Where Are They Now? Caribou Biosciences

By Ben Comer, Chief Editor, Life Science Leader

Then: At the beginning of 2022, my Life Science Connect colleague and chief editor at Clinical Leader, Dan Schell, spoke with Rachel Haurwitz, Ph.D., CEO at Caribou Biosciences, for an update on the company’s operations and activities. 2021 had been a big year for the company; that summer, Caribou dosed its first patient in a Phase 1 trial of CB-010, a genome-edited allogeneic anti-CD19 CAR-T cell therapy designed to treat relapsed/refractory B cell non-Hodgkin lymphoma (r/r B-NHL). The company had also raised $350 million in an IPO — all conducted virtually, due to COVID-19 precautions — the largest IPO of any genome-editing company at the time. Also in 2021, Caribou signed a collaboration and licensing agreement with AbbVie for use of Caribou’s CRISPRCas12a chRDNA technology, which came with a $30 million up-front payment, and future milestone payments worth up to $350 million, as well as global royalties on net sales of licensed products sold by AbbVie, should those products come to fruition.

“Keep in mind that 2021 was a really rough year for allogeneic CAR-T developers,” Mark Breidenbach, Ph.D., a managing director and senior analyst at Oppenheimer & Co. Inc., told Schell in the 2022 article. “In fact, to date, the allogeneic CAR-T field hasn’t quite won over the investment community to the extent we were hoping it would by the end of 2021. And in the back half of 2021, things were already sliding in terms of the biotech sector. But Caribou still managed to raise a lot of money in less than optimal circumstances. So I give Rachel and her team credit for that.”

Haurwitz told Schell that that the company looked forward to a data release on CB-010, and was “on track to file an IND for CB-011 [an allogeneic anti- BCMA CAR-T cell therapy designed for the treatment of relapsed or refractory multiple myeloma], which will ultimately be our second clinical program. And we intend to disclose the target selection for CB-020 [a CAR-NK preclinical program], our first solid tumor targeted therapy.”

For an early-stage allogeneic T cell developer in 2022, Caribou was well funded, and Haurwitz told Schell that partnerships and collaborations would likely continue to be a key piece of the company’s strategy going forward. Despite Caribou’s cash position, however, “They haven’t been super transparent with how much of a cash flow or operational runway they have,” noted Oppenheimer’s Breidenbach at the time. “For example, they haven’t given us an explicit cash-until-2024 type of estimate.”

Now: Breidenbach’s comment about cash flow transparency is interesting in hindsight. Last month, Caribou announced in an SEC filing that it would end preclinical CAR-NK research activities (aka CB-020), and reduce its workforce by 21 positions, approximately 12% of the company’s employee headcount. That reduction extends Caribou’s cash runway “by at least six months into the second half of 2026,” according to the filing, and places Caribou’s focus exclusively on its allogeneic CAR-T cell therapy clinical programs, of which there are now four: CB-010 (for both r/r B-NHL, as well lupus nephritis and extrarenal lupus), CB-011, and CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy indicated for relapsed or refractory acute myeloid leukemia.

In an interview during the J.P. Morgan Healthcare conference in January, Haurwitz said the 2021 IPO — hindsight is 20/20 — was a great time to go public. Combined with the AbbVie strategic partnership, as well as a private fundraising event, Caribou pulled in a total of $495 million that year. “That gave us an incredibly strong balance sheet, and yet, we’ve always been a company that is super focused,” said Haurwitz. “If you look at some of our peers, they have these incredibly long pipelines that are probably in many ways aspirational. We’ve always been very focused on a small number of programs where we believe we can execute: get to really meaningful go/no go decisions, meaningful milestones, and inflection points, and we will continue to progress and build our company that way.”

AbbVie’s own reprioritization activities resulted in a halt to its CAR-T collaboration with Caribou in late 2023, removing the potential for multi-hundred-million-dollar future milestones. However, Pfizer, flush with COVID-19 vaccine sales revenue, wrote Caribou a check for $25 million under the auspices of its Pfizer Breakthrough Growth Initiative. Alexander Neuhof, MD, a senior director and global development lead for hematology-oncology at Pfizer, also joined Caribou’s scientific advisory board. Additionally, the company released dose escalation data for CB-010 and conducted a public follow-on investment round. “Between those two, we raised another $170 million in 2023,” said Haurwitz. “We continue to practice what I’ll call financial discipline, even with three clinical stage assets, remaining very focused on how we prioritize our resources.”  

If all goes according to plan, Caribou will initiate a pivotal Phase 3 trial for CB-010 in the second half of 2025. Interestingly, Caribou is focused on the FDA for its first regulatory product approval, even though most of the patients in the Phase 3 trial won’t be Americans. “Our commercial and regulatory focus right now is centered on the United States,” Haurwitz told me at J.P. Morgan in January. “However, we know geography will be a tool to get us there. As we plan for the Phase 3 trial, we know that the majority of patients for that trial will come from ex-U.S. sites.”