Nerandomilast

PureTech has launched another of its hub-and-spoke subsidiaries, Celea Therapeutics, with a “mission to transform the treatment of respiratory diseases.\"\n Using its hub-and-spoke business model, PureTech is launching a new company to develop deupirfenidone (LYT-100), its promising candidate for idiopathic pulmonary fibrosis (IPF) and other fibrotic and inflammatory lung conditions.PureTech has established Celea Therapeutics with a “mission to transform the treatment of respiratory diseases,” the Boston-based company said in an Aug. 12 release.Running the London-listed subsidiary is former Teva North America CEO Sven Dethlefs, Ph.D., who has orchestrated the development of deupirfenidone for PureTech for the last year-plus.“I believe deupirfenidone has the potential to be a true turning point in the treatment of IPF,” Dethlefs said in the release. “Our phase 2b data demonstrated the potential for best-in-class efficacy with a favorable safety and tolerability profile—addressing two of the most critical limitations of current therapies.”Among the reasons he was entrusted with the job was the role he played at Teva in the launch of another deuterated product, Austedo, a blockbuster drug for Huntington’s disease and tardive dyskinesia.Deuteration is a process in which hydrogen atoms in a compound are replaced with a heavier isotope of hydrogen. It can improve the pharmacokinetic properties of existing drugs, increasing their efficacy and safety. Deupirfenidone is a deuterated version of Roche’s former IPF blockbuster Esbriet (pirfenidone), which became subject to generic competition in 2022.Boehringer Ingelheim’s Ofev is the only other drug on the market for IPF. A year ago, the German company reported success in a phase 3 trial of its Ofev follow-on, nerandomilast. The PDE4B inhibitor is up for an FDA decision in the fourth quarter of this year. PureTech says it hopes to meet with the FDA by the end of the third quarter to discuss the results of its phase 2b trial of deupirfenidone and its phase 3 trial plan.Results from the 2b trial showed the potential of deupirfenidone to stabilize lung function decline over 26 weeks, while maintaining a favorable safety profile. Open-label extension data have indicated the effect continues for at least 52 weeks.The launch of Celea is another example of PureTech’s approach, in which the company acquires promising assets and establishes subsidiaries to advance them individually. As an asset matures, it can draw new investments. With that comes an evolution of ownership, allowing PureTech to gain capital and the subsidiary to become more independent. Using this model, 20-year-old PureTech, which is listed on the London Stock Exchange, has not had to raise money since 2018, CEO Bharatt Chowrira, Ph.D., explained to Fierce Pharma in an interview last year centered on the approval of Bristol Myers Squibb’s schizophrenia treatment, Cobenfy (KarXT).PureTech spawned Karuna Therapeutics, which developed the treatment and was bought out by BMS in late 2023 for $14 billion. 

Boehringer Ingelheim's Hernexeos is one of two new drug approvals the company is expecting this year. With the FDA approval of its zongertinib in certain non-small cell lung cancer (NSCLC) patients, 175-year-old Boehringer Ingelheim is entering the oncology market.Zongertinib, which will be sold as Hernexeos, was specifically cleared to treat previously treated NSCLC patients who have the relatively rare HER2 activating mutations in the tyrosine kinase domain (TKD).It’s a patient population that has a “huge unmet need” and is estimated to be comprised of about 40,000 people across the globe, Boehringer’s senior vice president of oncology, Itziar Canamasas, Ph.D., told Fierce Pharma in a recent interview. The mutated cancer type occurs in approximately 2% to 4% of NSCLC cases. Hernexeos is now the first FDA-approved oral treatment that can specifically target the disease. It marks a welcome chemo-free treatment option for patients as well as a “big entry” for Boehringer into the oncology space, Canamasas said. The drug's benefits were supported by the Beamion Lung-1 phase 1b trial, in which Hernexeos proved an objective response rate of 75% among 71 patients who had received prior platinum-based chemotherapy but not a HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate, according to the FDA. Within this cohort, 58% of patient had their responses lasting for at least six months.Among 34 patients previously treated with platinum-based chemotherapy and a HER2-targeted ADC, the objective response rate was 44%, with 27% having a duration of response of at least six months.Additional data published in April showed that the drug may help patients in the first cohort live without their disease getting worse for a median of 12.4 months, although the data were immature. The results signaled Hernexeos' potential to "impact clinical practice," Boehringer said at the time. All in all, “nearly every patient” benefited from treatment in the study, Canamasas said, referring to a 96% disease control rate revealed in April.Fewer than 3 in 10 patients are alive five years after a diagnosis of HER2-mutant advanced NSCLC, according to Boehringer, with advanced disease causing a “physical, psychological, and emotional impact” in patients' daily lives. The mutation is linked with a high incidence of brain metastasis.As it stands, AstraZeneca and Daiichi Sankyo’s Enhertu is the only FDA-approved regimen cleared to treat the HER2-mutant NSCLC population, but that option comes with “chemotherapy-like side effects,” thoracic medical oncologist and lead study investigator Joshua Sabari, M.D., told Fierce Pharma over email. Hernexeos’ data, meanwhile, prove the drug as “truly a targeted therapy” with low dose reduction rates, “very low” discontinuation and very low-grade rash rate, he said.“To me, it's a game changer—a truly targeted agent for our patients with optimal activity, selectivity as well as quality of life and side effect profile,” Sabari said, adding that “most patients on this therapy do extremely well for prolonged periods of time with excellent quality of life.”The lung disease nod is just the start of Boehringer’s journey with Hernexeos, which Canamasas called a “pipeline in a product.” Next, the company hopes to be able to position the drug as a first-line treatment in its NSCLC indication and is currently studying the potential in a phase 3 trial, while additional explorations in pan tumors, breast cancer and gastric cancer are ongoing. The drug's current indication is granted under the FDA accelerated approval pathway, and Boehringer is on the hook to provide confirmatory evidence to further verify the drug's profile. Hernexeos headlines Boehringer’s cancer care ambitions, and more is on the horizon. The company’s oncology pipeline includes a T-cell engager that’s currently being evaluated in mid-stage trials in extrapulmonary neuroendocrine carcinoma and small-cell lung cancer. Oncology is certainly an area that Boehringer is putting its chips behind, as it recently opened a 27 million Swiss franc ($33.6 million) ADC R&D spot in Basel, Switzerland.Outside of oncology and Hernexeos, the company is awaiting another new drug approval this year for its PDE4B inhibitor nerandomilast in idiopathic pulmonary fibrosis. Boehringer expects to launch both treatments this year and, further ahead, is plotting 15 launches through 2030.