GSNOR

April 19, 2017 By Mark Terry , BioSpace.com Breaking News Staff Nivalis Therapeutics , located in Boulder, Colo., and Alpine Immune System , a private company located in Seattle, have agreed to merge . Alpine will merge with a wholly-owned subsidiary of Nivalis in an all-stock deal. The resulting public company will focus on inflammation and immuno-oncology utilizing its novel protein-based discovery platform. Alpine utilizes a variant immunoglobulin domain (vigD) technology platform. The company has plans to begin a Phase I trial with its first compound, a dual ICOS/CD28 antagonist that has been engineered for autoimmune and inflammatory diseases. It expects to initiate the trial in the second half of 2018. Nivalis had traditionally focused on developing drugs for cystic fibrosis (CF). Its developmental compounds have selectively targeted the enzyme S-nitrosoglutathione reductase (GSNOR), which regulates S-nitrosoglutathione (GSNO). Low levels of GSNO have been associated with CF, asthma, inflammatory bowel diseases and some cardiovascular diseases. In November 2016, Nivalis’ Phase II trial evaluating cavosonstat in adult CF patients who had two copies of the F508del-CTFR mutation and who were being treated with Orkambi, failed to meet its primary endpoint. John Carroll , writing for Endpoints News , says , “After Nivalis’ drug failed in a disastrous attempt to come up with an add-on to Vertex’s cystic fibrosis combo, about the only thing left after the inevitable slash and burn on staff and costs was a virtually empty public shell. Nivalis had managed to catch one of the last waves in the old IPO boom in cashing in on investors’ interest in biotech. But by the time the market closed today the market cap had shrunk down to a mere $41.3 million. And now [Mitch] Gold’s Alpine Immune System is taking that over in a reverse merger that will scoot it out into the public market.” As part of the merger, Frazier Healthcare Partners , Mitch Gold’s Alpine BioVentures , and OrbiMed Advisors plan to invest a combined $17 million into Alpine Immune Sciences. With the cash Alpine and Nivalis have, with the additional funds, the combined company will have about $90 million in cash. “This merger provides a unique opportunity to accelerate the development of our novel immunotherapy platform focused on both inflammation and immuno-oncology, Gold , Alpine’s executive chairman and chief executive officer, said in a statement. “We look forward to building on our early success by taking multiple novel programs into the clinic to help patients with significant medical needs.” The new company, named Alpine, will be led by Gold as chairman and chief executive officer. The board of directors will expand to include two Nivalis representatives. Ben Fidler , writing for Xconomy , says , “Nivalis’s failure has created an opportunity for Alpine to sidestep an IPO, a strategy a number of privately held biotechs have used over the years to go public more quickly and cheaply.” Gold is best known as the chief executive officer of Dendreon . During his tenure, he led the development of sipuleucel-T (Provenge), an immunotherapy for prostate cancer. He raised about $2 billion to bring Provenge to market and came away with about $27 million personally in two days after the U.S. Food and Drug Administration (FDA) approved the compound. Fidler writes, “But the treatment was a commercial bust for a variety of reasons, so Dendreon faltered, was buried in more than $600 million in debt, and filed for bankruptcy in 2014. Sipuleucel-T was ultimately sold to Valeant Pharmaceuticals .” Dendreon and Gold were ahead of the curve in terms of immuno-oncology, and it has since gotten to be a more stable and growing field. It still struggles with problems related to the personalized nature of the treatments, which were part of Dendreon’s downfall, although company’s seem to be working their way around that obstacle. After leaving Dendreon in 2012, Gold founded Alpine Biosciences , which sold to Oncothyreon (now Cascadian Therapeutics ) for $27 million in stock. Gold then launched Alpine BioVentures in 2013 and seeded Alpine in 2015.

January 4, 2017 By Mark Terry , BioSpace.com Breaking News Staff Boulder, Colo. – Nivalis Therapeutics announced yesterday that it is evaluating “strategic alternatives,” which may include the possibility of an acquisition, merger, or other strategic transaction. Nivalis is focused on identifying, developing and commercializing drugs for cystic fibrosis (CF). Previously known as N30 Pharmaceuticals , it changed to Nivalis in February 2015. The company went public in July 2015. On November 28, the company announced topline results from its Phase II clinical trial of cavosonstat, 200 mg and 400 mg, in patients with CF who had two copies of the F508del-CFTR mutation that were being treated with Orkambi. Although the drug had minimal side effects, it failed to show benefit in absolute change in percent predicted FEV1, which was the primary endpoint. “While we are disappointed in the outcome of this trial, we plan to continue to investigate the therapeutic potential of cavosonstat and our S-nitrosoglutathione reductase (GSNOR) inhibitor portfolio to determine next steps,” said Jon Congleton , president and chief executive officer of Nivalis, in a statement. In the company’s third-quarter financial report on November 7, 2016, the company published a net loss of $7.4 million, or ($0.48) per share, versus a net loss of $6.1 million ($0.39 per share) in the same quarter in 2015. Most of the loss was attributed to the two Phase II trials of cavosonstat. In the same month, Nivalis announced that Cynthia Smith , then the chief commercial officer of ZS Pharma , a subsidiary of AstraZeneca , had joined the company’s board of directors. She had also previously served as vice president, market access and commercial development at Affymax. In addition to today’s announcement, Nivalis indicated it plans to finish its ongoing SNO-7 clinical trial of cavosonstat in patients with CF currently on Kalydeco (ivacaftor). That trial is expected to be completed this quarter. To assist with its strategic alternatives, Nivalis had hired Ladenburg Thalmann & Co. Inc. , an advisory firm. In addition to a possible merger, sale or partnership, the company indicated it plans to streamline operations. Although that often means layoffs, nothing specific was said in the company announcement regarding job cuts. Greg Avery , writing for the Denver Business Journal, notes that as of September 30, 2016, Nivalis had $16 million in cash and $50 million in marketable securities. “That could make Nivalis a candidate for being acquired by another company looking to go public,” he writes. “Such reverse mergers became more common during the waning months of 2016 as the IPO market struggled and companies sought a cost-effective way to access public markets.” He cites Boulder-based Mirage Therapeutics merging with Carlsbad, California-based Signal Genetics in November as an example of such a deal. Another recent example is when Boston, Mass.-based Tokai Pharmaceuticals and tic Pharma , a privately-held pharma company, merged under the name of OticPharma . Arsalan Arif , writing for Endpoints News, said, “Last August, Tokai became the latest in a long string of public biotechs to hit a brick wall running at full speed. The late-stage failure of its cancer drug galeterone effectively shredded its stock price and its business plan, forcing the company to rapidly ax staffers and start looking for strategic alternatives in the face of an extinction-level event.” Nivalis is currently trading for $2.36.