On June 3, 2024 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported that results from the Company’s MOTION pivotal Phase 3 study of vimseltinib in patients with TGCT are being highlighted in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, Illinois, and have been published in The Lancet (Press release, Deciphera Pharmaceuticals, JUN 3, 2024, View Source [SID1234644003]).

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The article titled "Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a randomised phase 3 trial" is now available online and will be published in a future print issue of The Lancet.

"The results from the MOTION pivotal Phase 3 study provide compelling evidence that vimseltinib can address the unmet medical need in TGCT for an effective and well-tolerated therapy without cholestatic hepatotoxicity," said Hans Gelderblom, M.D., Ph.D., Chair of the Department of Medical Oncology at Leiden University Medical Center and senior author of the manuscript. "In addition to its robust antitumor activity and tolerability, vimseltinib also demonstrated clinically significant functional and symptomatic improvements in key quality-of-life measures, which can provide long-term, meaningful benefits to TGCT patients."

"Building upon the strong efficacy results disclosed previously at topline, we are excited to share details on the statistically significant and clinically meaningful improvements that vimseltinib offered TGCT patients across all six key secondary endpoints, along with its favorable safety profile," said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. "We remain on track to submit an NDA for vimseltinib in the second quarter of 2024, and an MAA in the third quarter of 2024, and look forward to bringing this important new therapy to TGCT patients globally."

In addition to the results from the MOTION pivotal Phase 3 study, the Company will also be presenting a trial-in-progress poster for the ongoing Phase 1/2 study of DCC-3116 in combination with ripretinib at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.

Both presentations are available on the Company’s website at www.deciphera.com/presentations-publications. Presentation details are as follows:

Abstract Number: 11500
Title: Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: Results from the phase 3 MOTION trial.
Presenter: William D. Tap, M.D., FASCO, Memorial Sloan Kettering Cancer Center
Presentation Date: Monday, June 3, 2024
Presentation Time: 3:00 – 3:12 PM CT
Key Highlights:

Study Design: The MOTION pivotal Phase 3 study is a two-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed).
In Part 1, patients (n=123) were randomized two-to-one to receive either 30 mg twice weekly of vimseltinib (n=83) or placebo (n=40) for 24 weeks. The results for Part 1 of the study are based on a data cutoff date of August 22, 2023.
The open-label Part 2 portion of MOTION, in which patients from both the vimseltinib and placebo arms receive treatment with vimseltinib, remains ongoing.
ORR: The primary endpoint of the study is ORR at Week 25 as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent radiologic review (IRR).
The study met its primary endpoint in the intent-to-treat (ITT) population demonstrating statistically significant and clinically meaningful improvement versus placebo in ORR at Week 25 based on IRR per RECIST v1.1.
In the ITT population, the ORR at Week 25 was 40% (95% CI: 29%, 51%) for the vimseltinib arm and 0% (95% CI: 0%, 9%) for the placebo arm resulting in a response difference (vimseltinib versus placebo) of 40% (95% CI: 29%, 51%) (p<0.0001).
Secondary Endpoints: In addition to meeting the primary endpoint, the study also achieved statistically significant and clinically meaningful improvements versus placebo in all six key secondary endpoints assessed at Week 25 including ORR by tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain.
ORR by TVS: The ORR at Week 25 based on IRR per TVS was 67% (95% CI: 56%, 77%) for the vimseltinib arm and 0% (95% CI: 0%, 9%) for the placebo arm (p<0.0001).
Active ROM: Treatment with vimseltinib demonstrated an improvement in mean change from baseline in active ROM at Week 25 of 18.4% versus a 3.8% improvement for placebo (p=0.0077).
Physical Function by PROMIS-PF: Treatment with vimseltinib demonstrated an improvement in mean change from baseline in PROMIS-PF at Week 25 of 4.6 versus 1.3 for placebo (p=0.0007).
Worst Stiffness Numeric Rating Scale (NRS): Patients treated with vimseltinib reported a decrease of 2.1 versus 0.3 for placebo in worst stiffness (p<0.0001).
Quality of Life by EuroQol Visual Analogue Scale (EQ-VAS): The mean change from baseline for EQ-VAS was significantly higher with 13.5 in the vimseltinib arm versus 6.1 in the placebo arm (p=0.016).
Brief Pain Inventory (BPI) Worst Pain Response Rate: The BPI worst pain response rate was 48% for patients receiving vimseltinib versus 23% for placebo (p=0.0056).
Safety and Tolerability:
Vimseltinib was well tolerated with most treatment-emergent adverse events (TEAEs) were grade 1 or 2.
There was no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair hypopigmentation.
Serum enzyme elevations were consistent with the known mechanism of action of CSF1R inhibitors.
TEAEs leading to treatment discontinuation was 6% in the vimseltinib arm.
If approved, vimseltinib offers an effective systemic treatment to patients with TGCT and provides proven functional health and symptomatic benefit to a population living with substantial morbidity and limited treatment options.
Abstract Number: TPS11587
Title: DCC-3116 in combination with ripretinib for patients with advanced gastrointestinal stromal tumor: A phase 1/2 study.
Presenter: Sreenivasa Chandana, M.D., Ph.D., START Midwest, The Cancer & Hematology Centers
Session Date: Saturday, June 1, 2024
Session Time: 1:30 – 4:30 PM CT
Key Highlights:

