Slide 1: CB-010 ANTLER Phase 1 trial update and KOL discussion
June 2, 2024 CB-010 ANTLER Phase 1 trial update and KOL discussion Transformative genome-edited therapies for patients
Slide 2: Forward-looking statements
Forward-looking statements All statements in this presentation, other than statements of historical facts, are forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements speak only as of the date of this presentation and a
Slide 3: The future of CAR-T cell therapies is off-the-shelf
The future of CAR-T cell therapies is off-the-shelf CB-010 ANTLER Phase 1 trial Rachel Haurwitz, PhD President & CEO Caribou Biosciences, Inc.
Slide 4: Today's guests
Today’s guests Boyu Hu, MD Mehdi Hamadani, MD Assistant professor, director of Professor of medicine and section chief of lymphoma and CLL in the division of hematologic malignancies hematology and hematologic malignancies Medical College of Wisconsin Huntsman Cancer Institute University of Utah KOL
Slide 5: Patients shouldn't have to wait for treatment
Patients shouldn’t have to wait for treatment Allogeneic therapy Screening Product The future of shipment N=many per batch cell therapy is Days Lymphodepletion off-the-shelf Sample Manufacturing, product shipment failure identification Autologous therapy Screening Queuing, leukapheresis Leukapheresi
Slide 6: Allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout for r/r B-NHL
CB-010 Allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout for r/r B cell non-Hodgkin lymphoma (B-NHL) KOL discussion CB-010 ANTLER Phase 1 data | June 2024 6 ©2024 Caribou Biosciences, Inc.
Slide 7: CB-010 has a PD-1 KO designed to reduce CAR-T cell exhaustion
CB-010 has a PD-1 KO designed to reduce CAR-T cell exhaustion CB-010 Armored with 3 genome edits 1 TRAC gene knockout (KO) PD-1 KO • Eliminates TCR expression, reduces GvHD risk Anti-CD19 3 TCR KO CAR Anti-CD19 CAR site-specific insertion into TRAC locus 2 2 PD-L1 1 • Eliminates random integration,
Slide 8: CB-010 ANTLER Phase 1 trial in 2L LBCL
CB-010 ANTLER Phase 1 trial in 2L LBCL Part A: 3+3 dose escalation – completed (N=16) Part B: dose expansion – enrolling • Eligibility: aggressive r/r B-NHL1 with ≥2 prior lines of • Eligibility: 2nd line LBCL2 chemoimmunotherapy or primary refractory • Exclusion: prior CD19-targeted therapy • Exclu
Slide 9: CB-010's foundational data: durable responses in dose escalation
CB-010’s foundational data: durable responses in dose escalation 4 of 4 DLBCL patients remain in CR since last data cutoff June 20, 2023 ≥4 Subtype Dose PLoT Pt # HLA FL1 40M 8 1 ✓ * DLBCL 40M 4 4 * DLBCL 80M 1 7 * DLBCL PMBCL2 80M 40M 1 2 8 5 * CR: complete response MCL 40M 2 13 ✓ PR: partial respo
Slide 10: CB-010 with partial HLA matching shows safety, efficacy, and durability can potentially rival autologous
CB-010 with partial HLA matching shows safety, efficacy, and durability can potentially rival autologous CAR-T cell therapies 1 dose per patient, 2L LBCL at RP2D 3 dose levels evaluated, RP2D selected 80x106 CAR-T cells CR rate: 50% all generally well tolerated Median duration of CR: NR Median PFS A
Slide 11: Improved PFS for all patients treated with CB-010 from a donor with partial HLA matching
Improved PFS for all patients treated with CB-010 from a donor with partial (≥4) HLA matching PFS by level of HLA matching PFS by level of HLA matching All patients LBCL patients N=46*, median PFS (95% CI) N=40*, median PFS (95% CI) 100 100 ≥4 matches ≥4 matches 2-3 matches 2-3 matches Survival prob
Slide 12: Preliminary PFS with partial HLA matching on par with approved autologous CAR-T
Preliminary PFS with partial HLA matching has potential to be on par with an approved autologous CAR-T cell therapy ANTLER LBCL patients with partial HLA matching and Yescarta ZUMA-7 trial 100 ANTLER 1st assessment at 28 days after CB-010 infusion ZUMA-7 1st assessment at 50 days after randomization
