Beam Therapeutics, a high-profile biotech developer of a more precise form of gene editing, is partnering with Apellis Pharmaceuticals to expand use of its DNA-altering tools into a wider and more varied set of diseases than currently targeted.
On Wednesday, the two companies revealed plans to develop gene editing therapies for diseases caused by excessive activation of the complement system, an important part of the body's immune defense against infection. Once overstimulated, the complement system can mistakenly attack healthy cells and tissue, driving inflammation and illness.
Beam and Apellis hope to apply gene editing to turn off this so-called complement cascade and thereby control diseases caused by the abnormal immune signaling. It's relatively new ground for gene editing research, which has to date focused principally on inherited conditions linked to mutations in a single gene, like sickle cell, beta thalassemia and rare eye disorders.
"We think this is a very forward-looking collaboration," said Beam CEO John Evans, "because it's showing the way for gene editing to increasingly expand beyond its roots into larger and larger unmet need."
Over five years, the companies will collaborate on as many as six research programs aimed at either C3, a linchpin protein of the complement system, or other similar targets in the eye, liver and brain. Apellis, which specializes in complement-driven diseases and recently won U.S. approval of its first medicine for one, will pay Beam $50 million upfront and another $25 million in one year.
It's by far Beam's biggest deal since the company started operations four years ago. The biotech, now worth about $8 billion, is developing a type of gene editing that's capable of changing a single genetic letter, or base, without breaking both strands of DNA, as earlier CRISPR-based approaches do.
Beam and Apellis have not yet specified which genes within the complement system they plan to target. But, by focusing on the eye, liver and brain, they'll be working in areas with which both companies are familiar. Apellis, for instance, is developing a complement-inhibiting drug for geographic atrophy, a type of age-related vision loss, and expects results from two Phase 3 studies of the treatment this fall.
The link between macular degeneration and the complement system was one of the first medical breakthroughs to emerge from the Human Genome Project, noted Cedric Francois, Apellis' CEO.
Associations like that are "just the tip of the iceberg," he said. "By making small [genetic] modifications, you can start thinking and dreaming about correcting a homeostatic system that gets out of control and bringing it back to where it needs to be."
Apellis' interest in gene editing for complement-driven diseases grew last summer, when company executives read research from Verve Therapeutics, another gene editing company affiliated with Beam. Early data from animal studies showed Beam's editing technique, known as base editing, could turn off a gene called PCSK9 in the liver, sharply lowering cholesterol levels.
"We read that publication and were so impressed with how that came to bear," said Francois. Apellis has been negotiating this collaboration with Beam over the roughly nine months since.
In theory, base editing can permanently turn off genes or otherwise alter gene expression. For certain diseases linked to singular damaged genes, such an approach can be appealing and, in some cases, mimic genetic variants found to occur naturally.
But the permanent nature of gene editing also spurs concerns about unintended consequences, a fear that may be more acute when targeting diseases caused by more complex biology.
Francois acknowledged those concerns, and suggested the development by Apellis and others of complement inhibitors may help.
"The natural fear that people have of the irreversibility of gene editing ... you kind of want to have the story of the normal pharmaceutical approach in front of it," he said. "You bring in a normal pharmaceutical approach where you can stop taking the drug. But if after years of dosing you find out that its safe, well, why not avoid having to take a drug all the time and make the correction once and for all?"
In May, Apellis won Food and Drug Administration for one such pharmaceutical approach, a targeted therapy called Empaveli for the rare blood disorder paroxysmal nocturnal hemoglobinuria, or PNH. The active ingredient in Empaveli is being used as an eye injection in the company's geographic atrophy studies.
With Empaveli, Apellis is following Alexion Pharmaceuticals, a drugmaker being acquired by AstraZeneca that's led development of complement inhibitors for years. Two Alexion drugs, Soliris and Ultomiris, are approved for PNH along with several other complement diseases.
Francois claimed gene editing is the missing piece that will help Apellis become a leader in the complement field for the next 10 or 20 years.
Per terms of the companies' partnership, Apellis will have exclusive rights to license each of the six programs — should they be advanced — after which it would take over development responsibilities. Beam will conduct preclinical research and holds an option to split development and commercialization rights with Apellis on one program.
Note: This story has been updated with additional details of Apellis' approved drug Empaveli.