On January 26, 2021 Boston-based Nirogy Therapeutics Inc. reported $16.5 million series A round is meant to enable a pipeline of small-molecule drugs targeting the solute carrier family of transporter proteins (SLCTs) embedded in the cell membrane, and let the firm bring its front oncology runner to the clinic in 2022 (Press release, Nirogy Therapeutics, JAN 26, 2021, View Source [SID1234577568]).
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"The first thing we’re going to do is select the lead compound for preclinical devel-opment" and start IND-enabling studies, founder, president and CEO Vincent Sandanayaka told BioWorld. Nirogy’s technology allows a "one-two punch" in pill form against cancer, he said, directly killing disease cells and activating the immune system at the same time. Early work suggests that the strategy could work well against triple-negative breast cancer (TNBC), melanoma and colorectal cancer – all challenging indications.
SLCTs, dubbed gatekeepers of physiological functions, are involved in nutrient uptake and metabolite disposal. They represent a largely underexplored source of new therapeutic targets, Nirogy pointed out. Fewer than 20 of more than 450 transporters are targeted by current drugs, leaving a bounty of others, many of which are orphan targets of which the biologi-cal function and substrate specificity are unknown.
Nirogy’s research starts with identifying a target of interest and building homology models based on known structural data, deploying in-house mutational studies and computational capabilities. Once a reasonable model has been established, the firm does virtual screening of compound databases and available tool compounds while developing physiologically rel-evant biological assays to come up with lead compounds. What Nirogy calls a "synchronous lead optimization strategy" lets the company quickly find leads to test in mouse models. Transla-tional bioinformatics helps select relevant mouse models, so that mechanisms of action can be better understood.
Monocarboxylate transporters (MCTs) make up a subfamily of SLCTs consisting of 14 metabolite transporters. Of those, MCT1 and MCT4 are key isoforms that transport lactate metabolite bidirectionally in and out of cells. Nirogy’s lead program targets lactate transporters (LTs) for cancer. Unlike normal cells, cancer cells consume large amounts of glucose and excrete a huge excess of lactic acid to the tumor microenvironment by way of LTs for their rapid growth and survival, the company noted.
Lactate-rich tumors create a hostile environment for immune cells, thereby knocking down antitumor immunity. LT inhibitors in the Nirogy hopper have shown robust antitumor efficacy in preclinical models as monotherapy and combo therapy. The pipeline includes a second transporter target in cancer and a third program in immunology. Another indication in the firm’s crosshairs is rheumatoid arthritis. There’s an effort in inflam-mation, too.
Taking its name from the Sanskrit word meaning "without illness," Nirogy has five full-time employees and over the next five or six months expects to increase the headcount to 15 to 20. The firm was founded in 2014 and received seed money in 2019.
Aggressive, recurrent and difficult to treat, TNBC has been the subject of much research lately. TNBC accounted for 12% of breast cancers diagnosed in the U.S. from 2012 to 2016, with a five-year survival rate 8% to 16% lower than hormone recep-tor-positive disease, a paper in The Cancer Journal pointed out. "However, preventive and screening strategies remain tailored to the demographics of less lethal luminal cancers," the authors said. The illness "disproportionately affects African American women and carriers of germline BRCA and PALB2 mutations," they noted. "Even controlling for treatment delays, stage, and socioeconomic factors, African Americans with TNBC remain nearly twice as likely to die of their disease."
Some encouraging news recently came out of the melano-ma space, with researchers at Dana Farber Cancer Institute, Brigham and Women’s Hospital, and the Broad Institute of MIT and Harvard reporting a study finding that, four years after pa-tients with melanoma were treated with a personalized cancer vaccine, the immune response generated stayed strong and effective. The vaccine is called Neovax, and the research was published in Nature Medicine.
More has lately been discovered about colorectal cancer as well. Scientists at the University of Virginia found that one side of the colon ages biologically faster than the other in African Americans and people of European descent, which is why those populations are more likely to suffer the disease at an earlier age. In African Americans, however, the right side ages signifi-cantly faster, explaining why African Americas are more likely to develop cancerous lesions on that side. The research was published in the Journal of the National Cancer Institute.
Sandanayaka said his firm’s approach, developed in-house, is "very different from everyone else, to our knowledge," but Nir-ogy is not entirely alone in the space. Jnana Therapeutics Inc., also of Boston, pulled down a $50 million series A financing in October 2019 backed by Polaris Partners, Avalon Ventures, Versant Ventures, Abbvie Ventures LLC and Pfizer Inc. In the summer of last year, Jnana bagged a deal with Basel, Switzer-land-based Roche Holding AG that brought $40 million up front and potentially upward of $1 billion more in research funding, preclinical, development and commercial milestones, as well as sales royalties, in the multitarget deal.
The Nirogy financing was co-led by Santé Ventures and Sporos. Dennis McWilliams of Santé and Joseph Kekst of Sporos will join Nirogy’s board, and Casey Cunningham of Santé will join Nirogy’s scientific advisory board.