Slide 13: ANTLER Phase 1 trial initial dose expansion data
ANTLER Phase 1 trial initial dose expansion data Boyu Hu, MD Director of Lymphoma and CLL Division of Hematology and Hematologic Malignancies Huntsman Cancer Institute
Slide 14: Disclosures
Disclosures Consulting: Novartis, Bristol Meyers Squibb, Eli Lilly, GenMab, ADC Therapeutics, ImmPACT Bio, Seattle Genetics, Regeneron, Caribou Biosciences, Abbvie Research Funding: Genentech, Celgene, CRISPR Therapeutics, Morphosys AG, Caribou Biosciences, Repare Therapeutics, Artiva Biotherapeutic
Slide 15: Patients in ANTLER all had aggressive r/r B-NHL
Patients in ANTLER all had aggressive r/r B-NHL All treated Dose escalation Dose expansion Patient and disease characteristics (N=46) (N=16) (N=30) Age, years, median (range) 65.0 (21-82) 66.0 (55-82) 63.0 (21-78) Men, n (%) 36 (78.3) 14 (87.5) 22 (73.3) ECOG performance status, n (%) 0 21 (45.7) 6
Slide 16: Rapid timeline to treatment key to patients choosing CB-010 over approved autologous CAR-T
Rapid timeline to treatment key to patients choosing CB-010 over approved autologous CAR-T cell therapies 2 days Lymphodepletion Rest (median, range 0-12) from confirmation of (7 days) (2 days) eligibility to LD CB-010 Reasons that investigators cited for enrolling patients in ANTLER1 Rapid disease
Slide 17: CB-010 is generally well tolerated
CB-010 is generally well tolerated Treatment-emergent adverse events (TEAE1) in ≥20% of all patients LBCL 2L LBCL RP2D All treated subgroup subgroup System organ class, n (%) (N = 46) (N=40) (N=20) Preferred term, n (%) Related Related Related Any grade Grade ≥3 Any grade Grade ≥3 Any grade Grade ≥3
Slide 18: CB-010 has generally well-tolerated safety profile
CB-010 has generally well-tolerated safety profile No Grade ≥3 CRS, no GvHD observed (N=46) All CB-010 treated Yescarta (N=46) (N=170) Any grade Grade ≥3 Any grade Grade ≥3 (n, %) (n, %) (n, %) (n, %) Prolonged cytopenias 9 (20)1 9 (20)1 49 (29)2 49 (29)2 CRS 26 (57)3 0 (0) 157 (92) 11 (6) Infection
Slide 19: ANTLER efficacy assessment all patients
CB-010 ANTLER efficacy assessment all patients Subtype PLoT ≥4 HLA FL 8 ✓ DLBCL 4 MCL 2 ✓ PMBCL 2 40M dose FL 2 MCL 4 DLBCL 1 ✓ DLBCL 1 ✓ DLBCL 2 tFL 1 HGBL 1 DLBCL HGBL 1 1 * DLBCL 1 DLBCL 1 DLBCL 1 DLBCL 2 ✓ DLBCL 1 ✓ MZL 4 DLBCL 1 HGBL 1 HGBL 1 ✓ 80M RP2D DLBCL 1 tFL HGBL 1 1 * HGBL 1 DLBCL 1 ✓ D
Slide 20: ANTLER efficacy assessment by all patients and LBCL subgroups
CB-010 ANTLER efficacy assessment by all patients and LBCL subgroups 2L LBCL Endpoints All patients LBCL 80M (N, %) (N=46) (N=40) (N=20) Overall response rate (ORR)1 35 (76%) 29 (73%) 15 (75%) DoR, median months (range) 5 (1-23+) 2 (1-23+) 5 (1-20+) Complete response (CR) rate1 21 (46%) 17 (43%) 10
Slide 21: ANTLER efficacy assessment with and without partial HLA matching
CB-010 ANTLER efficacy assessment with and without partial HLA matching All patients All patients LBCL Endpoints ≤3 HLA matches ≥4 HLA matches ≥4 HLA matches (N, %) (N=33) (N=13) (N=11) Overall response rate (ORR) 23 (69%) 12 (92%) 10 (91%) Duration of response (DoR), median months (range) 2.0 (1-23
Slide 22: Improved PFS for all patients treated with CB-010 from a donor with partial HLA matching
Improved PFS for all patients treated with CB-010 from a donor with partial HLA matching PFS by level of HLA matching PFS by level of HLA matching All patients LBCL patients N=46*, median PFS (95% CI) N=40*, median PFS (95% CI) 100 100 ≥4 matches ≥4 matches 2-3 matches 2-3 matches Survival probabili
Slide 23: CB-010 translational research data
CB-010 translational research data Kike Zudaire, PhD SVP of translational sciences and therapeutic discovery Caribou Biosciences
