Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Q4 2021 Earnings Presentation
30 slides from Circio Holding Asa's earnings presentation, Feb 17, 2022
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER 4Q & full year 2021 report 17 February 2022 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: 4Q & Full Year 2021 Highlights
4Q & FULL YEAR 2021 HIGHLIGHTS Reported class-leading ORR of 35% for ONCOS-102 in PD1-refractory melanoma, associated with broad and powerful immune activation in responding tumors Reported 25.0 months median Overall Survival (mOS) for ONCOS-102 combined with ONCOS-102 chemotherapy in first line mes
Slide 4: 4Q OPEX in Line with Previous Quarters
4Q OPEX IN LINE WITH PREVIOUS QUARTERS NOK m 4Q20 1Q21 2Q21 3Q21 4Q21 Total revenue 0 0 0 0 0 R&D expenses1 -8 - -9 - -9 -10 -10 Payroll and related expenses -12 -11 -13 -11 -13 Other operating expenses 2 -3 -2 -3 -2 -2 Total operating expenses -23 -23 -25 -23 -26 Operating loss -23 -23 -25 -23 -26
Slide 5: 4Q Financial Snapshot
4Q FINANCIAL SNAPSHOT Key figures Shareholder base Net cash flow in 4Q Estimated ownership1 NOK 175m 128 14.5 Rights Issue Shareholder Avanza Bank AB (nom.) Shares million Ownership 16.7 8.9 % NOK million USD million executed HealthCap 12.4 6.6 % December FJARDE AP-FONDEN 8.7 4.6 % Cash at end of 4Q
Slide 6: The Targovax Opportunity - High and Growing
THE TARGOVAX OPPORTUNITY - HIGH AND GROWING MEDICAL NEED FOR IMMUNE ACTIVATORS CPIs are revolutionizing …but most patients …leading to a high medical cancer therapy… do not respond… need for immune activators $25bn Global CPI market Progressing patients 44% Patients eligible for CPI2: 60 - 90% Non-r
Slide 7: The ONCOS Platform: Immune Activating Oncolytic Delivery System
THE ONCOS PLATFORM: IMMUNE ACTIVATING ONCOLYTIC DELIVERY SYSTEM Unblinds the tumor to the immune system Primes the patient´s T-cells to target cancer cells Reverses immunosuppressive defence mechanisms in the tumor Delivers immune stimulatory payloads 7
Slide 8: Targovax Is Centered Around Four Core Immune Activator Development Projects
TARGOVAX IS CENTERED AROUND FOUR CORE IMMUNE ACTIVATOR DEVELOPMENT PROJECTS 1 2 3 4 ONCOS-102 local ONCOS-102 systemic ONCOS circRNA delivery mutant KRAS delivery delivery platform immunotherapy Clinical phase 2 Pre-clinical in vitro / in vivo Discovery / in vitro PoC Clinical phase 1 o Efficacy and
Slide 9: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Next expected event enabling pivotal 1 PD1 Refractory Melanoma Multi-cohort 4Q22 / 1Q23 Combination w/anti PD1 trial in planning First patient in phase 2 trial 1H 2022 ONCOS-102 Mesothelioma
Slide 10: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Next expected event enabling pivotal 1 ONCOS-102 PD1 Refractory Melanoma Multi-cohort 4Q22 / 1Q23 local delivery Combination w/anti PD1 trial in planning First patient in phase 2 trial 1H 20
Slide 11: Class Leading ORR of 35% Shown in PD1 Refractory Melanoma Phase 1 Study
CLASS LEADING ORR OF 35% SHOWN IN PD1 REFRACTORY MELANOMA PHASE 1 STUDY CR PR 35% ORR ONCOS-102 5% 30% (7/20 pts.) 35% 35% ORR BNT111 0% (6/17 pts.) 31% ORR retreatment RP1 6% 25% Anti-PD1 (5/16 pts.) 20% 28% ORR TAVO 8% (15/54 pts.) 8% 7% 16% 23% ORR CMP-001 (23/98 pts.) 15% ORR Sotigalimab 15% (5/
