Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Presentation (February 2021)
32 slides from Circio Holding ASA's investor presentation, February 2021
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Company presentation February 2021 OSE: TRVX
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: Targovax at a Glance
TARGOVAX AT A GLANCE Lead product ONCOS-102 directed to the $20+ billion market for checkpoint inhibitors Class-leading clinical data in monotherapy and combinations with chemo and CPI Powerful immune activation supporting IO-combinations Pipeline with multiple additional value-creating opportunitie
Slide 4: Medical Need for Immune Activators
MEDICAL NEED FOR IMMUNE ACTIVATORS CPIs are revolutionizing …but only a minority of …leading to a high medical cancer therapy… patients respond… need for immune activators $20+ bn Global CPI market1 44% Patients eligible for CPI2: 10 - 40% Responders 1 Immune Checkpoint Inhibitors Markets Report, 20
Slide 5: Several Significant Oncolytic Virus Transactions
SEVERAL SIGNIFICANT ONCOLYTIC VIRUS TRANSACTIONS Acquirer Target Type of deal Deal value Strategic collaboration USD 120m near-term Co-development of multiple USD >900m total value vaccinia viruses, Pre-clinical M&A USD 400m RNA virus, Phase II cash acquisition M&A USD 140m up-front Herpes virus, Pr
Slide 6: ONCOS-102 Is an Oncolytic Adenovirus Armed with an Immune Activating Transgene
ONCOS-102 IS AN ONCOLYTIC ADENOVIRUS SEROTYPE 5 ARMED WITH AN IMMUNE ACTIVATING 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 6
Slide 7: ONCOS-102 Drives a Strong Immune Response Triggering Anti-Tumor Immunity
ONCOS-102 DRIVES A STRONG IMMUNE RESPONSE TRIGGERING ANTI-TUMOR IMMUNITY 1 Virus injection 2 Immune activation 3 T-cell generation 4 Anti-tumor immunity Intratumoral or intra- Oncolysis of tumor cells Antigen processing T-cell tumor infiltration peritoneal injection Inflammatory response by stimulat
Slide 8: Solid Clinical and Preclinical Pipeline
SOLID CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Collaborator Next expected event 1H 2021 Mesothelioma Survival updates Combination w/ pemetrexed/cisplatin Define next steps Melanoma 1H 2021 Combination w/Keytruda Define next steps ONCOS-102 Colorectal cancer Upd
Slide 9: Product Candidate Pipeline
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma Combination w/ pemetrexed/cisplatin ONCOS-102 Melanoma Combination w/Keytruda Colorectal Combination w/Imfinzi Prostate Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concepts 9
Slide 10: ONCOS-102 Anti-PD1 Refractory Melanoma: 35% ORR and Systemic Effect
ONCOS-102 ANTI-PD1 REFRACTORY MELANOMA 35% ORR AND SYSTEMIC EFFECT Advanced, unresectable melanoma Disease progression despite prior treatment with anti-PD1 Patient population Poor prognosis, with few treatment alternatives 20 patients, 11 stage III and 9 stage IV Part 1: 3 ONCOS-102 injections foll
Slide 11: Patient Demographics – More Advanced Disease in Part 2
PATIENT DEMOGRAPHICS – MORE ADVANCED DISEASE IN PART 2 Part 1 Part 2 Total Parameters (n=8) (n=12) (N=20) Median time from diagnosis to start ONCOS-102 6.9 2.9 4.5 (years) Average number of checkpoint inhibitor treatments 1.8 2.3 2.2 prior to study Average number of lesions at baseline 4.5 9.1 7.3 A
Slide 12: Best-in-Class Response Rate with ORR of 35%
BEST-IN-CLASS RESPONSE RATE WITH ORR OF 35% Best change in tumor burden from baseline, percent 100 Complete response Partial response 80 Stable disease 60 Progressive disease 40 20 0 -20 -40 -60 -80 -100 12 Response defined as tumor reduction of at least 30% in at least one CT scan, according to REC
