On May 17, 2023 Elevar Therapeutics, Inc., a wholly owned subsidiary of HLB Co., Ltd. and a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, reported that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for its investigational drug rivoceranib, an oral TKI, in combination with camrelizumab, a PD-1 inhibitor, as a first-line treatment option for unresectable hepatocellular carcinoma (uHCC) (Press release, Elevar Therapeutics, MAY 17, 2023, View Source [SID1234631805]).

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Each year, liver cancer is the cause of more than 830,000 deaths worldwide1. HCC is the most common type of liver cancer and typically has a poor prognosis with a lack of treatment options.

"Elevar Therapeutics’ submission of a New Drug Application for the combination of rivoceranib and camrelizumab marks an important milestone in our effort to provide an improved treatment option for patients confronted with uHCC," said Saeho Chong, chief executive officer of Elevar. "We thank the many physicians, institutions and patients who have contributed to rivoceranib’s development, and we look forward to working closely with the FDA during its evaluation period."

The NDA is supported by positive clinical data from the Phase 3 CARES 310 study (NCT03764293), in which rivoceranib plus camrelizumab demonstrated statistically significant and clinically meaningful prolonged overall survival and progression-free survival, and improved overall response rate versus sorafenib, a standard first-line treatment for uHCC.

Results from the randomized, open-label, international trial, which included 543 patients and was conducted at 95 study sites across 13 countries/regions, demonstrated median overall survival (OS) for camrelizumab + rivoceranib of 22.1 mos. [95% CI 19.1-27.2] vs. 15.2 mos. [13.0-18.5] for sorafenib; hazard ratio 0.62 [95% CI 0.49-0.80]; 1-sided p<0.0001. Median progression-free survival for camrelizumab + rivoceranib was 5.6 mos. [95% CI 5.5-6.3] vs. 3.7 mos. [2.8-3.7]; HR 0.52 [95% CI 0.41-0.65]); 1-sided p<0.0001, and confirmed objective response rate for camrelizumab + rivoceranib was 25.4% (95% CI 20.3-31.0), compared to 5.9% (3.4-9.4) for sorafenib.

With efficacy results generally consistent across all subgroups, the data suggested the combination confers a benefit in a global uHCC population. Also, it demonstrated efficacy among those with hepatitis C virus-based etiology and non-viral etiology, which comprises the majority of U.S. HCC cases2.

"The combination of camrelizumab and rivoceranib shows distinct promise as a potential therapy for advanced hepatocellular carcinoma," said Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston. "As an oncologist focused on evolving the standard of patient care in HCC, I am encouraged by Elevar’s NDA filing and look forward to the completion of the FDA’s review process."

In February 2023, the combination therapy of rivoceranib and camrelizumab was approved by the National Medical Products Administration (NMPA) as a first-line treatment for liver cancer in China.

Elevar is also developing rivoceranib as a monotherapy treatment option for adenoid cystic carcinoma (ACC), and as mono and combination therapies in other tumor cell types.

To learn more, visit ElevarTherapeutics.com.

1View Source 2Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017 May 29;16:1. doi: 10.4103/jcar.JCar_9_16. PMID: 28694740; PMCID: PMC5490340.

About Hepatocellular Carcinoma (HCC)

HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need.

About Rivoceranib

Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China as a first-line treatment for uHCC (February 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

About Camrelizumab

Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer) and treatment settings.

Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma, and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021.

On May 17, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported that it will present new data for CPI-818, the Company’s ITK inhibitor, at the International Conference on Malignant Lymphoma (ICML) meeting, which is taking place June 13-17, 2023 in Lugano, Switzerland (Press release, Corvus Pharmaceuticals, MAY 17, 2023, View Source [SID1234631804]).

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"We continue to make strong progress in the development of ITK inhibition as a potential platform opportunity with a novel mechanism of action that can address a broad range of hematologic and solid cancers and immune diseases," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We look forward to presenting data at ICML supporting the biology and mechanism of immune enhancement resulting from selective ITK inhibition, along with the latest clinical data from our Phase 1/1b clinical trial of CPI-818 for T cell lymphoma. CPI-818 is the main priority for Corvus and we remain on track for initiating a potential registrational Phase 3 randomized trial for T cell lymphoma later this year."

