Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Targovax — ABGSC Life Sciences Summit 2022
31 slides from Circio Holding Asa's conference presentation, May 19, 2022
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER ABGSC Life Sciences Summit Dr. Erik Digman Wiklund, CEO 19 May 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 the future and which, by their nature, will have an impact on the results of operations and the financial condition
Slide 3: 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 3 SOURCE: Research&Markets; Haslam & Prasad 2019, JAMA; Vaddepally et al. 2020, Cancers
Slide 4: 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 4 SOURCE: GlobalData, Research&Markets
Slide 5: 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 5 SOURCE: Haslam & Prasad, 2019, JAMA
Slide 6: The Solution: Immune Activation by Targovax's Oncolytic Virotherapy ONCOS
THE SOLUTION: IMMUNE ACTIVATION BY TARGOVAX´S ONCOLYTIC VIROTHERAPY ONCOS Reverses immuno-suppressive defence mechanisms in the tumor Primes the patient´s T-cells to target cancer cells Delivers immune stimulatory payloads 6
Slide 7: Targovax Development Pipeline
TARGOVAX DEVELOPMENT PIPELINE Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / 2022 Milestones enabling pivotal Multi-cohort 4Q 2022 / 1Q 2023 PD1 Refractory Melanoma trial in Initiation of phase 2 trial Combination w/anti PD1 planning 1H 2022 ONCOS-102 Mesothelioma Fu
Slide 8: Lead clinical program: ONCOS-102
Lead clinical program: ONCOS-102 8
Slide 9: PD1 Refractory Market Opportunity
PD1 REFRACTORY MARKET OPPORTUNITY GROWING UNMET NEED WITH INCREASED ANTI-PD1 USE ~100,000 new stage III/IV cases of malignant Incidence melanoma per year in the major markets ~50% recur and become unresectable Unresectable Total ~50,000 patients per year ~50% of cases become PD resistant PD1 resista
Slide 10: ONCOS-102 Has Demonstrated Highly Competitive ORR of 35% in PD1 Refractory Melanoma
ONCOS-102 HAS DEMONSTRATED HIGHLY COMPETITIVE ORR OF 35% IN PD1 REFRACTORY MELANOMA CR PR 35% ORR ONCOS-102 5% 30% (7/20 pts.) 35% 35% ORR BNT111 0% (6/17 pts.) 37% ORR retreatment RP1 6% 31% Anti-PD1 (6/16 pts.) 20% 28% ORR TAVO 8% (15/54 pts.) 8% 7% 16% 23% ORR CMP-001 (23/98 pts.) 15% ORR Sotigal
Slide 11: Multiple Examples of Systemic (Abscopal) Effect
MULTIPLE EXAMPLES OF SYSTEMIC (ABSCOPAL) EFFECT NON-INJECTED LESIONS COMPLETELY DISAPPEARED IN TWO PATIENTS Response in individual tumors % change from baseline; injected and non-injected target lesions Observed systemic effect: o 12 of 36 (33%) non-injected target lesions reduced in size o 8 of 15
Slide 12: Case Example: Partial Response in Patient Refractory to Both 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 13: Case Example: Partial Response Patient Refractory to T-VEC – T-Cell Infiltration
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 W
Slide 14: Strong Increase in Infiltration of T-Cells in Responding Patients
STRONG INCREASE IN INFILTRATION OF T-CELLS IN RESPONDING PATIENTS Multiplex immunofluorescence – T-cells CD8+ CD4+ CD8+ GrB+ 14
Slide 15: Evidence of Systemic Tumor Control by Antigen-Specific T-Cells
EVIDENCE OF SYSTEMIC TUMOR CONTROL BY ANTIGEN-SPECIFIC T-CELLS ONCOS-102 injected b2m loss-of-function T-cell specificity; PBMC IFNg elispot Genetic analyses; biopsy DNAseq Not ONCOS-102 injected b2m wild type Patient w/ complete response Baseline Week 3 Week 9 ONCOS-102 Control MAGE-A1 o Sustained
Slide 16: Gene Expression Data Confirms IHC Observations and Pro-Inflammatory Tumor Re-Programing
GENE EXPRESSION DATA CONFIRMS IHC OBSERVATIONS AND DETAILS BROAD PRO-INFLAMMATORY TUMOR RE-PROGRAMING Activation of immune related gene signatures Week 3 & 9 vs. Baseline DCR vs. progression RNAseq gene expression insights: o Pro-inflammatory “hot” tumor remodeling by multiple pathways o ”Hot” tumor
Slide 17: CTLA-4 Is Strongly Upregulated in Response to ONCOS-102 in Melanoma
CTLA-4 IS STRONGLY UPREGULATED IN RESPONSE TO ONCOS-102 IN MELANOMA 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 >25-fold up-regulation Day 64 of CTLA