Slide 13: Multiple Examples of Systemic (Abscopal) Effect
MULTIPLE EXAMPLES OF SYSTEMIC (ABSCOPAL) EFFECT TWO PATIENTS WHERE A NON-INJECTED LESION COMPLETELY DISAPPEARED Findings are based on early data assessment, systemic effects will be further assessed Used threshold of tumor reduction of 30%1 or more in a lesion Observed in patients in both Part 1 and
Slide 14: ONCOS-102 Efficacy Is Competitive to Leading Drug Candidates
ONCOS-102 EFFICACY IS COMPETITIVE TO LEADING DRUG CANDIDATES IN ANTI-PD1 REFRACTORY MELANOMA CR PR Comment 5% 30% 35% ORR o Adenovirus expressing GM-CSF ONCOS-102 (7/20 pts.) 31% ORR o Herpes virus expressing GM-CSF retreatment RP1 6% 25% and GALV (5/16 pts.) Anti-PD1 30% ORR o IL-12 DNA plasmid wit
Slide 15: Summary: Excellent Outcome Support Continued Development in Melanoma
SUMMARY: EXCELLENT OUTCOME SUPPORT CONTINUED DEVELOPMENT IN ANTI-PD1 REFRACTORY MELANOMA Excellent safety profile confirmed ONCOS-102 and Keytruda combination is well-tolerated Excellent clinical outcome 35% ORR: Tumor responses were observed in 7 out of 20 evaluable patients Systemic effect: Tumor
Slide 16: Product Candidate Pipeline: ONCOS-102
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma ONCOS-102 Combination w/ pemetrexed/cisplatin Melanoma Combination w/Keytruda Colorectal cancer Combination w/Imfinzi Prostate cancer Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concep
Slide 17: High Need for New Treatment Approaches in Malignant Pleural Mesothelioma
HIGH NEED FOR NEW TREATMENT APPROACHES IN MALIGNANT PLEURAL MESOTHELIOMA Surgery Radiotherapy Only 10% of patients Rarely effective due to suitable for resection tumor shape Often diagnosed too Hard to focus radiation late for surgery Mainly Technically challenging palliative care Chemotherapy Immun
Slide 18: Encouraging Clinical Outcomes in 1st Line
ONCOS-102 MESOTHELIOMA PHASE 1/2 COMBINATION WITH SoC CHEMO ENCOURAGING CLINICAL OUTCOMES IN 1ST LINE Trial design 1st and 2nd (or later) line Oncos-102 + SoC, n=8 SoC, n=6 ONCOS-102: 6 intra-tumoral injections SoC chemo: pemetrexed and cisplatin, 6 Median PFS, months cycles 9.8 7.6 Safety Experi- C
Slide 19: First Line Data Are Maturing and Already Competitive
FIRST LINE DATA ARE MATURING AND ALREADY COMPETITIVE - MOS WILL BE 18.2 MONTHS OR MORE ONCOS-102 +Pem/cis mPFS Pem/cis (or carbo) months Checkpoint trials 11 Targovax experimental8 10 Min. 9 8 Targovax control8 Min. Max. Zalcman5 7 Nowak7 Ceresoli3 Baas5 chemo/durva Scagliotti4 control Baas6 6 Vogel
Slide 20: Level of Immune Activation Predictive of Clinical Outcome (1 of 4)
LEVEL OF IMMUNE ACTIVATION PREDICTIVE OF CLINICAL OUTCOME (1 OF 4) CD8+ T-cells ONCOS-102 treated – Alive 18mo. -fold change ONCOS-102 treated – Deceased 18mo. Control – Alive 18mo. Control – Deceased 18mo. Cytotoxic CD8+ T-cells PD-L1 expression -fold change -fold change No immune activation observ
Slide 21: Level of Immune Activation Predictive of Clinical Outcome (2 of 4)
LEVEL OF IMMUNE ACTIVATION PREDICTIVE OF CLINICAL OUTCOME (2 OF 4) CD8+ T-cells ONCOS-102 treated – Alive 18mo. -fold change ONCOS-102 treated – Deceased 18mo. Control – Alive 18mo. Control – Deceased 18mo. Cytotoxic CD8+ T-cells PD-L1 expression -fold change -fold change Clear immune activation in
Slide 22: Level of Immune Activation Predictive of Clinical Outcome (3 of 4)
LEVEL OF IMMUNE ACTIVATION PREDICTIVE OF CLINICAL OUTCOME (3 OF 4) CD8+ T-cells ONCOS-102 treated – Alive 18mo. -fold change ONCOS-102 treated – Deceased 18mo. Control – Alive 18mo. Control – Deceased 18mo. Cytotoxic CD8+ T-cells PD-L1 expression -fold change -fold change Some immune activation also
