Less than a month after locking down a lease for a new U.S. headquarters, radiotherapy outfit AdvanCell is poised to push its lead prostate cancer candidate into phase 3 development with the help of a $315 million series D.
The round was led by Ally Bridge Group and Alpha Wave, with returning support from the investment arms of Sanofi and Eli Lilly and new funders like Bain Capital Life Sciences. The series D has its origins at January’s J.P. Morgan Healthcare Conference, where radiotherapy was at an inflection point, AdvanCell CEO Philina Lee, Ph.D., told Fierce this morning.
In addition to a general resurgence in the biotech sector, radiotherapy was bolstered by a $318 million IPO by Aktis Oncology at the start of the year and the continued success of Novartis’ prostate cancer med Pluvicto.
With its new cash in hand, AdvanCell is now positioned to stake its own claim in the surging field with a novel isotope, dubbed lead-212. The biotech’s lead asset, ADVC001, is currently in a phase 2 trial for metastatic prostate cancer, a disease that Lee suggested is ripe for innovation.
“For the current standard-of-care, Pluvicto, in prostate cancer, 30% of patients are upfront resistant to treatment,” Lee told Fierce. Novartis’ blockbuster is also a lutetium-based beta emitter, part of the first wave of radiotherapies that uses radioactive particles to break single strands of DNA. Only breaking one strand of DNA, Lee said, makes it easier for the cancer to heal and evolve resistance to the drug.
ADVC001, in contrast, is an alpha emitter, which breaks both strands of DNA, a wound much harder for cancer to bounce back from. Other alpha emitters, like Bayer’s Xofigo or Actinium Pharmaceuticals’ ATNM-400, use isotopes of radium or actinium. But lead has several key advantages over other elements, Lee said.
“The half-life of lead-212 is 10.6 hours,” the CEO said, meaning it doesn’t stick around in the body nearly as long as actinium or radium isotopes. “You can deliver that payload, lead to double-stranded DNA breaks of the tumor cells in a highly targeted way, and then quickly be gone, which could minimize the accumulation in surrounding healthy tissues.”
Manufacturing is another key sticking point for radiotherapies, as crafting radioactive elements is neither easy nor cheap. AdvanCell’s series D will also be put to use on further scaling up manufacturing, including in the U.S., in advance of the eventual phase 3 trial. AdvanCell has now made Boston its official home, while maintaining a presence in Australia.
The company’s “special sauce,” Lee said, is a proprietary automated generator that can pump out lead isotopes.
“It's a box about the size of a crate of wine that sits in a hot cell,” Lee said. “Over the course of one day, it can produce a batch of lead-212 in a fully automated way.”
Lee argues AdvanCell’s manufacturing prowess, leadership team and differentiated drug candidate make it stand out from others in the lead game, like Perspective Therapeutics, which is pursuing isotopes of the element primarily for neuroendocrine tumors. But, she added, there’s plenty of opportunity in radiopharma to go around.
“A rising tide lifts all boats,” Lee told Fierce. Not unlike Seagen’s pioneering work in antibody-drug conjugates, “there's just so much opportunity to unlock here in targeted radiotherapies.”