​What are you looking for?

May 3rd Week, 2025 ⭐ Regulatory Update   🎯 The US FDA granted the RMAT designation to  BrainChild Bio ’s BCB-276 (an autologous, B7-H3 CAR-T) for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG) based on the positive survival data from the Ph1 BrainChild-03/NCT04185038 trial (Ref 1)  ❓ Which other CAR-Ts are currently being investigated in clinical trials for DIPG?   ⭐ Clinical DataReadouts 🔬 Updated data from the pivotal Ph2, iMMagine-1/NCT05396885 trial of  Gilead Sciences  &  Arcellx ’s anitocabtagene autoleucel (an autologous, anti-BCMA CAR-T) in ≥ 4L Mutliple Myeloma (MM) demonstrated an ORR of 97.4% (67.5% CR/sCR) with a median follow-up of 12.6 mos in 117 pts (Ref 2)  ❓ Which other BCMA CAR-Ts are currently in registrational trials for the treatment of R/R MM? 🔬  Artiva Biotherapeutics  presented long-term Ph1/2, NCT04673617 data at ASGCT for AlloNK (AB-101; an allogenic, non-genetically modified NK cell therapy) + rituximab in patients with R/R B-NHL that were CAR-T naive (CRR: 64.3%; mDOR: not reached in 14 patients) (Ref 3)  ❓ How does the efficacy of AlloNK compare with the approved CD19 CAR-Ts for R/R B-NHL?   🔬  NeoImmuneTech  reported final topline Ph1b, NCT05075603 results for efineptakin alfa (NT-I7; IL-7Rα agonist) + CD19 CAR-T ( Novartis ’ Kymriah/ Gilead Sciences ’s Yescarta/ Bristol Myers Squibb ’s Breyanzi) for R/R LBCL with 100.0% ORR in high-dose cohort (n=8) (Ref 4)  ❓ What are the other key combination strategies being explored alongside CAR-T therapies in R/R LBCL? ⭐ Business Update  💼  Galapagos  decided to re-evaluate the previously proposed separation into two entities (Galapagos, on cell therapy, and SpinCo, on building a pipeline of innovative medicines) and will explore all strategic alternatives for its existing businesses (Ref 5)  ❓ Which CGT assets will be impacted by this strategic assessment?    To know answers to these questions and for additional insights, write to us at  support@oncofocus.com .   🌐 References:  1) https://brainchildbio.com/wp-content/uploads/2025/05/BrainChild-Bio-RMAT-PR_FINAL.pdf 2) https://ir.arcellx.com/news/news-details/2025/Arcellx-Announces-New-Positive-Data-for-Its-iMMagine-1-Study-in-Patients-with-Relapsed-andor-Refractory-Multiple-Myeloma/default.aspx 3) https://investors.artivabio.com/News-and-Events/news/news-details/2025/Artiva-Biotherapeutics-Announces-Longer-term-Phase-12-Data-Demonstrating-Prolonged-Durability-for-AlloNK-in-Combination-with-Rituximab-in-Patients-with-B-cell-Non-Hodgkin-Lymphoma-at-the-ASGCT-28th-Annual-Meeting/default.aspx 4) https://www.neoimmunetech.com/en/irpr/news/984 5) https://www.glpg.com/press-releases/galapagos-announces-strategic-update-on-proposed-separation-executive-leadership-transition-and-board-changes/

April 3rd & 4th, 2025 Regulatory Updates   🎯 The UK MHRA granted conditional marketing authorization for  Autolus Therapeutics ’ 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 (Ref 1)  ❓ In what ways does Aucatzyl’s fast off-rate CD19 binding domain differentiate it from existing CD19 CAR-Ts for B-ALL?    🎯  Lyell Immunopharma  received RMAT designation for LYL314 (formerly IMPT-314; an autologous, dual-targeting CD19/CD20 CAR-T) for the treatment of ≥3L LBCL based on promising clinical data from the ongoing Ph1/2 Duali-T-1/NCT05826535 trial in CAR-T naïve LBCL pts (Ref 2)  ❓ What are the next steps planned for this ongoing Ph1/2 trial of LYL314?  🎯 The US FDA granted Breakthrough Therapy Designation 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 (Ref 3)  ❓ What are the other CAR-Ts that are being studied in clinical trials for DIPG?  Clinical Data Readouts   🔬 Updated results from the Ph1 SENTI-202-101/NCT06325748 clinical trial evaluating SENTI-202 (an off-the-shelf, logic gated, selective CD33/FLT3-targeting CAR-NK) for R/R AML were presented at AACR 2025 (ORR was 71.4% in 7 evaluable pts) (Ref 4)  ❓ What advantages do logic-gated designs offer in minimizing off-target effects?  Deals and Collaborations :     🤝 DAAN Biotherapeutics signed an exclusive licensing agreement with  GC Cell , granting GC Cell sole rights to leverage DAAN's antibody sequence for R&D of CAR-T and CAR-NK therapies (Ref 5)  ❓ What key advantages does GC Cell gain by utilizing the antibody sequence?    Setbacks :  🛑  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 AMpLify/NCT06128044 trial for the treatment of R/R AML (Ref 6)  ❓ What early findings provide the rationale for prioritizing CB-010 and CB-011? To know answers to these questions and for additional insights, write to us at  support@oncofocus.com .  🌐 References 1) https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-license-aucatzylr-obecabtagene 2) https://ir.lyell.com/news-releases/news-release-details/lyell-immunopharma-receives-regenerative-medicine-advanced 3) https://www.brainchildbio.com/uploads/BTD_Press_Release_18April2025_FinalforNewswire.pdf 4) https://aacr.ent.box.com/s/27qq7rab526regolw78ias1pc7odjapy 5) https://daanbiotpx.com/bbs/board.php?bo_table=notice&wr_id=32 6) https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-strategic-pipeline-prioritization

