Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Q3 2021 Earnings Presentation
25 slides from Circio Holding ASA's earnings presentation, Nov 4, 2021
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER 3Q 2021 Presentation 4 November 2021
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 and highlights
Introduction and highlights 2. ONCOS-102 melanoma data 3. NextGen ONCOS vectors 4. Strategy 3
Slide 4: Targovax at a Glance
TARGOVAX AT A GLANCE ONCOS-102: Novel immune activator with clinical efficacy in several solid tumors in monotherapy and in combination with anti-PD1 and chemotherapy MoA confirmed in multiple indications: Broad local and systemic immune activation associated with clinical outcome ONCOS-102 is the b
Slide 5: 3Q 2021 Highlights
3Q 2021 HIGHLIGHTS Poster presentation at the European Society for Medical Oncology (ESMO) annual meeting in September Scientific Two posters accepted for presentation at the Society for Immunotherapy of Cancer (SITC) annual meeting in November Received grant of European Patent for ONCOS-102 in comb
Slide 6: Third Quarter Opex – Continued Low Cash Burn Rate
THIRD QUARTER OPEX – CONTINUED LOW CASH BURN RATE NOK m 3Q20 4Q20 1Q21 2Q21 3Q21 Total revenue 0 0 0 0 0 External R&D expenses 1 -9 -8 - -9 - -9 -10 Payroll and related expenses -9 -12 -11 -13 -11 2 Other operating expenses -4 -3 -2 -3 -2 Total operating expenses -22 -23 -23 -25 -23 Operating loss -
Slide 7: 3Q Financial Snapshot
3Q FINANCIAL SNAPSHOT Key figures Shareholder base1 Net cash flow in 3Q Ownership by professional -17 -2.0 institutions, e.g. NOK million USD million • HealthCap, Nordea, Radforsk, AP4, MP 30% Cash at end of 3Q Pension 54 6.4 NOK million USD million Largest shareholder • HealthCap 14% Market cap 500
Slide 8: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma 2022 Platform IO combination trial First patient Mesothelioma 2H 2021 ONCOS-102 Combination w/pemetrexed/cisplatin Survival update Metastatic Colorectal cancer 1H 2022 Comb
Slide 9: ONCOS-102 melanoma data
ONCOS-102 melanoma data 3. NextGen ONCOS vectors 4. Strategy 9
Slide 10: ONCOS-102 Has Demonstrated Class-Leading Efficacy in PD1-Refractory Melanoma
ONCOS-102 HAS DEMONSTRATED CLASS-LEADING EFFICACY IN PD1-REFRACTORY MELANOMA CR PR 35% ORR ONCOS-102 5% 30% (7/20 pts.) 35% ORR BNT111 0 35% (6/17 pts.) retreatment Anti-PD1 31% ORR RP1 6% 25% (5/16 pts.) 30% ORR TAVO 6% 24% (16/54 pts.) 23% ORR CMP-001 7% 16% (23/98 pts.) T-cell therapy combination
Slide 11: Case Example: Patient with Complete Response
CASE EXAMPLE: PATIENT WITH COMPLETE RESPONSE Tumor response, 1 of 1 injected lesion Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Monotherapy activity Progression on 3x ONCOS-102 only 3x ONCOS-102 & 3x ONCOS-102 & 3x ONCOS-102 & pembrolizumab (no pembrolizumab) 2x pembrolizumab 5x pembrolizumab 8x pe
Slide 12: Case Example: Patient with Complete Response Tumor T-Cell Infiltration
CASE EXAMPLE: PATIENT WITH COMPLETE RESPONSE TUMOR T-CELL INFILTRATION T-cell infiltrate, 1 of 1 injected lesion Baseline Week 3 Week 9 Total level of T-cells Wk 3 CD8+ T-cells Wk 9 Low CD8+ 15x increase CR, mainly necrotic tissue; BL level at baseline from baseline some T-cells still present Wk 3 C
Slide 13: Highest Increase in Tumor T-Cell Infiltrates Observed in Melanoma Responders