Slide 12: Gene Expression Data Shows Broad, Pro-Inflammatory Tumor Re-Programing
GENE EXPRESSION DATA SHOWS BROAD, PRO- INFLAMMATORY TUMOR RE-PROGRAMING RNAseq gene expression provides further insights: Change Day 64 vs. baseline o Pro-inflammatory “hot” tumor remodeling through multiple molecular pathways o ”Hot” tumor remodeling persists at least until Day 64, following 6 ONCO
Slide 13: ONCOS-102 Drives Robust Upregulation of Immune Checkpoint Inhibitors
ONCOS-102 DRIVES ROBUST UPREGULATION OF IMMUNE CHECKPOINT INHIBITORS, PARTICULARLY IN RESPONDERS Expression of immune checkpoint inhibtors, tumor biopsy RNAseq, difference PR vs. PD patients Day 1 / Baseline TIGIT Day 1 / Baseline Day 22 Day 22 Day 64 Day 64 Day 1 / Baseline CTLA4 Day 22 Day 64 Stro
Slide 14: Next Step: Multi-Cohort Phase 2 Trial to Identify Best Combination Partner
NEXT STEP: MULTI-COHORT PHASE 2 TRIAL TO IDENTIFY BEST COMBINATION PARTNER FOR REGISTRATIONAL TRIAL(S) Part 1 – run-in Part 2 – multi-cohort extension 1 ONCOS-102 3 ONCOS-102 + monotherapy Assess CTLA4 Randomize contribution of o Additional cohorts to explore components novel combinations ONCOS-102
Slide 15: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Next expected event enabling pivotal PD1 Refractory Melanoma Multi-cohort 4Q22 / 1Q23 Combination w/anti PD1 trial in planning First patient in phase 2 trial 1H 2022 ONCOS-102 Mesothelioma 1
Slide 16: ONCOS-102 Has Shown 25.0 Months mOS in 1L Mesothelioma
ONCOS-102 HAS SHOWN 25.0 MONTHS mOS IN 1L MESOTHELIOMA, WHICH IS THE BEST SURVIVAL DATA REPORTED IN THIS POPULATION ONCOS-102 +Pem/cis mPFS Pem/cis (or carbo) months Checkpoint trials 11 Targovax experimental8 10 9 8 Targovax control8 Baas6 Zalcman5 7 control Nowak7 Ceresoli3 chemo/durva Scagliotti4
Slide 17: Improved Survival Outcome Associated with Powerful ONCOS-102 Induced Immune Activation
IMPROVED SURVIVAL OUTCOME IS ASSOCIATED WITH POWERFUL ONCOS-102 INDUCED IMMUNE ACTIVATION Immuno-modulation in tumor tissue; mIHC, Day 36 vs. baseline CD8+ T-cells ONCOS-102 treated: Alive 18mo. (n=6) -fold change ONCOS-102 treated: Deceased 18mo. (n=9) Control: Alive 18mo. (n=2) Control: Deceased 1
Slide 18: ONCOS-102 Local Delivery: A Clinically Validated Oncolytic Immune Activator
ONCOS-102 LOCAL DELIVERY: A CLINICALLY VALIDATED ONCOLYTIC IMMUNE ACTIVATOR Tested in several Demonstrated Drives Phase 2 multi- treatment ability both to inflammatory cohort trial in refractory and shrink tumors response and aPD1-refractory immunologically and improve immunological melanoma under c
Slide 19: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Next expected event enabling pivotal PD1 Refractory Melanoma Multi-cohort 4Q22 / 1Q23 Combination w/anti PD1 trial in planning First patient in phase 2 trial 1H 2022 ONCOS-102 Mesothelioma F
Slide 20: The Next Frontier – Enabling Systemic Delivery of Oncolytic Viruses
THE NEXT FRONTIER – ENABLING SYSTEMIC DELIVERY OF ONCOLYTIC VIRUSES Ongoing pre- clinical activity Unlikely IV infusion of Packaging / coating of “Stealthing” OV by to work “naked” OVs OV in inert particles capsid modification o Short half-life o Extend half-life o Genetic modification to o Liver fi