April 2nd April, 2025 ⭐ Regulatory Events 🎯 The US FDA cleared an IND application of  CERo Therapeutics, Inc. ’s CER-1236 (anti-Tim-4L chimeric engulfment receptor T-cell (CER-T)) for a Phase 1 trial in advanced solid tumors specifically NSCLC and ovarian cancer (Ref 1)   ❓ What is the difference between CER-T and CAR-Ts and what benefits do CER-Ts offer?    ⭐ Setbacks 🛑  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 (Ref 2)   ❓ What is the status of its deal with  Moderna ?   ⭐ EBMT 2025  Highlights 👉 Academia-sponsored dual-targeting optimized hinge tandem CD19/20 CAR-T cell therapy demonstrated favorable outcomes particularly when administered following ASCT in a China-specific Phase 1/2 trial in R/R LBCL patients (Ref 3)   ❓ How do dual target CAR-Ts with a tandem design differ from those utilizing loop connections or parallel styles?  👉 Beijing Gobroad Hospital’s allogeneic, anti-CD7 CAR-T achieved a CR rate of 94.1% (N=17) in a Phase 1/ChiCTR2200058969 trial in patients with T-cell Lymphoma who relapsed following allo-HSCT. (Ref 4)  ❓ How many allogeneic CAR-Ts are in development for the treatment of T-cell Lymphoma?    👉 Goethe University & DKTK’s IL-15 armored LLAMA-derived VHH-based anti-CLEC12A CAR-NK cells showed superior in vivo anti-leukemic activity in an AML model outperforming scFv-based constructs (Ref 5)   ❓ What were the key findings from the in vitro and in vivo evaluations? To know answers to these questions and for additional insights, write to us at  support@oncofocus.com . 🌐 References:  1) https://www.cero.bio/press-release?storyId=6698663783956500 2) https://ir.carismatx.com/static-files/b6296641-fa2d-4463-aacf-26204495719c 3) https://ebmt2025.abstractserver.com/program/#/details/presentations/2008 4) https://ebmt2025.abstractserver.com/program/#/details/presentations/953 5) https://ebmt2025.abstractserver.com/program/#/details/presentations/2257

March 3rd Week, 2025 Regulatory Events 🎯 The European commission granted approval to  Bristol Myers Squibb ’ Breyanzi (lisocabtagene maraleucel; an autologous, anti-CD19 CAR-T) for the treatment of adult patients with ≥3L FL (Ref 1)  ❓ How many CAR-Ts are currently approved for FL, and what makes Breyanzi unique?  🎯 The US FDA granted Fast Track Designation (FTD) to  Imugene Limited ’s azercabtagene zapreleucel (azer-cel; an allogeneic, anti-CD19 CAR-T) for the treatment of R/R DLBCL patients who progressed on prior therapies, including autologous CAR-T (Ref 2)  ❓ How many allogeneic CAR-Ts have been granted FTD and what are they?  🎯  Anocca  received Clinical Trial Application (CTA) authorization from the regulatory authorities in four European countries under the EU harmonized framework for Phase 1/2/VIDAR-1 clinical trial evaluating ANOC-001 (KRAS G12V targeting non-viral gene edited TCR-T) for the treatment of PDAC. (Ref 3)  ❓ How do non-viral gene-edited TCR-T therapies, such as ANOC-001, stand out from viral edited TCR-T therapies?  Mergers and Acquisitions 🤝  AstraZeneca  concluded a $1 billion agreement to acquire  EsoBiotec , a company specializing in in vivo cell therapies. The EsoBiotec Engineered NanoBody Lentiviral (ENaBL) platform employs highly targeted lentiviruses to deliver genetic instructions directly to specific immune cells—such as T cells—programming them to recognize and destroy tumor cells. (Ref 4)  ❓ Which other companies are developing In Vivo cell therapies?  Setbacks 🛑  CARGO Therapeutics  discontinued its remaining assets, including CRG-023 (an autologous, anti-CD19/CD20/CD22 tri-specific CAR-T) that was in preclinical development for the treatment of B-cell malignancies and its allogeneic platform (Ref 5)  ❓ What led Cargo Therapeutics to discontinue its remaining assets? 🛑  Adaptimmune  has raised concerns about its sustainability, leading to the discontinuation of two preclinical programs—ADP-600 (an autologous, PRAME targeting TCR-T) for solid tumors, and ADP-520 (an autologous, CD70 targeting TCR-T). The company is also actively evaluating strategic options for its future. (Ref 6)  ❓ Why is Adaptimmune exploring strategic options despite having an approved product? 