Details regarding the CPI-818 poster presentation at ICML, which will be available on the Corvus website, are as follows:

Date and Time: Thursday, June 15, 2023, from 12:30 to 1:00 pm CEST (6:30 – 7:00 am ET)

Title: ITK inhibitor induces Th1 skewing and host anti-tumor response mediated by CD8+ TEMRA cells in refractory T cell lymphoma patients

Abstract #: 193

Presenter: Ning Ding, Ph.D., Peking University Cancer Hospital & Institute, Beijing, China

The poster will be available to attendees in the poster hall on Wednesday, June 14 from 12:00 – 6:00 pm CEST and Thursday-Friday, June 15-16 from 10:00 am – 6:00 pm CEST. It will also be accessible to attendees beginning on Wednesday, June 14 at 8:30 am CEST in the e-poster gallery.

CPI-818 is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. Corvus recently incorporated a minimum absolute lymphocyte count (ACL) as an eligibility criterion for enrollment in the clinical trial. Based on the current enrollment rate of the Phase 1/1b clinical trial, Corvus believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registrational Phase 3 randomized clinical trial. As recommended by the FDA, Corvus plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place during the third quarter of this year.

On May 17, 2023 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported clinical data on its Phase 1 AMELI-01 clinical trial (evaluating UCART123) that were unveiled in an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, as well as preclinical data on multiplex engineering for superior generation of CAR T-cells, at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2023 Annual Meeting (Press release, Cellectis, MAY 17, 2023, View Source [SID1234631803]).

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Oral presentation:

AMELI-01, a study evaluating UCART123, an allogeneic CAR T-cell product candidate, in relapsed/refractory acute myeloid leukemia (r/r AML)

The oral presentation highlights the following clinical data:

Preliminary Clinical Data from the AMELI-01 Study Presented at ASH (Free ASH Whitepaper) 2022

AMELI-01 is a Phase 1 open-label dose-escalation trial evaluating the safety, tolerability, expansion and preliminary activity of UCART123 given at escalating dose levels after lymphodepletion (LD) with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients with relapsed or refractory acute myeloid leukemia (r/r AML).

The oral presentation reviewed preliminary data from patients who received UCART123 at one of the following dose levels: dose level 1 (DL1) 2.5×105 cells/kg; dose level 2 (DL2) 6.25×105 cells/kg; intermediate dose level 2 (DL2i) 1.5×106 cells/kg; or dose level 3 (DL3) 3.30×106 cells/kg after lymphodepletion with FC ([n=8], DL1 – DL3) or FCA ([n=9], DL2 & DL2i).

Preliminary Safety Data

The FCA LD regimen resulted in robust lymphodepletion for greater than 28 days in all patients. Seven out of nine patients demonstrated UCART123 expansion, with maximum concentration (Cmax) ranging from 13,177 to 330,530 copies/µg DNA, an almost nine-fold increase compared with FC LD, and a significant increase in area under the curve (AUC) (0-28 days) (p=0.04; FC 10.2 vs. FCA 34.9).

Cytokine release syndrome (CRS) occurred in eight patients in the FC arm and nine patients in the FCA arm. In the FC arm, one patient experienced Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and two patients experienced Grade 4 protocol-defined dose limiting toxicities (DLTs) secondary to CRS. In the FCA arm, two patients experienced Grade 5 DLTs secondary to CRS.

Preliminary Efficacy Data

Evidence of UCART123 anti-tumor activity was observed in four patients out of fifteen at DL2 or above with best overall responses in the FCA arm. Two out of eight patients (25%) at DL2 in the FCA arm achieved meaningful response:

A patient who failed five prior lines of therapy experienced a durable minimal residual disease (MRD) negative complete response (CR) with full count recovery at Day 56 that continues beyond one year.
A patient with stable disease achieved greater than 90% bone marrow blast reduction (60% to 5%) at Day 28.
The preliminary data show that adding alemtuzumab to the FC LD regimen was associated with sustained lymphodepletion and significantly higher UCART123 cell expansion, which correlated with improved anti-tumor activity.

Patient Enrollment in a 2-Dose Regimen Arm

Overall, these preliminary data support the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML. Based on observed UCART123 expansion patterns and cytokine profiles, pursuant to an amended protocol, a second dose of UCART123 is given after 10-14 days to allow for additional UCART123 expansion and clinical activity without the use of additional lymphodepletion. The UCART123 cell expansion from the second dose of UCART123, in the setting of reduced disease burden, is expected to be safe and allow for clearance of residual disease.

"These clinically meaningful preliminary data from the AMELI-01 study are very encouraging for patients and for the future of allogeneic CART-cell therapy. AML is a disease with an urgent need for alternative treatment options for patients, and we are excited to be moving the study forward," said Dr. Mark Frattini, M.D., Ph.D., Chief Medical Officer at Cellectis. "We have now implemented a two-dose regimen arm for our AMELI-01 trial and we look forward to sharing future updates as they become available."

