— CB-010 allogeneic CAR-T cell remedy with partial HLA matching has potential to rival efficacy and security profile of authorised autologous CAR-T cell therapies —
— 14.4 months median PFS in ANTLER sufferers with partial HLA matching ( ‰¥4 alleles) —
— Plan to enroll ~20 further 2L LBCL sufferers in ANTLER to verify that partial HLA matching improves affected person outcomes; preliminary information anticipated in H1 2025 —
— Caribou expects to provoke a pivotal trial for CB-010 in H2 2025, upon affirmation of improved outcomes in partially HLA matched cohort —
— Off-the-shelf CB-010 is partially HLA matched to affected person inside present screening timelines —
— KOL webcast dialogue of knowledge from 46 ANTLER sufferers scheduled for at present at 7:00 pm CDT —
BERKELEY, Calif., June 02, 2024 (GLOBE NEWSWIRE) — Caribou Biosciences, Inc. (Nasdaq: CRBU), a number one clinical-stage CRISPR genome-editing biopharmaceutical firm, at present offered up to date scientific information from the continuing ANTLER Part 1 trial that signifies a single dose of CB-010, a available, off-the-shelf anti-CD19 CAR-T cell remedy with a PD-1 knockout, has the potential to rival the protection, efficacy, and sturdiness of authorised autologous CAR-T cell therapies. The scientific outcomes are being offered throughout a poster presentation on the 2024 American Society of Scientific Oncology (ASCO) Annual Assembly.
The Part 1 information from the ANTLER trial continues to be encouraging when it comes to each security and efficacy of an allogeneic CAR-T cell remedy, stated Boyu Hu, MD, director of lymphoma and CLL within the division of hematology and hematologic malignancies on the College of Utah and an investigator on the ANTLER trial. The partial human leukocyte antigen, or HLA, matching technique is extremely intriguing and additional analysis is supported by the ASCO information presentation. As many sufferers in ANTLER had been enrolled attributable to fast illness development that prohibited ready for an autologous CAR-T cell remedy, I sit up for enrolling sufferers who will obtain partially HLA matched CB-010 on this ongoing trial.
In ANTLER, three dose ranges of CB-010 had been evaluated (40×106, 80×106, and 120×106 CAR-T cells) in a complete of 46 sufferers. In dose escalation, 16 sufferers with a number of subtypes of aggressive relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) had been enrolled, and in dose growth, 30 sufferers with second-line giant B cell lymphoma (2L LBCL) had been enrolled. As of an April 1, 2024 information cutoff date, outcomes demonstrated:
- CB-010 was typically nicely tolerated. No Grade 3 or increased cytokine launch syndrome (CRS) and no graft-versus-host illness (GvHD) was noticed.
- A retrospective evaluation of all affected person information demonstrated that sufferers who acquired a dose of CB-010 manufactured from a donor with ‰¥4 matching HLA alleles (known as partial HLA matching) confirmed improved development free survival (PFS). Outcomes from sufferers who acquired partially HLA matched CB-010 embrace:
- Median PFS of 14.4 months (95% CI: 1.74, not estimable [NE]) was noticed in sufferers handled with CB-010 with ‰¥4 HLA matches (N=13), in comparison with 2.8 months (95% CI: 2.10, 3.48) for sufferers handled with CB-010 with ‰¤3 HLA matches (N=33).
- In sufferers with LBCL who acquired CB-010 with ‰¥4 HLA matches (N=11, together with N=10 2L LBCL and N=1 3L LBCL), median PFS has not been reached (95% CI: 1.58, NE).
- Translational information on CB-010:
- Pharmacokinetic (PK) information confirmed that increased numbers of matched HLA alleles between the CB-010 donor and recipient affected person correlated with elevated CAR-T cell growth and persistence in comparison with decrease numbers of matched HLA alleles.
- Pharmacodynamic (PD) information confirmed {that a} single dose of CB-010 resulted in prolonged B cell aplasia (~114 days) and a fast restoration of the affected person’s endogenous T and NK cells (~3 weeks).
- Primarily based on the general security, efficacy, and translational information analyzed, 80×106 CAR-T cells was chosen because the advisable Part 2 dose (RP2D) for CB-010.