🛑  BioNTech SE  has chosen to let its collaboration option expire for  Autolus Therapeutics ’ AUTO1/22 (an autologous, anti-CD19/CD22 dual CAR-T) as part of its portfolio prioritization (Ref 7)  ❓ What other collaboration opportunities remain for BioNTech with Autolus?  To know answers to these questions and for additional insights, write to us at  support@oncofocus.com . 🌐 References:  1) https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Receives-Approval-from-the-European-Commission-to-Expand-Use-of-CAR-T-Cell-Therapy-Breyanzi-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx 2) https://wcsecure.weblink.com.au/pdf/IMU/02926523.pdf 3) https://www.anocca.com/company/news/anocca-announces-authorisation-of-clinical-trial-application-to-start-first-in-human-trial-in-advanced-pancreatic-cancer 4) https://www.esobiotec.com/esobiotec-to-be-acquired-by-astrazeneca-to-advance-cell-therapy-ambition/ 5) https://investors.cargo-tx.com/news-releases/news-release-details/cargo-therapeutics-provides-corporate-update 6) https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/284/adaptimmune-provides-q4-and-full-year-2024-business-update 7) https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-reports-fourth-quarter-and-full-year-2024

March 1st Week, 2025 ⭐ Regulatory Events 🎯 China’s NMPA granted Breakthrough Therapy Designation (BTD) to  CARsgen Therapeutics ’ satricabtagene autoleucel (satri-cel; CT041; an autologous, anti-CLDN18.2 CAR-T) for the treatment of Claudin18.2-positive ≥third-line G/GEJ cancer (Ref 1)  ❓ What are CARsgen’s next steps in advancing satri-cel? Has CARsgen obtained similar designations in other markets? 🎯 The US FDA accepted  Bioheng Therapeutics ’ IND application for CTD402 (anti-CD7 UCAR-T) for the treatment of pediatric and adult patients with R/R T-ALL/LBL (Ref 2)  ❓ How many CD7 targeting UCAR-Ts are in development? How UCAR-Ts are different from conventional CAR-Ts?  ⭐ Setbacks   🛑  Atara Biotherapeutics  discontinued all development activities for ATA3219 (an allogeneic, anti-CD19 EBV CAR-T) currently in Phase 1 for the treatment of B-NHL, and ATA3431 (an allogeneic, anti-CD19/CD20 bispecific EBV CAR-T), which is in preclinical development for the treatment of B-cell malignancies (Ref 3)  ❓ Did the previous clinical hold on ATA3219 play a role in Atara's decision to discontinue its allogeneic CAR-T programs?   🌐 References:  1) https://www.carsgen.com/en/news/20250303/ 2) https://www.bioheng.com/News_Details/27.html 3) https://investors.atarabio.com/sec-filings/all-sec-filings/content/0000950170-25-030832/0000950170-25-030832.pdf

February 4th Week, 2025 📝 The US FDA granted RMAT designation for   ImmunityBio ’s Anktiva (n ogapendekin alfa inbakicept; IL-15 superagonist) and its PD-L1 t-haNK (an allogeneic, a-PD-L1 CAR-NK) for the reversal of lymphopenia in patients receiving SOC chemo/radiotherapy and in Multiply Relapsed Locally Advanced or Metastatic Pancreatic Cancer (Ref 1)  ❓ What are the next steps in the development process for Anktiva and PD-L1 t-haNK following the RMAT designation?  📝 UCARsgen  secured the exclusive rights in mainland China for the research, development, manufacture, and commercialization of the allogeneic CAR-T products from  CARsgen  Therapeutics (Ref 2)  ❓ Which allogeneic CAR-T products are covered under this agreement, and what are the financial details associated with it?  📝  Cellectis  unveiled its 'Smart CAR-T' strategy at AACR IO 2025, showcasing a design that enables CAR-inducible expression of the synthetically engineered FAP-IL-2 variant (IL-2v) immunocytokine to boost persistent anti-tumor activity of allogeneic CAR-Ts without associated IL-2 toxicity (Ref 3) ❓ How does the 'Smart CAR-T' strategy overcome the obstacles of targeting the solid tumor microenvironment (TME) while mitigating IL-2 toxicity, and what preclinical data supports this approach?  To know answers to these questions and for additional insights, write to us at  support@oncofocus.com . 🌐 References: 1) https://immunitybio.com/immunitybio-receives-fda-rmat-designation-for-anktiva-and-car-nk-for-the-reversal-of-lymphopenia-in-patients-receiving-standard-of-care-chemotherapy-radiotherapy-and-in-treatment-of-multiply-rel/ 2) https://www.carsgen.com/en/news/20250225/ 3) https://www.cellectis.com/en/press/cellectis-presents-smart-car-t-strategy-to-enhance-efficacy-against-solid-tumors-at-aacr-io-2025/

