Kena Betancur/Getty Images NGM Biopharmaceuticals and Merck announced they had amended their existing collaboration agreement. It will continue through March 2024, but have a narrower scope. The amended collaboration will focus more tightly on developing therapies in retinal and cardiovascular and metabolic (CVM) diseases, including heart failure. Merck will keep an option to license the program under the amended deal. NGM picks up global rights to its disclosed oncology portfolio, in addition to all preclinical, and current and future research, for assets outside the new, narrower scope, with low single-digit net sales royalties to Merck. “We are pleased to continue to collaborate with Merck to address retinal and CVM diseases that represent significant unmet needs, while moving forward with greater independence and flexibility to advance our broader portfolio of assets,” said David J. Woodhouse, chief executive officer of NGM. “We now have a portfolio of four disclosed wholly owned programs as well as multiple undisclosed preclinical and research programs, which puts us in a fundamentally different position.” Woodhouse added, “Moreover, our in-house discovery engine can now work on programs solely for NGM’s benefit outside of Merck’s targeted areas. Bolstered by a strong balance sheet with runway expected to take us into the first half of 2024, we are well-positioned to advance multiple value-driving opportunities for stockholders.” The main focus on retinal and CVM revolves around progress made on NGM621 and MK-3655, both discovered by NGM under the original collaboration deal. NGM621 is an anti-complement CD antibody being studied in the NGM-led Phase II CATALINA trial for geographic atrophy. MK-3655 is an FGFR1c/KLB agonist antibody previously licensed by Merck and is in a Merck-led Phase IIb trial in non-alcoholic steatohepatitis (NASH). NGM plans to continue research and development on two undisclosed retinal targets in addition to CVM targets with an initial focus on heart failure. NGM will work exclusively with Merck in heart failure during the rest of the collaboration period. Merck holds an option to license compounds directed to targets that NGM develops within the scope of the amended collaboration at proof of concept or even earlier as specified in the amendment. NGM’s disclosed oncology candidates all came from its in-house discovery engine and are now wholly owned by NGM. These include NGM120, a GFRAL antagonistic antibody in Phase II for metastatic pancreatic cancer and cancer-related cachexia (muscle wasting and extreme weight loss). NGM708 is an anti-ILT2/ILT4 dual antagonist antibody. NGM438 is a LAIR1 antagonist antibody. It also had total rights to existing preclinical and research assets and future assets it might develop from its own discovery engine. Under the new deal, Merck is paying an aggregate of about $120 million in research and development funding to NGM through March 2024, including $86 million for April 2021 through March 2022, and additional possible option payments if Merck goes exercises its license option. NGM has also committed to advancing an ocular program to a possible IND submission using its own funding after March 2022. “Key to the success of our collaboration with NGM has been our companies’ unwavering commitment to scientific excellence,” said Dean Li, president, Merck Research Laboratories. “Our continued investment in NGM is due to the concentrated and reproducible effort of NGM scientists to select a problem, dissect and understand the molecular basis for it, and think carefully about how to address it. This amended agreement now enables the application of NGM’s biology-centric discovery approach to further explore new opportunities in important therapeutics areas such as retinal and cardiometabolic diseases.”

抗体合作

2021-05-24

·BioSpace

NGM's Aldafermin Becomes Latest NASH Failure as it Misses Mark in Phase IIB

NGM Biopharmaceuticals’ aldafermin failed to hit its primary endpoint in the company’s Phase IIb ALPINE 2/3 trial for non-alcoholic steatohepatitis (NASH) with stage 2 or 3 liver fibrosis. NASH, a form of fatty liver disease in people who drink little or no alcohol, has been a tough nut to crack, with several high-pro in recent years. The ALPINE 2/3 study evaluated 171 patients with biopsy-confirmed NASH with stage 2 or 3 liver fibrosis (F2/F3). Patients received either 0.3 mg, 1 mg or 3 mg doses of aldafermin once a day via subcutaneous injections and were compared to placebo. The trial failed to hit the primary endpoint of a dose response showing improvement in liver fibrosis by greater than or equal to 1 stage with no worsening of NASH at week 24. It did achieve statistical significance compared to placebo on some secondary endpoints, including NASH resolution at the 3 mg dose and multiple non-invasive measures of NASH, including liver fat content reduction at the 1 mg and 3 mg doses. Aldafermin is an engineered analog of the human hormone FGF19. “These results are certainly disappointing, particularly given the dire unmet need in this patient population,” said David J. Woodhouse, chief executive officer of NGM. “The lack of significant fibrosis improvement was unexpected given the consistency of histology findings previously seen with aldafermin in our adaptive four-cohort Phase II study. "However, in line with the data from that study, ALPINE 2/3 achieved statistical significance on multiple non-invasive measures of NASH at the two higher doses," Woodhouse continued. "That said, given the failure to meet the primary endpoint, we have decided to shift resources that had previously been reserved for a Phase III F2/F3 NASH development program toward advancing our other programs.” That pipeline includes NGM621, an anti-complement C3 antibody in Phase II studies for geographic atrophy; NGM120, a GFRAL antagonistic antibody in Phase II for metastatic pancreatic cancer and cancer-related cachexia; and NGM707 and NGM438, anti-ILT2-ILT4 and LAIR1 myeloid checkpoint candidates, respectively. Both of those compounds are expected to start Phase I trials for advanced solid tumors this year. In addition, Merck is progressing its Phase IIb trial of MK-3655, an FGFR1c/KLB agonistic antibody for NASH, which NGM discovered via a collaboration with Merck. Woodhouse added, “NGM is a markedly different company than when we initiated ALPINE 2/3 in May 2019, when our clinical-stage pipeline consisted primarily of liver and metabolic programs. Over the past two years, we have steadily expanded that pipeline with programs generated from our productive in-house discovery engine, and today we are also an ophthalmology and oncology company with four Phase II programs underway. We look forward to advancing our clinical programs and moving additional programs into the clinic, supported by our cash balance that was in excess of $300 million at the end of the first quarter.” In mid-2020, France’s Genfit reported that its drug elafibranor failed a Phase III trial in NASH. The year before, Gilead Sciences’ selonsertib flunked a Phase III trial. Gilead’s firsocostat and cilofexor were also unsuccessful in NASH. Boehringer Ingelheim and Pharmaxis’ BI 1467335 also failed in trials. For quite some time, the leading company in the NASH race was Intercept Pharmaceuticals and its drug obeticholic acid (OCA). In June 2020, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) rejecting their application. The CRL stated that it could not be approved because of uncertainty about the efficacy of the treatment. There were also concerns over the risk-benefit pro the drug. NGM Bio took a hard hit at today’s news, with shares dropping 48.73% in premarket trading.

抗体

100 项与 Anti-FGFR1/KLB MAb(Genentech) 相关的药物交易

登录后查看更多信息