We’re excited to see that sufferers who obtain partially HLA matched CB-010 have improved efficacy and sturdiness outcomes which are on par with authorised autologous CAR-T cell therapies, stated Rachel Haurwitz, PhD, Caribou’s president and chief govt officer. We subsequent plan to prospectively consider this compelling commentary by enrolling roughly 20 further 2L LBCL sufferers, in both the inpatient or outpatient remedy setting, and we are going to be sure that they obtain {a partially} matched ( ‰¥4 HLA matches) dose of CB-010. We’re additionally excited to open the ANTLER examine for the primary time to sufferers who’ve relapsed following any prior CD19-targeted remedy in a proof-of-concept cohort for as much as 10 sufferers. We count on to report preliminary information from each the 2L LBCL and CD19 relapsed cohorts within the first half of 2025 and, upon affirmation of improved outcomes in further sufferers receiving {a partially} HLA matched dose of CB-010, we plan to provoke a pivotal Part 3 scientific trial in 2L LBCL sufferers, together with sufferers no matter HLA sort, within the second half of 2025.
ANTLER Part 1 trial of CB-010 “ median PFS analysesA photograph accompanying this announcement is offered at: https://www.globenewswire.com/NewsRoom/AttachmentNg/893722aa-a457-4e0f-a27e-457bf8b2c0d3
CI: confidence interval; HLA: human leukocyte antigen; NE: not estimable; partial HLA matching: affected person has ‰¥4 HLA alleles that match donor T cells used for CB-010 manufacturing Retrospective evaluation of HLA allele matching for sophistication I and sophistication II antigensANTLER Part 1 scientific trial as of April 1, 2024 cutoff date, information assortment ongoing
ANTLER Part 1 trial of CB-010 “ response information
Endpoints (N, %) | All sufferers ‰¤3 HLA matches(N=33) | All sufferers ‰¥4 HLA matches(N=13) | LBCL ‰¥4 HLA matches(N=11) |
General response fee (ORR) | 23 (69%) | 12 (92%) | 10 (91%) |
Period of response (DoR), median months (vary) | 2.0 (1-23+) | 13.5 (1-23+) | NR (1-15+) |
Full response (CR) fee | 15 (45%) | 6 (46%) | 4 (36%) |
Period of CR, median months (vary) | 5.0 (1-23+) | NR (5-23+) | NR (5-15+) |
6-month PFS | 25% | 62% | 53% |
PFS, median months (vary) | 2.8 (1-24+) | 14.4 (2-24+) | NR (2-16+) |
HLA: human leukocyte antigen; NR: not reached; PFS: development free survival ANTLER Part 1 scientific trial as of April 1, 2024 cutoff date, information assortment ongoing
ANTLER Part 1 trial of CB-010 “ security information
All handled (N=46) | ||
Any grade(n, %) | Grade ‰¥3(n, %) | |
Extended cytopenias | 9 (20)1 | 9 (20)1 |
CRS | 26 (57)2 | 0 (0) |
Infections | 22 (47)3 | 10 (22)3 |
ICANS | 10 (22)4 | 3 (7)5 |
Hemophagocytic lymphohistiocytosis (HLH) | 1 (2) | 0 |
GvHD | 0 | 0 |
CRS: cytokine launch syndrome; GvHD: graft-versus-host illness; ICANS: immune effector cell-associated neurotoxicity syndrome There have been 5 affected person deaths attributable to adversarial occasions following CB-010 infusion; 4 had been unrelated to CB-010 remedy and 1 loss of life presumably associated to CB-010 per investigator attributable to problems of a bladder perforation within the context of BK virus hemorrhagic cystitis1 Extended cytopenias are outlined as grade 3 or increased occasions lasting past 30 days following CB-010 infusion; 37/46 (80%) of sufferers recovered from cytopenias to grade ‰¤2 by day 35 put up CB-010 treatment2 Median time of onset was 3 days (vary 0-22), and median length was 3 days (vary 1-19) 3 An infection occasions reported had been on or after CB-010 infusion, with highest grade reported per affected person; median onset 8 days (vary 0-279) and median length is 14 days (vary 1-239)4 Median time of onset was 7.5 days (vary 6-34), and median length was 2 days (vary 1-27)5 2 Grade 3 and 1 Grade 4; all resolved with supportive care. Median time of onset was 8 days and median length was 2 days ANTLER Part 1 scientific trial as of April 1, 2024 cutoff date, information assortment ongoing
Primarily based on these encouraging information, Caribou plans to enroll roughly 20 further 2L LBCL sufferers in ANTLER to prospectively verify that partial HLA matching improves affected person outcomes. The affected person HLA allele typing happens inside the present screening timelines.
