Kojin Therapeutics gets $60 million to explore ferroptosis

Kojin Therapeutics has launched with $60 million to develop drugs that exploit the plasticity of cells, and in particular their tendency to become vulnerable to an iron-dependent process called ferroptosis.

Common wisdom in the field of oncology says that when a drug stops working it’s because tumor cells have mutated to evade it. But cancers have other sneaky ways of resisting our pharmacopeia, one of which is morphing into a state where they are vulnerable to a different kind of cell death. All of our current oncology drugs push tumors to their demise through a process called apoptosis, but some cancer cells alter their gene expression to become reliant on ferroptosis, explains Stuart Schreiber, cofounder of Kojin and a chemical biologist at Harvard University and Broad Institute of MIT and Harvard.

“Every cell in our body also has an inherent plasticity, an ability to switch,” Schreiber says. That switch is why some targeted therapies can often easily shrink tumors to barely detectable levels, but never really cure someone’s cancer. The lingering, slow-growing cells are no longer dependent on the drug’s target and instead have become vulnerable to ferroptosis, he says.

It’s that ferroptotic state that Kojin plans to exploit. The foundations of the company were laid out in Schreiber’s labs by a team led by postdoc Vasanthi S. Viswanathan. Now a cofounder and head of biology at Kojin, Viswanathan contributed several key insights, including unraveling the mechanism by which an enzyme called GPX4 can rescue cells from ferroptosis and finding chemical probes to show that inhibiting that enzyme can lead to cell death.

Kojin was founded with seed funding a little over a year ago, and since then its team has validated some targets within the ferroptosis pathway and explored small molecules that can modulate those targets, says board member Nagesh Mahanthappa. “A major priority in the coming year will be showing that this isn’t just a phenomenon in the culture plate, but to actually prove it out in relevant in vivo model systems,” Mahanthappa says.

The current round of funding, which came from a syndicate of investors including Polaris Partners, Newpath Partners, and Cathay Health, will allow the biotech firm to discover compounds that can go into human studies in the next 3–4 years, he adds.

While Kojin will initially focus on cancer and ferroptosis, Mahanthappa says its platform has the potential to broadly take advantage of the inherent plasticity of cells, citing opportunities in fibrosis and neurodegenerative diseases.