February 3rd Week, 2025 📝 BMS’ Breyanzi (liso-cel; an autologous, anti-CD19 CAR-T) received NICE recommendation as an option for treating Relapsed or Refractory Large B-cell Lymphoma after first-line chemoimmunotherapy when a stem cell transplant is suitable (Ref 1)  ❓ What new evidence led NICE to overturn its initial rejection of Breyanzi in Oct 2024?  📝 Anixa Biosciences received the approval to amend Ovarian Cancer Phase 1/NCT05316129 trial, allowing a second dose of FSHR CER-T (an autologous, Follicle Stimulating Hormone-specific chimeric endocrine receptor-T) and including more Ovarian Cancer histologies (sex cord-stromal tumors and Sertoli Leydig cell tumors) (Ref 2)  ❓ What is the significance of the protocol amendment for this trial? To know answers to these questions and for additional insights, write to us at  support@oncofocus.com 🌐 References: 1) https://www.nice.org.uk/guidance/ta1048/history 2) https://ir.anixa.com/press-releases/detail/1066/anixa-biosciences-announces-approval-of-protocol-amendment

February 2nd Week, 2025 📝 BMS’ Phase 2 TRANSCEND FL trial of Breyanzi (lisocabtagene maraleucel; an autologous, anti-CD19 CAR-T) met primary endpoint of ORR and key secondary endpoint of CRR in marginal zone lymphoma (MZL) cohort. Detailed results will be presented at an upcoming conference (Ref 1, 2) ❓ What are the current benchmarks in MZL? 📝 Imugene’s Azer-cel (an allogeneic, anti-CD19 CAR-T) + low dose IL-2 elicited two additional complete responses resulting in a CRR of 57.1% (4 out of 7 evaluable patients) in the Phase 1b trial in R/R Diffuse large B-cell lymphoma (DLBCL) patients, who previously failed 4-5 lines of therapy, including autologous CAR-T (Ref 3, 4) ❓ How did the inclusion of low dose IL-2 influence the outcomes? 📝 Galapagos deprioritized GLPG5201(point-of-care manufactured, an autologous, anti-CD19 CAR-T), and expanded the development of GLPG5101 (point-of-care manufactured, an autologous, anti-CD19 CAR-T) (Ref 5) ❓ What was the rationale behind deprioritization of GLPG5201? 📝 Lion TCR’s Liocyx-M004 (an autologous, HBV targeting mRNA-encoded TCR-T) received the US FDA clearance to initiate an international multi-centre Phase 2 clinical trial for the treatment of HBV-related Hepatocellular Carcinoma (Ref 6) ❓ Are there any other mRNA-encoded cell therapies under development? 📝 Due to the strategic reasons, Otsuka holdings discontinued multiple cancer assets including OPC-415 (MMG49 CAR-T targeting activated integrin β7), which is in Phase 1/2 trial conducted solely in Japan for R/R Multiple Myeloma (Ref 7, 8) ❓ What might be the reason behind the Otsuka's decision to discontinue OPC-415? To know answers to these questions and for additional insights, write to us at   support@oncofocus.com 🌐 References: 1) https://www.clinicaltrials.gov/study/NCT04245839 2) https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-for-Breyanzi-lisocabtagene-maraleucel-in-Adult-Patients-with-Relapsed-or-Refractory-Marginal-Zone-Lymphoma/default.aspx 3) https://www.clinicaltrials.gov/study/NCT03666000 4) https://wcsecure.weblink.com.au/pdf/IMU/02912851.pdf 5) https://www.glpg.com/press-releases/galapagos-reports-full-year-2024-results-and-provides-fourth-quarter-business-update/ 6) https://www.prnewswire.com/news-releases/lion-tcrs-liocyx-m004-receives-fda-clearance-to-launch-global-multicenter-phase-2-clinical-trial-in-hbv-related-hepatocellular-carcinoma-302373802.html 7) https://clinicaltrials.gov/study/NCT04649073 8) https://ssl4.eir-parts.net/doc/4578/ir_material_for_fiscal_ym3/171488/00.pdf

12/06/2025 MAIA Biotechnology and Roche announce a master clinical supply agreement for hard-to-treat cancer therapies ( Ref ) MAIA Biotechnology entered into a clinical master supply agreement with Roche for future trials evaluating MAIA’s ateganosine (THIO; telomere-targeting agent) in combination with Roche's atezolizumab (Tecentriq; anti-PD-L1) for the treatment of multiple hard-to-treat cancers. Ateganosine's highly synergistic and effective activity in combination with atezolizumab in preclinical studies was the basis of this agreement. Vlad Vitoc, Chairman and CEO, MAIA: “ In preclinical studies, ateganosine was found to be highly synergistic and effective in combination with Roche’s anti-PD-L1 agent atezolizumab. We are pleased to partner with world-renowned Roche and we look forward to further strengthening our mission to find safe and effective cancer treatments.” Alligator's Phase 3 trial of mitazalimab received positive scientific advice from the EMA ( Ref ) The European Medicines Agency (EMA) provided