M12: Astacin/Adamalysin

Novartis disclosed the scrapping of LRX712 alongside news that it has stopped development of GIZ943.\n Novartis has done a little spring cleaning, sweeping a phase 2 osteoarthritis prospect and first-in-human radioconjugate out of its pipeline after assessing evidence on the programs.The actions, which Novartis disclosed (PDF) in its first-quarter results, affect LRX712 and GIZ943. LRX712 was the more advanced of the two candidates. The Swiss drugmaker began a phase 2 trial of the asset in patients with knee osteoarthritis in 2020. A spokesperson for Novartis confirmed the removal of the drug candidate from the pipeline and the thinking behind the decision.“Novartis discontinued the clinical development of LRX712, a chondrogenic drug, investigating its impact on osteoarthritis of the knee following an interim analysis of its phase 2 study which ultimately demonstrated a favorable safety profile, but an insufficient effect on knee cartilage,” the spokesperson said.Researchers identified the synthetic small-molecule drug candidate via phenotypic screening. Preclinical tests suggested the molecule could drive cartilage repair without inducing abnormal bone formation. A drug with that profile could give patients an alternative to surgery, which can lead to fibrous or calcified cartilage that is unable to withstand the forces on the knee. LRX712 fell short of the hoped-for profile. News of the LRX712 discontinuation arrived shortly after Novartis terminated a phase 2 trial of another osteoarthritis prospect, QUC398. The drugmaker was studying the ADAMTS-5 inhibitor in osteoarthritis knee pain but pulled the plug after an interim analysis found an “insufficient effect on pain relief.”Novartis disclosed the scrapping of LRX712 alongside news that it has stopped development of GIZ943 in ovarian and lung cancers. GIZ943, also known as [177Lu] Lu-EVS459, is a radioligand therapy that targets cells that express folate receptor alpha (FRα). The spokesperson said Novartis stopped development “based on an assessment of potential benefit-risk from the phase 1 study.”The trial got underway last year. Novartis recently stopped enrollment after recruiting four patients, well short of its target of 96. The study was supposed to determine the recommended dose in an escalation part and then evaluate its effects in an expansion stage.FRα is overexpressed in many cancers, making it a potentially attractive target for radioligand therapies. Kidney toxicity is a long-standing concern, limiting the development of radioligand therapies against the target and helping antibody-drug conjugates become the modality of choice. AbbVie’s Elahere is already approved, and companies including Eisai and Genmab have FRα-directed ADCs in development. 

Novartis is discontinuing further development of QUC398 in knee osteoarthritis, a company spokesperson said.\n Novartis has terminated a phase 2 trial evaluating an investigational ADAMTS-5 inhibitor for patients with osteoarthritis knee pain.The Big Pharma company discontinued the study testing intra-articular injection QUC398 after an interim analysis found an “insufficient effect on pain relief,” a Novartis spokesperson told Fierce Biotech.The candidate demonstrated a “good safety profile,” the spokesperson added.As a result of the trial termination, Novartis is discontinuing further development of QUC398 in knee osteoarthritis, the spokesperson said.The randomized, placebo-controlled trial enrolled 101 patients, according to ClinicalTrials.gov. All participants will receive follow-up as per study protocol, the spokesperson told Fierce.The spokesperson said they did not have information about whether Novartis would assess QUC398 in any other indication. The asset is not included in the pharma’s online pipeline.In 2020, Novartis picked up an anti-ADAMTS5 nanobody from Merck KGaA for 50 million euros upfront. At the time, the asset known as M6495 was ready for phase 2 testing in osteoarthritis. It\'s unclear whether M6495 is QUC398. ADAMTS-5 is an enzyme expressed in human cartilage. Previously, Galapagos and Servier teamed up to take their ADAMTS-5 inhibitor GLPG1972 (also known as S201086) through development for knee osteoarthritis.However, the asset failed to demonstrate efficacy in a phase 2 study, with the partners sharing in a 2020 release that “no signal of activity was observed in the topline results.”Currently, there aren’t any anti-ADAMTS-5 treatments available on the market. 

Plus, news about Tiger Gene and Theratechnologies: Novartis scraps knee pain drug: The Swiss drugmaker discontinued a Phase 2 test of an under-the-skin treatment for knee osteoarthritis pain, a spokesperson confirmed to Endpoints News . The experimental medicine, codenamed QUC398, is an anti-ADAMTS-5 injectable. The drug “demonstrated a good safety profile but an insufficient effect on pain relief,” the spokesperson wrote in a Tuesday statement. — Kyle LaHucik Telix shares Phase 2 brain tumor results: The Australian biotech’s TLX101 given alongside standard external beam radiation therapy achieved an average 12.4 months of overall survival in the investigator-initiated trial of eight people with high-grade gliomas. Telix is on track to file an IND for the drug in the second half of the year. — Ayisha Sharma Tiger Gene rebrands, launches new venture: The Boston-based VC firm will now operate under the name 28 Capital. It said its latest fund will focus on “translating cutting-edge scientific discoveries into breakthrough therapies.” The value of the fund was not disclosed. — Ayisha Sharma Theratechnologies starts “open” sale process: The company said it will consider its exit options through a “non-exclusive” framework going forward. Earlier this week, Future Pak made its latest unsolicited bid to buy Theratechnologies for up to $255 million. — Ayisha Sharma