Replimune Group, Inc. · NASDAQ:REPL
Replimune — Corporate Update (June 2020)
64 slides from Replimune's corporate update, Jun 3, 2020
Slide 1: Next-Generation Oncolytic Immunotherapy Data Update
NEXT GENERATION ONCOLYTIC IMMUNOTHERAPY NEXT-GENERATION ONCOLYTIC IMMUNOTHERAPY Data Update June 3rd 2020
Slide 2: Safe harbor
Safe harbor 2 Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statemen
Slide 3: Agenda and presenters
3 3 IntroductionPhilip Astley-Sparke / Chief Executive Officer Summary of Interim ResultsRobert Coffin, Ph.D. / Founder & Head of R&D CSCC Data UpdateKevin Harrington, Ph.D. / The Royal Marsden Melanoma Data UpdateMark Middleton, Ph.D. / University of Oxford Pipeline UpdateRobert Coffin, Ph.D. / Fou
Slide 4: Presenter biography: Kevin Harrington
Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust Leads the Targeted Therapy Team which focuses on two main areas: (i) the use of viruses as anti-cancer agents; and (ii) the development o
Slide 5: Presenter biography: Mark Middleton
Professor of Experimental Cancer Medicine in the Department of Oncology, consultant Medical Oncologist at the Oxford Cancer and Haematology Centre and Head of the Department of Oncology at the University of Oxford. Research specializes on the development of new cancer drugs and on the treatment of m
Slide 6: Immulytic oncolytic immuno-gene therapy platform overview
6 Proprietary ‘Immulytic’ oncolytic immuno-gene therapy platform Intended to maximally activate the immune system against a patient’s cancer Intended to establish Replimune’s products as the second cornerstone of immuno-oncology RP1 – in multiple clinical trials, with current focus on immune-respons
Slide 7: RP1, RP2 and RP3 design
A potent underlying virus strain RP1 Enhanced potency oncolytic immunotherapy backbone RP2 Additionally expresses anti-CTLA-4 RP3 Expresses GALV-GP R-, anti-CTLA-4, CD40L & 4-1BBL Replimune believes HSV to be the most potent, versatile & clinically validated virus species for oncolytic use There is
Slide 8: Clinical development programs and data readouts
June 2019 Dec 2019 June 2020Dec 2020 Phase 2: Melanoma + Opdivo (N=30)* Phase 2: NMSC (mostly CSCC) + Opdivo (N=30)* Data readouts to support the registration directed trials RP1 Anti-PD1 refractory NSCLC + Opdivo Phase 2: MSI-H cancers + Opdivo (N=30)* Potential Registration studies Ph 2: RP1+anti-
Slide 9: Data update summary: CSCC and melanoma
Cutaneous squamous cell carcinoma data update Six of seven patients with follow up treated with RP1+Opdivo have ongoing PRs or CRs Four patients with ongoing CRs (including of uninjected distant tumors): Clear differentiation from anti-PD1 monotherapy Data continues to highlight RP1 is well tolerate
Slide 10: CSCC opportunity overview
10 CSCC opportunity overview
Slide 11: Lead indication overview: CSCC
Lead indication overview: CSCC 11 RP1 The second most common skin cancer with ≈700,000 patients annually in the U.S.1 Occurs when DNA damage from exposure to ultraviolet radiation or other agents triggers abnormal changes to squamous cells 10% have ‘high risk’ disease (recurs following initial surge
Slide 12: Regeneron has paved the way in CSCC
Regeneron has paved the way in CSCC 12 Libtayo generated ~$200M in 1st year sales Libtayo captured market share of systemic therapies 11% 9% 15% 14% 14% 13% 13% 11% 19%22% 11%12% 28% 31% 32% 35% 39% 41%42% 43% $14 $4 15%25%22% 21%20% 20%18% 10%9%9% 8%7% 7%7%6% USRO W 14%13%12%11% 11%9% 17% 15% 15% 1
Slide 13: Single agent anti-PD1 data in advanced CSCC
Single agent anti-PD1 data in advanced CSCC 13
Slide 14: Registration-directed randomized trial with Regeneron