positive scientific advice supporting the overall design of the planned Phase 3 trial of Alligator Bioscience's mitazalimab (stimulatory antibody targeting CD40) in metastatic pancreatic cancer. The advice confirms that the study of mitazalimab + mFOLFIRINOX is appropriately designed to support future marketing authorization application. Alligator is continuing preparations for the trial initiation in line with regulatory inputs. Søren Bregenholt, CEO, Alligator Bioscience: “We are very pleased with EMA’s endorsement of our Phase 3 trial design and mitazalimab’s Phase 3 readiness, confirming its path to regulatory approval in Europe. This advice from EMA aligns very well with previous input from FDA thus enabling a single global Phase 3 study leading to mitazalimab’s potential registration as a new treatment for patients with metastatic pancreatic cancer in these major territories.” Merck & Co./MSD's neoadjuvant pembro followed by adjuvant pembro + RT ± cisplatin has been approved in the US for PD-L1 CPS ≥1 pts ( Ref ) The US FDA approved pembrolizumab (Keytruda; anti-PD-1) single agent as a neoadjuvant Tx followed by adjuvant pembrolizumab + RT with or without cisplatin after surgery, and then as a single agent for adults with resectable locally advanced SCCHN with PD-L1 CPS ≥1. The approval has been granted based on a priority review of the results from the Ph3 KEYNOTE-689/NCT03765918 trial evaluating neoadjuvant pembro followed by adjuvant pembro + RT ± cisplatin vs upfront surgery followed by adjuvant RT ± cisplatin in newly diagnosed, stage III or IVA, resected, locally advanced SCCHN. Key outcomes in the PD-L1 CPS ≥1 pts (who accounted for ~95% of the enrolled population): mEFS: 59.7 mos vs 29.6 mos (HR 0.70, 95% CI 0.55 - 0.89; p=0.0014) MPR: 9.8% vs 0.0% pCR: 3.2% vs 0.0% The marketing authorization applications are also under review by regulatory authorities worldwide, including Europe and Japan.

🤝  Bristol Myers Squibb  is set to acquire  2seventy bio  in an all-cash transaction valued at approximately $286 million. After accounting for 2seventy bio’s cash reserves, the net acquisition cost for BMS stands at around $102 million. The deal is expected to close in H2'25. 👉 This acquisition gives BMS full control of Abecma (idecabtagene vicleucel), a BCMA-targeted CAR-T cell therapy indicated for the treatment of adult patients with R/R multiple myeloma after two or more prior lines of therapy. Notably, Abecma was co-developed by BMS and 2seventy bio.  ⭐ The attached image gives a quick overview of the journey of 2seventy bio—from its formation and key oncology deals to its acquisition. 👉 From this acquisition, several important questions emerge: ❓ Even with an active approved asset, why was 2seventy bio valued at only $286 million? ❓ What are the key competitors of Abecma in the multiple myeloma space? ❓ How is the multiple myeloma landscape expected to evolve over the next two to three years? ❓ What are the main benefits BMS can expect from this acquisition? For answers to these questions and additional insights, feel free to contact us at  support@oncofocus.com .

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 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 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    T-knife Therapeutics ' novel FAP-CAR Armored PRAME-TCR-T  Therabest ’s dual chemokine (CXCR4/CCR7) expressing iPSC CAR-NK  Gan & Lee Pharmaceuticals ’s bispecific CAR-T  First-time clinical results of Shanghai Cell therapy’s BZE2204  First-time clinical results of CD (Suzhou) Biopharma’s PZ04 for B-NHL  Mayo Clinic ’s novel MUC1 activated BCMA CAR-T for MM  ImmPACT Bio  (Acquired by Lyell)’s IMPT601  Oricell Therapeutics ’s OriCAR002  Inceptor Bio ’s IB-T101  Invectys ’s IVS-3001  and many more     📝 The ASCO’25 edition includes the updates from   CARsgen Therapeutics ’s satri-cel  Oricell Therapeutics ’s Ori-C101  Innovative Cellular Therapeutics (ICT) ’s GCC19CART  Verismo Therapeutics ’ SynKlR-110  Gilead Sciences ’s KITE-363  Wellington Zhaotai Therapies ’ WZTL002  Legend Biotech ’s LB2102  A2 Biotherapeutics, Inc.  ’s A2B694 & A2B530  Vittoria Biotherapeutics, Inc. ’s VIPER-101 Immatics ’ IMA203  and many more   📝 The ASGCT’25 edition includes the updates from   Precigen 's PRGN-3008  CARGO Therapeutics ' CRG-023  JW Therapeutics 药明巨诺 ’ JW004 Roche  ’s KRAS G12D Neoantigen targeting TCR-T  TScan Therapeutics ’ CD45 TCR-T  and many more   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

