Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Targovax — Carnegie Nordic Healthcare 2022
31 slides from Circio Holding Asa's conference presentation, Mar 15, 2022
Slide 1: Activating the patient's immune system to fight cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Carnegie Nordic Healthcare Dr. Erik D Wiklund, CEO 15 March 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: Introduction
Introduction 2. ONCOS-102 intra-tumoral delivery 3. NextGen circRNA ONCOS vectors 4. Summary 3
Slide 4: The immuno-oncology revolution
THE IMMUNO-ONCOLOGY REVOLUTION > 500,000 patients treated per year > 3,000 ongoing clinical trials > 40% of US cancer patients eligible > 10 approved products 4 SOURCE: Research&Markets; Haslam & Prasad 2019, JAMA; Vaddepally et al. 2020, Cancers
Slide 5: First generation immuno-oncology: checkpoint inhibitors
FIRST GENERATION IMMUNO-ONCOLOGY: CHECKPOINT INHIBITORS Cornerstone of current cancer treatment Deep and durable responses $25b annual sales globally 8 products approved to date, many more in development 5 SOURCE: GlobalData, Research&Markets
Slide 6: The challenge: make PD1 checkpoint inhibitors work for more patients
THE CHALLENGE: MAKE PD1 CHECKPOINT INHIBITORS WORK FOR 0-40% of treated patients respond MORE PATIENTS of responding >50% patients relapse 1 PD1 checkpoint inhibitor monotherapy not sufficient 6 6 SOURCE: Haslam & Prasad, 2019, JAMA
Slide 7: The solution: immune activation by Targovax's oncolytic virotherapy ONCOS
THE SOLUTION: IMMUNE ACTIVATION BY TARGOVAX´S ONCOLYTIC VIROTHERAPY ONCOS Unblinds the tumor to the immune system Primes the patient´s T-cells to target cancer cells Reverses immunosuppressive defense mechanisms in the tumor Delivers immune stimulatory payloads 7
Slide 8: Four core immune activator development projects
TARGOVAX IS CENTERED AROUND FOUR CORE IMMUNE ACTIVATOR DEVELOPMENT PROJECTS 1 2 3 4 ONCOS-102 intra-tumoral 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 Effi
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: ONCOS-102 intra-tumoral delivery
ONCOS-102 intra- tumoral delivery 10
Slide 11: 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 12: Class leading ORR of 35% 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 13: Case example: partial response in patient refractory to T-VEC and anti-PD1
CASE EXAMPLE: PARTIAL RESPONSE IN PATIENT REFRACTORY TO BOTH T-VEC AND ANTI-PD1 Tumor response, 2 of 2 injected lesions Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Lesion 1 of 2 Monotherapy activity Lesion 2 of 2 Monotherapy activity Progression on 3x ONCOS-102 3x ONCOS-102 & 3x ONCOS-102 & 3x ONCO
Slide 14: Case example: T-cell infiltration in partial response patient
CASE EXAMPLE: PARTIAL RESPONSE PATIENT REFRACTORY TO T-VEC - T-CELL INFILTRATION T-cell infiltrate, 1 of 2 injected lesions Baseline Week 3 Week 9 Total level of T-cells Wk 9 CD8+ T-cells Wk 3 BL Some CD8+ 3x increase 4.5x increase presence at baseline from baseline from baseline CD4+ T-cells* Wk 9
Slide 15: Increased T-cell infiltration consistent across patients and linked to response
INCREASED T-CELL INFILTRATION IS CONSISTENT ACROSS PATIENTS, AND ASSOCIATED WITH CLINICAL RESPONSE T-cell infiltrate (TIL) for individual patients; tumor mIHC, relative level Average T-cell level per group Baseline Baseline Week 3 Week 3, ONCOS only Week 9 * w/o pseudo-progressor CD8+ T-cells CR PR
Slide 16: Gene expression data confirms IHC observations and pro-inflammatory reprogramming
GENE EXPRESSION DATA CONFIRMS IHC OBSERVATIONS AND DETAILS 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 pathways and molecular mechanisms o ”Hot” tumor remodeling per
Slide 17: ONCOS-102 drives upregulation of immune checkpoint inhibitors in responders
ONCOS-102 DRIVES ROBUST UPREGULATION OF IMMUNE CHECKPOINT INHIBITORS, PARTICULARLY IN RESPONDERS Expression of immune checkpoint inhibtors, tumor biopsy RNAseq, difference in 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 D
Slide 18: 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 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 1
Slide 20: 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 21: Improved survival associated with 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 22: Intra-tumoral ONCOS-102: a clinically validated oncolytic immune activator
INTRA-TUMORAL ONCOS-102: A CLINICALLY VALIDATED ONCOLYTIC IMMUNE ACTIVATOR Tested in several Demonstrated Drives Phase 2 multi- treatment ability both to inflammatory cohort trial in aPD1- refractory and shrink tumors response and refractory immunologically and improve immunological melanoma buildin
Slide 23: NextGen circRNA ONCOS vectors
NextGen circRNA ONCOS vectors 23
Slide 24: RNA: emerging therapeutic class driven by COVID vaccine success
RNA: EMERGING THERAPEUTIC CLASS, DRIVEN BY STRONG RECENT SUCCESS IN COVID 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 24
Slide 25: RNA-based therapeutics face several challenges
RNA-BASED THERAPEUTCIS 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 26: RNA exists naturally in circular form and can be engineered for 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 27: Circular RNA has 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 28: Circular RNA gene therapy biotechs attracted mega Series A rounds
RECENT LAUNCHES OF CIRCULAR RNA GENE THERAPY BIOTECHS HAVE ATTRACTED MEGA SERIES A ROUNDS
Slide 29: 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 30: Summary
Summary ° targovax mae)
Slide 31: Broadly positioned for future success
BROADLY POSITIONED FOR FUTURE SUCCESS 1 Local ONCOS-102 o Class-leading data in PD1-refractory melanoma delivery melanoma 2 ONCOS systemic o Expand commercial opportunity through IV delivery delivery 3 NextGen vectors for o First-in-class circular RNA program driven by world- circRNA delivery leadin