This is a phase 1/2, multicenter study designed to evaluate the safety, tolerability, and efficacy of DCC-3116 in combination with ripretinib.
In Part 1, eligible patients will receive escalating oral doses of DCC-3116 combined with ripretinib 150 mg once daily (QD); the safety will be evaluated and the recommended phase 2 dose (RP2D) will be determined.
In Part 2, eligible patients will receive the RP2D of DCC-3116 in combination with ripretinib 150 mg QD; antitumor activity will be evaluated.
The trial is currently enrolling in the phase 1 dose escalation portion.

On June 3, 2024 Cullinan Therapeutics, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, reported positive initial data in patients receiving zipalertinib after prior treatment with amivantamab enrolled in its pivotal Phase 2b REZILIENT1 clinical trial (Press release, Cullinan Oncology, JUN 3, 2024, View Source [SID1234644002]).

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As of a January 12, 2024 data cut-off, 31 patients had been enrolled. Patients had received a median of three prior systemic anti-cancer regimens, including prior platinum-based chemotherapy, prior anti-PD1/L1 therapy, and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

At data cut-off, 18 patients were evaluable for response and showed similar anti-tumor activity compared with those post prior chemotherapy in the previously reported Phase 1/2a part of the study.

Module C (post chemo and Ami+/- other exon20ins treatment)​

(N=18)​

Phase 1/2a results (post chemo)1​

(N=39)​

ORR (confirmed)​

39%​

41%​

DCR2​

94%​

97%​

DOR (months)​

NE​

NE​

PFS (months)​

NE​

12​

NE=not yet estimable.

1 Piotrowska Z, et al. JCO 2023

2 DCR=(CR+PR+SD)/response-evaluable

Zipalertinib demonstrated a manageable safety profile, similar to what has been previously reported. There were no grade 4 or grade 5 treatment-related adverse events​.

"In an evolving treatment landscape, this is the first ever clinical data to systematically characterize the potential of an irreversible and selective EGFR exon20 insertion mutation TKI such as zipalertinib in patients who were heavily pre-treated and had received amivantamab. Given the recent approval of amivantamab as a first line treatment in combination with chemotherapy, we are encouraged by the initial results of the Phase 2b portion of the REZILIENT1 clinical trial, which show that in a post-amivantamab setting, zipalertinib demonstrated promising efficacy, similar to that in patients who progressed after platinum-based chemotherapy alone, and had a manageable safety profile" said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. "With a comprehensive development plan for zipalertinib, this data further strengthens our confidence in its potential to address a significant

unmet need for patients with NSCLC harboring EGFR exon 20 insertion mutations. We remain on track to complete enrollment in the pivotal Phase 1/2b REZILIENT1 trial by the end of this year."