Title: AMELI-01: A Phase I Trial of UCART123v1.2, an Anti-CD123 Allogeneic CAR-T Cell Product, in Adult Patients with Relapsed or Refractory (R/R) CD123+ Acute Myeloid Leukemia (AML)

Presenter: Daniel Lee, M.D., Director, Clinical Sciences at Cellectis

Session Date/Time: 5/17/2023 – 3:45 PM – 5:30PM PDT
Session Title: CAR Engineering and Production Advances for Targeting Hematologic and Solid Tumor Malignancies
Session Room: 502 AB

Final Abstract Number: 94

A copy of the ASGCT (Free ASGCT Whitepaper) oral presentation will be available on Cellectis’ website after the presentation: View Source

Poster Presentation:

Expanding the scope of multiplex engineering for superior generation of efficient CAR T-cells

In recent years, advances in genomic-based cellular engineering are bringing us a step closer to conquering solid tumors. This glimpse of success also demonstrated that we need to be able to creatively customize and equip CAR T-cells to target these tumors.

In this presentation, Cellectis shows that we can use the state-of-the-art TALEN technology to precisely edit up to four loci simultaneously while delivering several additional payloads to increase the efficacy and persistence of CAR T-cells.

The preclinical data demonstrate that multiplexed engineering does not compromise CAR T-cell function, which can even be enhanced and display improved anti-tumor activity. Thus, multiplexed engineering at superior efficiency rates while preserving genomic integrity has the potential to generate highly functional CAR T-cells to advance in the fight against solid tumors.

Cellectis takes it a step further and uses a curated combination of genome engineering technologies including TALE base editors (TALE-BE) to increase the efficiency of multiplexed gene editing while protecting genomic integrity.

"The immunosuppressive barriers of the tumor microenvironment antagonize CAR T-cells and have limited our ability to target solid tumors. These preclinical data show that we can precisely select and combine an array of gene and cell engineering approaches to produce armored CAR T-cells with high efficiency rates. With this strategy, we can focus on unmeet clinical needs and equip CAR T-cells with enhanced activity to help us in our quest to defeat solid tumors," said Beatriz Aranda Orgilles, Ph.D., Team Leader at Cellectis.

The poster presentation at ASGCT (Free ASGCT Whitepaper) highlights the following preclinical data:

Optimization of delivery timings and selection of compatible TALEN pairs provides high editing efficiency while attenuating potential TALEN crosstalk.

TALEN and TALE-BE technologies can be integrated in the generation of CAR T-cells to provide high gene editing rates while preserving genomic safety.

CAR T-cells can be engineered to carry multiple edits and simultaneously exhibit several key features to combat solid tumors: immuno-evasive properties, secretion of the pro-inflammatory cytokine IL-12, resistance to the immunosuppressive pathways PD-1 and TGFB1.

Multi-equipped CAR T-cells can efficiently target in vivo and in vitro models of triple negative breast cancer, an aggressive tumor that to date has limited therapeutic possibilities.
Title: Expanding the Scope of Multiplex Engineering for Superior Generation of Efficient CAR T-cells

Presenter: Beatriz Aranda Orgilles, Ph.D., Team Leader at Cellectis

Session Date/Time: 5/17/2023 12:00 PM PDT
Session Title: Wednesday Poster Session
Poster Board Number: 604

Final Abstract Number: 604

Poster of the presentation will be available on Cellectis’ website after the presentation: View Source

On May 17, 2023 Almac Diagnostic Services, a member of the Almac Group, reported significant updates to claraT, its unique software-driven solution for gene expression data analysis, which gives cancer researchers access to the most comprehensive and robust biomarker discovery support available (Press release, Almac, MAY 17, 2023, View Source [SID1234631802]).

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Almac’s claraT, which has supported over 60 oncology studies to date for multiple Biopharma and Academic clients, classifies the most biologically relevant gene expression signatures into a comprehensive easy-to-interpret report that covers all 10 Hallmarks of Cancer.

The updates include 16 new gene expression signatures across the Hallmarks of Cancer, improved functionality with online data access and simplified reporting through an interactive dashboard. Clients receive a unique, interactive report that allows the easy visualisation of the key discriminating biologies within either a large cohort or an individual tumour sample.

Toshimitsu Uenaka, President EPAT (Epochal Precision Anti-Cancer Therapeutics), at Eisai Inc., whose translational team have used Almac claraTstated: "We really found the claraT analysis of our studies to be very informative and a useful tool for our future drug discovery."

