Now that Alexion has secured an FDA approval for Ultomiris, the follow-on for its flagship drug Soliris, the biotech is back on the hunt for potential additions to its rare blood disorder portfolio.
One of them will be a targeted therapy for light chain amyloidosis, which Alexion has lassoed with a buyout option in its collaboration deal with Caelum Biosciences. Alexion is handing over $60 million for a minority stake and an exclusive option to acquire the rest — a decision they will make when the Phase II data are ripe for review.
Startup incubator Fortress Biotech launched Caelum in 2017 after licensing the anti-amyloid antibody they now call CAEL-101 from Columbia based on research by Alan Solomon of the University of Tennessee Graduate School of Medicine. Breaking from the old approach, which focuses on blocking production of new amyloids, he designed the therapy to break up pre-existing amyloid deposits clogging up in tissues to damage patients’ organs, particular hearts and kidneys.
“CAEL-101 appears to have a unique capability of binding to both kappa and lambda misfolded proteins,” Caelum CEO Michael Spector said in a statement. “Data from the Phase 1a/1b study indicate that CAEL-101 is a well-tolerated therapy that leads to a rapid and clinically relevant organ response, particularly in the heart and kidneys. Further, CAEL-101 showed a statistically significant improvement from baseline in global longitudinal strain, an endpoint that has been correlated with survival in patients with AL amyloidosis.”
For Alexion, this will be an opportunity to tap into a fatal disease with no approved therapies, R&D chief John Orloff said. Prothena took a stab at it but late-stage failures forced it to scrap its entire lead program.
Whether Prothena’s failure had to do with its drug (as Alexion believes) or the entire hypothesis about targeting AL amyloid is to be borne out, Stifel analysts wrote in a note, making this a cheap bet with not just high potential reward but also “fairly high risk.”
“Alexion’s argument here is that CAEL-101 benefits from a much stronger mechanistic rationale, though NEOD001 preclinical data paint a different picture,” they wrote. “In a presentation at the 2018 International Symposium on Amyloidosis, a preclinical poster suggested that NEOD001 binds an epitope on kappa and lamda light-chain proteins that in their view is “uniquely exposed during misfolding and aggregation”. It’s plausible (but how would we know) that this was not recapitulated in patients.”
Alexion will now play a part in shaping the Phase II program for CAEL-101 as Caelum remains responsible for the execution and manufacturing. If the data hold up, the buyout deal will amount to as much as $500 million.
The deal adds to a steady stream of early-stage assets Alexion has been bringing into its pipeline, including a preclinical C6 complement inhibitor from another option deal with Complement Pharma and a (much more expensive) drug for rare IgG-mediated diseases, which it bagged when acquiring Syntimmune for $400 million upfront.
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