Zipalertinib has a unique chemical structure that is distinct from other exon20 insertion directed agents, which makes it highly selective for mutant exon 20 versus wild-type EGFR. Cullinan entered into a partnership with Taiho in 2022, with an upfront cash payment of $275M and additional payments totaling $130M to be made for US regulatory approvals in 1L and 2L+ NSCLC. Cullinan also retains a 50/50 profit share in the U.S.

Cullinan and Taiho have a broad development program for zipalertinib through a suite of REZILIENT studies, including two ongoing pivotal studies in 1L and 2L+ exon20 insertion NSCLC as well as studies in other patient populations such as patients with active brain metastases and those with uncommon EGFR mutations. Both Module B2 (post chemo only) and Module C (post approved ex20ins treatments) of the pivotal REZILIENT1 trial remain on track to complete enrollment by end of 2024, consistent with prior projections.

Virtual and Live Investor Event

Cullinan Therapeutics will host an Investor Event on Saturday, June 1, 2024, at 6:30 PM Central Time, during which Dr. Jeff Jones, Chief Medical Officer at Cullinan Therapeutics, will present an overview of this zipalertinib data along with CLN-619 data shared at the 2024 ASCO (Free ASCO Whitepaper) annual meeting. Alexander Spira MD, PhD, FACP, FASCO and Director, Virginia Cancer Specialists Research Institute and Director, NEXT Oncology Virginia, will share an overview of the current treatment landscape for EGFR mutated NSCLC. Investors and analysts are invited to register to attend in person by emailing Chad Messer, VP Investor Relations ([email protected]). A live webcast will be available via the events page of the Company’s investor relations website at View Source, and a replay will be available shortly after the conclusion of the live event.

About Zipalertinib

Zipalertinib (CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was engineered to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. Cullinan Pearl Corp., which Taiho Pharmaceutical Co., Ltd., acquired from Cullinan Therapeutics, Inc. in 2022, previously licensed the rights to zipalertinib in Greater China to Zai Lab Limited in 2020.

On June 3, 2024 Century Therapeutics (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology and autoimmune and inflammatory disease, reported a poster presentation highlighting interim results from the ongoing Phase 1 ELiPSE-1 study evaluating CNTY-101 in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held May 31 – June 4, 2024 in Chicago, Illinois (Press release, Century Therapeutics, JUN 3, 2024, View Source [SID1234644001]).

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CNTY-101 is an investigational CD19 targeting allogeneic, iPSC-derived natural killer (NK) cell therapy with six precision gene edits powered by Century’s Allo-Evasion technology enabling repeat dosing without the need for continued lymphodepletion. ELiPSE-1 (NCT05336409) is an ongoing Phase 1, multicenter, open-label clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of CNTY-101 in patients with R/R, CD19-positive B-cell malignancies.

"These interim results continue to support our belief in the potential of CNTY-101, which shows additional responses across escalating doses and different types of B-cell malignancies in heavily pretreated patients with predominantly aggressive or high-risk histologies," said Adrienne Farid, PhD, Chief Operations Officer and Head of Early Development. "We are also encouraged by the safety profile we are seeing at higher doses, with no dose-limiting toxicities to date, after multiple treatment cycles, which we believe was achieved by leveraging our proprietary Allo-Evasion technology to avoid host rejection. Further, the majority of these cycles have been administered in the outpatient setting, providing additional support for CNTY-101 as a new paradigm for allogeneic cell therapies. We look forward to completing dose escalation and moving into dose expansion in the coming months."

