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CGT Watch Newsletter: April'25 Edition

Welcome to the April edition of our CGT Watch newsletter! 


Autolus’ Aucatzyl’s UK approval; BrainChild Bio’s BCB-276 BTD; Lyell’s LYL314 RMAT designation; TScan’s Ph1 trial update; CERo’s IND approval; CARGO's assets discontinuation; Carisma assessing strategic alternatives; BioNtech co-development option expiration; Caribou Bio restructuring. 


Stay informed on the latest advancements in the CGT space—subscribe now to receive insightful updates straight to your inbox. 


Dear Readers,

 

We’re excited to bring you April edition of CGT watch highlighting updates on novel targets, innovative approaches, first-of-its-kind combinations and key developments that unfolded throughout March and April. In addition, we feature highlights from AACR conference (based on the abstract data) that fall under this novel category. 

Since we’re keen to keep things concise and focused, this issue will exclusively cover cell therapies. 


Section 1: Key Monthly Updates


💰 Investments & Funding

 

⭐ France-based Allogenica’s secured €2.5 Million Grant (Ref) 


Allogenica secured €2.5 Million Grant from French government's France 2030 program and below are its allogeneic programs: 


  • XL-001, anti-CD19 CAR-T which is produced from immature T cells precursors (pre-T) derived from donor stem cells for the treatment of Blood Cancers. Allogenica aims to initiate Phase 1 clinical trials by 2027. 

  • XL-002, an armed CAR-pre-T therapy to target Leukemia 

  • XL-003, an engineered pre-T therapy for Solid Tumors 


👉 Why it matters: By utilizing donor-derived pre-T cells, Allogenica is aiming to address key challenges in cell therapies such as scalability, accessibility, and production timelines 


🚀 What’s new: 


⭐ First Cocktail CAR-T targeting five antigens for Solid Tumors (Ref) 


While cocktail CAR-T therapies targeting 2-4 antigens have been explored previously, researchers at the National Cancer Center Japan, collaborating with Optieum Biotechnologies Inc. are now developing cocktail CAR-T therapy targeting five antigens (ROBO1, EphB4, CLDN1, LAT1, and GPC3) for solid tumors for the first-time. 


👉 Why it matters: This approach aims to address the challenges posed by antigen heterogeneity in solid cancers and likely be usable against most solid tumors. Notably, no CAR-T therapies currently targeting CLDN1 or LAT1, making this innovation a pivotal entry point for these new antigen-targeting CAR-Ts into the therapeutic landscape. 


⭐ ELECTRIC CAR-T: A new spark in pediatric AML treatment (Ref) 


Stanford University School of Medicine’s ELECTRIC CAR-T cells were designed to achieve trivalent specificity by integrating SCF, TPO, FLT3LG, which are the cognate ligands to target KIT, MPL and FLT3 into a single trivalent ligand (ELECTRIC) protein. These second-generation CARs include a codon-optimized ELECTRIC domain linked to CD28 and CD3ζ signaling domains. 

These CAR-Ts are engineered to overexpress CXCR4 to enhance trafficking to the bone marrow and spleen, boosting anti-leukemic efficacy. By targeting AML LSCs, HSPCs, and pre-leukemic HSPCs, these can also be used as HSCT conditioning regimen.

 

👉 Why it matters? Previously, single-antigen CAR-T therapies targeting KIT, MPL, or FLT3 were explored for AML treatment. However, for the first time, a TRIVALENT CAR-T has been developed, incorporating a codon-optimized ELECTRIC domain to simultaneously target KIT, MPL, and FLT3. This multi-specificity addresses antigen heterogeneity within leukemia cells, potentially reducing the likelihood of escape of cancer cells. . 


⭐ Novel MSLN NKG2D BiTE CAR-T for TNBC (Ref) 


Although various BiTE-secreting CAR-T cells have been explored previously, the Chinese Academy of Sciences' development of a nanobody-based, mesothelin (MSLN)-targeting CAR-T cell that secretes NKG2D BiTEs represents a novel approach in the CGT field. In vivo, these BiTE-secreting CAR-T cells demonstrated potent antitumor activity in TNBC models, significantly reducing tumor burden and prolonging survival without detectable toxicity. 


👉 Why it matters: TNBC is an aggressive subtype with poor prognosis and limited treatment options. This approach uniquely overcomes tumor antigen heterogeneity and escape, showing enhanced cytotoxicity, T cell activation, and in vivo tumor regression with low immunogenicity and high stability. 