Slide 24: Partial HLA matching improves exposure of CB-010
Partial HLA matching improves exposure of CB-010 Pharmacokinetic (PK) exposure Partial HLA matching impact on PK ANTLER PK ddPCR 4 44 Log10(copies/µg gDNA +1) Log10(copies/µg gDNA +1) ≥4 matches 2-3 matches log10(copies/μg gDNA +1) 33 <2 matches 3 HLA Match <2 2 22 2-3 ≥4 1 11 0 00 0 10 20 30 0 10 D
Slide 25: Single dose of CB-010 results in extended B cell aplasia and rapid recovery of immune cells
Single dose of CB-010 results in extended B cell aplasia and rapid recovery of immune cells B cell, T cell, and NK cell depletion and recovery All treated, N=44 3 T cells • CB-010 specifically targets B Log10 of absolute cell counts cells, resulting in extended B cell NK cells 2 aplasia for ~114 day
Slide 26: CB-010 duration of B cell aplasia is similar to lupus case studies
CB-010 duration of B cell aplasia is similar to lupus case studies Duration of B cell aplasia Days CB-010 114 N=44 Mean (IQR 42-150) Müller et al 112 N=141 Mean (IQR 72-153) FOR ILLUSTRATIVE PURPOSES ONLY: The results of other CAR-T cell therapies presented on this slide have been derived from publi
Slide 27: Partial HLA matching does not impact time to treatment
Partial HLA matching does not impact time to treatment Partial HLA matching and DSA screening for How does HLA matching work? ANTLER and GALLOP Phase 1 trials Self cell Partially matched SINGLE Self cell HLA typing DOSE T cell DSA analysis CB-010 dose shipped CB-010 Self cell Screening Lymphodepleti
Slide 28: CB-010 is an off-the shelf CAR-T cell therapy that is easily matched to 2L LBCL patients
CB-010 is an off-the shelf CAR-T cell therapy that is easily matched to 2L LBCL patients ~13 different ~90% of 2L LBCL patients for planned Phase 3 batches clinical trial1 are expected to receive ≥4 HLA matched product Only a small number of manufacturing batches are needed to provide partially HLA
Slide 29: Advancing CB-010 development
Advancing CB-010 development Tonia Nesheiwat, PharmD VP of medical affairs and project leadership Caribou Biosciences
Slide 30: Broadening patient access through outpatient administration and expanding into an additional population
Broadening patient access through outpatient administration and expanding into an additional population of unmet need New protocol amendment enables Proof-of-concept cohort to evaluate CB-010 outpatient administration for patients who have relapsed following Sites have the option to provide outpatie
Slide 31: Advancing CB-010 for 2L LBCL patients
Advancing CB-010 for 2L LBCL patients Phase 1 trial dose expansion Phase 1 trial Phase 1 trial 2L LBCL2 dose escalation N=30 partial (≥4) HLA matching r/r B-NHL1 RP2D (80M) 2L LBCL2 N=~20 at RP2D Pivotal Phase 3 trial N=16 selected Generally well and CB-010 Improved CD19 relapsed LBCL tolerated 2L L
Slide 32: Fireside chat
Fireside chat CARIBOU Pm BIOSCIENCES’
Slide 33: Fireside chat with leaders in hematologic malignancies
Fireside chat with leaders in hematologic malignancies Rachel Haurwitz, PhD Boyu Hu, MD Mehdi Hamadani, MD President and CEO Assistant professor, director of Professor of medicine and section Caribou Biosciences lymphoma and CLL in the division of chief of hematologic malignancies hematology and hem
Slide 34: Q&A
Q&A CARIBOU Pm BIOSCIENCES’
Slide 35: Open to your questions
Open to your questions Rachel Haurwitz, PhD President and CEO Steve Kanner, PhD Jason O’Byrne CSO CFO Kike Zudaire, PhD Tonia Nesheiwat, PharmD Boyu Hu, MD Mehdi Hamadani, MD SVP, translational sciences VP, medical affairs and and therapeutic discovery project leadership Assistant professor, directo
Slide 36: Advancing CB-010 to establish new standard of care for 2L LBCL and broaden patient access
