Mukherjee said. “The fact that you can take the innate immune system, which is not designed to recognize one particular virus or microbe or cancer, but engineer the immune system to recognize cancer and become activated by the cancer … We’re enabling the most ancient part of the immune system to become cancer-specific and cancer-activated.”
Myeloid will dedicate much of the initial $50 million funding toward initiating clinical trials for its two main programs, which target T cell lymphoma, glioblastoma and other solid tumors. The team will also continue to design and advance a broad pipeline of targeted myeloid cell therapies, including primed myeloid cells, myeloid multi-specific engagers and other development candidates created with Myeloid’s novel mRNA delivery technologies.
The company expects to enter the clinic with its two lead programs in glioblastoma and T cell lymphoma in 2021.
Myeloid CEO Daniel Getts told Endpoints that throughout his career in the biotech industry, he’s been involved with other ventures that looked at the use of T cells in fighting cancerous tumors. But before now, it’s seemed like the technologies and cancer remedies available were disjointed, he said. Where Myeloid hopes to be different is that it combines the concepts of those past therapies into a single therapeutic through the myeloid-cell mechanism.
“I think the power of what we have is unsurpassed right now. And, you know, we’re beneficiaries,” Getts said. “We’re standing on the shoulders of a lot of these other gene engineering companies because they’re showing the world what’s possible.”