Adding these new gene expression signatures ensures that claraT remains current in the market with the most up to date content available. Almac claraT offers a unique solution in the market for biomarker discovery from either RNASeq data generated from sample profiling within Almac labs or from gene expression data sets generated elsewhere that require further bioinformatics analysis.

Professor Richard Kennedy, Global VP and Medical Director, Almac Diagnostic Services said: "Being able to equip leading Biopharma and academic cancer researchers globally with a powerful gene expression analysis platform has supported the identification of exciting new data.

"Conventionally gene expression signatures are applied individually to classify patients into molecular subgroups. Signatures designed to identify the same biology are often developed independently using different bioinformatics algorithms and therefore may not classify identically. To address this, we developed the claraT software solution which uses consensus between multiple published signatures, categorised into the Hallmarks of Cancer, to classify cancers in a more robust manner. Importantly, this standardised bioinformatics approach enables the analysis of datasets in a highly reproducible and cost-effective offering.

"Our proprietary claraT report has demonstrated its ability to accelerate mRNA-based research, enabling deeper insights into translational cohorts which leads to better drug development and trial stratification, potentially contributing to better patient outcomes in the future."

Almac Diagnostic Services is hosting a GenomeWeb Webinar on Tuesday 13th June alongside leading cancer researchers from the University of Kansas, USA. The webinar will focus on how claraT was utilised effectively within breast cancer studies.

The LIVE webinar will be held at 11am EDT / 4pm BST and interested parties can sign up here.

On May 17, 2023 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported new data featuring novel approaches combining the company’s platform CAR T cell and T cell receptor technology and unique cell therapy engineering capabilities to potentially enhance treatment potency in a range of cancers (Press release, 2seventy bio, MAY 17, 2023, View Source [SID1234631801]). The data were shared in three presentations at this year’s American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting in Los Angeles, California.

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"We’re excited to present new data related to our programs in acute myeloid leukemia, non-Hodgkin lymphoma and solid tumors," said Philip Gregory, D.Phil., chief scientific officer, 2seventy bio. "These presentations provide further evidence of our focus on generating potent and targeted anti-tumor activity while limiting toxicity through innovative approaches to controlling T cell responses. With this approach, we believe we can augment the tremendous potential of cell-based immunotherapy, with the goal of advancing next-generation treatments targeting a broad range of cancer types."

bbT369, a dual-targeted and CBLB gene edited autologous CAR T product for non-Hodgkin lymphoma, showed edit-driven enhanced activity in preclinical in vitro and in vivo models

bbT369 is 2seventy’s novel investigational CD79a/CD20 dual-targeting CBLB gene edited CAR T cell therapy for the treatment of patients with relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). This preclinical study evaluated the role of the CBLB edit across multiple aspects of CAR T cell function compared to unedited controls. In the study, in vitro assays were designed to model known challenges to maximal CAR T cell activity within the tumor, such as chronic activation, antigen downregulation, and immunosuppression.

The data demonstrated that the CBLB gene edit significantly enhanced the activity of the bbT369 CAR T cells across each of the in vitro model systems tested.
bbT369 T cells also drove greater T cell expansion and durable tumor control compared with unedited controls in vivo using a xenograft NSG mouse model.
RESET, a novel TCR coupled antigen receptor architecture, showed targeting sensitivity and pharmacologically- controlled anti-tumor activity in models of acute myeloid leukemia

For some tumors, available target antigens lack ideal expression, necessitating improvements in targeting sensitivity, potency, control, and/or exhaustion mitigation to achieve robust anti-tumor efficacy. While classical CAR T cells require high levels of target antigen for maximum activity, the endogenous T cell receptor (TCR) is significantly more sensitive to low target antigen abundance. To address this gap, a novel receptor architecture called RESET (rapamycin-enabled, switchable endogenous TCR) was developed to more closely mimic TCR activation, thus potentially improving T cell killing of low antigen expression tumor cells. RESET combines the antibody-based targeting of CARs, the drug-regulated activity of the DARIC (a rapamycin-regulated CAR) technology and the natural signaling proficiency and inherent sensitivity of TCRs. The RESET receptor comprises two functional units that are designed to enable toggling of RESET T cells between inert and activated states through rapamycin-induced dimerization:

When challenged with low antigen density tumor cells in vitro, CD33-targeted RESET T cells (RESET33) were more potently reactive to CD33+ tumor cells after rapamycin dimerization, secreting approximately three times more cytokine than CD33-targeted regulated CAR T cells.
This enhancement was also observed in preclinical NSG mouse models in vivo, where RESET33 T cells more deeply controlled systemic CD33+ AML tumor models, providing a significant survival benefit in comparison to DARIC33 T cells.
A novel TGFβ switch receptor drove robust MAGE-A4 TCR anti-tumor activity with a favorable safety profile

