5AM, Avidity, Fidelity lead $100M infusion into next-gen, targeted complement approach
When the FDA first approved Alexion’s Soliris — then eculizumab — in 2007, experts celebrated how the first-of-its-kind drug transformed the way physicians could treat a rare disease called paroxysmal nocturnal hemoglobinuria.
As Soliris racked up more landmark OKs, the C5 inhibitor also became a wildly successful franchise for the company, spurring blockbuster sales that led to a follow-on drug and a $39 billion buyout by AstraZeneca while inspiring new players to jump into the complement space.
Dianthus Therapeutics believes it can make an even bigger leap than what’s been proposed to date — and the startup is taking the wraps off a $100 million Series A as it explains the mission.
“This field is ripe for patient centric innovation and improvements,” CEO Marino Garcia told Endpoints News.
With basic understanding of how dysregulation of the complement pathway triggered the complement cascade and autoimmune disorders, the first-generation products “hit where they could,” CMO Simrat Randhawa said. The original C5 inhibitors proved highly effective in taming down the problematic immune reaction, but they also shut down a lot else, including the immune reactions one needs to fend off foreign attacks. As a result, the drug labels came with boxed warnings about life-threatening bacterial infections.
As the science evolves — and it’s still evolving — scientists have unearthed new ways of approaching this part of the innate immune system.
For instance, Dianthus’s lead compound is designed to selectively hit the active forms of C1s in order to only target the classical complement pathway — one of three pathways that trigger the complement cascade.
“What we’re trying to provide is pretty much the most targeted approach to a complement inhibitor that is available,” Randhawa said.
Other than potentially being safer, the biotech hopes that the selectivity will also mean that it will need to deliver a lot less antibody than the first-generation complement inhibitors, lending itself to subcutaneous self-administration.
Garcia noted that Dianthus worked with a partner to explore half-life extension technologies that made the antibodies last even longer.
With the team of 15 scattered across the US — the incoming head of quality will be working out of Ohio, while the head of clinical operations resides in Seattle and the head of tech ops reports from the Philadelphia area — the company hopes to be in the clinic by the end of the year.
Lonnie Moulder’s Tellus BioVentures provided the initial funding alongside Fairmount, while Venrock helped with the seed. 5AM Ventures, Avidity Partners and Fidelity led the round, with participation from Wedbush Healthcare Partners.
Although Dianthus has no wet labs, it hopes to leverage its network of technical experts in becoming a next-gen leader in complement therapies — an ambition hinted in its name, which combines the Greek words for god (“dios”) and flower (“anthus”).
“The whole idea was that the anthus flower was created by Zeus to sort of surpass the beauty and the scent of the lily,” Garcia said. “And I mean, it’s a great symbol for the company, because essentially, that’s what we’re trying to do.”