Slide 23: Level of Immune Activation Predictive of Clinical Outcome (4 of 4)
LEVEL OF IMMUNE ACTIVATION PREDICTIVE OF CLINICAL OUTCOME (4 OF 4) CD8+ T-cells ONCOS-102 treated – Alive 18mo. -fold change ONCOS-102 treated – Deceased 18mo. Control – Alive 18mo. Control – Deceased 18mo. Cytotoxic CD8+ T-cells PD-L1 expression -fold change -fold change Surviving ONCOS-102 patient
Slide 24: Clinical and Immune Data Support Triple Combination with Checkpoint Inhibitor
CLINICAL AND IMMUNE DATA SUPPORT TRIPLE COMBINATION WITH CHECKPOINT INHIBITOR Excellent safety profile confirmed ONCOS-102 and SoC chemotherapy combination is well-tolerated Clear clinical activity mOS not yet reached but at least 18.2 months mPFS of 9.8 months in first line randomized ONCOS-102 tre
Slide 25: Product Candidate Pipeline
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma Combination w/ pemetrexed/cisplatin Melanoma Combination w/Keytruda ONCOS-102 Colorectal cancer Combination w/Imfinzi Prostate cancer Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concep
Slide 26: Strong Collaboration in Colorectal Cancer with Phase 1/2 Trial Combining ONCOS-102 and Imfinzi
STRONG COLLABORATION IN COLORECTAL CANCER WITH PHASE 1/2 TRIAL COMBINING ONCOS-102 AND IMFINZI Collaboration Patient population Colorectal cancer with peritoneal metastases Refractory to standard-of-care platinum chemotherapy Intraperitoneal admin of ONCOS-102 Dose escalation Expansion Safety lead-i
Slide 27: Signs of Efficacy and Dose Response in Safety Lead-in
SIGNS OF EFFICACY AND DOSE RESPONSE IN SAFETY LEAD-IN Disease control Tumor change1 and best overall response Dosing cohorts (best response) by RECIST 1.1 Cohort A 0 of 2 120 Cohort B A: Low-dose ONCOS-102 PD 100 Cohort C then Imfinzi 80 PD B: Low-dose ONCOS-102 + 0 of 2 60 Cohort C Imfinzi 40 PD PD
Slide 28: Product Candidate Pipeline
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma Combination w/ pemetrexed/cisplatin Melanoma Combination w/Keytruda ONCOS-102 Colorectal cancer Combination w/Imfinzi Prostate cancer Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concep
Slide 29: Next Generation ONCOS Viruses Have Double Transgenes and Distinct Modes of Action
NEXT GENERATION ONCOS VIRUSES HAVE DOUBLE TRANSGENES AND DISTINCT MODES OF ACTION Mode of action Target tumors ONCOS-210 & -212 o Interfere with tumor’s ability to o Highly invasive or Inhibition of tumor growth break down surrounding tissue metabolic tumors and vascularization o Induce cell cycle a
Slide 30: Expanding Mutant RAS Platform Through Strategic Partnerships
EXPANDING MUTANT RAS PLATFORM THROUGH STRATEGIC PARTNERSHIPS Targovax mutRAS immunotherapy strategy Ongoing mutRAS initiatives o Test new indications Option to license TG vaccines for o Test new combinations Greater China and Singapore Expand mutRAS clinical use o Test new adjuvant Clinical stage o
Slide 31: Funded Well Beyond Important Value Inflection Points
FUNDED WELL BEYOND IMPORTANT VALUE INFLECTION POINTS The company Share liquidity Cash at end of 3Q Raised NOK ~200% of shares traded last 12 months 78 8 75m in Share turnover per month1 NOK million USD million Oct 2020 Million shares Net cash flow - total 3Q -24 -2.5 NOK million USD million Market c
Slide 32: In Summary
IN SUMMARY Lead product ONCOS-102 directed to the $20+ billion market for checkpoint inhibitors ➢ Poised to lead and grow the global market for checkpoint inhibitors (CPIs) with lead product, ONCOS-102 ➢ By activating the immune system, ONCOS-102 may enhance CPI sensitivity and expand the market Cla