Solid tumors frequently secrete TGFβ, a pleiotropic cytokine that suppresses T cell responses. To counteract the immunosuppressive effects of TGFβ within engineered T cells, a synthetic receptor (CTBR12) was developed to leverage an immunosuppressive cytokine to convert TGFβ binding into pro-inflammatory signaling events that enhance anti-tumor function:

T cells co-expressing a pairing enhanced MAGE-A4 TCR with the CTBR12 switch receptor demonstrated robust antigen-dependent responses that were significantly enhanced upon exposure to TGFβ, whereas MAGE-A4 TCR controls lacking CTBR12 were suppressed by this anti-inflammatory cytokine.
CTBR12 co-expression did not alter the safety profile of the MAGE-A4 TCR.
In two murine xenograft tumor models with abundant TGFβ, T cells co-expressing the MAGE-A4 TCR and CTBR12 both controlled tumors at T cell doses that elicited only minimal responses without CTBR12 co-expression and exhibited superior durability of response overall.
About SC-DARIC33

SC-DARIC33 is an investigational CD33-specific cell therapy that utilizes 2seventy bio’s proprietary Dimerizing Agent Regulated Immunoreceptor Complex (DARIC) T cell platform. SC-DARIC33 is designed as a regulatable, potentially first-in-class autologous T cell therapy and is now being studied at Seattle Children’s in a Phase 1 trial, PLAT-08 (NCT05105152), as a first-in-human investigation of the DARIC T cell platform in relapsed/refractory pediatric and young adult AML.

DARIC separates the antigen binding and signaling functions of a CAR, with the intent that these two components are brought together by the small molecule rapamycin, resulting in a functional CAR construct. In preclinical studies, SC-DARIC33 has shown robust drug-dependent anti-tumor activity (similar to CD19 CAR T controls). Importantly, SC-DARIC33 has been shown to be activated by low non-immunosuppressive concentrations of rapamycin in the blood and, when rapamycin is removed, DARIC returns to an inactive state. SC-DARIC33 tests the hypothesis that a pharmacologically regulated CAR can enable potent AML targeting while limiting toxicities associated with normal myeloid and myeloid progenitor cell targeting.

The investigation of SC-DARIC33 in the Phase 1 PLAT-08 study of pediatric and young adult AML patients and the scientific translation of these data are intended to establish the safety profile of SC-DARIC33 and evaluate feasibility of the reversable modulation (OFF-ON-OFF) of SC-DARIC33.

SC-DARIC33 is not approved for any indication in any geography.

About bbT369

bbT369 is an investigational dual-targeting CAR T cell therapy with a gene edit being evaluated for the treatment of patients with relapsed and/or refractory B-NHL currently being evaluated in a first-in-human Phase 1/2 trial (CRC-403 NCT05169489). bbT369 was purposely designed with three layers of innovation to address the potential mechanisms of anti-CD19 CAR T cell therapy failure, including dual targeting of CD79a/CD20, which is a novel combination of antigens highly expressed in B cell lymphomas, a split co-stimulation signaling technology intended to drive more robust T cell activation, and a gene edit to remove the function of CBLB, a known negative regulator of T cells.

In the 3L+ relapsed and/or refractory B-NHL setting, 60-70% of patients treated with commercially available CAR T cell therapies do not achieve a long-term remission, highlighting a significant unmet clinical need.

In December 2021, the FDA cleared the Investigational New Drug (IND) application for bbT369.

The clinical development program for bbT369 includes the Phase 1/2 CRC-403 study (NCT05169489). Safety and potential efficacy of bbT369 in patients with specific subtypes of relapsed and/or refractory B-NHL will be assessed, including patients who relapsed after CD19 CAR T cell therapy as well as patients who are CAR-naïve.

bbT369 is not approved for any indication in any geography.

About the MAGE-A4 Program

MAGE-A4 is a member of the MAGE family of cancer-testis antigens expressed in a number of solid tumor types. The program employs a highly potent TCR discovered in our MediGene collaboration that recognizes HLA-presented MAGE-A4 peptides and further enhances the potency of these re-directed T cells using our CTBR12 TGFβ "flip" receptor technology — which converts the immunosuppressive effects of TGFβ into an activation signal for the T cells. Regeneron and 2seventy bio are co-developing the program under their collaboration entered into in 2018.