Interim Results from the ELiPSE-1 Study: A Phase 1, Multicenter, Open-Label Study of CNTY-101 in Subjects with Relapsed or Refractory CD19-Positive B-Cell Malignancies

Poster Board Number: 6

Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Session Date & Time: Monday, June 3, 2024, from 9:00 am – 12:00 pm CDT

CNTY-101 is Century’s lead iNK cell therapy and the first iPSC-derived NK cell therapy engineered with six precision gene edits, featuring antigen-specific killing of CD19+ B cells, homeostatic cytokine support for enhanced persistence, Allo-Evasion edits to prevent rejection by the patients’ immune system, and a safety switch. CNTY-101 is being assessed in heavily pre-treated relapsed or refractory NHL patients with predominantly aggressive or high-risk indolent histologies who have received two to five prior therapies, four of whom received prior CAR-T therapy. The Company previously announced initial data in December 2023, demonstrating a favorable safety profile in the initial seven patients treated with Dose Level 1 (100 million cells) and Dose Level 2 (300 million cells) on a once monthly schedule. In these low dose levels, CNTY-101 demonstrated encouraging early response signals, including two complete responses (CRs) and one partial response (PR).

As of the interim data cutoff date of March 27, 2024, preliminary safety and efficacy were evaluated across Dose Level 1, Dose Level 2 and Dose Level 3 (one billion cells) and two dosing schedules (Schedule A with single infusion, and Schedule B with three weekly infusions, per cycle). CNTY-101 infusions of up to one billion cells per cycle (as a single infusion of one billion cells, or 3 weekly infusions of 300 million cells) demonstrated a favorable safety profile with no observations of graft-versus-host disease (GvHD) or dose-limiting toxicities (DLT), and 8/12 subjects received at least one cycle of CNTY-101 in an outpatient setting. Preliminary efficacy in all evaluable patients (n=10) across dose schedules and histologies demonstrated a complete response rate (CRR) of 30% and an objective response rate (ORR) of 40% in heavily pretreated patients, with a 40% CRR and 60% ORR observed in the five patients treated with the two higher Schedule A dose levels, 300 million cells and one billion cells.

Pharmacokinetics (PK) evaluated by a novel cell-free DNA (cfDNA) method for detecting total body PK showed that CNTY-101 rapidly traffics out of circulation and persists outside the bloodstream, with AUC trending to increase with dose level. In patients who received additional cycles of CNTY-101 without lymphodepleting chemotherapy, three out of four patients had positive detection of CNTY-101 on Day 3 and beyond. The ELiPSE-1 study is currently ongoing in the dose escalation phase and is enrolling in Dose Level 3B (one billion cells in three weekly infusions per cycle), and Dose Level 4A (single infusion of 3 billion cells per cycle).

The full poster will be available on the Scientific Resources page of Century’s website at the start of the poster presentation.

About CNTY-101

CNTY-101 is an investigational off-the-shelf immunotherapy product candidate that utilizes iPSC-derived natural killer (NK) cells with a CD19-directed chimeric antigen receptor (CAR) and includes Century’s core Allo-Evasion edits designed to overcome the three major pathways of host versus graft rejection – CD8+ T cells, CD4+ T cells and NK cells. In addition, the product candidate is engineered to express IL-15 to provide homeostatic cytokine support, which has been shown preclinically to improve functionality and persistence. Further, to address potential safety considerations, the iNK cells were engineered with an EGFR safety switch, and preclinical proof-of-concept studies have demonstrated that the cells can be quickly eliminated in vivo by the administration of cetuximab, an antibody against EGFR approved by the U.S. Food and Drug Administration for certain cancers. Century is currently assessing CNTY-101 in patients with relapsed or refractory CD19-positive B-cell lymphomas in its Phase 1 ELiPSE-1 clinical trial. The Company intends to initiate its second Phase 1 clinical trial assessing CNTY-101 in patients with moderate to severe systemic lupus erythematosus, in addition to pursuing additional regulatory filings in other prioritized autoimmune disease indications.

