J-Pharma chases Telix in LAT1

A few months ago there were no LAT1-targeting agents in pivotal trials, but soon there will be two: J-Pharma’s intravenous LAT1 inhibitor nanvuranlat is set to start a US phase 3 study in December, only a month after Telix’s radiopharmaceutical TLX101 began its registrational trial.

However, Telix’s Ipax-Bright study is in second-line glioblastoma, whereas J-Pharma’s Beacon-BTC will evaluate nanvuranlat in second-line biliary tract cancer. The latter has been a long-time coming: the Japanese group announced that an investigational drug application had been approved by the FDA in September 2024.

The first part of Beacon-BTC will test three doses of nanvuranlat: 50mg or 75mg as a once daily 90-minute infusion for five days, or 375mg as a 46-hour infusion given once every two weeks. The second portion will compare the chosen regimen against physician’s choice of Folfox or Folfiri chemo, or best supportive care, with a primary endpoint of overall survival.

In a Japanese phase 2 trial in relapsed BTC nanvuranlat reduced the risk of progression or death by 44% versus placebo; however, overall survival was not statistically different between groups.

A subgroup analysis later found that overall survival favoured patients with intrahepatic, extrahepatic and gallbladder carcinoma (excluding duodenal papillary cancer), and those who had previously received only one line of prior therapy. Beacon-BTC is therefore focused on patients who fit these criteria.

J-Pharma has noted the high unmet need in BTC where, it says, the five-year survival rate is just 25%. The first-line standard of care is PD-(L)1 inhibitors plus chemo, while in the second line targeted therapies are used in patients with certain mutations. According to J-Pharma only around 30% of patients have actionable mutations, however – and it reckons nanvuranlat could be used in the other 70%.

LAT1 competition

LAT1, standing for large amino acid transporter 1, is a protein that transports large amino acids across cell membranes, and is overexpressed in some cancers. 

The most advanced player, aside from J-Pharma, is Telix, whose ex-US phase 3 trial of TLX101, Ipax-Bright, is now activating its first sites in Australia. The study also has approval to begin enrolment in Europe.

Ipax-Bright recruits patients with first recurrence of glioblastoma. It also has two parts, the first assessing safety and radiation dosing, and the second testing TLX101 plus lomustine chemo, versus lomustine alone.

The move into phase 3 was backed by two mid-stage trials: Ipax-1, and the investigator-sponsored Ipax-Linz trial. Telix also has a front-line phase 1 trial, Ipax-2, although this had been set to complete in June 2025, with no word on results as yet.

TLX101 is labelled with iodine-131, and Telix also has a follow-on anti-LAT1 radiopharmaceutical, TLX102, which uses the alpha emitter astatine-211, and is in preclinical development.

According to OncologyPipeline there are only a handful of LAT1-targeting projects in the clinic, and no other radiopharmaceuticals. J-Pharma also has an oral inhibitor project, JPH-034, but early trials in pancreatic cancer appear to have stalled; according to the company’s website the focus in oncology is now in glioma, where the asset is preclinical.

Biopharma projects targeting LAT1

Source: OncologyPipeline.