Advancing CB-010 to establish new standard of care for 2L LBCL and broaden patient access Progression free • With partial HLA matching, safety, efficacy, durability has the survival potential to rival approved autologous CAR-T cell therapies1 • Generally well-tolerated safety profile 14.4 months med
Slide 37: Potential to address high unmet medical need in 2L LBCL
Potential to address high unmet medical need in 2L LBCL LBCL patient treatment journey (U.S. incidence 2022) Diagnosed ~32.4K patients 1L ~30.8K patients ~13 ANTLER Future: manufacturing batches dose 2L ~10.0K patients planned pivotal allow for partial (≥4) HLA expansion Phase 3 trial matching for ~
Slide 38: Upcoming clinical catalysts
Expected Program Clinical milestone timing Present initial data on partial HLA matching (~20 patients, Upcoming CB-010 some outpatient), CD19 relapsed (~10 patients) from the ANTLER Phase 1 clinical trial H1 2025 clinical 2L LBCL H2 2025 Initiate pivotal Phase 3 trial catalysts CB-011 Present initia
Slide 39: With gratitude for patients, caregivers, investigators contributing to CB-010's clinical development
With gratitude for patients, caregivers, investigators contributing to CB-010’s clinical development Alabama University of Alabama Birmingham (Mehta) ANTLER Phase 1 trial: 29 active sites in US, Australia, and Israel Arizona HonorHealth Cancer Institute (Kanate) University of Arizona (Husnain) Banne
Slide 40: Thank you
Thank you https://cariboubio.com info@cariboubio.com
Slide 41: Appendix
Appendix CARIBOU Pm BIOSCIENCES’
Slide 42: ANTLER efficacy assessment in 2L LBCL at RP2D
CB-010 ANTLER efficacy assessment in 2L LBCL at RP2D Overall depth and duration of response in 2L LBCL at 80x106 CAR-T cells (N=20) ≥4 HLA Subtype PLoT matches DLBCL 1 DLBCL 1 DLBCL 1 ✓ DLBCL 1 HGBL 1 HGBL 1 ✓ DLBCL 1 tFL 1 HGBL 1 HGBL 1 DLBCL 1 ✓ DLBCL 1 CR: complete response DLBCL 1 ✓ DLBCL 1 PR:
Slide 43: ANTLER efficacy assessment for patients with ≥4 HLA matching
CB-010 ANTLER efficacy assessment for patients with ≥4 HLA matching (N=13) Subtype PLoT Dose FL 8 40 DLBCL 2 80 MCL 2 40 tFL 1 120 DLBCL 1 120 CR: complete response DLBCL 1 80 HGBL 1 80 PR: partial response DLBCL 1 40 SD: no response/stable DLBCL 1 40 disease DLBCL 1 80 PD: progressive disease DLBCL
Slide 44: ANTLER efficacy assessment all patients
CB-010 ANTLER efficacy assessment all patients Subtype? PLoT ≥4 HLA FL 8 ✓ DLBCL 4 DLBCL 1 DLBCL 1 DLBCL 2 ✓ MCL 2 ✓ tFL 1 ✓ DLBCL 1 ✓ DLBCL 1 ✓ PMBCL 2 MZL 4 DLBCL 1 HGBL 1 FL 2 MCL 4 HGBL 1 ✓ DLBCL 1 ✓ DLBCL 1 tFL HGBL 1 1 * DLBCL 2 DLBCL 2 DLBCL 1 tFL 1 DLBCL 1 ✓ HGBL 1 DLBCL 1 ✓ DLBCL 1 ✓ DLBCL
Slide 45: ANTLER efficacy assessment by dose level
CB-010 ANTLER efficacy assessment by dose level 80x106 selected as RP2D r/r B-NHL CB-010 dose level Endpoints All patients 40M 80M 120M (N, %) (N=46) (N=14) (N=23) (N=9) Overall response rate (ORR) 35 (76%) 9 (64%) 18 (78%) 8 (89%) Duration of response (DoR), median months (range) 5 (1-23+) 7.9 (1-2
Slide 46: Allogeneic CAR-T cell manufacturing process overview for CB-010
Allogeneic CAR-T cell manufacturing process overview for CB-010 Caribou’s process development team created the manufacturing process and transferred it to a CMO to generate phase 1 cGMP clinical material cGMP starting Genetic modification via Gene-modified In vitro expansion of Removal of residual F
Slide 47: CB-010 demonstrated differentiated, long-term antitumor activity in preclinical studies
CB-010 demonstrated differentiated, long-term antitumor activity in preclinical studies A single dose of CB-010 resulted in profound tumor regression of metastatic CD19+ tumor xenografts and led to a significantly longer antitumor response and survival vs. conventional CD19-specific allogeneic CAR-T