Integrating the partial HLA matching into manufacturing for CB-010 is simple, enabling Caribou to ship CB-010 as a available off-the-shelf CAR-T cell remedy that may serve a broad affected person inhabitants, stated Tim Kelly, Caribou’s chief expertise officer. In our deliberate 2L LBCL pivotal Part 3 trial, we are going to present the very best matched dose of CB-010 to every affected person primarily based on lot availability. With at the very least 13 manufacturing batches of CB-010 readily available, we count on that roughly 90% of all sufferers who may enroll in our trial would obtain a dose of CB-010 with ‰¥4 matched alleles.
Webcast convention name Sunday, June 2, at 7:00 pm CDTCaribou will host a dwell webcast on Sunday, June 2, at 7:00 pm CDT for a dialogue with KOLs and administration on the CB-010 ANTLER Part 1 information presentation. The presenters will embrace:
- Boyu Hu, MD, director of lymphoma and CLL within the division of hematology and hematologic malignancies, College of Utah
- Mehdi Hamadani, MD, professor of medication, part chief of hematologic malignancies, Medical School of Wisconsin
- Rachel Haurwitz, PhD, president and chief govt officer, Caribou Biosciences
Further contributors from Caribou Biosciences embrace:
- Steve Kanner, PhD, chief scientific officer
- Jason O’Byrne, chief monetary officer
- Kike Zudaire, PhD, senior vice chairman, translational sciences and therapeutic discovery
- Tonia Nesheiwat, PharmD, vice chairman of medical affairs and undertaking management
The listen-only webcast with an accompanying presentation can be accessible below Occasions within the Traders part of Caribou’s web site. The archived audio webcast can be obtainable on the corporate’s web site following the decision and can be obtainable for 30 days.
ASCO poster presentation on Monday, June 3, 9:00 am-12:00 pm CDTParticulars of the ANTLER poster presentation on the 2024 ASCO Annual Assembly are as follows:
A CRISPR-edited allogeneic anti-CD19 CAR-T cell remedy with a PD-1 knockout (CB-010) in sufferers with relapsed/refractory B cell non-Hodgkin lymphoma (r/r B-NHL): Up to date Part 1 outcomes from the ANTLER trialPresenter: Boyu Hu, MD, assistant professor, director of lymphoma and CLL, division of hematology and hematologic malignancies, Huntsman (NYSE:) Most cancers Institute on the College of UtahDate and time: Monday, June 3, 2024, 9:00 am-12:00 pm CDTSession: Hematologic Malignancies “ Lymphoma and CLL Location: Corridor A, Poster Board 8, McCormick (NYSE:) Place, ChicagoSummary quantity: 7025
About CB-010CB-010 is the lead clinical-stage product candidate from Caribou’s allogeneic CAR-T cell remedy platform, and it’s being evaluated in sufferers with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) within the ongoing ANTLER Part 1 scientific trial and can be evaluated in sufferers with lupus nephritis (LN) and extrarenal lupus (ERL) within the GALLOP Part 1 scientific trial. In ANTLER, Caribou is enrolling second-line sufferers with giant B cell lymphoma (LBCL) comprised of various subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, tFL, and tMZL). To Caribou’s data, CB-010 is the primary allogeneic CAR-T cell remedy within the clinic with a PD-1 knockout, a genome-editing technique designed to enhance exercise towards ailments by limiting untimely CAR-T cell exhaustion. CB-010 can also be, to Caribou’s data, the primary anti-CD19 allogeneic CAR-T cell remedy to be evaluated within the second-line LBCL setting and, for r/r B-NHL, CB-010 has been granted Regenerative Medication Superior Remedy (RMAT), Quick Monitor, and Orphan Drug designations by the FDA. Further data on the ANTLER trial (NCT04637763) may be discovered at clinicaltrials.gov.
About Caribou’s novel next-generation CRISPR platformCRISPR genome modifying makes use of simply designed, modular organic instruments to make DNA modifications in residing cells. There are two primary parts of Class 2 CRISPR methods: the nuclease protein that cuts DNA and the RNA molecule(s) that information the nuclease to generate a site-specific, double-stranded break, resulting in an edit on the focused genomic web site. CRISPR methods are able to modifying unintended genomic websites, often called off-target modifying, which can result in dangerous results on mobile perform and phenotype. In response to this problem, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced chardonnays) that direct considerably extra exact genome modifying in comparison with all-RNA guides. Caribou is deploying the ability of its chRDNA expertise to hold out excessive effectivity a number of edits, to develop CRISPR-edited therapies.