Registration-directed randomized controlled trial in collaboration with Regeneron 240 patients Randomized 2:1 (RP1+ Libtayo vs. Libtayo alone) Primary endpoint ORR Secondary endpoints include CR rate, duration of response, PFS, OS Aim to show 15% delta improvement in ORR Control arm ORR expectation
Slide 15: Single agent RP1 trial in organ transplant recipients
30 patient clinical trial of single agent RP1 open for enrollment in solid organ transplant recipients (liver & kidney) Organ transplant recipients are at increased risk of malignancy, with CSCC most prevalent 70% of patients develop CSCC within 20 years1 Anti-PD1 therapy contra-indicated due to the
Slide 16: Current CSCC data
Current CSCC data <} Replimune
Slide 17: Nine patients treated with RP1 + Opdivo
So far, nine patients have been treated with RP1 + Opdivo: 4 locally advanced, 5 metastatic, 56% had prior systemic therapy 6/7 patients with follow up in ongoing response Patient 1: Ongoing CR Patient 2: Ongoing CR (previously PR) Patient 3: PD Patient 4: Ongoing PR Patient 5: Ongoing CR Patient 6:
Slide 18: Change in tumor diameter by patient
Time from first dose * Maximum change in tumor diameter -33% -63% * Patient died from progressive disease before formal assessment
Slide 19: Patient 1: recurrent CSCC of the neck
16th June 2019 (baseline) 1st July 2019 (post one dose of RP1, no Opdivo) 16th July 2019 (post 2 doses of RP1 & 1 dose of Opdivo) Patient with recurrent CSCC of the neck (bilateral, right injected), retroperitoneal nodes & bone metastases (not injected) Previously treated with cisplatin-based chemor
Slide 20: Patient 1: biopsy tumor free
The protocol mandated biopsy of the injected tumor taken at day 43 was tumor free No tumor was found to remain when a biopsy was attempted from the left neck
Slide 21: Patient 1: retroperitoneal tumors resolved
Baseline16 weeks The patient also had baseline retroperitoneal tumors which have completely resolved
Slide 22: Patient 1: bone lesions radiological CR
29.5.198.8.197.10.19 Complete sclerosis of all bone lesions with no areas of active disease. Declared radiological CR. Confirmed by PET scan (next slide) Indicates area of increased bony sclerosis, indicative of healing response of lytic metastases
Slide 23: Patient 1: PET scan confirms CR
Bone metastases had substantially increased by CT between the prior PET scan (June 2018) and initiating the trial (June 2019), but no PET scan was performed at screening. The PET scan to confirm CR of bone mets performed Feb 2020 showed no active disease
Slide 24: CD8 T cell and PD-L1 staining
Patient 2 (4402-2001): CD8 T cell & PD-L1 staining 25 D43 CD8PD-L1
Slide 25: Patient 2: recurrent CSCC of the neck
2nd Sept 2019 (pre-dosing) 16th Sept (post single RP1 dose, no Opdivo) 15th Oct 2nd Dec13th Jan Baseline scan Recurrent CSCC of the neck (injected) and lung metastases (not injected) Previously treated with radiotherapy with immediate relapse The large injected tumor in the neck flattened considerab
Slide 26: Patient 2: lung lesions reduced
28th August 201925th October 2019 The only other sites of disease were lesions in the lung, which have also significantly reduced
Slide 27: Patient 3: CSCC of the left cheek
25th Sep 2019 (Baseline) 9th Oct 2019 (post single RP1 dose, no Opdivo) 23rd Oct 20196th Nov 201920th Nov 20194th Dec 201916th Jan 2020 Recurrent, rapidly progressing CSCC of the left cheek with bone invasion through the maxillary region, previously treated with surgery & radiation before trial entr
Slide 28: Patient: CSCC of the nasal region
23rd December 2019 (Baseline) 6th January 2020 (post single RP1 dose, no Opdivo) 20th January 20202nd March 2020 Recurrent, rapidly progressing CSCC of the nasal region (3.5cm tumor), previously treated with carboplatin & radiation before trial entry
