StockWatch: Caribou Plunges as It Pursues Strategic Alternatives

Caribou Biosciences (Nasdaq: CRBU), whose co-founders include Jennifer Doudna, PhD, capped a one-year 83% freefall of its stock after announcing plans to evaluate strategic alternatives, as investors responded with a selloff that sent shares of the CRISPR genome-editing cell therapy developer plunging 62% this past week.

Caribou announced plans to carry out an unspecified “substantial” reduction of its workforce—which numbered 97 people as of February 27, according to its most recent Form 10-K Annual report, filed March 5—as well as a halt to trials of its two clinical-phase pipeline candidates, both allogeneic chimeric antigen receptor (CAR) T-cell therapy programs, and other cost reduction measures also yet to be specified.

“Caribou’s story has taken a heartbreaking turn,” co-founder, president, and CEO Rachel Haurwitz, PhD, posted on LinkedIn, announcing the company’s strategic review. “This decision is not a loss of belief in our science, our clinical data, or what these programs could mean for patients. It reflects the difficult reality that the current financing environment for allogeneic CAR T-cell therapies has made it impossible to secure the capital required to responsibly advance them.”

Haurwitz co-established Caribou in 2011 along with Doudna and two other co-founders: Martin Jínek, PhD, a former postdoctoral fellow in Doudna’s lab, now at the University of Zurich, who led the seminal 2012 study leading to the Nobel Prize; and James Berger, PhD, professor in the department of biophysics and biophysical chemistry at Johns Hopkins University School of Medicine.

Caribou became operational in 2012, which would make it the oldest CRISPR therapeutics company as far as Haurwitz could recall in a 2021 interview. That year, Caribou went public through an upsized initial public offering (IPO) that raised $321 million in aggregate net proceeds after deducting underwriting discounts and commissions and other offering expenses. Caribou sold 21.85 million shares at an IPO price of $16 a share, up from earlier plans to sell 13.5 million shares.

Two years later, Haurwitz shared with GEN her journey from graduate student in Doudna’s lab to launching a biotech start-up: “This is the only job I’ve ever had!”

Trials halted

As a result of the strategic review, Caribou has halted trials of vispacabtagene regedleucel (vispa-cel, formerly CB-010) a treatment for relapsed or refractory (r/r) B cell non-Hodgkin lymphoma. Caribou has said vispa-cel is the first allogeneic CAR T-cell therapy “to our knowledge” that has reached the clinic with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR T-cell exhaustion.

To manufacture vispa-cel, Caribou applies Cas9 hybrid RNA-DNA guide or “chardonnay” (chRDNA) to make three edits: A knockout of the TRAC gene to remove the T cell receptor; a site-specific insertion of an anti-CD19 CAR into the TRAC gene; and a knockout of PD-1.

Also halted were clinical studies of CB-011, an allogeneic anti-BCMA CAR-T cell therapy for the treatment of patients with r/r multiple myeloma (RRMM). To manufacture CB-011, Caribou uses Cas12a chRDNAs designed to direct precise genome editing, in order to make four edits:

• A knockout of the TRAC gene to remove the T-cell receptor
• A site-specific insertion of a humanized anti-BCMA CAR into the TRAC gene
• A site-specific insertion of a gene encoding a B2M–HLA-E-peptide fusion into the B2M gene
• The resulting knockout of the endogenous B2M

“This method simultaneously eliminates endogenous HLA class I presentation on the surface of the CAR T cells and expresses HLA-E, a minor HLA class I antigen, to blunt both T and NK cell-mediated rejection of the CAR T-cell therapy by the patient’s immune system,” Caribou explained on its website.

Strategic pivot

The development of CB-011 and vispa-cel followed a strategic pivot by Caribou from a platform company for biopharma partners applying genome editing in research or product development, to a developer of genome-edited therapies based on its own next-generation CRISPR technology.

While that pivot has generated positive data readouts, it has not shielded Caribou from the financial challenges faced by numerous gene-edited therapy developers. In April 2025, Caribou chopped its workforce by 32% and pruned its pipeline by ending all preclinical research, the Phase I GALLOP trial (NCT06752876) of vispa-cel in lupus (before the first patient could be dosed), and development of CB-012, including the Phase I AMpLify trial (NCT06128044) assessing the candidate in relapsed or refractory acute myeloid leukemia (AML).