Slide 18: Strong Rationale for Combining ONCOS-102 with a CTLA-4 Checkpoint Inhibitor
STRONG RATIONALE FOR COMBINING ONCOS-102 WITH A CTLA-4 CHECKPOINT INHIBITOR Reverse CTLA-4 blockade depletes inhibitory regulatory immuno- T-cells both within the tumor and systemically suppression Enhance anti- CTLA-4 blockade enhances the priming of tumor T-cell tumor-specific cytotoxic T-cells pr
Slide 19: Next Step: Multi-Cohort Phase 2 Trial Including ONCOS-102 + Anti-CTLA-4 Combination
NEXT STEP: MULTI-COHORT PHASE 2 TRIAL TO INCLUDE ONCOS-102 + ANTI-CTLA-4 COMBINATION Part 1 – run-in Part 2 – multi-cohort extension collaboration: ONCOS-102 Balstilimab: anti-PD-1 1 ONCOS-102 + monotherapy Assess 3 Botensilimab: Fc-enhanced botensilimab contribution of anti-CTLA-4 Randomize compone
Slide 20: Circular RNA pipeline program
Circular RNA pipeline program 20
Slide 21: 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 22: Emerging Circular RNA Technology Opens Novel Opportunities for the ONCOS Platform
EMERGING CIRCULAR RNA TECHNOLOGY OPENS NOVEL OPPORTUNITIES FOR THE ONCOS PLATFORM circRNA discoverers are in the Targovax team Dr. Thomas B. Hansen Dr. Erik D. Wiklund 22
Slide 23: Circular RNA Have Multiple Advantageous Characteristics as Anti-Cancer Therapeutics
CIRCULAR RNA HAVE MULTIPLE ADVANTAGEOUS CHARACTERISTICS AS ANTI-CANCER THERAPEUTICS Reducing oncogenic microRNAs Production of proteins of choice Circular RNA is resistant to exonuclease degradation ? Transcriptional regulation of target Immunological activation through genes to promote cancer cell
Slide 24: ONCOS Provides a Versatile, Clinically Validated Vector System for Circular RNA Delivery
ONCOS PROVIDES A VERSATILE, CLINICALLY VALIDATED, VECTOR SYSTEM FOR CIRCULAR RNA DELIVERY Novel ONCOS circRNA vectors Near term objectives for circRNA program: o Validate advantages of circRNA o In vitro proof-of-concept data by Circular 2H 2022 RNA o Solidify IP portfolio Gene therapy / Onco-microR
Slide 25: Targovax' Advantage in Hot Circular RNA Space
TARGOVAX´ ADVANTAGE IN HOT CIRCULAR RNA SPACE o Delivery system: The ONCOS platform provides a clinically validated delivery platform for circRNA o Mechanistic insights: Targovax has deep understanding of ONCOS activity based on clinical patient tumor data o Manufacturing: AdV manufacturing capabili
Slide 26: Corporate strategy
Corporate strategy ) targovax °
Slide 27: Multiple Paths to Significant Value Creation
MULTIPLE PATHS TO SIGNIFICANT VALUE CREATION Value creation strategy Out-license ONCOS-102 based on data from melanoma multi-cohort trial o Opportunity to “knock-it-out-of-the-park” with novel, differentiated scientifically based IO combinations o Sufficient sizing to de-risk program for big pharma/
Slide 28: 1Q Financial Snapshot
1Q FINANCIAL SNAPSHOT Key figures Shareholder base Net cash flow in 1Q Estimated ownership1 - 32 - 3.1 Shareholder Avanza Bank AB (nom.) Shares million Ownership 14.7 7.8 % NOK million USD million HealthCap 12.4 6.6 % FJARDE AP-FONDEN 8.7 4.6 % Cash at end of 1Q ABN Amro Global (nom.) 6.5 3.4 % 150
Slide 29: Targovax Executive Summary
TARGOVAX EXECUTIVE SUMMARY ONCOS-102: Oncolytic immunotherapy with demonstrated clinical efficacy and excellent safety profile in multiple solid tumors and treatment combinations Highly competitive response rate: 35% ORR in anti-PD1 refractory melanoma confirmed by deep mechanistic analyses of local
Slide 30: Erik Digman Wiklund CEO
Erik Digman Wiklund Lubor Gaal CEO CFO 30 erik.wiklund@targovax.com lubor.gaal@targovax.com
Slide 31: Strong, International Senior Management Team with a Versatile Range of Backgrounds
STRONG, INTERNATIONAL SENIOR MANAGEMENT TEAM WITH A VERSATILE RANGE OF BACKGROUNDS Dr Erik D Wiklund Dr Lubor Gaal Dr Lone Ottesen Dr Victor Levitsky Ola Melin Dr Ingunn M Lindvig Chief Executive Chief Financial Chief Medical Chief Scientific Head of VP Regulatory Officer Officer Officer Officer Man