Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Day (October 2018)
52 slides from Circio Holding ASA's investor day presentation, Oct 15, 2018
Slide 1: Agenda & Speakers
Agenda & Speakers: 08:30-08:40 Welcome Remarks @ystein Soug, CEO, Targovax 08:40-09:20 Resected Pancreatic Cancer: Overview and TG01 Full Data, Prof. Daniel Palmer 09:20-09:40 Update onTG Strategy @ystein Soug, CEO, Targovax 09:40-09:50 ONCOS Overview, Dr. Erik Digman Wiklund, CBO, Targovax 09:50-10
Slide 2: Important Notice and Disclaimer
Important NOTICE AND DISCLAIMER This report contains certain forward-looking statements based on uncertainty, since they relate to events and depend on circumstances that will occur in future and which, by their nature, will have an impact on the results of operations and the financial condition of
Slide 3: Welcome remarks
Welcome remarks 2. Resected pancreatic cancer: overview and TG01 full data - Prof. Daniel Palmer 3. Update on TG strategy 4. ONCOS overview 5. ONCOS-102 interim data in melanoma and mesothelioma 6. Financial and closing remarks
Slide 4: Targovax aims to activate the patient's own immune system to fight cancer
TARGOVAX AIMS TO ACTIVATE THE PATIENT’S OWN IMMUNE SYSTEM TO FIGHT CANCER Targovax focus Immune Immune activators modulators Oncolytic viruses, Checkpoint vaccines inhibitors Surgery - Radio - Chemo Immune Targeted boosters therapy CAR-Ts, TCRs PARPs, gene therapy, etc. 4
Slide 5: Targovax has 2 assets in clinical development
TARGOVAX HAS 2 ASSETS IN CLINICAL DEVELOPMENT Lead product candidate o Genetically armed adenovirus o Alerts the immune system to the presence of cancer antigens ONCOS o Induces T-cells specific to the patients’ tumor Activates the Oncolytic virus immune system o 4 ongoing trials Triggers patient- s
Slide 6: Early TG clinical efficacy data
EARLY TG CLINICAL EFFICACY DATA TG vaccination has shown 20% 10 year survival in monotherapy trials 10 year survival in historical TG trials in resected pancreatic cancer1 (n=20, TG monotherapy) 100 90 80 o 4/20 (20%) of treated patients Survival (%) alive after 10 years 70 60 o 0/87 untreated patie
Slide 7: Resected pancreatic cancer: overview and TG01 full data
Resected pancreatic cancer: overview and TG01 full data Prof. Daniel Palmer 3. Update on TG strategy 4. ONCOS overview 5. ONCOS-102 interim data in melanoma and mesothelioma 6. Financial and closing remarks
Slide 8: For Prof. Palmer's presentation, please contact Targovax
For Prof. Palmers presentation, please contact [email protected] 8
Slide 9: Update on TG strategy
Update on TG strategy 4. ONCOS overview 5. ONCOS-102 interim data in melanoma and mesothelioma 6. Financial and closing remarks
Slide 10: The RAS gene is mutated in 90% of pancreatic and 50% of colorectal cancers
The RAS gene is mutated in 90% OF PANCREATIC AND 50% OF COLORECTAL CANCERS Frequency of RAS mutations Global cancer incidents per 10,000 (xx) = no. of cancer patients o RAS mutations are oncogenic and result in uncontrolled cell division High Pancreas (340,000) o There are no existing therapies targ
Slide 11: TG01 in resected pancreatic cancer: signal of efficacy seen in phase I/II trial
TG01 IN RESECTED PANCREATIC CANCER SIGNAL OF EFFICACY SEEN IN PHASE I/II TRIAL 33.4 vs. 27.6 months reported in the ESPAC4 trial for gemcitabine alone Median overall (counting from time of surgery) survival (N=32) o First patient cohort 33.1 months mOS (n=19) o Second patient cohort mOS not yet reac
Slide 12: Key learnings from TG01-01
KEY LEARNINGS FROM TG01-01 Relevant insights for future TG trials Safety TG is generally well-tolerated Dosing schedule Avoiding concomitant chemo and vaccination seems beneficial. Dosing schedule for subsequent trial established TG vaccination works Over 90% of patients have mutRAS immune activatio