“It was really about right sizing the organization relative to our focused priorities,” Haurwitz explained last year in an interview. Asked how hopeful she was about an improving economic environment over the next 12 months, she replied: “I remain a believer and I remain an optimist. I’d probably be in the wrong job in the wrong line of work if I weren’t.”

“I certainly think for the work that we are doing, I continue to fully believe that doing right by patients is the North Star, because business success falls out from that in terms of nearer term clinical catalysts and opportunities that come from doing right by patients. And longer-term commercial opportunity also comes from doing right by patients,” Haurwitz added.

Caribou has retained Wedbush Securities as its exclusive financial advisor to assist in evaluating strategic options.

Caribou announced its pursuit of strategic alternatives after the closure of financial markets on October 6. The following day, Caribou shares began three days of stock declines, nosediving 46% from $1.14 to 62 cents. Those shares tumbled another 22% Thursday to 48 cents, but closed Friday with another 4% decline, finishing the week at 46 cents.

Cash crunch

Daina M. Graybosch, PhD, senior managing director, immuno-oncology and a senior research analyst with Leerink Partners, reported in a research note that Caribou was facing an increasingly pressing cash crunch at a time when the company needed significant capital to fund its planned Phase III ANTLER-3 trial, designed to assess vispa-cel in second-line auto-CAR T ineligible diffuse large B-cell lymphoma (DLBCL).

Caribou never enrolled patients in the pivotal study, though it reached agreement with the FDA in May on a design for the trial, which was expected to be a randomized, controlled clinical study enrolling approximately 250 CD19-naïve second line (2L) large B cell lymphoma patients ineligible for transplant and not candidates or not eligible for autologous CAR T-cell therapy.

“We are sympathetic to management’s stated rationale for exploring strategic alternatives,” Graybosch commented. “Evidently, investors were unwilling to fund the trial on what would have been highly dilutive terms, especially in the context of lingering clinical risk and uncertainty around the strength of vispa-cel’s Ph[ase I/II] outcomes and partial HLA-matching strategy, as well as substantial in- and out-of-class competition.”

That competition, she wrote, included epcoritamab, a bispecific T-cell engager (BiTE) therapy already marketed as Epkinly® by Genmab (Nasdaq Copenhagen and Nasdaq: GMAB) and AbbVie (NYSE: ABBV).

On October 5—the day before Caribou’s strategic alternatives announcement—Genmab and AbbVie reported positive topline data from the Phase III EPCORE DLBCL-2 trial (NCT05578976) showing that the combination of epcoritamab, rituximab, the corticosteroid prednisone, and three chemotherapy drugs showed statistically significant and clinically meaningful improvement in progression-free survival (PFS) in frontline diagnosed DLBCL patients.

The combination therapy, nicknamed R-CHOP, consists of rituximab—the CD20-directed cytolytic antibody marketed by Genentech, a member of the Roche Group (SIX Swiss: RO and ROP) and Biogen (Nasdaq: BIIB) as Rituxan®—plus cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone. In DLBCL patients with an International Prognostic Index (IPI) score of 2 to 5, R-CHOP reduced the risk of disease progression or death by 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001).

“Interesting” timing

“The timing of [Caribou’s] initiative is interesting,” Graybosch observed. “We believe there is enhanced strategic value and clinical rationale for allogeneic cell therapies in a world where TCEs [T-cell engagers] become entrenched in the 1L [first-line] setting.”

As for CB-011, it began development much earlier than vispa-cel, “with an appreciably more challenging competitive setup in RRMM, where we saw elevated clinical risk for its post-BCMA therapy development path due to potential efficacy-compromising loss-of-antigen,” the Leerink Partners analyst added.

