RP2

P2, N=4, Active, not recruiting, Replimune Inc. | N=60 --> 4

P2, N=60, Active, not recruiting, Replimune Inc. | Recruiting --> Active, not recruiting

Safety will be assessed by physical examination, clinical laboratory evaluations, vital signs, and monitoring for adverse events (AEs; including serious AEs). Clinical trial information: NCT05733611.

P2, N=60, Recruiting, Replimune Inc. | Not yet recruiting --> Recruiting

AE severity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.Clinical trial identification: NCT05733611.Editorial acknowledgement: Medical writing and editorial support were provided by Marita Chakhtoura, PhD, of AlphaBioCom, LLC, a Red Nucleus Company (King of Prussia, PA, USA) and were funded by Replimune Inc. (Woburn, MA, USA).Legal entity responsible for the study: Replimune Inc.

P2 | N=60 | Not yet recruiting | Sponsor: Replimune Inc.

A particularly striking change was observed in a biopsy obtained from a liver lesion from a tebantafusp and ipi/pembro-failed uveal melanoma patient. The biomarker data presented indicates broad immune activation by RP2 and demonstrates that clinical response does not correlate with baseline PD-L1 and CD8 expression status. Clinical responses were often associated with increases in gene signatures associated with cytotoxic T, NK and Th1 cells. These data indicate the potential for broad utility of RP2 in a range of tumor types, including in patients with primary or acquired resistance to immune checkpoint blockade.

The tumor inflammation signature score (TIS) was also calculated.Preliminary Phase 1/2 biomarker data from paired tumor biopsies include the following: Immunohistochemistry for CD8 and PD-L1 (n=30) indicated robust and increased infiltration of CD8+ T cells and PD-L1 expression, both after combined treatment with RP1 and nivolumab and after single agent RP2 across different tumor types, and including reversal of T cell exclusion following prior combined treatment with ipilimumab and nivolumab in melanoma. Consistent with the pre-clinical data, preliminary clinical biomarker data indicate substantial increase in CD8 T cell infiltration and PD-L1 expression, as well as increased TIS score in the majority of patients treated with RP2 alone or RP1 and nivolumab combination. Particularly marked effects were seen in some patients with clinical responses which occurred independent of both baseline PD-L1 and prior anti-PD1 therapy status, which suggests potential broad utility of the RP1/2 treatment approach in igniting an anti-tumor immune response. Tumor mutation burden analysis and T cell receptor sequencing are currently underway and further updates of the dataset will be presented.