About Caribou Biosciences, Inc.Caribou Biosciences is a clinical-stage CRISPR genome-editing biopharmaceutical firm devoted to growing transformative therapies for sufferers with devastating ailments. The corporate’s genome-editing platform, together with its Cas12a chRDNA expertise, permits superior precision to develop cell therapies which are armored to probably enhance antitumor exercise. Caribou is advancing a pipeline of clinical-stage off-the-shelf cell therapies from its CAR-T cell platform as available therapies for sufferers with hematologic malignancies and autoimmune ailments. Observe us @CaribouBio and go to www.cariboubio.com.
Ahead-looking statements This press launch comprises forward-looking statements inside the which means of the Non-public Securities Litigation Reform Act of 1995. In some circumstances, you possibly can establish forward-looking statements by phrases resembling could, will, ought to, count on, plan, anticipate, may, intend, goal, undertaking, ponder, consider, estimate, predict, potential, or proceed, or the damaging of those phrases or different related expressions, though not all forward-looking statements comprise these phrases. These forward-looking statements embrace, with out limitation, statements associated to Caribou’s technique, plans, and goals, and expectations relating to the timing of standing and updates from its ANTLER Part 1 scientific trial for CB-010, together with expectations relating to the enrollment of 20 further 2L LBCL sufferers to additional examine partial HLA matching outcomes, the timing of reporting of preliminary information from each 2L LBCL and CD 19 relapsed cohorts, the timing of reporting further dose growth information from the ANTLER trial, and the timing of initiation of a pivotal Part 3 scientific trial for CB-010 in 2L LBCL sufferers, together with the situations to fulfill that timeline. Administration believes that these forward-looking statements are affordable as and when made. Nonetheless, such forward-looking statements are topic to dangers and uncertainties, and precise outcomes could differ materially from any future outcomes expressed or implied by the forward-looking statements. Dangers and uncertainties embrace, with out limitation, dangers inherent within the growth of cell remedy merchandise; uncertainties associated to the initiation, price, timing, progress, and outcomes of Caribou’s analysis and growth packages, preclinical research, and scientific trials; and the chance that preliminary, preliminary, or interim scientific trial information won’t finally be predictive of the protection and efficacy of Caribou’s product candidates or that scientific outcomes could differ as affected person enrollment continues and as extra affected person information turns into obtainable and is totally evaluated; the power to acquire key regulatory enter and approvals in addition to different threat elements described once in a while in Caribou’s filings with the Securities and Alternate Fee, together with its Annual Report on Kind 10-Ok for the yr ended December 31, 2023 and subsequent filings. In gentle of the numerous uncertainties in these forward-looking statements, you shouldn’t rely on forward-looking statements as predictions of future occasions. Besides as required by regulation, Caribou undertakes no obligation to replace publicly any forward-looking statements for any purpose.
Warning ought to be exercised when deciphering outcomes from separate trials involving different CAR-T cell therapies. The outcomes of different CAR-T cell therapies offered or referenced on this press launch have been derived from publicly obtainable stories of scientific trials not performed by Caribou, and Caribou has not carried out any head-to-head trials evaluating any of those different CAR-T cell therapies with CB-010. As such, the outcomes of those different scientific trials might not be corresponding to scientific outcomes for CB-010. The design of those different scientific trials varies in materials methods from the design of the ANTLER scientific trial for CB-010, together with with respect to affected person populations, follow-up occasions, scientific trial phases, and topic traits. In consequence, cross-trial comparisons could haven’t any interpretive worth on Caribou’s present or future scientific outcomes. For additional data and to grasp these materials variations, you need to learn the stories for the opposite CAR-T cell remedy scientific trials and the sources included within the webcast slide presentation.
Caribou Biosciences, Inc. contacts:Traders:Amy Figueroa, [email protected]
Media:Peggy Vorwald, [email protected]
ANTLER Part 1 trial of CB-010 “ median PFS analyses
ANTLER Part 1 trial of CB-010 “ median PFS analyses
Supply: Caribou Biosciences, Inc.