Welcome to the May edition of our CGT Watch newsletter!   CARsgen’s satri-cel priority review & Ph2 results; Autolus’ obe-cel positive CHMP opinion; BrainChild Bio’s BCB-276 RMAT; Gilead & Arcellx’s anito-cel Ph2 updated results; Senti Bio’s SENTI-202 updated Ph1 results; CARsgen’s CT0596 first-time Ph0 results; Artiva Bio’s AlloNK long-term Ph1/2 results; NeoImmuneTech’s NT-17 + CAR-T Ph1 topline results; Nkure and CRISPR Therapeutics partnership; Chong Kun Dang & AbClon partnership; Vor Bio assessing strategic alternative; Galapagos re-evaluation of proposed separation   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 May edition of CGT watch highlighting updates on novel targets, innovative approaches, first-of-its-kind combinations, and key developments that unfolded throughout April and May.     Since we’re keen to keep things concise and focused, this issue will exclusively cover cell therapies.   Section 1: Key Monthly Updates 🚀 What’s new:   ⭐   GARP – A new CAR-T target for Aggressive Glioma   ( Ref )   A Ph1, NCT06964737 trial, sponsored by the   The Ohio State University   Comprehensive Cancer Center, is evaluating anti-GARP CAR-T in recurrent Grade III/IV Gliomas.  GARP is a transmembrane protein found to express highly on the surface of activated Tregs, playing a crucial role in immune regulation by facilitating TGF-β activation.   👉 Why it matters:  High grade Gliomas create a highly immunosuppressive tumor microenvironment, making effective treatment challenging. Anti-GARP CAR-T   aims to disrupt the immune suppression driven by Tregs and TGF-β signaling, potentially restoring immune function and improving outcomes.   ⭐   Novel dual-antigen combination of CD73/AXL for hypoxia-activated CAR-T  ( Ref )   Previously, hypoxia activated CAR-Ts have targeted single antigens. For the first time, a novel dual-antigen combination of CD73 (ecto-5'-NT) and AXL was used. A Ph1/2 CHN-PLAGH-BT-095/NCT06939270 trial, sponsored by The Chinese PLA General Hospital, is evaluating CD73/AXL HypoSti. CAR-T to enhance anti-tumor responses and reduce T cell exhaustion in advanced or metastatic Solid Tumors.   👉   Why it matters:   The dual targeting of CD73 and AXL with a hypoxia activation enhances anti-tumor activity by countering immune suppression and tumor progression. This strategy ensures CAR-T cells remain inactive in normal tissues but activate in hypoxic tumor environments, improving specificity and efficacy.   ⭐  Novel conjugation of CAR-Ts with IL-21 loaded CaMnCO3 “Vitality Backpacks” ( Ref )   Shandong Provincial Hospital introduced a novel strategy of combining CAR-Ts with acid-sensitive CaMnCO₃ nanoparticles (CMC-NP) with IL-21 (CMC-21) as "vitality backpacks."   These backpacks provide sustained IL-21 release, enhancing CAR-T persistence and additionally, CMC-NP actively neutralizes acidity and generate oxygen, countering hypoxia and improving the survival and function of CAR-T cells in Solid Tumors.   👉   Why it matters:   Unlike earlier nanoparticle approaches that primarily supported CAR-T delivery, these nanoparticles reshape the tumor environment, overcoming its immunosuppressive barriers. IL-21-loaded CaMnCO₃ CAR-Ts represent a next-generation nanoparticle-based CAR-T therapy. ⭐  Thinking Biomed’s CAR-T clinical entry ( Ref )   A Ph1 TH027-ST001/ NCT06951425 clinical trial evaluating TH027 (anti-B7-H3 CAR-T) for the treatment of Ovarian Cancer and R/R Solid Tumors has been listed on CT.gov with study start date Jun 06, 2025.   👉 Why it matters:   Out of 209 CAR-T programs aimed at treating Ovarian Cancer, only 43 have progressed to clinical development. Given the urgent need for more CAR-Ts entering clinical trials, this company's CAR-T clinical entry for Ovarian Cancer stands out as a significant advancement.   ⭐  Novel CAR-T target Eva1 (MPZL2) for Lung and Pancreatic Cancer ( Ref )   Cured Inc and Nagoya University Graduate School of Medicine introduced humanized anti- Eva1 (MPZL2) CAR-T for the treatment of Solid Tumors, showing promising therapeutic efficacy in preclinical models for both Lung and Pancreatic Cancer.   👉 Why it matters:   Lung and Pancreatic Cancer remain highly challenging to treat, despite the availability of 27 unique antigen targets for clinical CAR-T programs. There is a need for more effective targets with strong therapeutic potential.   🎯 Regulatory updates:   ⭐   China’s NMPA had granted Priority Review to  CARsgen Therapeutics   ’ satri-cel for ≥3L advanced GC/GEJC pts   ( Ref ;  Ref )   China’s NMPA granted Priority Review to satricabtagene autoleucel (satri-cel; CT041; an autologous, anti-CLDN18.2 CAR-T) for the treatment of CLDN18.2 positive advanced GC/GEJA in patients who have failed at least two prior lines of therapy.   