Immatics NV (IMTX)

[FACT-MASTER]

IMTX News:

https://fintel.io/doc/sec-immatics-nv-1809196-6k-2022-august-23-19227-6314

The importance of CD4 T cells for the duration of responses has been demonstrated by Immatics in preclinical assays where IMA203CD8 showed enhanced potency and prolonged anti-tumor activity compared to IMA203 alone. These findings are in line with a growing body of literature from CD19 CAR-T cells in hematological cancers that suggest a relevant role of engineered CD4 T cells in maintaining durable anti-tumor responses over a long period. Immatics? proprietary lentiviral vector enables CD4 and CD8 T cells to be engineered with the PRAME-specific IMA203 TCR and a CD8?? construct. In the preclinical studies, this approach showed functional superiority over multiple other CD8 constructs in conjunction with the PRAME-specific IMA203 TCR. Immatics has successfully developed a proprietary 4-in-1 vector that includes both IMA203 TCR? and TCR? as well as CD8? and CD8? chains while maintaining a high transduction rate, circumventing the challenges associated with increasing the lentiviral vector payload.



The IMA203CD8 Phase 1b dose expansion cohort is expected to enroll up to 24 patients with different types of solid tumors across several clinical trial sites in the U.S. and in Germany. Following personalized manufacturing and lymphodepletion, patients will receive a single dose of IMA203CD8. Initially, 3 patients will be treated at a dose level 3 (DL3, up to 0.48 billion total transduced T cells per m? body surface area) before patient treatment at the provisional recommended Phase 2 dose, DL4 (up to 1.2 billion total transduced cells per m? body surface area). The primary objective of this Phase 1b cohort is to evaluate the safety profile of IMA203CD8. Secondary objectives include evaluating initial anti-tumor and biological activity.



The 2nd generation TCR-T IMA203CD8 is part of Immatics? strategy to realize the full clinical potential of IMA203 TCR-T targeting PRAME. This strategy includes three Phase 1b expansion cohorts, which have all been initiated during the first half of 2022 and build on the promising early clinical results during the company?s Phase 1a trial. Interim data showed a 50% objective response rate (8/16 patients) across several solid tumor indications including melanoma, head and neck cancer, uveal melanoma and synovial sarcoma.


o Cohort A ? IMA203 as monotherapy at the provisional, recommended Phase 2 dose (RP2D) plus exploration of a higher dose level DL5 (up to 4.7 billion transduced CD8 T cells per m? body surface area)


o Cohort B ? IMA203 in combination with an immune checkpoint inhibitor, Opdivo? (nivolumab)


o Cohort C ? IMA203CD8, a 2nd generation monotherapy in which IMA203 is co-transduced with a CD8 co-receptor



Each Phase 1b expansion cohort is designed to evaluate the observed objective response rate, demonstrate durability of response and provide the basis for entering registration trials. The next data readout for the IMA203 monotherapy cohort at RP2D is expected during 2H 2022 and an initial data readout for Cohort B and Cohort C is planned for YE2022.