RYZ-101

ARTBIO has secured $132 million in fresh funding to accelerate development of its lead-212 (Pb212)-based alpha radioligand therapy (ART), while building out a decentralised supply chain aimed at addressing one of the field's biggest bottlenecks: reliable access to radioisotopes.The series B will primarily support clinical development of ARTBIO's lead candidate, AB001, currently in early development for metastatic castration resistant prostate cancer (mCRPC). "Prostate-specific membrane antigen (PSMA) imaging shows AB001 to be well-tolerated in scans of a patient who recently received AB001 through a compassionate use request (publication here)," CEO Emanuele Ostuni told FirstWord, adding that an IND submission is "imminent."Promising substitute Traditional radioligand therapies tend to rely on beta emitters like lutetium-177, but the field has increasingly turned to alpha emitters, such as actinium-225, given the potential for greater safety and efficacy. However, global shortages of actinium — causing even programmes like Bristol Myers Squibb's Phase III trial of RYZ101 to pause enrolment last year — have prompted companies to explore alternatives, with Pb212 seen as a promising substitute (see – Spotlight On: Pb212 emerges as alternative isotope for radiopharmaceuticals)."Pb212 is highly stable in the carrier molecules we develop," said Ostuni. "Following the emission of the first and only alpha from Pb212, the low rate of recoil of the isotope avoids any unintended radiation toxicity in non-tumour areas." He added that the 10.6-hour half-life of Pb212 "matches the properties of the small-molecule carriers we use thereby delivering most of its energy (80-90% transfer) into the tumour." Meanwhile, unlike other ARTs in which the alpha isotopes are made in nuclear reactors or centralised facilities with rigid production schedules, ARTBIO is pioneering what it touts as a more efficient method to isolate the isotopes it needs.Discrete manufacturing sitesThe company's "first-of-its-kind" AlphaDirect system offers several advantages, including its benchtop format that allows it to be operated in different manufacturing facilities, and a simple separation-free process that yields isotopes with over 99.9% purity. Further, in order to minimise uncertainty and cost, the supply chain starts with materials derived from accessible nuclear industry stockpiles, reducing reliance on reactors or cyclotrons."Through strategic partnerships spanning the US, Europe and Asia, ARTBIO can maximise patient access through a network of discrete manufacturing sites," Ostuni said. "This approach mitigates single point of failure concerns."Maha Katabi, general partner at Sofinnova Investments, which co-led the series B along with B Capital, called ARTBIO's technology "a game-changer for navigating around supply and production challenges for radioisotopes in today's complex environment."The round also included participation from existing investors F-Prime, Omega Funds and Third Rock Ventures, along with new backers Qatar Investment Authority and Alexandria Venture Investments.