About Allo-Evasion

Century’s proprietary Allo-Evasion technology is used to engineer cell therapy product candidates with the potential to evade identification by the host immune system so they can be dosed multiple times without rejection, enabling increased persistence of the cells during the treatment period and potentially leading to deeper and more durable responses. More specifically, Allo-Evasion 1.0 technology incorporates three gene edits designed to avoid recognition by patient/host CD8+ T cells, CD4+ T cells and NK cells. Knockout of beta-2-microglobulin or β2m, designed to prevent CD8+ T cell recognition, knock-out of the class II major histocompatibility complex transactivator, or CIITA, designed to prevent CD4+ T cell recognition, and knock-in of the HLA-E gene, designed to enable higher expression of the HLA-E protein to prevent killing of CNTY-101 cells by host NK cells. Allo-Evasion technology may allow the implementation of more flexible and effective repeat dosing protocols for off-the-shelf product candidates.

On June 3, 2024 Celularity Inc. (NASDAQ: CELU) ("Celularity"), a regenerative and cellular medicine company developing placental-derived allogeneic cell therapies and advanced biomaterial products, reported that it presented in vivo data from its T-cell therapy platform at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Celularity, JUN 3, 2024, View Source [SID1234644000]). These data show that PT-CD16VS, Celularity’s T-Cell preclinical asset, has potent in vitro and in vivo activity and has the potential to be combined with various monoclonal antibodies to target multiple cancers. Please find the link to the abstract here.

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Celularity has adopted a "universal receptor" approach to develop a platform of genetically modified T-cells expressing a proprietary CD16 to be combined with various approved antibodies to address multiple cancers and other conditions.

Data demonstrating PT-CD16VSs activity in combination with trastuzumab against HER2-positive cancers has already been presented at AACR (Free AACR Whitepaper) in April. These data further build on this to demonstrate much broader potential across multiple hematological and solid tumors.

"These important data further demonstrate the potential of combining Celularity’s placental-derived cell therapy platform with currently available antibody therapies to address difficult-to-treat cancers and avoid some of the challenges of traditional cell therapy, including antigen escape and tolerability," said Dr. Robert Hariri, Celularity’s CEO and Founder. "We are also continuing to advance our pipeline to address aging-related healthcare challenges beyond cancer including cellular senescence. This work highlights the deep expertise and capabilities in cell therapy resident at Celularity and our ability to modify and engineer those cells in our state-of-the-art manufacturing facility."

On June 3, 2024 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported updated clinical data from the ongoing ANTLER Phase 1 trial that indicates a single dose of CB-010, a readily available, off-the-shelf anti-CD19 CAR-T cell therapy with a PD-1 knockout, has the potential to rival the safety, efficacy, and durability of approved autologous CAR-T cell therapies (Press release, Caribou Biosciences, JUN 3, 2024, View Source [SID1234643999]). The clinical results are being presented during a poster presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"The Phase 1 data from the ANTLER trial continues to be encouraging in terms of both safety and efficacy of an allogeneic CAR-T cell therapy," said Boyu Hu, MD, director of lymphoma and CLL in the division of hematology and hematologic malignancies at the University of Utah and an investigator on the ANTLER trial. "The partial human leukocyte antigen, or HLA, matching strategy is incredibly intriguing and further evaluation is supported by the ASCO (Free ASCO Whitepaper) data presentation. As many patients in ANTLER were enrolled due to rapid disease progression that prohibited waiting for an autologous CAR-T cell therapy, I look forward to enrolling patients who will receive partially HLA matched CB-010 in this ongoing trial."

In ANTLER, three dose levels of CB-010 were evaluated (40×106, 80×106, and 120×106 CAR-T cells) in a total of 46 patients. In dose escalation, 16 patients with multiple subtypes of aggressive relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) were enrolled, and in dose expansion, 30 patients with second-line large B cell lymphoma (2L LBCL) were enrolled. As of an April 1, 2024 data cutoff date, results demonstrated:

