On January 26, 2021 Nirogy reported that it will narrow its lactate transporter inhibitor candidates down to one for preclinical development and IND-enabling studies (Press release, Nirogy Therapeutics, JAN 26, 2021, View Source [SID1234577594]).

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After years working under the radar, Nirogy Therapeutics is offcially launching with $16.5 million and a mission to drug a family of membrane proteins called solute carriers. The proceeds will see the company’s lead cancer program through phase 1, CEO Vincent Sandanayaka, Ph.D., said.

Solute carriers are embedded in the cell membrane and control the movement of metabolites such as glucose, cholesterol and amino acids in and out of cells or to the right locations within cells. They’re the gatekeepers of processes like nutrient uptake and metabolite disposal, which go awry in many diseases. Nirogy’s lead program targets lactate transporters to take out cancer with a one-two punch.
Unlike healthy cells, cancer cells consume a large amount of glucose and produce lots of lactic acid as a waste product that they expel into the tumor microenvironment through lactate transporters. Tumors with high levels of lactate are a hostile environment for immune cells, so they tamp down anti-tumor immunity.

"If we block these transporters, we can directly kill cancer cells and simultaneously activate anti-tumor immunity," Sandanayaka said. Nirogy hopes to move its lead program into the clinic in 2022.

"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 Dennis McWilliams, a partner at Santé Ventures, in a statement. Santé led the series A round alongside Sporos.

Despite being an attractive drug target, solute carriers have been largely untapped due to technology challenges.

"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," Sandanayaka said.

Others have drugged solute carriers before, but approached them individually rather than as a family with shared characteristics. Like Jnana Therapeutics, another biotech working to drug solute carriers, Nirogy built technology to go after these targets.

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Jnana Roche, take aim at metabolite transporters in $40M discovery deal.

"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," Sandanayaka said in the statement.

Solute carriers aren’t all Jnana and Nirogy have in common. Both companies’ names are derived from Sanskrit: Jnana means "knowledge," while Nirogy means "without illness."

"Our vision is to create a path to really end patient suffering," Sandanayaka said.

Over the next year, Nirogy will narrow its lactate transporter inhibitor candidates down to one for preclinical development and IND-enabling studies. Though the compound on its own acts as a combination of targeted therapy and an immunotherapy drug, it could be added to other cancer-fghting agents to boost their effcacy, Sandanayaka said.

So far, it’s looked at combining its prospects with anti-PD1 and anti-CTLA4 immunotherapies in mouse models of triple- negative breast cancer, melanoma and colorectal cancer.

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.

On January 26, 2021 Nirogy Therapeutics, based in Boston, reported that launched with a $16.5 million Series A financing round (Press release, Nirogy Therapeutics, JAN 26, 2021, View Source [SID1234577567]). The round was co-led by Santé Ventures and Sporos.

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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 noted 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 began investigating its own SLCT, GNS561. In November 2020, the company announced 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 announced 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."

On Jan. 26, 2021 Agenus Inc., an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported that it has entered into a clinical collaboration with Nelum Corp. to evaluate the safety and efficacy of zalifrelimab, Agenus’ anti-CTLA-4 antibody, in combination with NLM-001, Nelum’s small molecule hedgehog inhibitor, and chemotherapy for first-line advanced pancreatic cancer. (Press release, Agenus, JAN 26, 2021, View Source [SID1234577556])

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"This collaboration with Nelum is an exciting next step in our partnership strategy to broaden combinations and indications with our late stage checkpoint antibodies," said Julie DeSander, Vice President of Business Development and Alliance Management. "Zalifrelimab, our first generation anti-CTLA-4 antibody, shows promising results alone and in combination with balstilimab, our anti-PD-1 antibody, and offers the potential to expand therapeutic benefit in novel combinations."

Nelum’s NLM-001 is a best-in-class small-molecule hedgehog inhibitor that targets cancer-associated fibroblasts. It synergizes with checkpoint inhibitors by promoting immune cell infiltration into the tumor microenvironment and increases tumor penetration of chemotherapy. NLM-001 is active and well-tolerated in patients with solid tumors, as demonstrated in a Phase I study.

"NLM-001 is designed to disrupt the tumor microenvironment for increased responsiveness to checkpoint inhibition and improved delivery of chemotherapy," said Evelio Perea, Chairman of the Board of Nelum. "We look forward to evaluating NLM-001 in combination with Agenus’ checkpoint inhibitor zalifrelimab to expand therapeutic options for patients with advanced pancreatic cancer."

Under the terms of the agreement, Agenus will supply zalifrelimab to Nelum for the combination study. Nelum will sponsor and be responsible for the conduct of the trial, which is set to begin enrolling in 1H 2021.

On January 26, 2021 Novo Nordisk reported initiated a share repurchase programme in accordance with Article 5 of Regulation No 596/2014 of the European Parliament and Council of 16 April 2014 (MAR) and the Commission Delegated Regulation (EU) 2016/1052 of 8 March 2016 (the "Safe Harbour Rules") (Press release, Novo Nordisk, JAN 26, 2021, View Source [SID1234577312]). This programme is part of the overall share repurchase programme of up to DKK 17 billion to be executed during a 12-month period beginning 5 February 2020.

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Under the programme initiated 3 November 2020, Novo Nordisk will repurchase B shares for an amount up to DKK 2.7 billion in the period from 4 November 2020 to 1 February 2021.

With the transactions stated above, Novo Nordisk owns a total of 39,263,659 B shares of DKK 0.20 as treasury shares, corresponding to 1.7% of the share capital. The total amount of A and B shares in the company is 2,350,000,000 including treasury shares.

Novo Nordisk expects to repurchase B shares for an amount up to DKK 17 billion during a 12- month period beginning 5 February 2020. As of 22 January 2021, Novo Nordisk has since 5 February 2020 repurchased a total of 39,325,522 B shares at an average share price of DKK 425.27 per B share equal to a transaction value of DKK 16,723,794,610.