Slide 13: TG02-01: vaccine trial targeting mRAS in colorectal cancer
TG02-01 VACCINE TRIAL TARGETING mRAS IN COLORECTAL CANCER o Safety o Evaluate ability to generate mutRAS specific T-cells Study Objectives o Investigate functionallity of mutRAS specific T-cells in tumor tissue, also in combination with pembrolizumab Study Design A Non-Randomised Open-Label Phase Ib
Slide 14: Opportunities to develop the TG program
OPPORTUNITIES TO DEVELOP THE TG PROGRAM Rationale for further development of TG “With the emergence of immune checkpoint inhibitors, therapeutic vaccine strategies are primed for a rebirth” Clinical relevance Well-defined target Growing interest o Meaningful clinical benefit o Cancer neoantigens are
Slide 15: Several patient populations where TG could meet a strong medical need
Several patient populations where TG COULD MEET A STRONG MEDICAL NEED Potential patient populations Resected patients with disease recurrence after adjuvant Pancreatic chemotherapy cancer Unresectable locally advanced pancreatic cancer (Stage III) that has stabilized after first-line chemotherapy >9
Slide 16: Clinical development strategy
TG neoantigen vaccine CLINICAL DEVELOPMENT STRATEGY 1 2 3 4 Resected pan- Colorectal Lung cancer All mutRAS creatic cancer cancer (NSCLC) cancers TG01 indication TG02 lead indication TG02 potential TG02 + TG03 long- o Ph I/II completed o Ph I trial ongoing future indication term potential o Next ste
Slide 17: TG development strategy overview
TG DEVELOPMENT STRATEGY OVERVIEW TG pivotal development Future indication TBD Collaborative CPI combination Pre-clinical pancreas trial clinical trial package Pursue Evaluate clinical Generate support- opportunities for benefit of TG ing pre-clinical TG investigator-led vaccination Sc in data packag
Slide 18: ONCOS-102 Program update
ONCOS-102 Program update 5. ONCOS-102 interim data in melanoma and mesothelioma 6. Financial and closing remarks
Slide 19: Oncolytic virus lead product candidate
Targovax has two programs in clinical development, with an ONCOLYTIC VIRUS LEAD PRODUCT CANDIDATE Lead product candidate o Genetically armed adenovirus o Alerts the immune system to the presence of cancer antigens ONCOS o Induces T-cells specific to the patients’ tumor Activates the Oncolytic virus
Slide 20: ONCOS-102 is a cancer targeting adenovirus armed with an immune stimulating transgene
ONCOS-102 is a cancer targeting adenovirus armed with an IMMUNE STIMULATING TRANSGENE 1 2 3 Selective replication Boosting the immune Enhanced infection in cancer cells activation of cancer cells ∆24 bp ∆6.7K/gp19K ∆Ad5 knob E1A E3 Fiber knob ITR ITR GM-CSF Transgene Ad3 knob 20
Slide 21: ONCOS-102 Phase I proof of concept: immune activation demonstrated
ONCOS-102 Phase I proof of concept IMMUNE ACTIVATION DEMONSTRATED Cold tumor turned hot CD8+ T-cell staining ONCOS-102 Phase I trial design: o 12 patients, 7 different solid tumors o No other treatment options left o Monotherapy 9 injections Top-line results: o 100% innate immune activation o 11/12
Slide 22: CD8+ T-cell infiltration correlates with survival
ONCOS-102 Phase I single agent proof of concept CD8+ T-CELL INFILTRATION CORRELATES WITH SURVIVAL Fold-change CD8+ T-cell count vs. survival r = 0.75 p = 0.005 10,000 CD8+ fold-change from baseline 1,000 Case example o Ovarian cancer 100 o Failed on 5 previous lines of therapy o Tumor specific T-cel
Slide 23: ONCOS clinical development strategy
ONCOS CLINICAL DEVELOPMENT STRATEGY 1 2 3 4 Path-to-market Proof-of-concept Proof-of-concept Next generation Mesothelioma CPI refractory New CPI indication oncolytic viruses Target launch Indications with no/ Peritoneal Targeting new indication limited effect of CPIs malignancies indications o Orpha
Slide 24: ONCOS-102 phase I/II development strategy: covering the bases