⭐ PTGFRN - A New CAR-T Target for Glioblastoma (Ref) 


Osaka University’s researchers identified PTGFRN as a potential target for CAR-T therapy for GBM. Out of 3,200 clones, 5E17 mAb bound to tumor cells in 6 of 7 GBM patients while sparing non-malignant brain cells, identifying PTGFRN as its target. Although cytotoxicity was observed in vitro, there was no significant effect of intracranial injection of PTGFRN CAR-T cells on overall survival in vivo. 


Targeting patients with increased PTGFRN expression and optimizing CAR-T cell delivery methods, such as integrating intracavitary, intraventricular, and IV administration, could enhance survival outcomes. Nevertheless, these factors were not examined in the present study, highlighting the need for additional research. 


👉 Why it matters: Out of approximately 251 CAR-T programs focused on Glioma/GBM, only 39 have progressed to the clinical phase. This underscores the need for novel therapeutic targets and strategies in GBM treatment. PTGFRN has now emerged as a promising target in addressing this need. 


⭐ Novel Synthetic Chimeric T-cell receptors (ChTCRs) (Ref) 


Fred Hutch’s novel synthetic ChTCR conferred superior antigen sensitivity compared with CARs and previous hybrid TCR designs and was readily adapted for bispecific targeting. 

The concept of linking an antigen-binding domain to the TCR to improve sensitivity is not new. However, earlier designs faced challenges such as mispairing between the engineered ChTCR chains and the endogenous TCR chains, as well as competition for CD3 molecules.

 

To address these issues, the researchers used base editing to disrupt the expression of endogenous TCR chains (TRAC and TRBC genes). This method avoids double-strand DNA breaks, reducing risks like chromosome losses or translocations. 


👉 Why it matters: In vivo models demonstrated that Bi-ChTCR T cells outperform bispecific CAR-T cells and two monospecific CAR-T products in treating tumors with heterogeneous antigen expression. This reduces the likelihood of antigen-low tumor cells escaping therapy. 


⭐ New target HLA-DRB1 for AML (Ref) 


Osaka University identified HLA-DRB1 as a leukemia-specific target of CAR-T/NK cells in patients with AML after allo-HCT. The KG2032 monoclonal antibody specifically binds to AML cells with mismatched HLA-DRB1, offering a targeted approach for patients relapsing after allo-HCT. 


👉 Why it matters: This targeted approach of mismatched HLA-DRB1 has the potential to tackle the challenge of relapse and may improve outcomes through precise targeting while minimizing off-target effects. 


⭐ New multi-targeting super Hi-TCR-T (Ref) 


A new Phase 1/2 trial has been listed on CT.gov evaluating Eastern Hepatobiliary Surgery Hospital’s super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP for the treatment of refractory/recurrent advanced HCC and other solid tumors. Peripheral blood lymphocytes were collected and Hi-TCR-T cells targeting three targets (including FAP) were prepared. 


👉 Why it matters: Previously, Hi-TCR-T therapies focused on targeting single antigens. This multi-target Hi-TCR-T clinical trial seeks to address challenges such as antigen loss and tumor heterogeneity. 


⭐ TScan’s new T-plex combinations (Ref) 


TScan Therapeutics’s Phase 1/TSCAN-002 basket trial update unveiled new T-plex combinations for the treatment of Solid Tumors. TSC-202 (anti-MAGE-A4) is being tested with different other TCR-Ts (TSC-200 (anti-HPV16), TSC-201 (anti-MAGE-C2), TSC-203 (anti-PRAME) and TSC-204 (anti-MAGE-A1)) with different HLA combinations. 


👉 Why it matters: TScan T-Plex is a multiplexed cell therapy consisting of two to three distinct TCR-Ts selected from its ImmunoBank repository. With this T-plex, TScan is evaluating many combinations with different HLA types to address the antigen heterogeneity and other challenges associated with Solid Tumors. 


🎯 Regulatory Updates: 


⭐ The UK’s approval of Autolus’ Aucatzyl (Ref) 


The UK MHRA granted conditional marketing authorization for Aucatzyl (obecabtagene autoleucel; an autologous, anti-CD19 CAR-T) for the treatment of adult R/R B-ALL patients based on the results from the Ph1/2 FELIX/NCT04404660 study. 


