Slimmed-down 2seventy charts own course after bluebird split

 In many ways, 2seventy bio feels like a startup, according to CEO Nick Leschly.

Entering its first full year as an independent company since formalizing a spinoff from bluebird bio to focus solely on oncology products, the energy among 2seventy's leaders is palpably youthful. The biotech has a genuine focus on its newest technology rather than the more proven part of its pipeline: Abecma.

"I hope in five years we have something that’s better than Abecma,” said Leschly, who spent 11 years as CEO of bluebird before splitting off to lead 2seventy. Abecma, a CAR-T cell therapy jointly developed with Bristol Myers Squibb, was approved by the FDA a year ago to treat advanced multiple myeloma. 

But in reality, 2seventy bio is not a new company.

It launched with banked credibility—in large part due to Abecma—and banked cash. 2seventy entered 2022 with roughly $360 million on hand. Leschly also brought CSO Philip Gregory over from bluebird during the split. As a result, the expectations are high, and until proven otherwise, Abecma remains the bar. 

The drug, made in collaboration with Celgene before the company was absorbed by BMS, was approved by the FDA in March 2021 for patients with multiple myeloma who had already completed at least four rounds of treatment. In a trial of 127 patients, nearly three-quarters partially or fully responded to the treatment and more than a quarter shed all signs of the disease. 2seventy expects as much as $300 million in revenue from the therapy this year, which will fund the rest of the company’s pipeline beginning in 2023.

Ultimately, 2seventy is betting that separating from bluebird will allow the slimmed-down team to have the bandwidth to develop more programs that can set the company apart. 

“By pulling out the oncology programs, and separating them from the rare disease programs, you get a set of people who aren’t distracted by the latest question on sickle cell disease or the latest question on thalassemia,” Gregory said in a joint interview with Leschly. 

While 2seventy walked away with the oncology program, bluebird kept the rare disease pipeline, a deep roster that includes four therapies that have reached phase 3 trials. Among them is a treatment called Zynteglo for beta thalassemia, a genetic disease that limits people's ability to produce enough red blood cells. The therapy was approved in the EU in 2019, but is being withdrawn from the market due to disagreements over pricing. 

The question that Leschly and Gregory are instead asking is how can they improve CAR-T therapies? The answer, according to Gregory, lies in part in addressing gene therapy’s “dirty secret": that the synthetic antibodies in CARs, or Chimeric antigen receptors, that target antigens on the outside of cancer cells lack the sensitivity of engineered t-cell receptors (TCR) that do the work on the inside of cancer cells. 

2seventy is developing a new architecture to try and target both. The idea is on display in a new therapy for B cell non-Hodgkin lymphoma patients that received clearance for human studies late last year. 2seventy is also using the same receptor technology to regulate CARs with small molecules, an advancement that’s believed to improve their performance and tolerability, which is also being tested in pediatric and young adult patients with acute myeloid leukemia. The company expects some evidence to prove the concept for both of those trials later this year. 

To help see out this vision, 2seventy has turned to translational scientist and physician Steven Bernstein, who was named chief medical officer last week. Bernstein most recently led translational science at Turnstone Biologics after more than 20 years as a physician and oncologist. Leschly believes Bernstein will ground the company in being patient-driven as the pipeline is expanded. 

"He loves to tinker and stew and he's got the skill set to do it," said Leschly, who described a dinner with himself, Gregory and Bernstein where the latter two were so engrossed in talking scientific shop that Bernstein forgot his future boss was even there. 

"It was just him and Phillip, that just were going at it, quoting papers from the '60s, the '70s, with acronyms I've never heard about; I was like, 'this is our guy.'" he said. 

As for established Abecma programs for patients with multiple myeloma, Leschly and Gregory had nothing to tease but expressed optimism that when given to patients that were less sick and had undergone less treatment, the therapy would perform even better. Data from their phase 2 trial in second-line patients is expected at the end of this year and a readout of the phase 3 trial in patients with two to four lines of prior treatment is slated for 2023. 

Leschly also said the company would consider future partnerships. So far, 2seventy has teamed up with BMS and Regeneron, along with the Seattle Children's Hospital for its AML target in a more research-focused capacity. 

"We're going to continue to contemplate where are the right places to get knowledge, insight, capabilities," he said. "Whether they happen this year, next year, etc., but we're absolutely going to continue to drive that direction."

Looking ahead, Leschly and 2seventy believe the way to be “better than Abecma” is by investing in the science and applying early findings to their platform, instead of waiting for years-long readouts. 

“It’s become a very sort of comprehensive, if you will, focused, oncology play,” he said. “And that’s doable.”

https://www.fiercebiotech.com/biotech/it-looks-define-itself-2seventy-bio-believes-abecma-floor-not-ceiling