HIGHEST INCREASE IN TUMOR T-CELL INFILTRATES OBSERVED IN MELANOMA RESPONDERS 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 SD PD CR 1 PR SD PD PD
Slide 14: Gene Expression Data Confirms IHC Observations and Details Pro-Inflammatory Reprogramming
GENE EXPRESSION DATA CONFIRMS IHC OBSERVATIONS AND DETAILS BROAD PRO-INFLAMMATORY TUMOR RE-PROGRAMING RNAseq gene expression provides further insights: Change week 9 vs. baseline o Pro-inflammatory “hot” tumor remodelling through multiple pathways and molecular mechanisms o ”Hot” tumor remodelling p
Slide 15: More Substantial and Sustained Pro-Inflammatory Tumor Re-Programming in Responders
MORE SUBSTANTIAL AND SUSTAINED PRO-INFLAMMATORY TUMOR RE-PROGRAMMING IN RESPONDERS Gene expression of immune related signatures, responders vs. non-responders, log(2) -fold difference 15
Slide 16: 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 inhibitors, tumor biopsy RNAseq, difference in PR vs. PD patients Day 1 / Baseline Day 1 / Baseline TIGIT Day 22 Day 22 Day 64 Day 64 Day 1 / Baseline CTLA 4 Day 22 Day 64
Slide 17: ONCOS-102 Also Drives Robust Upregulation of Co-Stimulatory Molecules
ONCOS-102 ALSO DRIVES ROBUST UPREGULATION OF CO-STIMULATORY MOLECULES, PARTICULARLY IN RESPONDERS Expression of costimulatory molecules, tumor biopsy RNAseq, difference in PR vs. PD patients Day 1 / Baseline Day 22 GITR Day 64 OX40 4-1BB CD28 ICOS-L 17 Higher in progressors -fold difference (log2) H
Slide 18: Next Step: Melanoma Platform Trial to Explore Multiple ONCOS-102 Combinations
NEXT STEP: MELANOMA PLATFORM TRIAL TO EXPLORE MULTIPLE ONCOS-102 COMBINATIONS DRIVEN BY PHASE 1 DATA Part 1 – run-in Part 2 – multi-cohort extension 1 ONCOS-102 4 ONCOS-102 + monotherapy PD1 + CTLA4 Assess contri- o Additional cohorts to explore Randomize bution of novel combinations components ONCO
Slide 19: NextGen ONCOS vectors
NextGen ONCOS vectors 4. Strategy
Slide 20: Novel RNA Delivery Formats: RNA Exists Naturally in Circular Form
NOVEL RNA DELIVERY FORMATS: RNA EXISTS NATURALLY IN CIRCULAR FORM 768 citations 20 20
Slide 21: Two Recent Launches of Circular RNA Biotechs Have Attracted Mega Series A Rounds
TWO RECENT LAUNCHES OF CIRCULAR RNA BIOTECHS HAVE ATTRACTED MEGA SERIES A ROUNDS 21
Slide 22: ONCOS Provides an Ideal, Clinically Validated Platform for Circular RNA
ONCOS PROVIDES AN IDEAL, CLINICALLY VALIDATED PLATFORM FOR CIRCULAR RNA Novel ONCOS circular RNA vectors Circular RNA Express transgenes Encode tumor antigens Immunological activation Onco-microRNA sponge Highly versatile delivery system 22
Slide 23: Strategy
Strategy
Slide 24: Targovax Core Development Strategy
TARGOVAX CORE DEVELOPMENT STRATEGY Let the science guide us: 1 Make smart, scientifically based decisions based on data and insights generated in the phase 1/2 program Advance ONCOS-102 in aPD1 refractory melanoma: 2 Boost response rates beyond the current 35% ORR by identifying the best combination
Slide 25: R&D Strategy: Validating ONCOS as a Versatile Delivery Tool
R&D STRATEGY: VALIDATING ONCOS AS A VERSATILE DELIVERY TOOL AND IDENTIFY BEST COMBINATION APPROACH o Lead clinical-stage product candidate Clinical o Phase 2 multi-cohort trial in melanoma ONCOS-102 platform trial o Assess multiple combinations in parallel to identify best partner and schedule Two-p