ONCOS-102 phase I/II development strategy COVERING THE BASES Delivery route Combination therapy Local Intra-tumoral injection ✓ Chemotherapy Cytostatics, SoC ✓ ✓ ✓ Compartmental Sc Checkpoint inhibitor Intra-peritoneal infusion PD-1 & PD-L1 blockade Systemic Intra-venous infusion TBD future Cell the
Slide 25: ONCOS clinical program overview
ONCOS CLINICAL PROGRAM OVERVIEW Mesothelioma o Shortest path-to-market Phase I/II - o Orphan drug designation randomized o Combination with SoC chemo 30 patients o Randomized vs. SoC Melanoma o PoC in CPI refractory patients Phase I o Combination with Keytruda® Up to 12+12 patients o Memorial Sloan
Slide 26: ONCOS-102 interim data in melanoma and mesothelioma
ONCOS-102 interim data in melanoma and mesothelioma 6. Financial and closing remarks
Slide 27: ONCOS-102 in melanoma
ONCOS-102 in melanoma
Slide 28: Checkpoint inhibitors have revolutionized the treatment of melanoma
CHECK POINT INHIBITORS HAVE REVOLUTIONIZED THE TREATMENT OF MELANOMA… Patient example – Yervoy® checkpoint inhibitor trial Prior to Yervoy® 1 year after 28 28
Slide 29: ...although every other patient doesn't respond
…ALTHOUGH EVERY OTHER PATIENT DOESN’T RESPOND Response rate to checkpoint inhibitors (CPIs) Melanoma ~40% “Tumor regression Renal Cell carcinoma ~70% after PD-1 blockade requires pre-existing CD8+ T cells” Triple Negative Breast ~70%-80% Paul Tumeh et al, Nature 2014 Lung Carcinoma (NSCLC) ~80% Chec
Slide 30: Targovax study in melanoma
TARGOVAX STUDY IN MELANOMA Hypothesis: can ONCOS-102 change the tumor microenvironment (produce the right type of T cells, increase PD-1 expressions etc) to make Keytruda work in melanoma patients who don’t respond to check point inhibition? 30
Slide 31: Study schema
STUDY SCHEMA Biopsy Baseline DAY 22 DAY 64 Imaging 31
Slide 32: Patient case: prior surgery, Keytruda, T-VEC, radiotherapy
87 year old female Surgery, Keytruda, T-VEC, Radiotherapy prior study ORR: PD (did not receive full dose of ONCOS-102) Day 10 Baseline Day 22 32
Slide 33: Patient case: prior surgery, Keytruda
73 year old male Surgery, Keytruda prior study ORR: PD (did not receive full dose of ONCOS-102) Baseline Day 22 33
Slide 34: Patient case: complete response after 2 Keytruda infusions
60 year old male Surgery, Yervoy, Keytruda prior study ORR: CR (after only 2 Keytruda infusions) Baseline Day 22 Day 63 34
Slide 35: 3 more patients
3 MORE PATIENTS 79 year old male; Yervoy, Keytruda, T-VEC prior study Shrinkage in injected lesion but new distant lesion ORR: PD 74 year old female; surgery and Opdivo prior study ORR: PD 78 year old female; Yervoy, Opdivo, Keytruda prior study ORR: PD 35
Slide 36: ONCOS-102 induce innate immune response
ONCOS-102 INDUCE INNATE IMMUNE RESPONSE o Increase of pro-inflammatory cytokines (IFN-y, TNF-a, IL-12p40, GM-CSF) after ONCOS- 102 administration o Increase of pro-inflammatory cytokines (IL-6 and IL-8) after ONCOS-102 administration o Temporarily elevation level of IL-10 after second ONCOS-102 admi
Slide 37: ONCOS-102 induce adaptive immune response
CD4+ T cells 01-001-01 Fold change from the baselin 01-001-02 Fold change from the baselin 12 01-001-02 01-001-0415 01-001-04 10 01-001-04ref 01-001-04ref ONCOS-102 INDUCE ADAPTIVE IMMUNE RESPONSE 8 6 01-001-0510 01-001-05 4 5 2 0 0 1 22 64 1 22 64 Days Days CD8+ T cells 01-001-01 CD3+ T cells 01-00
Slide 38: ONCOS-102 induce cancer antigen specific T cells
ONCOS-102 INDUCE CANCER ANTIGEN SPECIFIC T CELLS Measured by IFN gamma ELISPOT in PBMCs (baseline vs. post-treatment samples) One patient had de novo induction and development of tumor specific T cells against NY-ESO-1 and MAGE-A1 present in the PBMC on Week 3 and 9 Patient with CR had presence of t
Slide 39: Lessons learnt and next steps
