OPB-111077

Otsuka was developing three of the candidates exclusively in Japan.\n Otsuka has dumped a clutch of clinical cancer candidates on Valentine\'s day. The Japanese drugmaker said (PDF) “strategic reasons”—the pharma equivalent of “it’s not you, it’s me”—underpinned the decision to ax the assets.OPB-111077, the only one of the candidates that Otsuka was developing in the U.S., has the longest clinical development history. Otsuka took the oral STAT inhibitor into the clinic in 2012 and began several more trials over the following years, culminating in the initiation of a study that tested OPB-111077 with bendamustine and rituximab in lymphoma patients in 2019.Otsuka stopped enrollment in the lymphoma trial well short of its initial target last year. The trial is due to end next month, according to ClinicalTrials.gov, but the company has already read the last rites to the program.The drugmaker moved into lymphoma after it emerged as the most promising indication in a study that overall only saw “modest clinical activity.” Evidence that STAT promotes tumor progression has attracted multiple research groups to the target but, like Otsuka, they struggled to realize the target’s promise. The challenges include finding molecules that are selective for STAT3 over its siblings. Otsuka was only developing the other three candidates in Japan. TAS0313 is a peptide vaccine that was in development as a treatment for advanced solid tumors. Taiho Pharmaceutical, a subsidiary of Otsuka, began a phase 1 trial in 2018 to test whether its use of long peptides targeting multiple cancer antigens, rather than a mix of lengths, would lead to better efficacy than earlier vaccine prospects.Researchers published first-in-human data in 2021. At the time, the team outlined work to further test the efficacy of TAS0313, both as a monotherapy and in combination with Merck & Co.’s Keytruda. Last year, researchers called Keytruda combination data in bladder cancer “promising,” but the result failed to save TAS0313 from Otsuka’s ax.The company also ended its relationship with OPC-415, a MMG49 CAR-T cell therapy that was in clinical development in multiple myeloma. Otsuka in-licensed the candidate from Osaka University in 2018 and began a phase 1/2 trial in 2021.Finally, Otsuka ended development of OPF-501C in cancerous skin ulcers. The company started a phase 2 trial of the topical zinc chloride candidate in 2023 but has opted against taking the program any further.