On July 6, 2023 Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY), reported that The New England Journal of Medicine (NEJM) published detailed results from the BRUIN Phase 1/2 trial evaluating the efficacy and safety of an investigational use of pirtobrutinib, a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, in adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were previously treated with a BTK inhibitor (Press release, Eli Lilly, JUL 6, 2023, View Source [SID1234633078]).

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The NEJM publication provides additional clinical details from the data set that was presented at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The data set includes 247 BTK inhibitor pre-treated CLL/SLL patients enrolled across both the Phase 1 and Phase 2 portions of the BRUIN study.

"Patients with relapsed or refractory CLL or SLL following treatment with a covalent BTK inhibitor represent a population with limited treatment options," said the study’s co-lead author Jennifer A. Woyach, M.D., professor and hematologist-oncologist at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. "These data support the potential for pirtobrutinib to extend the benefit of BTK inhibition for patients with CLL or SLL with a once-daily oral therapy."

"We are pleased to have the detailed safety and efficacy results of pirtobrutinib in adults with CLL or SLL published in NEJM and shared with the broader medical community," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "Treating clinicians have expressed the desire to fully exhaust BTK inhibition prior to switching their patients to another therapy class. These data continue to reinforce pirtobrutinib’s ability to help reestablish BTK inhibition following treatment with a covalent BTK inhibitor."

Overview of Data Published in NEJM

The efficacy cohort consisted of 247 BTK inhibitor pre-treated CLL/SLL patients enrolled across both the Phase 1 and Phase 2 portions of the BRUIN study as of July 29, 2022. The median number of prior therapies was three (range: 1-11). Most patients discontinued prior BTKi therapy due to disease progression (77%). Consistent with a very heavily pre-treated population with advanced disease, high-risk molecular features were common including the presence of a del(17p) and/or TP53 mutation (47%), complex karyotype (42%), and unmutated IGHV (85%). The primary endpoint was best overall response rate (ORR), comprising partial response (PR) or better, according to the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria. This was assessed by an independent review committee (IRC) blinded to investigator assessments. Additional endpoints were ORR when including PR with lymphocytosis, progression-free survival (PFS), overall survival (OS), safety, and exploratory analyses of biomarkers. All efficacy data, except for OS, were assessed by both the investigator and an IRC.

Efficacy results are summarized below:

Prior BTKi
(N=247)

Prior BTKi+BCL2i
(N=100)

Overall Response Rate, % (95% CI)

73.3 (67.3-78.7)

70.0 (60.0-78.8)

Overall Response Rate including PR-L, % (95% CI)

82.2 (76.8-86.7)

79.0 (69.7-86.5)

CR, n (%)

4 (1.6)

0 (0.0)

PR, n (%)

176 (71.3)

70 (70.0)

PR-L, n (%)

22 (8.9)

9 (9.0)

SD, n (%)

26 (10.5)

11 (11.0)

Progression-free Survival

Median, months 95% CI

19.6 (16.9-22.1)

16.8 (13.2-18.7)

Censored patients, n (%)

126 (51)

44 (44)

Median follow-up, months

19.4

18.2

CI, confidence interval; CR, complete response; PR, partial response; PR-L, partial response-lymphocytosis; SD, stable disease.

Response status per iwCLL 2018 according to independent review committee assessment.

In a subgroup analysis of BCL2 inhibitor naïve patients (n=147), the ORR including PR-L was 84.4% (95% CI: 77.5-89.8) and the median PFS was 22.1 months (95% CI: 19.6-27.4).

Safety was reported in all patients with CLL/SLL who had received at least one dose of pirtobrutinib (n=317). As of the data cutoff date, 87.4% of patients had received at least one dose of pirtobrutinib at the recommended Phase 2 dose of 200 mg once daily, and the median time on treatment was 16.5 months (range: 0.2-39.9). The safety profile reported was consistent with previously reported data for pirtobrutinib. Overall, the most common treatment-emergent adverse events (TEAEs) were infections (71.0%), bleeding (42.6%), and neutropenia (32.5%). The most frequently reported TEAEs of Grade 3 or higher were infections (28.1%) and neutropenia (in 26.8%), and the most frequently reported treatment-related adverse event (AE) of Grade 3 or higher was neutropenia (14.8%). Incidence of treatment-related Grade 3 or higher atrial fibrillation (1.3%), hemorrhage (6.9%), and hypertension (3.8%) were relatively low. In patients with CLL/SLL, treatment-related AEs leading to dose reductions occurred in 4.7% and permanent discontinuations in 2.8% of patients.

