CGT Watch Newsletter: May'25 Edition

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 

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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