For this indication, detailed results from the confirmatory China-only, Phase 2 CT041-ST-01/NCT04581473 trial demonstrated encouraging outcomes but associated with higher Gr ≥3 TRAEs as per ASCO 2025 data readout.   In ITT population (N=156), the results for satri-cel (n=104) vs TPC (n=52) were as follows:   mPFS: 3.25 vs 1.77 mos (HR 0.366; p<0.0001)  mOS 7.92 vs 5.49 mos (HR 0.693; one-sided p=0.0416)  Gr ≥3 TRAEs: 98.9%  👉   Why it matters:   This marks the first randomized Phase 2 trial data release for CAR-T therapy in the treatment of Solid Tumors. ⭐  CHMP gives green light to Autolus’s Obe-Cel: Hope for adult B-ALL patients ( Ref ) Autolus Therapeutics ’ obecabtagene autoleucel (obe-cel; an autologous, anti-CD-19 CAR-T) received a positive CHMP opinion in the EU for the treatment of R/R B-ALL in adults, based upon Ph1/2 FELIX/NCT04404660 study results (76.6% CR/CRi response rate; median EFS of 11.9 months in cohort IIA (n=94). 👉 Why it matters:   Obe-cel is already approved in the US and UK.   Gilead Sciences ’ Tecartus remains the only CAR-T approved in Europe for adult B-ALL patients. If granted approval, it would become the second CAR-T therapy for this population in Europe. Meanwhile,   Novartis ’ Kymriah is approved in Europe for pediatric and young adult (≤25 years) R/R B-ALL.   ⭐   BrainChild Bio’s BCB-276 secured RMAT designation for DIPG ( Ref )   The US FDA granted RMAT designation to   BrainChild Bio ’s BCB-276 (an autologous, B7-H3 CAR-T) for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG) based on the positive 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. BCB-276 is the second CAR-T therapy to receive RMAT designation for DIPG treatment, following   Stanford University ’s anti-GD2 CAR-T. 🔬 Clinical Data Readouts:   ⭐   Gilead & Arcellx’s anito-cel scored Big: ORR of 97.4% in R/R MM ( Ref )  Updated data from the pivotal Ph2, iMMagine-1/NCT05396885 trial of   Gilead Sciences   &   Arcellx ’s anitocabtagene autoleucel (an autologous, anti-BCMA CAR-T) in ≥ 4L Multiple Myeloma (MM) demonstrated an ORR of 97.4% (67.5% CR/sCR) with a median follow-up of 12.6 mos in 117 pts.   👉 Why it matters:  Anito-cel had shown encouraging efficacy for the treatment of R/R MM. Arcellx and Gilead are planning for commercial launch in 2026. If approved, this would become the fifth BCMA-targeted CAR-T worldwide and the third to receive approval in the US.   ⭐   AlloNK combo matches CAR-T power, without the toxicity in R/R B-NHL ( Ref )   Artiva Biotherapeutics   presented long-term Ph1/2, NCT04673617 data at ASGCT for AlloNK (AB-101; an allogenic, non-genetically modified NK cell therapy) + rituximab in patients with R/R B-NHL that were CAR-T naïve. The results showed a CRR of 64.3% with mDOR not reached in 14 patients. Notably, among the 45 patients dosed, there were no cases of high-grade CRS, ICANS, or GvHD.   👉 Why it matters:  AB-101 is an allogeneic, non-genetically modified NK cell therapy, has the potential to provide quicker and more accessible treatment options. If further studies confirm its benefits, AB-101 could emerge as a promising alternate therapy. ⭐   NeoImmuneTech’s NT-I7 boosts CAR-T in R/R LBCL ( Ref )   NeoImmuneTech   reported final top-line Ph1b, NCT05075603 results for efineptakin alfa (NT-I7; IL-7Rα agonist) + CD19 CAR-T (   Novartis ’ Kymriah/   Gilead Sciences ’ Yescarta/   Bristol Myers Squibb   ’s Breyanzi) for R/R LBCL with 100.0% ORR in high-dose cohort (n=8).   👉 Why it matters:  These findings demonstrated that NT-I7 improved efficacy compared to CAR-T therapy alone. Notably, none of the 17 patients experienced CRS or ICANS after receiving NT-I7, highlighting its ability to enhance therapeutic outcomes without adding toxicity.   ⭐   Updated Ph1 results of Senti Bio’s SENTI-202 Logic-gated CAR-NK ( Ref )   Updated results from the Ph1/NCT06325748 trial of   Senti Biosciences ’ SENTI-202 (an allogeneic, logic-gated selective CD33/FLT3 CAR-NK) were presented at AACR’25, showing an ORR of 71.4% in 7 evaluable pts with R/R AML, with no DLTs observed.   👉 Why it matters:  This is the first logic-gated CAR-NK therapy with clinical data, demonstrating encouraging early results. However, due to the small sample size and limited follow-up, long-term data is much awaited.   ⭐  CARsgen’s CT0596 showed strong Ph0 results in R/R MM ( Ref )   First-time results from an early exploratory study of   CARsgen Therapeutics ’ CT0596 (an allogeneic, anti-BCMA CAR-T using THANK-u Plus platform) achieved 60.0% sCR/CR in 5 efficacy evaluable pts with no DLTs, Gr ≥3 CRS, ICANS among the 8pts recruited with ≥4L R/R MM.   