Replimune to Present New Biomarker & Pre-clinical Data for Lead Oncolytic Immunotherapy Programs at the 2021 American Association for Cancer Research Annual Meeting
Data confirms potent anti-tumor activity & activation of robust systemic immune responses by
- Increased infiltration of CD8+ T cells and PD-L1 expression for patients dosed with
RP1in combination with Opdivo® (nivolumab) and single agent RP2in human biomarker samples
- Pre-clinical evidence of innate immune activation mediated by GALV-GP R- expression
- Gene expression profiling supportive of broad immune activation in both humans & mice
- Further pre-clinical demonstration of potent lytic activity in tumors
“We developed Replimune’s Immulytic platform with the intention of developing therapies with both enhanced tumor killing potency and with an enhanced ability to initiate a systemic anti-tumor immune response. This pre-clinical and clinical biomarker data provides further evidence that these objectives are being achieved, and that
Details of the presentations are as follows:
Abstract Title: Clinical biomarker studies with two fusion-enhanced versions of oncolytic HSV (
- In patients dosed with
RP1in combination with nivolumab or single agent RP2alone and in combination with nivolumab, immunohistochemistry for CD8 and PD-L1 from paired tumor biopsies demonstrated robust and increased infiltration of CD8+ T cells and PD-L1 expression across different tumor types, including reversal of T cell exclusion following prior combined treatment with ipilimumab and nivolumab in melanoma.
- A significant increase in the expression levels of genes associated with innate and adaptive immune activation and genes previously reported to be associated with responsiveness to anti-PD1 therapy was demonstrated.
- In patients dosed with
RP2monotherapy, an increase in CD8+ T cell infiltration as well as robust changes in expression of key tumor and immune cell signalling pathway genes was observed.
- Peripheral blood T cell receptor (TCR) sequencing indicated the expansion of existing T cell clones and generation of new T cell clones.
- Increased CD8+ T cell infiltration and PD-L1 expression, coupled with changes in TCR clonal expansion in PBMC samples, suggest systemic immune activation.
Abstract Title: Immunomodulatory effects of a novel, enhanced potency gibbon ape leukemia virus (GALV) fusogenic membrane glycoprotein-expressing herpes simplex virus platform with increased efficacy combined with anti PD-1 therapy – Abstract #1917
This poster presentation is a collaboration between
- In a histological examination of tumors injected with
RP1or RP2, large areas of necrosis in syngeneic mouse tumours were observed, even in a model where GALV-GP R- is not functional. In models where GALV-GP R- is functional, including in human xenograft tumors in nude mice (which have no adaptive immune system, but retain innate, e.g. NK cell mediated, immune function), GALV-GP R- was observed to give anti-tumor activity in both injected and in uninjected tumors, whereas a virus without GALV-GP R- only exhibited anti-tumor activity in injected tumors. These effects in uninjected tumors were presumed to result from enhanced innate immune activation mediated by GALV-GP R-. RP1increased PD-L1 expression, particularly on neutrophils, and increased CD3 T cell infiltration in injected and contralateral tumors.
- Profound effects on the gene expression profile were also seen in both injected and contralateral tumors which are consistent with potent and broad immune activation. These were significantly greater than that seen with single agent anti-PD1, and were further enhanced when
RP1was combined with anti-PD1.
Opdivo® is a registered trademark of Bristol Myers Squibb.
Forward Looking Statements
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