Immatics (IMTX) Study Update summary

Study design and patient population

• IMA203 targets PRAME, a highly prevalent antigen in multiple solid tumors, focusing on PD-1 refractory metastatic melanoma in a phase 1b dose expansion study and planning for a phase III trial later this year.

• The phase 1b dose expansion cohort included 28 melanoma patients at the recommended phase II dose, with a total safety population of 70 patients across all indications.

• The phase III SUPREME trial will enroll 360 HLA-A*02:01-positive patients with unresectable or metastatic melanoma, randomizing them to IMA203 or investigator's choice of approved treatments.

• Only cutaneous, acral, and melanoma of unknown origin will be included in phase III; mucosal and uveal melanoma are excluded for homogeneity.

• The therapy is also being evaluated in a Phase 1 trial with a CD8aβ co-receptor (IMA203CD8 GEN2).

Safety and tolerability

• IMA203 was well tolerated, with most adverse events being expected cytopenias from lymphodepletion and mild to moderate cytokine release syndrome (CRS).

• Grade III CRS occurred in 8 of 70 patients; infrequent ICANS events were fully resolved, and no treatment-related deaths occurred.

• Tolerability in the melanoma subset was consistent with the overall safety profile.

• Low-dose IL-2 was used post-infusion, well tolerated, and manageable in an outpatient setting.

• No treatment-related Grade 5 adverse events were reported, and most side effects were mild to moderate.

Efficacy and clinical outcomes

• Confirmed objective response rate in melanoma was 54%, with 7 of 14 responses ongoing at data cutoff.

• 88% of patients showed tumor shrinkage, and disease control was achieved in 92%.

• Median duration of response was 12.1 months, with some responses ongoing for over two years.

• Median progression-free survival (PFS) was six months; median overall survival (OS) was not reached at 8.6 months follow-up.

• Deep responders (≥50% tumor reduction) had median PFS over one year.