Immatics’ Solid Tumor Cell Therapy Pipeline Evolves

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Immatics is prioritizing its TCR-T and TCER cell therapy programs and leaving behind its first-generation programs.

Immatics is discontinuing a clinical stage and delaying a preclinical solid tumor cell therapy program, according to a corporate update. These programs are IMA201, currently in a phase 1/2 trial (NCT03247309), and IMA204, in preclinical studies.1

The company is focusing its resources on the T-cell receptor T-cell (TCR-T) therapy IMA203 as both a monotherapy and a combination therapy in solid tumors, as well as the second-generation IMA203CD8. All versions of IMA203 are being evaluated in a phase 1/2 clinical trial (NCT03686124). The trial is evaluating IMA203 as a monotherapy in cohort 1, IMA203 in combination with nivolumab in cohort B, and IMA203CD8 as a monotherapy in cohort C.

“Our ACTengine® IMA203 clinical trial has gained significant traction over the past year with promising data for our monotherapy candidate targeting PRAME. As we continue demonstrating the potential of our first- and second-generation product candidates in patients, we have commenced establishing our in-house GMP cell therapy manufacturing facility in Houston, TX. This positions us to scale our cell therapies for registration-directed trials and commercial supply,” Harpreet Singh, PhD, chief executive officer and Co-Founder, Immatics, commented in a statement.1 “In addition, we have significantly advanced our clinical TCR Bispecifics pipeline with 1 TCER® program targeting MAGEA4/8 now in the clinic and a second TCER® program targeting PRAME commencing clinical studies this year. We demonstrated our ability to execute and deliver on our goals in 2022 and look forward to continuing on this path in 2023.”

READ MORE: Improving Outcomes in Solid Tumors With Personalized Cell Therapies

IMA201 is an ACTengine therapy targeting MAGEA4/8 and will be replaced by the TCR bispecific program IMA401 targeting the same marker. The phase 1a dose escalation is ongoing in the IMA201 clinical trial. IMA204 targets collagen type VI alpha-3 (COL6A3) and has shown efficacy in mouse models. Immatics is delaying the investigational new drug application (IND) for IMA203 to focus on its other clinical stage programs.

IMA203 is a TCR-T therapy targeted against PRAME. Immatics announced positive data from the therapy’s trial in October 2022 that showed a confirmed objective response rate (ORR) was 50% (n = 6) at the target dose or higher (at least 1 billion infused cells) and 80% (n = 4) in phase 1b patients across a variety of solid tumor types.2 IMA203 also had a manageable safety profile.

“The data presented today highlight the clinical potential of PRAME as one of the most promising multi-tumor targets to achieve meaningful benefits for a large cancer patient population,” Cedrik Britten, MD, chief medical officer, Immatics, said in a statement at that time.2 “In addition to this first data from IMA203 monotherapy today, we are awaiting data from 2 additional dose expansion cohorts: IMA203 together with an immune checkpoint inhibitor and our 2nd generation product candidate IMA203CD8.

Also in October 2022, GlaxoSmithKline decided to terminate its collaboration with Immatics for access to 2 TCR-T therapies announced in February 2020.3 The termination went into effect on December 26, 2022.

REFERENCES
1. Immatics Announces Full Year 2022 Financial Results and Corporate Update. News release. Immatics. March 21, 2023. https://www.marketscreener.com/quote/stock/IMMATICS-N-V-109287208/news/Immatics-Announces-Full-Year-2022-Financial-Results-and-Corporate-Update-43299148/ 
2. Immatics reports interim clinical data update on ACTengine® IMA203 TCR-T monotherapy targeting PRAME. News release. Immatics. October 10, 2022. https://www.globenewswire.com/news-release/2022/10/10/2530925/0/en/Immatics-Reports-Interim-Clinical-Data-Update-on-ACTengine-IMA203-TCR-T-Monotherapy-Targeting-PRAME.html 
3. Immatics Announces Third Quarter 2022 Financial Results and Business Update. News release. Immatics. November 17, 2022. https://investors.immatics.com/news-releases/news-release-details/immatics-announces-third-quarter-2022-financial-results-and 
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