Replimune Group, Inc. · NASDAQ:REPL

Replimune — Investor Presentation (August 2019)

23 slides from Replimune's investor presentation, August 2019

  1. Slide 1: Next-Generation Oncolytic Immunotherapy

    NEXT GENERATIONONCOLYTIC NEXT-GENERATION ONCOLYTIC IMMUNOTHERAPY IMMUNOTHERAPY Corporate Presentation August 2019

  2. Slide 2: Safe harbor

    Safe harbor 2 This presentation contains forward-looking statements, including statements regarding our expectations about the advancement of our clinical trials, our goals to develop and commercialize our product candidates, our plans to establish our own in-house manufacturing capabilities, our pr

  3. Slide 3: Company overview and key highlights

    3  Founded in 2015 by the ex-BioVex management team  Proprietary ‘Immulytic’ oncolytic immunotherapy platform intended to maximally activate the immune system against a patient’s cancer  RP1 being studied in multiple tumor types in Part 2 of an ongoing 150 patient clinical trial combining with ni

  4. Slide 4: The most experienced oncolytic immunotherapy team

    The most experienced oncolytic immunotherapy team 4 ROB COFFIN PHILIP ASTLEY-SPARKE COLIN LOVE Chief Executive Officer Executive Chairman Chief Operating Officer Founder & CTO at BioVex, VP at CEO BioVex, Chairman at uniQure SVP BioVex; VP at Amgen through T- Amgen Vec BLA filing HOWARD KAUFMAN PAME

  5. Slide 5: Oncolytic immunotherapy

    Oncolytic immunotherapy 5  The use of viruses that selectively replicate in & kill tumors to treat cancer  Highly inflammatory  Activates both innate and adaptive immunity  Releases the full array of tumor antigens into an inflamed environment  Systemically activates the immune system against t

  6. Slide 6: Single agent oncolytic immunotherapy works

    Single agent oncolytic immunotherapy works 6  436 pts randomized 2:1 to T-VEC or GM-CSF T-VEC phase 3 data  Stage IIIb, IIIc, IVM1a-c; 1st line & previously treated in melanoma  DRR 16.3%; ORR 26.4%; CR rate 17%  Median OS (ITT) 23.3 mo vs 18.9 mo (HR 0.79)  Increased benefit in stage IIIb-IVM1

  7. Slide 7: Oncolytic immunotherapy + checkpoint blockade

    Oncolytic immunotherapy + checkpoint blockade 7 Immune response to neo- ‘Brakes removed’ from the antigens, inflamed tumor immune response generated  Oncolytic and immune-based  Without a pre-existing neo- efficacy in its own right antigen response, nothing to remove the brakes from  Patient-spec

  8. Slide 8: Oncolytic immunotherapy is synergistic with checkpoint blockade

    Oncolytic immunotherapy is synergistic with checkpoint blockade 8 T-vec+pembrolizumab T-vec+ipilimumab Ribas et al Cell 2017 170: 1109-1119* Chesney et al JCO, 2017* 62% ORR ** 33% CR rate *** 18% ORR ** N=16 39% ORR ** *Studies conducted in patients with melanoma ** ORR = Overall response rate ***

  9. Slide 9: Oncolytic immunotherapy turns "cold" tumors "hot"

    Figure 4 Oncolytic immunotherapy turns “cold” tumors “hot” 9 T-Vec+pembrolizumab Ribas et al Cell 2017 170: 1109-1119 T-VEC T-VEC alone +pembro * ** *** CRs in ‘cold’ tumors &/or low CD8 density Baseline After T-VEC alone After T-VEC+ pembrolizumab * CR = Complete response ** PR = Partial response *

  10. Slide 10: Our Immulytic platform uses HSV

    Our Immulytic platform uses HSV 10  HSV as an oncolytic agent has ideal properties for cancer immunotherapy:  Biology & disabling mutations well understood  Genetically stable, non-integrating  Improves safety & efficacy, including in combination with checkpoint blockade  Infects human tumor ce