Slide 21: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Next expected event enabling pivotal PD1 Refractory Melanoma Multi-cohort 4Q22 / 1Q23 Combination w/anti PD1 trial in planning First patient in phase 2 trial 1H 2022 ONCOS-102 Mesothelioma F
Slide 22: RNA: Emerging Therapeutic Class, Driven by Strong Recent Success in COVID mRNA Vaccines
RNA: EMERGING THERAPEUTIC CLASS, DRIVEN BY STRONG RECENT SUCCESS IN COVID mRNA VACCINES Antisense oligos (ASO) siRNA / miRNA mRNA vaccines BioNTech / Pfizer and Moderna COVID vaccines first approved mRNA therapeutics No circRNA therapeutic candidates are approved or in clinical stage development 22
Slide 23: RNA-Based Therapeutics Face Several Challenges
RNA-BASED THERAPEUTICS FACE SEVERAL CHALLENGES Challenges for RNA-based therapies ONCOS solves these RNA is chemically unstable issues through a clinically validated DNA based Efficient delivery of RNA drugs delivery system that remains a major obstacle ensures local RNA expression and persistence i
Slide 24: RNA Exists Naturally in Circular Form and Can Be Engineered for Protein Translation
RNA EXISTS NATURALLY IN CIRCULAR FORM AND CAN BE ENGINEERED FOR PROTEIN TRANSLATION 768 citations circRNA discoverers are in the Targovax team Thomas B. Hansen Erik D. Wiklund
Slide 25: Circular RNA Have Multiple Advantageous Characteristics as Anti-Cancer Therapeutics
CIRCULAR RNA HAVE MULTIPLE ADVANTAGEOUS CHARACTERISTICS AS ANTI-CANCER THERAPEUTICS Sponging of oncogenic microRNAs Translation for local gene therapy Circular RNA is resistant to exonuclease degradation ? Immunological activation through Transcriptional regulation of pattern recognition receptors (
Slide 26: Recent Launches of Circular RNA Gene Therapy Biotechs Have Attracted Mega Series A Rounds
RECENT LAUNCHES OF CIRCULAR RNA GENE THERAPY BIOTECHS HAVE ATTRACTED MEGA SERIES A ROUNDS
Slide 27: ONCOS Provides an Ideal, Clinically Validated Platform for Circular RNA
ONCOS PROVIDES AN IDEAL, CLINICALLY VALIDATED PLATFORM FOR CIRCULAR RNA Novel ONCOS circRNA vectors Aims of ONCOS circRNA program: o Generate in vitro proof-of-concept data package by 2H 2022 o Build technology platform IP Circular portfolio and know-how RNA o Construct multi-functional novel circON
Slide 28: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Next expected event enabling pivotal PD1 Refractory Melanoma Multi-cohort 4Q22 / 1Q23 Combination w/anti PD1 trial in planning First patient in phase 2 trial 1H 2022 ONCOS-102 Mesothelioma F
Slide 29: Building Mutant KRAS Immunotherapy Program Through Strategic Partnerships
BUILDING MUTANT KRAS IMMUNOTHERAPY PROGRAM THROUGH STRATEGIC PARTNERSHIPS Targovax mutRAS immunotherapy strategy mutant KRAS immunotherapy pipeline TG01 mutRAS vaccine – trial o Enhanced versions of to launch in 2022 testing novel Polyvalent mut KRAS TG vaccines and novel indications and IO combinat
Slide 30: Delivering on the Core Development Projects
DELIVERING ON THE CORE DEVELOPMENT PROJECTS o Execute multi-cohort trial in PD1 refractory melanoma 1 Local ONCOS-102 o Boost ORR by novel, data-driven IO combinations delivery melanoma o Expand in skin cancers and other injectable tumors o Evaluate technologies to shield virus in circulation 2 ONCO