Nirogy Therapeutics, based in Boston, with a $16.5 million Series A financing round. The round was co-led by Santé Ventures and Sporos.
Nirogy is focusing on small-molecule drugs that target the solute carrier family of transporter proteins (SLCTs). These proteins are embedded in the cell membrane and act as gatekeepers of a number of functions, including nutrient uptake and metabolite disposal. The lead programs are targeting cancer.
“Cellular transporters, which are central to many aspects of cell biology and dysregulated in myriad diseases, have not been effectively targeted due to the complex structures of SLCTs,” said Vincent Sandanayaka, founder, president and chief executive officer of Nirogy. “Our team’s strength in computational modeling, medicinal chemistry and cancer biology has enabled us to overcome the challenge of drugging these critical untapped targets. We are fortunate to have a world-class scientific advisory board, highly committed investor partners and a dedicated team with proven scientific and drug development expertise.”
The lead program targets lactate transporters for cancer therapy. The company believes it will be able to take this compound into clinical trials in 2022. Cancer cells utilize large amounts of glucose, while excreting a huge additional quantity of lactic acid into the tumor microenvironment by way of lactate transporters. Tumors that are lactate-rich create a hostile environment for immune cells, which suppressed anti-tumor immunity. In preclinical research, the company’s lactate transport inhibitors demonstrated robust anti-tumor efficacy, either by themselves or in combination with other drugs.
Nirogy’s pipeline includes two other compounds, the second also a transporter target for cancer and the third in immunology.
As part of the financing, Dennis McWilliams of Santé Ventures and Joseph Kekst of Sporos are joining Nirogy’s board of directors. “We recognize the potential of the Nirogy team and its proprietary drug discovery engine in SLCTs, which could yield over 450 potential druggable targets and open up new treatment modalities for a number of life-threatening diseases,” said McWilliams.
SLCTs have been attractive drug targets, in theory, but have largely been unexplored and certainly unexploited so far.
Sandanayaka that, “These are highly complex proteins bound to cell membranes. If we take them out of the cell membrane, their functional state is destroyed and therefore, it’s very hard to design drugs against them.”
For example, in 2017, France-based Genoscience Pharma its own SLCT, GNS561. In November 2020, the company it had successfully completed its Phase Ib trial of GNS561 in primary and secondary liver cancer patients. It expects to begin Phase II trials this year. GNS561 is a palmitoyl protein thioesterase-1 (PPT-1) inhibitor that blocks autophagy, which is activated in tumor cells in response to specific conditions.
Autophagy is how the body cleans out damaged cells in order to regenerate newer, healthier cells. GNS561 is able to enter the lysosomes and bind to its target, inhibiting activity on late-stage autophagy, which causes tumor cell death.
Last Friday, January 23, Nirogy it was awarded a $2 million NIH/NCI SBIR grant to develop dual monocarboxylate transport inhibitors (dMCTi) for triple negative breast cancer (TNBC). dMCTi blocks lactate excretion to the tumor microenvironment, and in preliminary research, has shown it has potent activity against multiple TNBC cell lines.
“We are delighted to receive this highly competitive award from NIH/NCI under its small business innovation research grant program,” said Sandanayaka. “We are appreciative of the continued support from NCI for our breast cancer program. I believe that this award attests to the validity of our science strategy to target the untapped class of solute carrier transporters (SLCT) family of proteins for cancer, and the progress we have made so far in this breast cancer program.”
Nirogy Therapeutics is a biotechnology company based in Boston, MA, developing novel small molecules to target cellular transporters. The company is currently advancing a class of small molecules intended to disrupt metabolic and immune mechanisms operative in the tumor microenvironment. Follow-on platform programs are targeting additional disease pathways in oncology as well as autoimmune diseases.