Single target allogeneic BCMA CAR-T treatments have posed a potential risk of RRMM relapse through antigen loss as myeloma cells mutate or downregulate BCMA to evade the CAR T cells. To minimize that risk, Caribou designed its Phase I CaMMouflage trial (NCT05722418) to limit the therapy dosing to BCMA-naïve patients—an approach that proved successful when the company last year announced positive data from a 12-patient, BCMA-naïve cohort showing a 92% overall response rate (11/12 patients), a 75% or greater complete response rate (9/12), and 91% minimal residual disease (MRD) negativity (10/11 evaluable patients).

To avoid the risk of antigen loss, several developers of allogeneic BCMA CAR-Ts have designed dual targeting CAR Ts. For example, Allogene Therapeutics (Nasdaq: ALLO) is developing ALLO-329, which targets CD19 on B cells and CD70 on activated T cells. ALLO-329 generated positive preclinical data in April, with a data update from the Phase I RESOLUTION trial (NCT07085104) expected later in Q4.

Another challenge to CB-011 and other allogenic therapies for RRMM: The multiple myeloma space has been reshaped by autologous BCMA CAR-T therapies that have won approval by demonstrating safety and effectiveness—including Carvykti^® (ciltacabtagene autoleucel), co-marketed by Legend Biotech (Nasdaq: LEGN) and Johnson & Johnson (NYSE: JNJ); and Abecma^® (idecabtagene vicleucel), marketed by Bristol Myers Squibb (NYSE: BMY).

Souring on the stock

Graybosch downgraded Caribou’s rating from “Outperform” to “Market Perform” and chopped the firm’s 12-month price target 75%, from $4 to $1. Graybosch was among several Wall Street analysts who responded to Caribou’s news by souring on the company’s stock, downgrading their ratings:

• Brookline Capital Markets (Leah Ruch Cann)—From “Buy” to “Hold,” no price target.
• H.C. Wainwright (Robert Burns)—From “Buy” to “Neutral,” no price target.
• RBC Capital Markets (Luca Issi, PhD)—From “Outperform” to “Sector Perform,” price target slashed 90% from $10 to $1.

Caribou reported $113.8 million in cash, cash equivalents, and marketable securities as of the end of the second quarter on June 30—a 4% dip from the $118.6 million reported at the end of Q1, but a 20% drop from the $142.8 million Caribou had as of December 31, 2025, and a 38% slide from the $183.9 million reported June 30, 2025.

“We expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operations for at least the next 12 months from the date this Form 10-Q is filed with the SEC [U.S. Securities and Exchange Commission],” Caribou stated in its most recent Form 10-Q quarterly report detailing second-quarter results, filed August 13.

Leaders and laggards

• Arrivent BioPharma (Nasdaq: AVBP) shares plummeted 47% October 6 from $28.46 to $15.09 after the cancer drug developer announced that its lead pipeline candidate firmonertinib failed the Phase III FURVENT trial (NCT05607550) designed to assess the oral, mutation-selective epidermal growth factor receptor (EGFR) inhibitor in previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. Firmonertinib did not meet its primary endpoint of meaningful progression free survival (PFS) compared to chemotherapy as evaluated by blinded independent central review (BICR). Arrivent said that clinical benefit was seen in secondary endpoints such as PFS by investigator’s assessment and confirmed objective response rate by BICR. A trend toward improved overall survival was also seen, the company added.
• Pacira BioSciences (Nasdaq: PCRX) shares soared 44% Thursday from $25.20 to $36.39 after Viatris (Nasdaq: VTRS) agreed to acquire the non-opioid pain drug developer for $1.65 billion. The deal adds to Pacira’s portfolio with two marketed drugs—the postsurgical pain relief therapy Exparel® (bupivacaine liposome injectable suspension), and the osteoarthritis knee pain treatment Zilretta® (triamcinolone acetonide extended-release injectable suspension). Viatris said it plans to apply its intellectual property expertise and ability to extend product lifecycles and sustain meaningful sales post-competition “to maximize the long-term value of the Pacira portfolio” and expects to expand its reach across select markets. Pacira generated approximately $746 million in revenue and approximately $177 million in adjusted earnings before interest, taxes, depreciation, and amortization (EBITDA) during the 12 months ending June 30. Viatris plans to commence a tender offer for all outstanding Pacira common stock shares for $36.50 per share cash. The deal is set to close by year’s end.

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