👉 Why it matters: This will be the second CAR-T to receive approval from the UK MHRA for the treatment of R/R B-ALL in adults after Gilead Sciences’s Tecartus (an autologous, anti-CD19 CAR-T). Autolus Therapeutics , being a UK-based biopharma, could leverage its local presence for added advantage. 


 ⭐ Lyell’s LYL314 received RMAT Designation for R/R LBCL (Ref) 


The US FDA granted RMAT designation to Lyell’s LYL314 (formerly IMPT-314; an autologous, anti-CD19/CD20 CAR-T) for the treatment of adult patients with ≥3L R/R LBCL. The designation was granted based on the clinical data from the ongoing Phase 1/2 trial which was presented at ASH 2024 conference (ORR was 94.1% (CR: 70.6%) in 17 evaluable CAR-T naïve LBCL pts). 


👉 Why it matters: LYL314 was originally developed by ImmPACT Bio which was later acquired by Lyell Immunopharma. Previously, this CAR-T received Fast Track Designation for ≥3L multiple types of B-cell Lymphoma. This will be the second CD19/CD20 dual CAR-T to receive RMAT designation. AbelZeta’s Prizloncabtagene autoleucel is the first CD19/CD20 bispecific CAR-T to get the RMAT designation for the treatment of R/R DLBCL (Ref). These designations highlight the potential of dual targeting CAR-Ts for aggressive Hematological Cancers. 


⭐ BrainChild Bio’s BCB-276 received Breakthrough Designation for DIPG (Ref) 


The US FDA had granted Breakthrough Therapy Designation (BTD) for BrainChild Bio’s BCB-276 (an autologous, anti-B7-H3 CAR-T) for the treatment of diffuse intrinsic pontine glioma (DIPG) based on the encouraging survival data from the Ph1 BrainChild-03/NCT04185038 trial. 


👉 Why it matters: DIPG is a rare and aggressive Brain Tumor which primarily affects children between the ages of 5 and 10. BCB276 is the first CAR-T to receive BTD for the treatment of DIPG. 


⭐ CERo Therapeutics’s CER-1236 received FDA greenlight for Phase 1 in Solid Tumors (Ref)


The US FDA cleared CERo Therapeutics, Inc. ’s IND for CER-1236, a first-in-class CER-T (anti-Tim-4L chimeric engulfment receptor T-cell), for Phase 1 trials in advanced solid tumors specifically, NSCLC and ovarian cancer 


👉 Why it matters: CER-1236 is the first CAR-T to target TIM-4L and integrate phagocytic activity into T cells. Preclinical data suggest that this dual mechanism may help overcome key resistance barriers that have hampered solid tumor CAR-T trials. 


🛑 Setbacks: 


⭐ CARGO Therapeutics discontinued remaining CAR-T Programs (Ref)

 

CARGO Therapeutics discontinued its remaining assets, including CRG-023 (an autologous, anti-CD19/CD20/CD22 tri-specific CAR-T) which was in preclinical development for the treatment of B-cell malignancies and its allogeneic platform 


👉 Why it matters: Cargo Therapeutics invested much of its resources on firi-cel (an autologous, anti-CD22 CAR-T) which faced discontinuation due to safety issues and an inability to demonstrate a favorable benefit-risk profile. The company had decided to suspend the development efforts of both CRG-023 and CARGO’s allogeneic platform to lead the company through a reverse merger or other business combination.


⭐ Carisma Therapeutics has been exploring strategic options for CAR-M assets (Ref) 


Carisma Therapeutics paused R&D activities and is exploring strategic alternatives to maximize value, including selling or licensing its assets, collaborating with other companies, or a merger or outright sale of the company 


👉 Why it matters: The discontinuation of Carisma Therapeutics' R&D activities is particularly significant considering its promising collaboration with Moderna on in vivo CAR-M therapies. Preclinical studies demonstrated that systemic administration of anti-GPC3 in-vivo CAR-M significantly reduced tumor burden and effectively suppressed liver metastasis. Additionally, this partnership includes four other nominated targets within the oncology domain. The discontinuation raises questions about the future development of these in vivo therapies 

 

⭐ BioNTech passes on Autolus’ CD19/CD22 CAR-T AUTO1/22 (Ref) 


BioNTech SE has opted out of co-developing Autolus Therapeutics’ AUTO1/22 (an autologous, anti-CD19/CD22 dual CAR-T), allowing its option to expire as part of its pipeline prioritization strategy. 