Slide 29: Nasal region scans
18th Dec 2019 (Screening) 2nd Feb 202014th April 2020* The alternative to study treatment was rhinectomy * CT done in a different plane to prior scans to maximally capture the affected area
Slide 30: Patient 4402-2006: CD8 and PD-L1 staining
Patient 6 (4402-2006): Ongoing CR a cD8 PD-L1 a SCR 4 D43 ms wil } Replimune
Slide 31: Anti-PD-1 refractory melanoma opportunity overview
33 Anti-PD-1 refractory melanoma opportunity overview
Slide 32: Anti-PD1 refractory melanoma market opportunity
Anti-PD1 refractory melanoma – market opportunity 34 Approximately half of advanced melanoma patients still die of their disease, despite multiple approved therapies now being available Anti-PD1, anti-CTLA-4, combined anti-CTLA-4/anti-PD1, BRAF targeted agents Approximately 7,230 US deaths annually
Slide 33: Anti-PD1 refractory melanoma study underway
Anti-PD1 refractory melanoma; 125 patient study underway 35 RP1 Enrollment of a 125 patient potentially registrational cohort underway RP1 combined with Opdivo Hurdle for success intended to be discussed with FDA late 2020 ORR to a second line of anti-PD1 is estimated at 6-7%1 Targeting patients wit
Slide 34: Current melanoma data
Current melanoma data <} Replimune
Slide 35: Melanoma patients treated with RP1 + Opdivo
36 melanoma patients have been enrolled & treated with RP1 combined with Opdivo, with the last patient enrolled on Jan 7th 2020* As of May 2nd 2020 (data cut off), the status of the patients in this immature data set was: Anti-PD1 refractory cutaneous melanoma (N=16 [8 having had prior anti-CTLA-4 a
Slide 36: Melanoma patient characteristics
All Cutaneous melanoma Mucosal melanoma Uveal melanoma Number 36 24 6 6 Age: Range 28-95 28-95 40-78 44-85 Prior anti-PD1 25 16* 5 4 Prior single agent anti-PD1 9 7 1 1 Prior anti-PD1/anti-CTLA-4 16 9 4 3 Prior anti-PD1 % 69% 67% 83% 67% Stage IIIc 2 2 0 0 Stage IV M1a 7 3 4 0 Stage IV M1b 11 10 1 0
Slide 37: Example melanoma patients
Example melanoma patients <} Replimune
Slide 38: Anti-PD1 refractory cutaneous melanoma patients
Anti-PD1 refractory cutaneous melanoma patients
Slide 39: Liver lesion reduction, tumor-free biopsy
22nd Oct 2019 (Screening) 9th March 2020 D43 liver biopsy tumor free Reduction of injected & uninjected liver lesions
Slide 40: Reduction of uninjected lung lesions
22nd Oct 2019 (Screening) 9th March 2020 Reduction of uninjected lung lesions
Slide 41: Disease in foot, leg and groin nodes
1st July 2019 (screening) 26th August 2019 22nd October 2019 5th November 20197th April 2020 Biopsy awaited to confirm CR Disease in the foot, leg & nodes in the groin Initial progression in the leg/foot followed by response
Slide 42: Melanoma patient scans
2nd July 201917th Sept 201919th Nov 20197th April 2020 (screening)
Slide 43: Disease in thigh, groin and lungs
10th June 2019 24th June 2019 (pre Opdivo) 2nd September 2019 16th March 2020 Baseline disease in the thigh, groin & lungs Tumors in the thigh flattened after the first dose of RP1, i.e. prior to Opdivo & extensive oedema rapidly reduced
Slide 44: Patient quality of life improved
May 2019 (Baseline) August 2019 Patient quality of life has also greatly improved, from being essentially immobile to being fully mobile Patient remains on treatment at 10 months December 2019
Slide 45: Reduction of uninjected lung lesions
22nd May 2019 16th March 202022nd May 201916th March 2020 Reduction of uninjected lung lesions
Slide 46: CD8 and PD-L1 baseline and biopsy
CD8PD-L1 Baseline Day 43 biopsy
Slide 47: Mucosal melanoma patients
49 Mucosal melanoma patients
Slide 48: Mucosal melanoma: D43 biopsy tumor free
