On January 5, 2021 Replimune Group, Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported it has dosed the first patient in a Phase 1, open-label, dose-escalation and expansion clinical trial of RP3 both alone and in combination with anti-PD-1 therapy (Press release, Replimune, JAN 5, 2021, View Source [SID1234573489]). RP3, Replimune’s third product candidate to enter clinical development, encodes for CD40L and 4-1BBL in addition to the GALV-GP R(-) fusogenic protein encoded in RP1 and the anti-CTLA-4 molecule encoded in RP2. Expression of CD40L and 4-1BBL are intended to further stimulate an anti-tumor immune response through immune co-stimulatory pathway activation.
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Replimune’s product candidates are designed to comprehensively activate an anti-tumor immune response to a patient’s cancer through the delivery of potent immune activating signals into the tumor, such that each of the stages of immune activation are maximized. The signals provided are (i) potent antigen release and presentation, so-called immunologic "Signal 1", provided by robust tumor destruction and immunogenic cell death through the use of the high potency oncolytic backbone expressing the GALV-GP R- fusogenic protein in all of our product candidates; (ii) the inhibition of signals which block full immune activation, provided by expression of anti-CTLA-4 in both RP2 and RP3; (iii) provision of potent immune co-stimulatory signals, so-called immunologic "Signal 2", provided by expression of CD40L and 4-1BBL in RP3; and (iv) the production of inflammatory cytokines, so-called immunologic "Signal 3", also intended to be stimulated by the expression of CD40L and 4-1BBL in RP3. RP3 therefore represents the culmination of this approach to date, and is intended to build on the compelling clinical data generated with RP1 and RP2, including in immune non-responsive tumor types.
"We are pleased to be advancing our third oncolytic immune-gene therapy into the clinic," said Robert Coffin, PhD, Founder, President and Chief Research & Development Officer of Replimune. "Having demonstrated the potential of our platform through positive clinical data readouts with both RP1 and RP2 in multiple tumor types, we have armed RP3 to express additional immune-activating proteins intended to further enhance the ability of our product candidates to treat less immune-responsive tumor types. We believe that the combined properties of RP3 are unique in the field of immune oncology and demonstrate the power of our platform to generate product candidates with multiple mechanisms of action which together potently activate a patient’s immune system against their cancer. We look forward to providing initial data with RP3, along with our other clinical programs over the course of 2021."
The Phase 1, dose-escalation clinical trial is currently enrolling patients with advanced solid tumors. The clinical trial is primarily designed to assess safety and tolerability of RP3 and to determine the recommended Phase 2 dose. Following dose selection, the second part of the clinical trial is intended to dose patients with RP3 in combination with anti-PD1 therapy to further assess for both safety and initial efficacy.