  11. Slide 11: Our Immulytic platform

    Our Immulytic platform 11 Enhanced potency RP1 additionally RP1 additionally 1. A potent oncolytic expressing expressing anti- RP1 immunotherapy RP2 anti-CTLA-4 RP3 CTLA-4 and underlying backbone co-stimulatory ligands HSV-1 strain Immunologically Immunologically Immunologically warm/hot tumors cold

  12. Slide 12: GALV enhances efficacy in vivo

    GALV enhances efficacy in vivo 12 Vehicle Virus without GALV Virus with GALV (RP1) A549 lung cancer Vehicle Virus without GALV Virus with GALV (RP1) MDA-MB-231 breast cancer 3 injections over 1week; virus dose 5x103 pfu

  13. Slide 13: RP1 treats large injected & uninjected tumors

    RP1 treats large injected & uninjected tumors 13 Not injected Injected Vehicle Immune competent rat model (dual flank) Right flank tumors injected 5x with 5x106 pfu 60 50 40 30 20 10 10 20 30 40 50 60 mRP1 60 50 40 30 20 10 Days 10 20 30 40 50 60

  14. Slide 14: RP1: Developing for tumor types with underlying sensitivity to anti-PD1

    14 RP1: Developing for tumor types with underlying sensitivity to anti-PD1 Potential rapid path to initial approval

  15. Slide 15: RP1 clinical strategy

    RP1 RP1 clinical strategy 15 Phase 1 (complete except MSI high ) Phase 2 (underway except MSI high) Safety confirmation & determination of dose for Defined indications phase 2, all comers (N≈30 patients per group) (N≈30) (dependent on data & FDA Melanoma + nivolumab*2 Phase 1/2 PROMISING COHORTS cli

  16. Slide 16: CSCC – potential path to initial approval

    RP1 CSCC – potential path to initial approval 16  4,000-9,000 US deaths annually  Anti-PD-1 therapy active  Cemiplimab (Regeneron) demonstrated 46% response rate, but low CR rate  BLA filed  Tumors are frequently accessible for direct intra-tumor injection  We believe CSCC provides a rapid rou

  17. Slide 17: RP2/3: Target anti-PD1/L1 non-responsive tumor types

    17 RP2/3: Target anti-PD1/L1 non-responsive tumor types

  18. Slide 18: Intratumoral anti-CTLA-4 & co-stimulatory pathway agonists

    Intratumoral anti-CTLA-4 & co-stimulatory pathway agonists 18  Focus on delivery of proteins which act as the immune response is being generated  Systemic antibody approaches probably don’t act at the right place or the right time  Potential for toxicity  RP2 RP2  Delivery of anti-CTLA-4 direct

  19. Slide 19: Expression of anti-mCTLA4 enhances efficacy

    RP2 Expression of anti-mCTLA4 enhances efficacy 19 Left Right Left Right RP1 mRP2 Immune competent A20 mouse tumor model Subtherapeutic dose for RP1 (5x104 pfu) injected 3x into the right tumor only

  20. Slide 20: Similarly increased effects with co-stimulatory pathway ligands

    RP3 Similarly increased effects with co-stimulatory pathway ligands 20 Left Right RP1 Left Right Left m4-1BBL Right mCD40L

  21. Slide 21: Critical focus on manufacturing

    Critical focus on manufacturing 21  Product candidates currently manufactured by a CMO for ongoing clinical development  For later stage development & commercialization, in-house manufacturing is preferable  The team has extensive manufacturing experience  63,000 ft2 manufacturing facility lease

  22. Slide 22: Key target milestones

    Key target milestones 22 RP1 2021: Initiated phase 2 in 3/4 Initiating ≈240 patient H2 2019: Phase 1 H2 2020: Randomized tumor types in registration directed data RP1 alone & RP1+nivolumab controlled combination with phase 2 in CSCC RP1+ nivolumab Phase 2 data Phase 2 data in nivolumab CSCC 2019 202

  23. Slide 23: Maximally activating the immune system against cancer

    23 Maximally activating the immune system against cancer  Multi-product candidate oncolytic immunotherapy platform company  Broad clinical development program underway  RP1 intended to enter a registration-directed 240 patient phase 2 clinical trial in cutaneous squamous cell carcinoma (CSCC) imm

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