RYZ-101

Bristol Myers Squibb has opened its $160 million radiopharmaceutical manufacturing facility in Indianapolis, which was a key piece of its $4.1 billion acquisition of RayzeBio in December of 2023. Bristol Myers Squibb has opened its radiopharmaceutical manufacturing facility in Indianapolis, which played a major role in the company’s $4.1 billion acquisition of RayzeBio in December 2023.The isotope and drug production plant is now fully operational, BMS said on Friday. CEO Chris Boerner helped cut the ribbon on the $160 million, 77,000-square foot complex, which is equipped to produce next-generation radiopharmaceutical cancer treatments based on the alpha-emitting isotope actinium-225 (Ac225).As radiopharmaceuticals have picked up momentum in oncology, the radioisotopes underpinning them have been developed with improved stability in mind, allowing the therapeutic class to deliver targeted radiation to tumors with minimal side effects.“Cancer has been at the forefront of what we do, and we believe this technology has an important role to play,” Boerner said during the event on Friday, as quoted by local ABC affiliate WRTV Indianapolis. The facility—which RayzeBio president Ben Hickey dubbed “a first-of-its-kind model in the country,” combines isotope production and drug product manufacturing. It's currently producing doses for clinical use. RayzeBio’s top radiopharmaceutical candidate, RYZ101, is in phase 3 testing for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and early-stage development for small cell lung cancer. Last year, because of a shortage of actinium, RayzeBio temporarily halted enrolment in the phase 3 trial.When BMS set out to acquire RayzeBio in late 2023, analysts at William Blair suggested that the deal “reemphasize[d] the premium value ascribed to pure-play radiopharmaceutical companies that have ownership over manufacturing.”The Ac225 approach to nuclear medicines differs from approved radiotherapies such as Novartis’ Lutathera and Pluvicto, which use a beta-emitting isotope known as lutetium.  Ac225’s alpha particles are more potent, killing cancer cells and minimizing damage to surrounding healthy tissue. Another advantage of Ac225 radionuclides is that their potency half-life extends to roughly 10 days as opposed to six for the beta-emitting types, allowing for a larger window for delivery and administration.In announcing the facility debut, BMS highlighted that the plant is part of its $40 billion investment pledge in the U.S. over the next five years, which the company unveiled in early May. 

Bristol Myers Squibb is scaling up its radiopharmaceutical game with the opening of a $160-million manufacturing site in Indianapolis, a key investment since entering the space through its 2024 takeout of RayzeBio for $4.1 billion. The Pike Township facility will have the capacity to manufacture tens of thousands of doses of radiopharmaceutical treatments annually when scaled to support commercial supply."We believe this technology has an important role to play," said Chris Boerner, BMS's chief executive, at the site's opening last Friday, noting that "there is an incredible talent pool here" in Indianapolis. The facility is currently staffed with about 100 full-time employees, with the intent to bump up the number to 130 full-timers, a BMS spokesperson told FirstWord. The company plans to invest another $50 million more in the site.Three-day turnaroundThe 77,000 square-foot facility is built to be a fully integrated, end-to-end operation for both isotope production and drug product manufacturing, enabling on-demand output and direct delivery to treatment centres within three days of release after production."Indianapolis is a key national distribution hub offering unmatched reach — 50% of the US is within a 10-hour drive," the company spokesperson said, noting that multiple major airports are within a three-hour radius. "This allows for the reliable transfer of doses through road or air transport to destinations across the country and around the world."RYZ101 production baseAt the heart of BMS's radiopharma push is RayzeBio's lead candidate RYZ101 (225Ac-dotatate), which harnesses alpha-emitting isotope actinium-225 (Ac225) to target somatostatin receptor 2 (SSTR2), commonly overexpressed in neuroendocrine tumours (NETs) and small-cell lung cancer (SCLC). Alpha-emitters like actinium are gaining attention as next-generation alternatives to beta-emitters like lutetium-177, used in Novartis' FDA-approved Pluvicto (lutetium Lu 177 vipivotide tetratexan) and Lutathera (lutetium Lu 177 dotatate). Unlike lutetium, actinium delivers higher-energy radiation over shorter distances, potentially increasing tumour cell killing while minimising off-target toxicity.However, that promise has come with growing pains. Shortly after the RayzeBio acquisition, isotope shortages forced BMS to temporarily halt enrollment in the Phase III ACTION-1 trial, which is evaluating RYZ101 for gastroenteropancreatic NETs in patients previously treated with lutetium-177 based therapies.Enough supplyThe 288-patient trial has since resumed, with primary completion expected by year-end. Clinical doses of RYZ101 are being produced at the Indianapolis facility. "RayzeBio has sufficient Ac225 supply for current clinical and anticipated commercial needs," the BMS spokesperson said.Meanwhile, RayzeBio is pushing RYZ101 into other cancer types as well. The candidate is being tested in a Phase I study for newly diagnosed extensive-stage SCLC, and last July, it initiated the Phase I/II TRACY-1 study in patients with ER-positive/HER2-negative metastatic or unresectable breast cancers that express SSTRs. The BMS unit also initiated a Phase I/Ib study of the theranostic pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to identify and treat subjects with GPC3-positive, unresectable hepatocellular carcinoma.