On August 8, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the second quarter of 2023 and reviewed recent business updates (Press release, Caribou Biosciences, AUG 8, 2023, View Source [SID1234633959]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2023, we have advanced our programs to build value across the pipeline and position Caribou for continued momentum ahead," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "For our lead program, we are excited by the positive CB-010 dose escalation data demonstrating response rates that rival those from the approved autologous CAR-T cell therapies. As we develop CB-010 for the larger second-line LCBL patient population, we continue to enroll patients in dose expansion and anticipate reporting initial dose expansion data in the first half of 2024. We also look forward to meeting with the FDA later this year to discuss a potential pivotal clinical trial in second-line LBCL patients. Additionally, we continue to enroll patients in our CaMMouflage trial for CB-011 and plan for an IND submission for CB-012 in the second half of this year."

Accomplishments and highlights

Pipeline and technology
•CB-010: Caribou reported [View Source long-term follow-up data from all 16 patients treated in dose escalation of the ongoing ANTLER Phase 1 clinical trial of CB-010, an allogeneic anti-CD19 CAR-T cell therapy. In ANTLER dose escalation, three dose levels of CB-010 were evaluated (40×106, 80×106, and 120×106 CAR-T cells) in patients with multiple subtypes of aggressive relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). As of the June 20, 2023 data cutoff date, results demonstrated:
◦CB-010 was generally well tolerated with adverse events consistent with autologous and allogeneic anti-CD19 CAR-T cell therapies.
◦94% overall response rate (ORR; 15 of 16 patients) was observed following a single dose of CB-010.
◦69% of patients (11 of 16) achieved a complete response (CR).

◦44% of patients (7 of 16) had a CR at ≥6 months; 24 months is the longest CR maintained to date.
◦For the subset of patients with large B cell lymphoma (LBCL) (N=10):
▪A 90% ORR (9 of 10) was observed.
▪70% (7 of 10) achieved a CR.
▪50% (5 of 10) had a CR at ≥6 months; 18 months is the longest CR maintained to date.
◦Based on these positive data, Caribou is enrolling second-line patients with LBCL in the ongoing dose expansion portion of the ANTLER clinical trial. In expansion, the mid dose and the high dose from escalation (80×106 and 120×106 CAR-T cells) are being evaluated in approximately 30 second-line patients (approximately 15 patients per dose level) to determine the recommended Phase 2 dose (RP2D). Once the RP2D is determined, Caribou may enroll additional patients in ANTLER.
•CB-011: Caribou is enrolling patients at dose level 1 (50×106 CAR-T cells) in the dose escalation portion of the ongoing CaMMouflage Phase 1 trial of CB-011, an allogeneic anti-BCMA CAR-T cell therapy, for relapsed or refractory multiple myeloma (r/r MM).
•CB-012: Caribou is advancing IND-enabling activities for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, for relapsed or refractory acute myeloid leukemia (r/r AML).

Anticipated milestones
•CB-010: Caribou plans to meet with the FDA to discuss a potential pivotal clinical trial in second-line LBCL patients and plans to share FDA feedback by YE 2023. The Company also plans to report initial dose expansion data in second-line LBCL patients from the ongoing ANTLER trial in H1 2024.
•CB-011: Caribou plans to provide updates on dose escalation as the CaMMouflage Phase 1 clinical trial in r/r MM advances.
•CB-012: Caribou plans to submit an IND application for r/r AML in H2 2023.

Corporate updates
•$25.0 million Pfizer investment: On June 30, 2023, Pfizer invested [View Source $25.0 million in Caribou common shares. In conjunction with the investment, Sriram Krishnaswami, PhD, joined Caribou’s scientific advisory board [View Source Caribou will use the proceeds from this investment to advance CB-011. Caribou maintains full ownership and control of CB-011 and its other allogeneic CAR-T and CAR-NK cell therapies.
•Completed successful $134.6 million follow-on financing: In the third quarter of 2023, Caribou completed an underwritten public offering of 22,115,384 shares of its common stock, which included the full exercise of the underwriters’ option to purchase additional shares. The approximate net proceeds to Caribou were $134.6 million.

Second quarter 2023 financial results

Cash, cash equivalents, and marketable securities: Caribou had $292.5 million in cash, cash equivalents, and marketable securities as of June 30, 2023, which included the $25.0 million proceeds from the Pfizer investment, compared to $317.0 million as of December 31, 2022. This amount does not include the approximately $134.6 million in net proceeds from the Company’s underwritten public offering completed in the third quarter of 2023. Caribou expects its cash, cash equivalents, marketable securities, and net proceeds from the recent public offering will be sufficient to fund its current operating plan into Q4 2025.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $3.8 million for the three months ended June 30, 2023, compared to $4.2 million for the same period 2022. The decrease was primarily due to a reduction in revenue recognized under the AbbVie Collaboration and License Agreement, partially offset by a revenue increase related to a veterinary therapeutics licensing agreement.
R&D expenses: Research and development expenses were $26.5 million for the three months ended June 30, 2023, compared to $22.6 million for the same period in 2022. The increase was primarily due to personnel-related expenses, including stock-based compensation; costs to advance pipeline programs, including the ANTLER and CaMMouflage Phase 1 trials; and facilities and other allocated expenses.

G&A expenses: General and administrative expenses were $10.1 million for the three months ended June 30, 2023, compared to $10.0 million for the same period in 2022. The increase was primarily due to facilities and other allocated expenses; patent prosecution and maintenance costs; and personnel-related expenses, including stock-based compensation, due to headcount increases. The increase was partially offset by lower insurance and legal expenses.
Net loss: Caribou reported a net loss of $29.5 million for the three months ended June 30, 2023, compared to $26.7 million for the same period in 2022.

About CB-010
CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). In the ongoing ANTLER Phase 1 trial, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprising four different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, and tFL). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. To Caribou’s knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion. To Caribou’s knowledge, CB-010 is also the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the second-line LBCL setting and it has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations by the FDA. Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

About CB-011
CB-011 is the second product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA technology. To Caribou’s knowledge, CB-011 is the first allogeneic CAR-T cell therapy in the clinic that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track designation by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

About CB-012
CB-012 is the third product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in investigational new drug (IND)-enabling studies. To Caribou’s knowledge, CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with five genome edits, enabled by Caribou’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.