Lutetium (177Lu) zadavotide guraxetan

Lantheus finally came clean about the fate of its experimental radiopharmaceutical for prostate cancer, confirming Wednesday that it has dropped the asset. The company had licensed the β-emitter, known as PNT2002, from Point Biopharma in 2022 . Point was later bought by Eli Lilly. The asset technically succeeded in its Phase 3 trial in late 2023, but its efficacy left much to be desired when compared with the leading prostate cancer radioligand, Novartis’ Pluvicto. Lantheus said that its trial, called SPLASH, had reached 100% of its prespecified overall survival events. The results were no better than those from earlier readouts “and remain confounded by patient crossover within the study.” The company confirmed that it would neither seek approval for PNT2002 nor invest any more money in the product’s development. The move means Lantheus must make a commercial success of another product licensed from Point under the 2022 deal. Codenamed PNT2003, this is a generic version of Novartis’ Lutathera, the leading radiopharmaceutical for a rare neoplasm called gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lantheus’ US filing for PNT2003 was accepted in January 2024. Another competitor could soon enter here, however. A very similar radioligand developed by the German company ITM Isotope Technologies Munich succeeded in a Phase 3 GEP-NETs trial in January , though detailed data were not released. Bristol Myers Squibb also has a horse in this race, though RYZ-101 is slightly different from the others since it uses the α-emitter actinium-225 as the active isotope rather than lutetium-177. RYZ-101’s Phase 3 trial was briefly halted last year, and ought to yield data in 2026 . Lantheus’ shares $LNTH closed down 23% on the Nasdaq, which was also due to its mixed first-quarter results. Its total revenues for the first three months of 2025 were $372.8 million, which was around 2% below consensus, according to Leerink analysts. At $1.53, earnings per share were about 8% below consensus. The company has made moves to improve its performance, buying a company developing an Alzheimer’s imaging agent and a contract manufacturer at the start of this year.

Wednesday saw a slew of biotechs report data for their respective clinical programmes. Some of the most notable readouts came from Marea Therapeutics and MAR001, its monoclonal antibody (mAb) against ANGPTL4; Lantheus' 177Lu-PNT2002, a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) that's partnered with Eli Lilly; and Theriva Biologics, which shared data for its oncolytic adenovirus VCN-01 (zabilugene almadenorepvec) in pancreatic cancer. Triglyceride levels loweredAt the European Atherosclerosis Society (EAS) congress this week, Marea shared results from a Phase IIa study evaluating MAR001 in patients with hypertriglyceridaemia.The trial randomised 55 participants to receive placebo or one of three dose levels of the mAb every two weeks: 150 mg, 400 mg, or 450 mg. At 12 weeks, the 19 patients in the high-dose cohort saw a 52.5% placebo-adjusted mean reduction in remnant cholesterol and a 52.7% placebo-adjusted mean reduction in triglycerides. Of those with significantly elevated triglyceride levels at baseline (≥200 mg/dL), MAR001 led to a 66% placebo-adjusted mean reduction in remnant cholesterol and a 64% placebo-adjusted mean reduction in triglycerides.In regards to safety, the mAb was well-tolerated with no serious adverse events (AEs) or AEs that led to discontinuation from MAR001. Marea expects to launch a Phase IIb study this quarter. No further investments in RLTLantheus said that the final survival results of the Phase III SPLASH study, evaluating PNT2002 in patients with metastatic castration-resistant prostate cancer following progression on an androgen receptor pathway inhibitor (ARPI), were "confounded by patient crossover within the study." As such, the company will not submit a regulatory application for the RLT to the FDA, nor does it plan to "further invest in this asset."After reaching 100% of prespecified overall survival (OS) events, the results of SPLASH were comparable to earlier readouts, Lantheus said. However, when the drugmaker reported data from SPLASH at the European Society of Medical Oncology (ESMO) congress in September, it had claimed that PNT2002 met its primary endpoint, achieving a median radiographic progression-free survival (PFS) of 9.5 months versus 6 months for those in the ARPI control arm. Lantheus said it is now working with Lilly to review the full dataset. The former in-licensed exclusive worldwide rights for PNT2002, outside of certain Asian territories, from POINT Biopharma in December 2022; Lilly acquired POINT for $1.4 billion at the end of 2023.Theriva planning PhIIITheriva revealed topline data from the Phase IIb VIRAGE study, which is comparing VCN-01 plus standard-of-care (SOC) chemotherapy gemcitabine/nab-paclitaxel against chemotherapy alone in patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC). At the time of the analysis, 48 patients had received VCN-01 — a tumour selective stroma-degrading oncolytic adenovirus — and at least one dose of SOC chemotherapy, and 48 patients in the gemcitabine/nab-paclitaxel comparator group had received treatment.Patients who received the experimental treatment saw a median OS of 10.8 months compared with 8.6 months for chemotherapy alone (hazard ratio = 0.57); a median PFS of 7 months versus 4.6 months (hazard ratio = 0.55); and a median duration of response of 11.2 months versus 5.4 months (hazard ratio = 0.22), respectively. The most common AEs seen in patients who received VCN-01 were pyrexia, flu-like illness, vomiting, nausea and elevated transaminases, but the symptoms were transient and reversible. The results, Theriva said, will help inform the design of a planned Phase III confirmatory trial.