Apellis, Beam team up to test base editing against the broad field of complement disorders
Last summer, as Apellis was preparing for the approval of its potential blockbuster PNH drug Empaveli, CEO Cedric Francois sat down with his team and began plotting the post-Empaveli future.
Apellis had spent most of its 12-year history developing that one drug. The pipeline listed online consisted of seven items, six of which were different formulations or applications of the molecule. But in 2018, they started diving deeper into complement biology — the broad immunology sub-field where Empaveli operates — in hopes of expanding their reach.
By 2020, the team had almost everything it needed in place.
“We looked at what we were hoping to create, and we saw one missing piece of the puzzle,” Francois told Endpoints News. “And that was gene editing.”
So Francois struck a deal. On Wednesday Apellis announced it’s teaming with Beam Therapeutics to develop gene editing therapies that target the complement pathway, the ancient branch of the immune system responsible for helping clear out pathogens and implicated in a range of autoimmune disorders.
Under the five-year collaboration, Apellis will pay Beam $75 million cash — $50 million upfront and $25 million on the one-year anniversary of the deal — along with unspecified milestones in exchange for preclinical work on six different programs. These will be base editing approaches to different genes in the complement system in three different organs that are accessible with current delivery technologies: the eye, brain and liver. Apellis will handle subsequent development, although Beam has the right to go 50-50 developing and commercializing one of them in the US.
It’s the second collaboration Beam has signed since it launched out of David Liu’s Harvard lab, after its cardiovascular-focused deal with Verve. CEO John Evans said the company will look to sign more in the future, applying its base editing technology to diseases where that tech could help but where they lack the resources or expertise to develop the drug alone.
“There are these areas where we may have the technological expertise to do something but we certainly lack the biology insight,” Evans told Endpoints. “This is exactly the kind of deal we want to do more of.”
Apellis and Beam are remaining tight-lipped about how exactly they’ll deploy gene editing on the complement system, although Francois said the company would try to use it both in areas where they can be “confident it will work” and areas that are more exploratory.
Effectively, that means trying both to create one-and-done treatments for diseases where researchers have already proven, with conventional therapies, that blocking the complement system is effective (i.e. PNH) and diseases where there isn’t that proof of concept.
The deal is part of a growing push to move CRISPR gene editing out of rare genetic disorders and into more common and more complex ailments. Francois and Evans said Apellis picked Beam because its base editing technology allows for subtler, base-by-base alterations of DNA than traditional CRISPR. It was particularly suited for complement disorders, they said, where the goal is less to knock out any particular gene — as conventional CRISPR technologies do well — than to restore a complex, immunological system to balance.
“These are the consequences of a disregulated homeostatic system,” Francois said. “With a gene editing approach, you can turn the buttons in a way where that homeostatic system can re-find its nature balance. Which may take time — may take one year or two years — but really be a curative approach.”