👉 Why it matters:  This CAR-T is developed by using THANK-u Plus platform which is an enhanced version of its proprietary THANK-uCAR allogeneic CAR-T technology to address the potential impact of NKG2A expression levels on therapeutic efficacy. If further studies confirm its benefits, it could emerge as a promising approach for allogeneic cell therapies.   🤝 Deals and Collaborations:   ⭐   NKure and CRISPR Therapeutics partnered to co-develop CTX112 in India. ( Ref )   NKure Therapeutics   and   CRISPR Therapeutics   partnered to co-develop CRISPR’s CTX112 (an allogeneic, anti-CD19 CAR-T) for the treatment of R/R B-cell malignancies in India. NKure plans to seek CDSCO approval by Jun’25 to begin Ph2 trials in India.   👉 Why it matters:  India currently has two approved autologous CAR-Ts. The partnership plans to initiate Ph2 trials, marking a key milestone in the development of allogeneic CAR-T therapies in India.   ⭐ ₩12.2B CAR-T Deal: Chong Kun Dang & AbClon partnership ( Ref )   Chong Kun Dang Pharm.   acquired a 7.3% stake in   AbClon   and received priority rights to commercialize nespecabtagene autoleucel (AT101; an autologous, anti-CD19 CAR-T) which is in Ph2, NCT05338931 clinical trial for the treatment of R/R B-cell NHL. Both the companies plan to jointly develop additional CAR-T therapies.   👉 Why it matters:  Chong Kun Dang's investment will support AbClon's clinical trials and R&D efforts for its core pipeline, including nespecel.   Novartis ' Kymriah is currently the only CAR-T approved in Korea for Lymphoma indication.   Curocell ’s Rimqarto (anbal-cel) and   Gilead Sciences ’ Yescarta are expected to receive approval this year. If approved, nespecel will also be added to this list of autologous, anti-CD19 CAR-Ts.   🛑 Setbacks: ⭐   Vor Biopharma has been exploring strategic alternatives ( Ref )  Vor Bio   announced its exploration of strategic alternatives, citing an assessment of clinical program data and ongoing fundraising challenges as key factors in the decision. The company clarified that the wind-down is not driven by safety concerns related to any of its assets.   👉 Why it matters:  VCAR33 (an allogeneic, anti-CD33 CAR-T) is one of the key assets from the company that got discontinued which is in Ph1/2 VBP301/NCT05984199 clinical trial for the treatment of R/R AML after allogeneic hematopoietic cell transplantation. 💼 Business update:   ⭐   Galapagos is re-evaluating the proposed separation and exploring strategic alternatives ( Ref )  Galapagos   decided to re-evaluate the previously proposed separation into two entities (Galapagos, on cell therapy, and SpinCo, on building a pipeline of innovative medicines) and will explore all strategic alternatives for its existing businesses. 👉 Why it matters:  The future of Galapagos' key assets, GLPG5101 (point of care (POC) manufactured, anti-CD19 CAR-T) and GLPG5301 (POC manufactured, anti-BCMA CAR-T), along with its collaboration with   Adaptimmune   for TCR-T and its decentralized manufacturing platform, remains uncertain as the company undergoes a strategic review.     Section 2: Cell Therapies Pipeline Landscape – An Overview ⭐   New Antigens : GARP; Eva1 (MPZL2)   ⭐   New antigen combinations : CD73 & AXL   ⭐   Novel strategy : Conjugation of CAR-Ts with IL-21 loaded CaMnCO3 “Vitality Backpacks”   As an oncology-focused business consulting firm, we closely monitor emerging modalities in the oncology space. Our weekly tracking now covers over 4,733 (vs 4700+ previously) preclinical and clinical CGT programs, covering 75 critical parameters—ranging from basic details and molecular characteristics to clinical outcomes.   CAR-T therapies, with around 3,900 programs (vs 3800+ previously), including 31 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 May). Moving to TCR-T therapies, a different type of engineering observed on T-cells, TCR-T therapies are steadily gaining prominence, with around 410+ (vs 410 previously) programs 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 May.   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, 384 (vs 360 previously) CAR-NK programs are under development, with 258 (vs 239 previously) still in the early stages, reflecting strong research interest in this modality.   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 reply or reach out. We look forward to exploring more breakthroughs with you in our next newsletter.   Until next time,   The CGT Watch Team