ZPL-389

January 25, 2017 By Mark Terry , BioSpace.com Breaking News Staff While there’s a tendency to focus on big deals, such as Pfizer ’s acquisition of Medivation for $14 billion, Novartis has been quietly making small—very small—deals. In fact, Novartis has indicated that its business plan involves small acquisitions in the $2 to $5 billion range, but in December made four deals well under that size. The company’s chief executive office, Joe Jiminez, recently said at the Novartis annual results news conference, “We look at everything, the bigger the target the higher the premium seems to be right now. We have gone upstream, and, if you heard, in the fourth quarter we announced four transactions that were quite early-stage, but they supplement the pipelines of our innovative medicines divisions.” On November 21, 2016, Novartis announced it had acquired Selexys Pharmaceuticals Coporation , which focuses on hematologic and inflammatory disorders. Terms of the deal could hit $665 million in upfront, acquisition and milestone payments. The company has SelG1, an anti-P-selectin antibody, in late-stage trials to treat vaso-occlusive pain crises in sickle cell disease patients. On December 16, 2016, Novartis acquired Ziarco Group Limited , a privately held company focused on dermatology. As part of the deal, Novartis picked up a once-daily oral H4 receptor antagonist, ZPL389, being developed for atopic dermatitis, better known as eczema. Financial details weren’t released. On December 19, 2016, Novartis inked an exclusive option, collaboration and license agreement with Conatus Pharmaceuticals . Conatus focuses on liver disease. The two companies will jointly develop emricasan, an investigational, first-in-class, oral, pan-caspase inhibitor for non-alcoholic steatohepatitis (NASH) with advanced fibrosis and cirrhosis. Novartis made an upfront payment of $50 million. Once other criteria are met, there will be an additional exercise fee. And on December 20, 2016, Novartis acquired Encore Vision , a private company in Forth Worth, Texas. Encore focuses on treatments for presbyopia, better known as farsightedness. No financial details were released. Encore’s lead product is EV06, a first-in-class topical treatment for presbyopia. In a Phase I/II, placebo-controlled proof of concept study, 50 patients were given daily doses for 90 days of EV06, and 25 received a placebo. EV06 showed a statistically significant improvement in distance vision over placebo. At the meeting, Jiminez didn’t provide information about the company’s $13 billion stake in Roche . But, at the World Economic Forum held in Davos earlier this month, he said he was in no hurry to sell the shares in Roche. Reuters wrote , “The shareholding that amounts to a third of Roche’s voting rights continues to pad Novartis’s profits, adding $464 million to its bottom line in 2016.” Although Novartis only got into immuno-oncology in 2015, it currently has 18 immuno-oncology drugs in its pipeline ranging from immune stimulating drugs, T-cell engineered therapeutics, T-cell modulators and molecules that affect the tumor microenvironment. Jay Bradner , president of the Novartis Institute for Biomedical Research (NIBR) , speaking at the company’s fourth-quarter press conference, said, “Data emerging over the next 12-18 months from Novartis and competitor trials will inform the most impactful paths forward.” Top of the list, CAR-T therapeutic CTL019, expected to be filed for pediatric acute lymphoblastic leukemia (ALL) soon. It also expects a follow-up marketing application in diffuse large B-cell lymphoma (DLBCL) by the end of 2017. “Unlike checkpoint inhibitors,” Bradner noted, “these are definitive medicines. With an 82 percent overall response rate and many patients free of disease five years later, there’s a lot to be learned from this ‘first blush’ of CAR-T cell therapy.”

December 16, 2016 By Mark Terry , BioSpace.com Breaking News Staff Switzerland-based Novartis announced today that it is acquiring Ziarco Group Limited , a private company in the dermatology space. No financial details were disclosed. Part of the deal includes Ziarco ’s one-daily oral H4 receptor antagonist currently being developed for atopic dermatitis (AD), or eczema. ZPL389 is a potential first-in-class treatment for the disease. “There is an unmet need for innovative, effective and safe oral treatment options for people living with eczema,” said Vasant Narasimhan , global head, Drug Development and chief medical officer of Novartis, in a statement. “We are proud of our dermatology capabilities shown by the recent successful launches of Cosentyx and Xolair. Now we’re excited about a potential new medicine for people with eczema through the acquisition of Ziarco and the addition of a first-in-class H4 receptor antagonist to our growing pipeline.” John Carroll , writing for Endpoints News, points out that this is only two days after Pfizer received U.S. Food and Drug Administration (FDA) approval for an atopic dermatitis drug. “The object of (Novartis’) affection is Ziarco, a 5-year-old upstart that has gathered positive midstage data together for ZPL389, an oral drug that achieved statistically significant results for its H4 receptor antagonist. The Phase IIa delivered a 50 percent drop in EASI scores at 8 weeks, compared to 27 percent for the placebo. And the SCORAD marks registered a drop of 43 percent against 26 percent. The Phase IIb was slated to start in the second half of this year.” Pfizer ’s EUCRISA (crisaborole) ointment 2% is a non-steroidal topical phosphodieterase-4 (PDE-4) inhibitor for mild to moderate atopic dermatitis. “The approval of EUCRISA is great news for the children and adults suffering from mild to moderate eczema, a community that has not had a new prescription treatment for more than 10 years,” said Albert Bourla , group president, Pfizer Innovative Health , in a statement. “This is also an important milestone for Pfizer as we continue to build on our heritage in Inflammation and Immunology by offering innovative treatment options to patients who need them.” Particularly notable is increased interest in atopic dermatitis within the industry. Regeneron and Sanofi received priority review in late September for dupilumab, a potential blockbuster drug for atopic dermatitis. The PDUFA date is March 29, 2017. Dupilumab is an inhibitor of IL-4 and IL-13, which was supported by stellar Phase III trial results. Analysts have projected dupilumab as potentially generating annual sales of $2.5 billion to $5 billion. Other companies are also trying to edge into the market. Danish company LEO Pharma acquired the rights to AstraZeneca ’s tralokinumab earlier this year. AstraZeneca released Phase IIb data for the drug, which is an anti-IL-13 monoclonal antibody, in the first quarter of this year. Galderma Pharma acquired the rights to an anti-IL-31 receptor A monoclonal antibody from Roche ‘s Chugai Pharmaceuticals , but no data beyond Phase II has been released. In 2012, Ziarco entered into a deal with Pfizer for exclusive rights to commercialize a number of clinical, preclinical and research assets. The company was founded by Mike Yeadon , formerly vice president and chief scientific officer of Pfizer’s Allergy and Respiratory Research Unit, and three former Pfizer executives, Steve Liu , vice president and chief scientific officer, Lynn Purkins , vice president and head clinical development, and Arif Shivji , vice president and head development operations and business development. The H4antagonist program was one of the compounds Ziarco licensed from Pfizer. Pfizer Venture Investments was also one of the investors in the initial Series A financing.