Loxo@Lilly is studying pirtobrutinib in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found at lillyloxooncologypipeline.com or by visiting clinicaltrials.gov.

About the BRUIN Phase 1/2 Trial

The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of pirtobrutinib in patients previously treated for mantle cell lymphoma (MCL), CLL, SLL, or other non-Hodgkin lymphomas (NHL).

The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by ORR for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an IRC. Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DOR), PFS, OS, safety, and PK.

About Pirtobrutinib

Pirtobrutinib is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including CLL.2,3 Pirtobrutinib was developed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, and preserve activity in the presence of the C481 acquired resistance mutations.

Pirtobrutinib was approved under the FDA’s Accelerated Approval pathway as Jaypirca (pirtobrutinib) on January 27, 2023. Jaypirca is indicated for the treatment of adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients treated with Jaypirca. In the clinical trial, Grade ≥3 infections occurred in 17% of 583 patients with hematologic malignancies, most commonly pneumonia (9%); fatal infections occurred in 4.1% of patients. Sepsis (4.5%) and febrile neutropenia (2.9%) occurred. Opportunistic infections after Jaypirca treatment included, but are not limited to, Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 2.4% of 583 patients with hematologic malignancies treated with Jaypirca, including gastrointestinal hemorrhage; fatal hemorrhage occurred in 0.2% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 14% of patients. Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (1.7%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Grade 3 or 4 cytopenias, including neutropenia (24%), anemia (11%), and thrombocytopenia (11%), have developed in patients with hematologic malignancies treated with Jaypirca. In a clinical trial, Grade 4 neutropenia (13%) and Grade 4 thrombocytopenia (5%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Atrial Fibrillation and Atrial Flutter: Atrial fibrillation or flutter were reported in 2.7% of patients, with Grade 3 or 4 atrial fibrillation or flutter reported in 1% of 583 patients with hematologic malignancies treated with Jaypirca. Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 6% of 583 patients with hematologic malignancies treated with Jaypirca monotherapy. The most frequent malignancy was non-melanoma skin cancer (3.8%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Embryo-Fetal Toxicity: Based on animal findings, Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats during organogenesis caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential risk to a fetus and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients with Mantle Cell Lymphoma Who Received Jaypirca
Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last dose of Jaypirca occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1%).

Dose Modifications and Discontinuations: ARs led to dosage reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation of Jaypirca in >1% of patients included pneumonia.

ARs (all Grades %; Grade 3-4 %) in ≥10% of Patients: fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -), peripheral neuropathy (14; 0.8), cough (14; -), rash (14; -), fever (13; -), constipation (13; -), arthritis/arthralgia (12; 0.8), hemorrhage (11; 3.1), abdominal pain (11; 0.8), nausea (11; -), upper respiratory tract infections (10; 0.8), dizziness (10; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

All grade ARs with higher frequencies in the total BRUIN population of patients with hematologic malignancies (n=583) were decreased neutrophil count (41%), bruising (20%), diarrhea (20%).

Drug Interactions
Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca adverse reactions. Avoid use of strong CYP3A inhibitors during Jaypirca treatment. If concomitant use is unavoidable, reduce Jaypirca dosage according to the approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase the Jaypirca dosage according to the approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gP, BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Inform pregnant women of potential for Jaypirca to cause fetal harm. Verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk and effects on the breastfed child or on milk production is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, 392 (67%) were ≥65 years of age. Patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment (eGFR 15-29 mL/min) increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to the approved labeling. No dosage adjustment is recommended in patients with mild or moderate renal impairment.

PT HCP ISI MCL APP

Please see Prescribing Information and Patient Information for Jaypirca.

On July 6, 2023 Curis, Inc., (Nasdaq: CRIS), a biotechnology company focused on the development of emavusertib, an orally available small molecule triple target inhibitor (IRAK4, FLT3 and CLK) for the treatment of hematologic malignancies, reported that the U.S. Food and Drug Administration (FDA) has removed the partial clinical hold on the TakeAim Leukemia Phase 1/2 study of emavusertib (Press release, Curis, JUL 6, 2023, View Source [SID1234633077]). Further, the recommended phase 2 dose (RP2D) for emavusertib as a monotherapy has been established at 300 mg BID in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndromes (MDS).

