Ex-MD Anderson chief DePinho is helping launch another biotech — and he's sticking with familiar ground
Years after co-founding SINE-focused Karyopharm and stirring up controversy at MD Anderson, Ronald DePinho is helping uncloak a new biotech targeting solute carrier transporter proteins — and Karyopharm’s former head of chemistry is leading the charge.
Nirogy Therapeutics emerged from stealth mode on Tuesday with a $16.5 million Series A round and plans to hit the clinic by 2022. The financing should be enough to carry the startup’s lead program, a small molecule lactate transport inhibitor, through Phase I, CEO Vincent Sandanayaka said.
Sandanayaka said he first became intrigued by tumor metabolism while leading the chemistry unit at Karyopharm — another oncology company that DePinho helped start before joining MD Anderson. That biotech landed a Series A in 2010 for its work on selective inhibitors of nuclear export (SINE), and raised eyebrows last year when its multiple myeloma drug got approval from the FDA despite objections from 8 of the 13 experts on an outside panel.
After co-founding Karyopharm, DePinho served a six-year tenure as president at MD Anderson, during which time the center reported operating losses of more than $460 million over 16 months and hundreds of staffers were laid off. He stepped down in 2017.
But while many researchers in the space were going after intracellular targets, not many were working on solute carrier transporters — membrane-bound proteins that block or regulate metabolites like glucose, Sandanayaka said. Solute carrier transporter proteins (SLCTs) act as gatekeepers of important physiological functions, including nutrient uptake and metabolite disposal. The proteins are aberrantly altered in many diseases — but they’re difficult to isolate, and thus difficult to study.
“If you take these transporters out of the membrane, like if you’re trying to isolate it, you may lose the functional state of the protein,” Sandanayaka said. Nirogy gets around the issue by using computational modeling.
The CEO founded Nirogy in 2014 and reached out to DePinho in 2019, the same year the startup got some seed funding. Their lead program takes a two-pronged approach to fight cancer. Unlike normal cells, cancer cells consume large amounts of glucose, and excrete lactic acid into the tumor microenvironment through lactate transporters. This creates a hostile environment for immune cells to survive.
But if that lactic acid isn’t released, it accumulates, causing the cell to die, Sandanayaka said. Nirogy’s candidate fights cancer cells by inhibiting them from expelling the lactate, while also boosting immune response.
Sandanayaka believes this “one-two punch” is what differentiates it from Jnana Therapeutics, which struck an alliance with Roche in July to explore SLCT targets in immune-mediated and neurological diseases. That deal starts small at $40 million, but can add up to $1 billion if the pharma partner commits to developing the programs.
“As you might imagine for a lot of drugs cancer cells develop resistance. So that’s part of the problem, it may be active initially, but then cancer cells develop a resistance… So, that is why we thought we want to have a multi-pronged approach to address this drug resistance,” Sandanayaka said.
The startup plans to test the lactate inhibitor both as a monotherapy and combination therapy, and has done preclinical models in triple negative breast cancer, melanoma, and colorectal cancer, in combination with anti-PD1 and anti-CTLA4 immunotherapies.
In addition to the lead program, Nirogy has a second transporter target in cancer and a third program in immunology. The tiny five-person company could grow to 15-20 people over the next few months, Sandanayaka said.