LESSONS LEARNT AND NEXT STEPS ONCOS-102 is well tolerated There is preliminary efficacy in a patient with PD-1 refractory disease Correlative analyses in the first 4 patients provide evidence supporting the proposed mechanism of action Transient shrinkage is seen for larger baseline lesions when inj
Slide 40: ONCOS-102 in mesothelioma
ONCOS-102 in mesothelioma
Slide 41: Malignant pleural mesothelioma
ONCOS-102 target launch indication MALIGNANT MESOTHELIOMA PLEURAL HEALTHY LUNG DISEASED LUNG MESOTHELIOMA Mesothelial Mesothelial tissue tissue o Orphan disease, estimated 15,000 new cases per year (EU, USA, Australia) LUNG LUNG o Incidence is increasing worldwide and Cancer is predicted to peak in
Slide 42: Mesothelioma is shortest path-to-market
MESOTHELIOMA IS SHORTEST PATH-TO-MARKET Rationale for ONCOS-102 opportunity in mesothelioma: Become frontline therapy Orphan Drug Designation Limited competition o Preclinical data and phase o High unmet medical need, o CPIs show some early signs I results indicate potential of ONCOS-102 has orphan
Slide 43: Synergy between ONCOS-102 and chemotherapy
SYNERGY BETWEEN ONCOS-102 AND CHEMOTHERAPY mesothelioma mouse model Anticancer effect of ONCOS-102 and standard of care chemotherapy in xenograft mouse mesothelioma model Effects observed at Day 60: % change in tumor volume, 7 animals per group (14 tumors/group) ONCOS vs. mock 56% tumor volume reduc
Slide 44: ONCOS-102 can turn mesothelioma lesions hot
ONCOS-102 CAN TURN MESOTHELIOMA LESIONS HOT Phase I CD8+ T-cells in tumor CD4+ T-cells in tumor PD-L1 positive tumor cells Tumor biopsy staining Fold change % of total Mesothelioma – Phase I, patient 14 6.5 19.5 130x 16x 1 1.2 Baseline Week 5 Baseline Week 5 Baseline Week 5 Mesothelioma – Phase I, p
Slide 45: Phase I/II study design in combination with SoC
PHASE I/II STUDY DESIGN IN COMBINATION WITH SoC Randomized part Safety lead-in completed currently enrolling Experimental group (n=14) ONCOS-102 (6 Patient population Safety lead-in (n=6) administrations) Non-randomized Randomized SoC pem/cis (6 cycles) Advanced malignant ONCOS-102 pleural mesotheli
Slide 46: Clinical responses in safety cohort
CLINICAL RESPONSES IN SAFETY COHORT Partial response o 50% tumor reduction (CT) o Partial metabolic response (PET) Stable disease Disease progression o Stabilized tumor (CT) 1st line treatment o No metabolic change (PET) o Previously progressed on Safety lead-in cohort pem/cis in 1st line o Stabiliz
Slide 47: Signal of efficacy in the first 6 patients
SIGNAL OF EFFICACY IN THE FIRST 6 PATIENTS 1 2 3 4 Safety Innate immune Adaptive immune Clinical benefit activation activation ✓ ONCOS-102 well- ✓ Systemic ✓ Increase in tumor ✓ Signal of clinical tolerated in increase of pro- infiltration of benefit seen in combination with inflammatory CD4+ and CD
Slide 48: Development strategy and indicative timelines
ONCOS-102 in malignant pleural mesothelioma DEVELOPMENT STRATEGY AND INDICATIVE TIMELINES 2018 2019 2020 2021 2022 Ongoing Planned Future Phase I/II, randomized Expansion of randomized Phase II Phase III 30 patients ~60 additional patients (N = ~90) n=TBD o Randomized ORR and OS o Randomized ORR and
Slide 49: Financial and Closing remarks
Financial and Closing remarks
Slide 50: Targovax has a sound financial position
TARGOVAX HAS A SOUND FINANCIAL POSITION with cash to complete the planned clinical program into 2020 Operations The share Cash end of 2Q - Jun 30th 2018 Market Cap - at share price NOK ~11 201 25 600 70 NOK million USD million NOK million USD million Net cash flow - total 2Q Daily turnover - rolling
Slide 51: R&D pipeline overview and milestones
R&D PIPELINE OVERVIEW AND MILESTONES Product Phase Phase Phase Next expected Platform Preclinical Last event candidate I II III event Phase Ib safety lead-in cohort, 1H 2020 Mesothelioma incl. immune activation and Randomized ORR data Comb. w/ pemetrexed/cisplatin1 ORR data (6 pts) 30 pts 1H 2019 Me
Slide 52: Slide 52