On January 27, 2021 Nuvalent, Inc., a biotechnology company creating precisely targeted therapies for clinically proven kinase targets in cancer, reported a $50M Series A financing from Deerfield Management (Press release, Nuvalent, JAN 27, 2021, View Source [SID1234574363]). The company also announced its launch of a portfolio of innovative small molecule kinase inhibitors with parallel lead programs in non-small cell lung cancer (NSCLC), including NUV-520 – a potential best-in-class ROS1-selective inhibitor – and NUV-655 – an ALK-selective inhibitor. These novel molecules have been designed through Nuvalent’s proprietary discovery efforts to specifically solve for the dual challenges of kinase resistance and selectivity, with the goals of minimizing adverse events and driving more durable responses for patients with cancer. Chief Executive Officer James Porter, Ph.D., leads an experienced team with deep expertise in structure-based drug design, oncology drug development and company building.

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"Kinase inhibitors remain at the leading edge of targeted therapies for patients with cancer, but the clinical utility of currently available treatments is limited by resistance mutations and off-target effects," said Dr. Porter. "At Nuvalent, we are leveraging our expertise in structure-based design to solve for the dual challenges of resistance and selectivity, with the goal of driving deeper and more durable responses for patients living with cancer. We have partnered with leading physician-scientists to understand the limitations of existing cancer therapies that target proven oncogenic kinases and assembled an accomplished team to translate those insights into a novel pipeline of precisely targeted therapies."

The founding technology was developed at Nuvalent under the guidance of Matthew Shair, Ph.D., Professor of Chemistry and Chemical Biology at Harvard University. Professor Shair serves as Founder, Head Scientific Advisor and member of the Board of Directors for Nuvalent.

"Our goal at Nuvalent is to develop medicines with the potential to achieve deep and durable responses with minimal side effects. Off-target kinases sometimes differ from mutant oncogenic kinases by minor differences at the drug binding site, which has made it challenging for drug developers to achieve the desired level of selectivity," said Professor Shair. "The Nuvalent approach leverages deep expertise in structure-based drug design and innovative molecular structures, allowing us to thread the needle and achieve high affinity and unparalleled selectivity against drug-resistant targets in cancer."

Nuvalent’s first lead program, NUV-520, is a novel ROS1-selective inhibitor and potential best-in-class therapy for patients with advanced NSCLC driven by a ROS1 fusion. NUV-520 inhibits wild-type ROS1 and is designed to remain active in tumors that have developed treatment resistance, including tumors with the prevalent G2032R solvent front mutation, in addition to other key mutations D2033N, L2026M and S1986F. NUV-520 has been optimized for central nervous system (CNS) penetrance to improve treatment options for patients with CNS metastases. In addition, NUV-520 has been shown to selectively inhibit ROS1 compared to the structurally related tropomyosin receptor kinase (TRK) family. NUV-520 offers the potential to minimize TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients with ROS1-mutant variants. Nuvalent anticipates initiating a Phase 1/2 trial investigating NUV-520 in ROS1-positive NSCLC in the second half of 2021.

Nuvalent’s second lead program is NUV-655, a novel ALK-selective inhibitor created for patients with advanced NSCLC tumors driven by an ALK fusion. NUV-655 is designed to inhibit wild-type ALK and remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M or G1202R / G1269A. NUV-655 has been optimized for CNS penetrance and ALK selectivity to improve treatment options for patients with CNS metastases and minimize CNS adverse events related to off-target inhibition of the structurally-related TRK family. A Phase 1/2 trial investigating NUV-655 in ALK-positive NSCLC is planned to begin in the first half of 2022.

In addition to selective ROS1 and ALK inhibition, Nuvalent is exploring a robust pipeline of programs with a focus on addressing the limitations of existing therapies for other clinically proven kinase targets in oncology.

"Cancer remains one of the most challenging diseases to treat, with many patients inevitably running out of therapeutic options," said Cameron Wheeler, Ph.D., Chairman of the Board of Nuvalent and a Partner at Deerfield Management. "Nuvalent has assembled a team with leading expertise in structure-based drug design and the deep clinical and development insights needed to address prioritized areas of patient need. Backed by the confidence and experience of an accomplished team of collaborators and advisors, Nuvalent is well positioned to deliver on its mission of delivering precisely targeted therapy options that bring renewed hope to patients in need."

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 Apellis Pharmaceuticals, Inc. (Nasdaq:APLS), a global biopharmaceutical company and leader in targeted C3 therapies, reported the closing of its previously announced privately negotiated exchange transactions (the "Exchange Transactions") with certain holders of its 3.500% Convertible Senior Notes due 2026 issued in September 2019 (the "Notes") (Press release, Apellis Pharmaceuticals, JAN 26, 2021, View Source [SID1234574290]). In the Exchange Transactions, the holders exchanged approximately $126.1 million in aggregate principal amount of Notes and Apellis issued an aggregate of 3,906,869 shares of its common stock.

