Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Day (2021)
12 slides from Circio Holding ASA's investor day presentation, Apr 14, 2021
Slide 1: Immune activation
Immune activation 5. Preclinical pipeline update 6. 4Q update 7. Closing remarks
Slide 2: The importance of immunological read-outs
THE IMPORTANCE OF IMMUNOLOGICAL READ-OUTS o Understand mechanism- o Strength of immune of-action of ONCOS-102 responses o Confirm delivery of o Breadth of ONCOS-102 into the immunological tumor remodelling Function Power o Persistence of the Duration Impact o Association between immune response immu
Slide 3: Four critical phases of tumor-specific immune response
FOUR CRITICAL PHASES OF TUMOR-SPECIFIC IMMUNE RESPONSE T-cell migration and 2 infiltration into the tumor 1 Access to tumor antigens, cross-presentation by APCs and priming of T-cells Expansion and survival m 3 of T-cells in the tumor 4 Tumor cell recognition and elimination 55 Adapted from Chen & M
Slide 4: Four critical phases of tumor-specific immune response
FOUR CRITICAL PHASES OF TUMOR-SPECIFIC IMMUNE RESPONSE T-cell migration and 2 infiltration into the tumor 1 Access to tumor antigens, cross-presentation by APCs Problem: T-cells do not and priming of T-cells reach the tumor Problem: Low tumor immunogenicity and Expansion and survival ineffective T-c
Slide 5: ONCOS-102 activates danger signaling: mesothelioma
ONCOS-102 ACTIVATES DANGER SIGNALING: MESOTHELIOMA TLR9 expression in tumor RNAseq -fold change D36 vs. baseline1, mesothelioma Injected lesion Non- Control injected lesion 57 1 Unpublished company data
Slide 6: ONCOS-102 activates danger signaling: melanoma
ONCOS-102 ACTIVATES DANGER SIGNALING: MELANOMA * * 001-01-13 – no data for Day 64 58 Unpublished company data
Slide 7: Robust increase of tumor infiltration by T-cells following ONCOS-102 treatment
ROBUST INCREASE OF TUMOR INFILTRATION BY T-CELLS FOLLOWING ONCOS-102 TREATMENT ONCOS-102 induced tumor T-cell infiltration Ovarian cancer patient case example, monotherapy Tumor biopsy mIHC – CD8+ T-cells o >1000-fold increase of CD8+ T-cells in tumor o Ovarian cancer patient – stable disease for th
Slide 8: Robust increase in T-cell tumor infiltration following ONCOS-102 treatment: mesothelioma
ROBUST INCREASE IN T-CELL TUMOR INFILTRATION FOLLOWING ONCOS-102 TREATMENT: MESOTHELIOMA CD8+ T-cells ONCOS-102 treated - Alive -fold change ONCOS-102 treated - Deceased Control - Alive Control - Deceased Cytotoxic CD8+ T-cells PD-L1 expression -fold change -fold change M1:M2 macrophage Ratio of cyt
Slide 9: Immune-permissive reshaping of tumor microenvironment by ONCOS-102: melanoma
IMMUNE-PERMISSIVE RESHAPING OF TUMOR MICROENVIRONMENT BY ONCOS-102: MELANOMA Modulation of gene expression; Fraction (%) of genes modulated within the indicated gene groups Day 22 vs. Baseline Day 64 vs. Baseline Part 1 Part 2 Day 22 & Day 64 (n=2) Day 22 (n=10) & Day 64 (n=7) Baseline (n=6) Baselin
Slide 10: ONCOS-102 treatment increases cytotoxic potential of intratumoral T-cells: mesothelioma
ONCOS-102 TREATMENT INCREASES CYTOTOXIC POTENTIAL OF INTRATUMORAL T-CELLS: MESOTHELIOMA Relative level of cytotoxic GrB+ / CD8+ T-cells at Modulation of tumor gene expression, Fraction day 36 of genes Alive vs. deceased at 12 months, mesothelioma ONCOS-102 treated vs. untreated, mesothelioma ONCOS-1
Slide 11: ONCOS-102 treatment increases cytotoxic potential on intra-tumoral T-cells: melanoma
ONCOS-102 TREATMENT INCREASES CYTOTOXIC POTENTIAL ON INTRA-TUMORAL T-CELLS: MELANOMA 63 Unpublished company data
Slide 12: ONCOS-102 immune activation - conclusions
ONCOS-102 IMMUNE ACTIVATION - CONCLUSIONS ONCOS-102 activates the immune system and counteracts multiple mechanisms of immuno-suppression operating at different steps of the cancer immunity cycle Multifaceted modulation of the tumor micro-environment induced by ONCOS-102 is linked to clinical benefi