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"We are pleased to announce that FDA has removed the partial clinical hold on the TakeAim Leukemia study and that we are proceeding with 300 mg BID as our RP2D. We are working with our clinical sites to enroll targeted patients with AML (patients with a FLT3 or spliceosome mutation who have received ≤ 2 prior lines of treatment). We also plan to initiate a front-line combination study of emavusertib with azacitidine and venetoclax. We believe emavusertib has the potential to be the cornerstone agent in the treatment of hematological malignancies." said James Dentzer, President and Chief Executive Officer of Curis. "In 2024, we expect to have updated data from the TakeAim Leukemia monotherapy study, clarification of a monotherapy registrational study design, and initial data from an azacitidine and venetoclax combination study."

On April 4, 2022, the Company announced that the FDA placed a partial clinical hold on the TakeAim Leukemia study. On August 30, 2022, the Company announced that the FDA notified Curis that it may resume enrollment of additional patients in the monotherapy dose finding phase of the TakeAim Leukemia study, so that the Company could enroll at least nine additional patients at the 200 mg BID dose level. On July 6, 2023, the Company announced the FDA had removed the partial clinical hold on the TakeAim Leukemia study and that the RP2D has been established at 300 mg BID.

In the TakeAim Leukemia study, as of the March 17, 2023 data cutoff for patients dosed prior to February 9, 2023, 84 patients received emavusertib monotherapy, ranging from doses of 200 mg to 500 mg BID. Significant blast count reductions have been observed across all patient groups, regardless of dose level, mutation status, or number of prior lines of treatment. Emerging from these data are two genetically-defined subpopulations of relapsed/refractory (R/R) patients who have demonstrated compelling responses in monotherapy: AML patients with FLT3 mutation and AML patients with spliceosome mutation (U2AF1 or SF3B1 mutation) who have received ≤ 2 prior lines of treatment. In these subpopulations of evaluable patients (patients whose disease has been determined to be evaluable for objective response with baseline and post-treatment marrow assessments) treated with 300 mg BID, 2 of 3 patients with a FLT3 mutation achieved a CR (Complete Response), and 2 of 3 patients with spliceosome mutation achieved a CR or CRh (Complete Response with Partial Hematologic Recovery). The duration of response for these patients ranged from 5.6 to 7.0 months.

"A significant unmet need remains for patients with AML and MDS with the majority of front-line patients relapsing with currently available treatment options," said Dr. Reinhard von Roemeling, Senior Vice President of Clinical Development of Curis. "Emavusertib has the potential to be uniquely positioned as an addition to frontline therapy in combination with standard of care and also as a monotherapy in targeted R/R patient populations."

About emavusertib (CA-4948)

Emavusertib is a triple target inhibitor (IRAK4, FLT3 and CLK). IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Preclinical studies targeting IRAK1/4 in combination with FLT3 have demonstrated the ability to overcome the adaptive resistance incurred when targeting FLT3 alone. Further, emavusertib has shown anti-tumor activity across a broad range of hematologic malignancies including monotherapy activity in patient-derived xenografts and synergy with both azacitidine and venetoclax.

About TakeAim Studies

TakeAim Leukemia Study (NCT04278768) – study is open for enrollment.
TakeAim Lymphoma Study (NCT03328078) – study is open for enrollment.

On July 6, 2023 Curis, Inc. (Nasdaq: CRIS), a biotechnology company focused on the development of emavusertib, a triple target inhibitor (IRAK4, FLT3 and CLK) for the treatment of hematologic malignancies, reported that it has entered into definitive agreements led by existing investors for the purchase of 18.4 million of its shares of common stock at a purchase price of $0.82 per share in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Curis, JUL 6, 2023, View Source [SID1234633076]).

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Gross proceeds to the Company from the offering are expected to be approximately $15.1 million, before deducting the placement agents’ fees and other offering expenses payable by Curis. Curis intends to use the net proceeds from the offering on research, development, working capital, and other general corporate purposes. The closing of the offering is expected to occur on or about July 10, 2023, subject to the satisfaction of customary closing conditions. Cantor Fitzgerald & Co. and Truist Securities, Inc. are acting as the placement agents for the offering.

The shares are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-254362) that was filed with the United States Securities and Exchange Commission ("SEC") on March 16, 2021, as amended by Post-Effective Amendment No. 1 to Form S-3 Registration Statement and Post-Effective Amendment No. 2 to Form S-3 Registration Statement, each filed with the SEC on February 24, 2022. A prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. The offering is being made only by means of a prospectus and related prospectus supplement. When available, electronic copies of the prospectus supplement and the accompanying prospectus may also be obtained from Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, NY, 10022, by email at [email protected] or from Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, or by email at [email protected]. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On July 6, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported the publication of preclinical data on soquelitinib (formerly known as CPI-818), the Company’s ITK inhibitor product candidate, which highlighted the selective inhibition of ITK to potentially enhance anti-tumor immune response to hematologic and solid tumors and provide a novel approach to cancer immunotherapy (Press release, Corvus Pharmaceuticals, JUL 6, 2023, View Source [SID1234633075]).