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The shares of Apellis’ common stock issued in the exchanges were not registered under the Securities Act of 1933, as amended, or the securities laws of any state or other jurisdiction, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and such other jurisdictions.

This press release does not constitute an offer to sell or a solicitation to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful.

On January 26, 2021 Kiromic BioPharma, Inc. (Nasdaq: KRBP), an immuno-oncology target discovery and gene-editing company, with a proprietary artificial intelligence neural network platform (Diamond AI) to develop novel oncology therapeutics, reported the completion of the chPD1 licensing agreement with Longwood University (Press release, Kiromic, JAN 26, 2021, View Source [SID1234574310]).

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PD-1 has always been a challenge for CAR-T development.
PD-1 is the brakes of the immune system, inhibiting immune cells from killing tumor cells. Traditional PD-1 inhibitors block the PD-1 receptor, "removing the brakes" of T-cell activity.
Kiromic’s chPD1 not only "removes the brakes" but also engages the PD-1 receptor to "accelerate" T-cell activity.
Upon interaction with the PD-1 ligand, the chPD1 receptor activates CD3 zeta (the main activating intracellular domain for T cells), and Dap10 (costimulatory domain). The activation of these two intracellular domains induces T cell activation, cytokine secretion, and tumor cell lysis.
"Longwood University is proud to have completed this chPD1 licensing agreement with Kiromic. We believe that Kiromic has a strong Allogenic Off-The-Shelf CAR-T program which will be even stronger with chPD1. The role that chPD1 plays in the modulation of the tumor micro-environment (TME) can never be underestimated when treating solid tumors," says Dr. Amorette Barber, PhD, Associate Professor of Biology and Director of the Office of Student Research at Longwood University.

"The completion of the licensing agreement for chPD1 marks a major milestone for Kiromic CAR-T development. With chPD1, we believe our chimeric PD1 CAR-T will be able to overcome the challenging tumor micro-environment (TME) which has plagued other CAR-T programs," says Dr. Maurizio Chiriva-Internati, PhD, CEO of Kiromic BioPharma.

"We believe that the licensing agreement of chPD1 from Longwood will make Kiromic the only CAR-T development program with a built-in capability to meet other CAR-T programs head-on who do not have a bundled chPD1 CAR-T. We believe that the licensing agreement will place Kiromic in a solid position to begin first in-human in solid tumors," says Mr. Gianluca Rotino, Chief of Strategy and Innovation of Kiromic BioPharma.

On January 26, 2021 Seelos Therapeutics, Inc. (Nasdaq: SEEL), a clinical-stage biopharmaceutical company focused on the development of therapies for central nervous system disorders and rare diseases, reported the pricing of an underwritten public offering of 15,243,903 shares of its common stock, at a price to the public of $2.05 per share (Press release, Apricus Biosciences, JAN 26, 2021, View Source [SID1234574291]). In addition, the Company granted the underwriters a 30-day option to purchase up to 2,286,585 additional shares of its common stock to cover over-allotments, if any. All of the shares of common stock in the offering are being sold by Seelos.

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BTIG is acting as the sole book-running manager for the offering.

Seelos anticipates the aggregate net proceeds from the offering will be approximately $29.1 million, after deducting the underwriting discounts and commissions and estimated offering expenses payable by Seelos, but excluding any exercise of the underwriters’ option to purchase additional shares of common stock. Seelos intends to use an aggregate of $3.3 million of the net proceeds from the offering for the partial repayment of certain outstanding convertible promissory notes and the remainder for general corporate purposes and to advance the development of its product candidates. This offering is expected to close on or about January 28, 2021, subject to the satisfaction of customary closing conditions.

The securities described above were offered by Seelos pursuant to an effective "shelf" registration statement on Form S-3 (File No. 333-251356) previously filed with the Securities and Exchange Commission (the "SEC") on December 15, 2020, amended on December 22, 2020, and declared effective by the SEC on December 23, 2020. The securities may be offered only by means of a prospectus. A preliminary prospectus supplement and the accompanying prospectus relating to and describing the offering has been filed with the SEC. Electronic copies of the preliminary prospectus and, when available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained by visiting the SEC’s website at www.sec.gov or by contacting BTIG, LLC, Attention: Equity Capital Markets, 65 East 55th Street, New York, NY 10022, by calling (212) 593-7555 or by e-mail at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.