•CB-010 was generally well tolerated. No Grade 3 or higher cytokine release syndrome (CRS) and no graft-versus-host disease (GvHD) was observed.
•A retrospective analysis of all patient data demonstrated that patients who received a dose of CB-010 manufactured from a donor with ≥4 matching HLA alleles (referred to as partial HLA matching) showed improved progression free survival (PFS). Results from patients who received partially HLA matched CB-010 include:
◦Median PFS of 14.4 months (95% CI: 1.74, not estimable [NE]) was observed in patients treated with CB-010 with ≥4 HLA matches (N=13), compared to 2.8 months (95% CI: 2.10, 3.48) for patients treated with CB-010 with ≤3 HLA matches (N=33).
◦In patients with LBCL who received CB-010 with ≥4 HLA matches (N=11, including N=10 2L LBCL and N=1 3L LBCL), median PFS has not been reached (95% CI: 1.58, NE).
•Translational data on CB-010:
◦Pharmacokinetic (PK) data showed that higher numbers of matched HLA alleles between the CB-010 donor and recipient patient correlated with increased CAR-T cell expansion and persistence compared to lower numbers of matched HLA alleles.
◦Pharmacodynamic (PD) data showed that a single dose of CB-010 resulted in extended B cell aplasia (~114 days) and a rapid recovery of the patient’s endogenous T and NK cells (~3 weeks).
•Based on the overall safety, efficacy, and translational data analyzed, 80×106 CAR-T cells was selected as the recommended Phase 2 dose (RP2D) for CB-010.

"We are excited to see that patients who receive partially HLA matched CB-010 have improved efficacy and durability outcomes that are on par with approved autologous CAR-T cell therapies," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "We next plan to prospectively evaluate this compelling observation by enrolling approximately 20 additional 2L LBCL patients, in either the inpatient or outpatient treatment setting, and we will ensure that they receive a partially matched (≥4 HLA matches) dose of CB-010. We are also excited to open the ANTLER study for the first time to patients who have relapsed following any prior CD19-targeted therapy in a proof-of-concept cohort for up to 10 patients. We expect to report initial data from both the 2L LBCL and CD19 relapsed cohorts in the first half of 2025 and, upon confirmation of improved outcomes in additional patients receiving a partially HLA matched dose of CB-010, we plan to initiate a pivotal Phase 3 clinical trial in 2L LBCL patients, including patients regardless of HLA type, in the second half of 2025."

ANTLER Phase 1 trial of CB-010 – median PFS analyses
A photo accompanying this announcement is available at: View Source;fileGuid=893722aa-a457-4e0f-a27e-457bf8b2c0d3

ANTLER Phase 1 trial of CB-010 – response data
Endpoints (N, %)
All patients
≤3 HLA matches
(N=33)
All patients
≥4 HLA matches
(N=13)
LBCL
≥4 HLA matches
(N=11)
Overall response rate (ORR)
23 (69%)
12 (92%)
10 (91%)
Duration of response (DoR), median months (range)
2.0 (1-23+)
13.5 (1-23+)
NR (1-15+)
Complete response (CR) rate
15 (45%)
6 (46%)
4 (36%)
Duration of CR, median months (range)
5.0 (1-23+)
NR (5-23+)
NR (5-15+)
6-month PFS
25%
62%
53%
PFS, median months (range)
2.8 (1-24+)
14.4 (2-24+)
NR (2-16+)

HLA: human leukocyte antigen; NR: not reached; PFS: progression free survival
ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing

ANTLER Phase 1 trial of CB-010 – response data
All treated (N=46)
Any grade
(n, %)
Grade ≥3
(n, %)
Prolonged 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 release syndrome; GvHD: graft-versus-host disease; ICANS: immune effector cell-associated neurotoxicity syndrome
There were five patient deaths due to adverse events following CB-010 infusion; 4 were unrelated to CB-010 treatment and 1 death possibly related to CB-010 per investigator due to complications of a bladder perforation in the context of BK virus hemorrhagic cystitis
1 Prolonged cytopenias are defined as grade 3 or higher events lasting beyond 30 days following CB-010 infusion; 37/46 (80%) of patients recovered from cytopenias to grade ≤2 by day 35 post CB-010 treatment
2 Median time of onset was 3 days (range 0-22), and median duration was 3 days (range 1-19)
3 Infection events reported were on or after CB-010 infusion, with highest grade reported per patient; median onset 8 days (range 0-279) and median duration is 14 days (range 1-239)
4 Median time of onset was 7.5 days (range 6-34), and median duration was 2 days (range 1-27)
5 2 Grade 3 and 1 Grade 4; all resolved with supportive care. Median time of onset was 8 days and median duration was 2 days
ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing

