Linda Burkly, Ph.D., was 37 years into a career at Biogen when Editas Medicines CEO Gilmore O’Neill—himself an alum of the neurological disease-focused big biotech—came knocking.
After working on everything from biologics to small molecules and nucleic acids, Burkly didn’t need to make a change. But there was something about gene editing that made the decision easy.
“The science is really one of the things that dragged me from Biogen,” Burkly said in an interview on the sidelines of the American Society of Gene and Cell Therapy (ASGCT) annual meeting in Baltimore on Thursday afternoon. She took up the role as Editas' executive vice president and chief scientific officer in July 2023.
At Biogen, she had worked in inflammatory diseases, peripheral autoimmune and neurological disorders, where the challenge is getting through the blood-brain barrier. She worked on gene therapy and all sorts of new modalities.
“And as I did that, I got to realize, I just wanted things that were more transformative and the curative potential of gene editing is just so disruptive. It's going to be so amazing. And this is really what enlightened me to the potential of Editas,” Burkly said.
She also knew O’Neill, having overlapped for a time at Biogen. Directly prior to joining Editas, Gilmore was vice president of R&D and chief medical officer at Sarepta Therapeutics. But before that, he spent 15 years at Biogen working on gene and cell therapy, rare diseases, neuromuscular diseases, Alzheimer’s and more.
“I met the team that he was building and I could see the experience … and the passion that everyone had,” Burkly said. She also appreciated the company culture. “It was just aligned with my goals.”
But for all the promise, Editas has been in a tough spot of late. O’Neill executed a major overhaul early last year, cutting the pipeline down to just a handful of assets and laying off workers. The company also watched as peers Vertex Pharmaceutical and CRISPR Therapeutics accelerated toward FDA approval in the same indication, sickle cell diseases, as Editas' lead asset renizgamglogene autogedtemcel (reni-cel, previously known as EDIT-301). The partnered companies snagged an FDA approval for the gene editing therapy Casgevy in December 2023, as did bluebird bio for Lyfgenia.
Burkly calls the approval of Casgevy a major breakthrough for gene editing.
“It's so good for the patients and it's so good for the field. It's a validation of the technology,” she said.
But it also means that Editas—and Burkly—have their work cut out to show that reni-cel is differentiated.
Reni-cel still has a shot at gaining market share, according to Burkly, because it works differently. Instead of knocking down the expression of the repressor gene BCL11A, reni-cel delivers patient-derived CD34+ hematopoietic stem and progenitor cells that are edited at the gamma globin gene promoters to upregulate the gamma globin. This boosts naturally occurring fetal hemoglobin.
“We do think that our reni-cel asset has promise for potential differentiation from that based on the robustness of the total hemoglobin levels and the cure of anemia,” Burkly said.
Editas is closely watching the launch of Casgevy. Burkly and the team don’t mind being second in line and getting a chance to watch the process unfold.
“It's to our advantage, in this case, to be a fast follower,” Burkly said.
Burkly is following O’Neill’s three-pronged rebuilding strategy, which includes advancing reni-cel to a biologics license application. She was specifically brought on to build out the in vivo pipeline and is charged with coming up with a plan to do so.
For now, Burkly is keeping the specifics of her in vivo strategy very close to the chest. But on Wednesday, the company presented first-quarter earnings, detailing a plan to pursue a functional upregulation strategy for in vivo therapies for genetically determined diseases. Burkly believes the upregulation strategy will help differentiate Editas from other companies working in the space.
“We can play in areas that standards of care and established modalities like siRNAs and ASOs can't play with knockdown strategies and also where many of our peers haven't chosen to play,” Burkly said. “We're very excited about the differentiation that we can bring and we can leverage our core indel {CRISPR] technology to do this.”
At ASGCT, Editas delivered a trio of preclinical, proof-of-concept studies in an oral presentation Friday. One showed the platform’s lipid nanoparticle delivery capabilities, another the validity of the proprietary nucleases to edit in vivo, and finally, the third detailed guide modifications that increase the potency of the company’s editing.
Editas also recently won a major advantage from the courts in the long-running CRISPR-Cas 9 legal battle. As a result of a February 2022 court decision, Vertex paid $100 million for non-exclusive licensing rights to Editas’ Cas9 tech for ex vivo gene-editing medicines targeting the BCL11A gene. Burkly said the biotech is looking at ways to further that partnering activity for the intellectual property.
This year will be busy for Editas, which is awaiting four key readouts at mid- and end-of-year: two for reni-cel in sickle cell and two for the asset in transfusion-dependent beta thalassemia.
And finally, the company is set to release data showing in vivo preclinical proof-of-concept for an undisclosed indication by the end of the year. That indication is being kept top-secret due to the cut-throat nature of the gene editing space.
“We may not reveal the indication that we're going after just to protect our competitive position,” Burkly said, noting that they will present the data without revealing the indication. “We just need to maintain our competitive position until we get a little bit closer to clinic.”