👉 Why it matters: AUTO1/22 aims to reduce antigen-negative relapses. Per preliminary results, MRD-negative CRR was 83.3% (10 out of 12) in pediatric B-ALL patients (Ref). BioNTech's decision to pass on its co-development raises potential questions about AUTO1/22's clinical efficacy, with updated Phase 1 results anticipated to provide further insights. 

 

⭐ Caribou Biosciences is restructuring to focus on key programs (Ref) 


Caribou Biosciences announced strategic pipeline prioritization to focus on clinical assets CB-010 (an allogeneic, anti-CD19 CAR-T) and CB-011(an allogeneic, anti-BCMA CAR-T); discontinued CB-012 (an allogenic, anti-CLL-1 CAR-T) which was in Ph1 trial for the treatment of R/R AML and preclinical research 


👉 Why it matters: These changes are expected to extend Caribou’s cash runway by one year, funding the company’s current operating plan into H2’27, compared to H2 2026 as previously reported. Additionally, key clinical data from CB-010 and CB-011 are expected to be released in H2’25, providing insights into the progress of its allogeneic CAR-T programs. 

 

Section 2: Cell Therapies Pipeline Landscape – An Overview 


⭐ New Antigens: PTGFRN; Mismatched HLA-DRB1; CLDN1 (CLD1/SEMP1); LAT1 (SLC7A5)

 

⭐ New antigen combinations: ROBOI (DUTT1) + EPHB4 (HTK, MYKI, TYRO11) + CLDN1 (CLD1/SEMP1) + LAT1 (SLC7A5) + GPC3; MAGE-A1 + MAGE-A4; HPV-16 E7+ MAGE-A4; PRAME + MAGE-A4; MAGE-C2 + MAGE-A4

 

CD117 (KIT/SCFR) & MPL & FLT3 (CD135, FLK2, STKI) (+ is used to represent the cocktail CAR-Ts; & is used to represent dual/triple/multiple antigens targeting CAR-T) 


⭐ Novel strategies: Novel ChTCR; Cocktail CAR-T with five antigens; Electric CAR-T 

As an oncology-focused business consulting firm, we closely monitor emerging modalities in the oncology space. Our weekly tracking now covers over 4,600 (vs 4500+ previously) preclinical and clinical CGT programs, covering 75 critical parameters—ranging from basic details and molecular characteristics to clinical outcomes. 


CAR-T therapies, with over 3,800 programs (vs 3700+ previously), including 30 programs in the regulatory phase (refer exhibit 1a). dominate the CGT landscape. Globally, thirteen unique CAR-T therapies have been approved for treating various hematological malignancies, and two remain under regulatory review remain same with no changes reported based on updates from the month of March. 


Moving to TCR-T therapies, a different type of engineering observed on T-cells, TCR-T therapies are steadily gaining prominence, with around 410 programs (vs 380 previously) in development (refer exhibit 1b). Notably, one TCR-T therapy has been approved for the treatment of synovial sarcoma, marking a significant milestone in the field. However, there has been no change in this number based on the updates from March.


An Overview of CAR-Ts and TCR-Ts
An Overview of CAR-Ts and TCR-Ts

Beyond CAR-T and TCR-T therapies, CAR-NK therapies are emerging as a promising alternative, leveraging the natural cytotoxic capabilities of NK cells for therapeutic applications. Currently, 360 (vs 330 previously) CAR-NK programs are under development, with 239 (vs 217 previously) still in the early stages, reflecting strong research interest in this modality. 


An Overview of CAR-NKs and CAR-NKTs
An Overview of CAR-NKs and CAR-NKTs

Other cell therapies, such as CAR-macrophages and CAR-NKTs, are also being explored, but their numbers remain limited. 


A Request 


We’d love your feedback—what did you find most interesting? If you have any questions or insights, feel free to hit reply or reach out. We look forward to exploring more breakthroughs with you in our next newsletter. 


We have developed Newsletter Special Editions for AACR'25, ASCO'25, and ASGCT'25 Conferences 



📝 The AACR'25 edition includes the updates from  



 

📝 The ASCO’25 edition includes the updates from 




📝 The ASGCT’25 edition includes the updates from 




If you're interested in receiving the Special Edition Newsletter, comment with "Interested - AACR'25/ASCO'25/ASGCT'25" or "Interested - All Three" to get it sent directly to you! 

Until next time, 

The CGT Watch Team 

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