12th Nov 2019 (Screening) 12th March 2020 D43 biopsy tumor free
Slide 49: Mucosal melanoma: excision biopsy tumor free
20th Aug 2019 (Screening) 15th Jan 2020 Excision biopsy tumor free 1st April 2020
Slide 50: Uveal melanoma patients
Uveal melanoma patients } Replimune
Slide 51: Uveal melanoma patient response
Baseline (2nd Jan 2019)24th April 2019 Baseline disease included multiple c/sc deposits up to 4cm, 5-13mm lung & liver mets, multiple intra-abdominal up to 2cm. Initial response in numerous c/sc deposits, including uninjected (some biopsied showing no remaining residual tumor) and large scalp lesion
Slide 52: Uveal melanoma liver disease reduction
25th Sept 2019 (Screening) 3rd April 2020 Patient with extensive disease in the liver 27.3% reduction by RECIST (unidimensional), 61% reduction by WHO (bi-dimensional) Treatment ongoing
Slide 53: Safety of RP1 combined with Opdivo
Safety of RP1 combined with Opdivo in patients with skin cancers Treatment related treatment emergent adverse events (TEAEs) N=41 Preferred term Grade 1-2 Grade 3 (all) Grade 4 Grade 5 (>15%) # (%) (all) (all) # (%) # (%) # (%) Pyrexia 17 (41.5) 1 (2.4) 0 0 Chills 16 (39.0) 0 0 0 Influenza like symp
Slide 54: RP1 in other tumor types
RP1 in other tumor types <0} Replimune
Slide 55: Activity in a patient with angiosarcoma
Activity in a patient with angiosarcoma (ongoing PR) 57 Patient withdrew from treatment due to Opdivo side effects 6th November 201918th February 2020
Slide 56: MSI-H rectal cancer patient response
22 year old female with MSI-H rectal cancer Prior neoadjuvant FOLFOXIRI Treated with RP1 combined with Opdivo Ongoing PR Biopsy “No tumour present - strips of dysplastic epithelium and inflammatory exudate only” 9th October 201920th November 201915th January 202025th March 2020
Slide 57: MSI-H rectal cancer scans
Latest scan (March 2020) shows 87% reduction (including of uninjected abdominal disease) 4th Dec 2019 (C5)29th Jan 2020 (C8)25th March 2020 (C11)
Slide 58: Heavily pre-treated esophageal cancer
Heavily pre-treated esophageal cancer (8 prior therapies) Lung lesions & lesions around the esophagus. Treated with RP1 combined with Opdivo Ongoing PR at 10 months BaselineC5C11BaselineC11
Slide 59: Esophageal cancer: CD8 and PD-L1 staining
Esophageal cancer: CD8 T cell & PD-L1 staining 61 CD8PD-L1 Baseline Day 43 biopsy
Slide 60: New anti-PD1 refractory NSCLC cohort; bladder cohort terminated
New cohort in anti-PD1 refractory NSCLC & termination of bladder cohort 62 Due to the changing competitive landscape in bladder cancer Replimune has elected to direct resources to a new high-value target & terminate the enrollment of the bladder cancer cohort Anti-PD1 refractory NSCLC is an area of
Slide 61: Beyond immune responsive tumor types: RP2 and RP3
63 Beyond immune responsive tumor types: RP2 & RP3
Slide 62: RP2 and RP3 delivery of immune proteins
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 RRPP2 RRPP3 Delivery of anti-CTLA-4 directly into the tumor Blocks Treg activation/inhibition of T cell activa
Slide 63: Summary of RP1 opportunity
RP1 - CSCC Significant expected commercial opportunity Clear path to market Frequency of CRs provides clear differentiation to anti-PD1 alone Biomarkers (CD8 T cells & PD-L1) supportive RP1 - Anti-PD1 refractory melanoma Significant expected commercial opportunity Clear activity in Yervoy/Opdivo fai
Slide 64: Upcoming milestones
RP1 - CSCC Complete recruitment of 30 patient NMSC cohort with Opdivo Present data from first patients dosed in single agent transplant study Plan for neoadjuvant study RP1 - Anti-PD1 refractory melanoma Discuss potential path to market with FDA Report mature data set from 30 patient completed cohor