Based on these encouraging data, Caribou plans to enroll approximately 20 additional 2L LBCL patients in ANTLER to prospectively confirm that partial HLA matching improves patient outcomes. The patient HLA allele typing occurs within the current screening timelines.

"Integrating the partial HLA matching into manufacturing for CB-010 is straightforward, enabling Caribou to deliver CB-010 as a readily available off-the-shelf CAR-T cell therapy that can serve a broad patient population," said Tim Kelly, Caribou’s chief technology officer. "In our planned 2L LBCL pivotal Phase 3 trial, we will provide the best possible matched dose of CB-010 to each patient based on lot availability. With at least 13 manufacturing batches of CB-010 on hand, we expect that approximately 90% of all patients who could enroll in our trial would receive a dose of CB-010 with ≥4 matched alleles."

Webcast conference call Sunday, June 2, at 7:00 pm CDT
Caribou will host a live webcast on Sunday, June 2, at 7:00 pm CDT for a discussion with KOLs and management on the CB-010 ANTLER Phase 1 data presentation. The presenters will include:
•Boyu Hu, MD, director of lymphoma and CLL in the division of hematology and hematologic malignancies, University of Utah
•Mehdi Hamadani, MD, professor of medicine, section chief of hematologic malignancies, Medical College of Wisconsin
•Rachel Haurwitz, PhD, president and chief executive officer, Caribou Biosciences

Additional participants from Caribou Biosciences include:
•Steve Kanner, PhD, chief scientific officer
•Jason O’Byrne, chief financial officer
•Kike Zudaire, PhD, senior vice president, translational sciences and therapeutic discovery
•Tonia Nesheiwat, PharmD, vice president of medical affairs and project leadership

The listen-only webcast with an accompanying presentation will be accessible under Events (View Source) in the Investors section of Caribou’s website. The archived audio webcast will be available on the company’s website following the call and will be available for 30 days.

ASCO poster presentation on Monday, June 3, 9:00 am-12:00 pm CDT

Details of the ANTLER poster presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting are as follows:

Title: A CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout (CB-010) in patients with relapsed/refractory B cell non-Hodgkin lymphoma (r/r B-NHL): Updated Phase 1 results from the ANTLER trial
Presenter: Boyu Hu, MD, assistant professor, director of lymphoma and CLL, division of hematology and hematologic malignancies, Huntsman Cancer Institute at the University of Utah
Date and time: Monday, June 3, 2024, 9:00 am-12:00 pm CDT
Session: Hematologic Malignancies – Lymphoma and CLL
Location: Hall A, Poster Board 8, McCormick Place, Chicago
Abstract number: 7025

About CB-010
CB-010 is the lead clinical-stage product candidate from Caribou’s allogeneic CAR-T cell therapy platform, and it is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) in the ongoing ANTLER Phase 1 clinical trial and will be evaluated in patients with lupus nephritis (LN) and extrarenal lupus (ERL) in the GALLOP Phase 1 clinical trial. In ANTLER, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprised of different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, tFL, and tMZL). 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 activity against diseases by limiting premature CAR-T cell exhaustion. CB-010 is also, to Caribou’s knowledge, the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the second-line LBCL setting and, for r/r B-NHL, CB-010 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 (View Source).

About Caribou’s novel next-generation CRISPR platform
CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its chRDNA technology to carry out high efficiency multiple edits, to develop CRISPR-edited therapies.