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The publication, entitled "Selective Inhibition of Interleukin 2 Inducible T Cell Kinase (ITK) Enhances Anti-Tumor Immunity in Association with Th1-skewing, Cytotoxic T cell Activation, and Reduced T Cell Exhaustion," provides a detailed overview of the chemical structure, enzymatic activity and immunobiologic properties of soquelitinib. The published research was a result of collaborations between scientists at Corvus and researchers at the University of Michigan, The Ohio State University, Peking University and Stanford University. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website.

"This significant scientific report demonstrates the potential of highly selective ITK inhibition, now enabled by soquelitinib. The data indicate that this mechanism, if approved, may become the backbone of a new immunotherapy approach to cancer and we believe it will extend the opportunity for the continued development of soquelitinib as a single agent or in combination with other therapies to treat a variety of cancer tumor types," said Richard A. Miller., co-founder, president and chief executive officer of Corvus.

The findings reported indicate that ITK is a novel drug target and its blockade may enhance the body’s immune response to cancer. ITK is an enzyme predominantly expressed by T lymphocytes. ITK plays a major role in the function of T cells which are generally acknowledged as a critical cell in the immunotherapy of cancer. Soquelitinib is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed T cell lymphoma (TCL). Corvus plans to meet with the FDA in the third quarter of 2023 to discuss a Phase 3 registration clinical trial in patients with relapsed TCL.

Key results from the preclinical studies described in the publication demonstrated that soquelitinib:

Is a covalent, irreversible inhibitor that selectively binds to and inhibits ITK function while sparing other closely related kinases, including resting lymphocyte kinase (RLK).
Inhibited Th2 T cell function and the production of various Th2 cytokines leading to Th1 skewing and production of interferon gamma and tumor necrosis factor, which are important cytokines in tumor rejection. Th2 cytokines have been previously implicated in promoting tumor growth and are also involved in autoimmune and allergic diseases.
Activated cytotoxic killer cells and increases infiltration of these cells into tumors.
Reduced and reversed T cell exhaustion resulting in a more potent and prolonged immune response. T cell exhaustion is often a major reason for resistance to immune checkpoint therapy.
Led to in vivo anti-tumor activity in several mouse tumor models, including colon, renal, melanoma, B cell and T cell tumors.

On July 6, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported that Pfizer Inc. (NYSE: PFE) has made a $25 million equity investment in the company (Press release, Caribou Biosciences, JUL 6, 2023, View Source [SID1234633074]). Pfizer purchased 4,690,431 of Caribou common shares at a price of $5.33 per share, pursuant to the terms of a Securities Purchase Agreement dated June 29, 2023. The purchase by Pfizer closed on June 30, 2023. In conjunction with the investment, Dr. Krishnaswami has joined Caribou’s Scientific Advisory Board (View Source).

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"We believe Pfizer’s investment in Caribou highlights the potential of our clinical programs and we are excited to establish this partnership with one of the world’s premier biopharmaceutical companies," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "We are actively advancing our allogeneic CAR-T cell therapy pipeline and look forward to providing updates from all of our programs over the next six months, including 6-month dose escalation data from our ANTLER Phase 1 clinical trial for CB-010, dose escalation updates on our CaMMouflage Phase 1 clinical trial for CB-011, and submission of an investigational new drug application for CB-012."

"We are encouraged by Caribou’s chRDNA genome-editing technology and the potential of allogeneic cell therapies as a promising off-the-shelf approach to cancer treatment," said Dr. Krishnaswami. "Pfizer has a long history of supporting early, innovative science in the biotech ecosystem, and we look forward to supporting Caribou as they continue to advance their ANTLER Phase 1 trial for CB-010, as well as their clinical program for CB-011, an allogeneic anti-BCMA cell therapy for multiple myeloma."

Caribou will use the proceeds of this investment to advance CB-011, an immune cloaked allogeneic CAR-T cell therapy currently being evaluated in the CaMMouflage Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma (r/r MM). Caribou will maintain full ownership and control of its pipeline of allogeneic CAR-T and CAR-NK cell therapies.

The securities sold in this financing were made in a transaction not involving a public offering and have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. This press release shall not constitute an offer to sell or the solicitation of an offer to buy the common shares, nor shall there be any sale of the common shares in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

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. CB-010 is the first allogeneic CAR-T cell therapy in the clinic, to Caribou’s knowledge, 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 setting and 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.