Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Day (February 2021)
26 slides from Circio Holding ASA's investor day presentation, Feb 18, 2021
Slide 1: Melanoma and oncolytic adenoviruses
Melanoma and oncolytic adenoviruses Alexander Shoushtari, MD Assistant Attending Physician Melanoma and Immunotherapeutics Service Memorial Sloan Kettering Cancer Center New York, NY February 18, 2021 @alexshoushtari
Slide 2: Immunotherapy has revolutionized the treatment of malignant melanoma
Immunotherapy has revolutionized the treatment of malignant melanoma Real world example – Patient in an ipilimumab checkpoint inhibitor trial Prior to starting ipilimumab One year of ipilimumab treatment 2 Photo courtesy Jedd Wolchok
Slide 3: PD-1 blockade has surpassed CTLA-4, and become the cornerstone of melanoma treatment
PD-1 blockade has surpassed CTLA-4, and become the cornerstone of melanoma treatment Nivo + Ipi Nivo Ipi Source: Larkin et al, NEJM 2019 3
Slide 4: SITC treatment algorithm for late stage melanoma
SITC treatment algorithm for late stage melanoma Checkpoint inhibitors and BRAFi/MEKi are the mainstay frontline therapy in unresectable melanoma Few alternatives exist following progression on CPI and/or BRAFi/MEKi Treatment resistance – option of clinical trial or best supportive care 4 SOURCE: So
Slide 5: PD-1 checkpoints are effective in melanoma
PD-1 checkpoints are effective in melanoma Two main checkpoint inhibitor (CPI) treatment choices o Anti-PD-1 monotherapy: Pembrolizumab or Nivolumab o Anti-PD-1 + anti-CTLA4 combination therapy: Nivolumab plus Ipilimumab 45 - 60% objective response rate o Responses can last for years, but not foreve
Slide 6: Post PD-1/CTLA4/BRAF-MEKi progression, only experimental and off-label options are available
Post PD-1/CTLA4/BRAF-MEKi progression, only experimental and off-label options are available Standard options post PD-1 Non-standard options post PD-1 After PD-1 monotherapy Clinical Trials (selected) o BRAF-MEK, if V600 mutant o PD-1 combination with: o Nivolumab plus ipilimumab − Oncolytic virus o
Slide 7: Response rates reported from PD-1 checkpoint inhibitor refractory melanoma clinical trials
Response rates reported from PD-1 checkpoint inhibitor refractory melanoma clinical trials 5% 30% 35% ORR o Adenovirus expressing GM-CSF ONCOS-102 (7/20 pts.) CR PR Company Comment 31% ORR o Herpes virus expressing GM-CSF RP1 6% 25% and GALV (5/16 pts.) retreatment Anti-PD1 30% ORR o IL-12, DNA plas
Slide 8: Promising experimental therapies available for PD-1 resistant patients
Promising experimental therapies available for PD-1 resistant patients Oncolytic viruses TLR-9 agonists • Trigger oncolysis and inflammatory • Stimulate innate immune response response via TLR-9 and other via TLR-9 danger signaling • Reverses local immuno-suppression • Trials ongoing in combination
Slide 9: Overview of the most common oncolytic virus classes
Overview of the most common oncolytic virus classes Small RNA viruses Adenovirus Herpes viruses Vaccinia virus o Highly oncolytic o Highly inflammatory o Large payload capacity o Large payload capacity o Highly inflammatory o Versatile DNA backbone o Only approved virus class o Used as vector for fi
Slide 10: Study design of ONCOS-102 phase I trial in PD1 checkpoint-refractory melanoma
Study design of ONCOS-102 phase I trial in PD1 checkpoint-refractory melanoma Part 1 (n=8): BL 1 2 3 6 9 12 15 18 21 24 27 Weeks 3x ONCOS-102 injections Sequential treatment CPO ONCOS-102 pembrolizumab Part 2 (n=12): BL 1 2 3 6 9 12 15 18 21 24 27 Weeks 12x ONCOS-102 injections Combination treatment
Slide 11: Patient and disease characteristics
Patient and disease characteristics Part 1 Part 2 Total Parameters (n=8) (n=12) (N=20) Age (median) 70.5y 72y 72y Time from diagnosis to start of ONCOS-102 (median) 6.9y 2.9y 4.5y Number of treatments prior to study (average) 5.3 5.9 5.6 - Surgery (average) 2.1 1.9 2.0 - Treatments ex. surgery (aver
Slide 12: Objective responses observed in 7 out of 20 patients (35% ORR)
Objective responses observed in 7 out of 20 patients (35% ORR) Relative change (percent) in tumor burden from baseline to best response 100 Complete response Partial response 80 Stable disease 60 Progressive disease 40 IV III IV III III 20 IV IV III IV IV 0 III III -20 III -40 III IV IV III -60 IV -
Slide 13: 6 of 7 responders had last aPD1 treatment less than 3 months prior to entering the trial
6 of 7 responders had last aPD1 treatment less than 3 months prior to entering the trial Best Checkpoint inhibitor treatment prior to ONCOS-102 response CPI treatment prior to Part 1 001-02-002 PD trial inclusion: 001-01-001 PD 001-01-005 CR 001-01-009 PR 15 / 20 patients last 001-01-004 SD 001-02-0
Slide 14: Case example – patient with complete response
Case example 1 – patient with complete response Tumor stage at enrollment: IIIc Prior therapies: Surgery T4a, N2b, M0 Radiation Ipilimumab RECIST 1.1: CR Dabrafenib + Trametinib Pembrolizumab Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Target lesion 1 of 1 Progression on 3x ONCOS-102 3x ONCOS-102 &
Slide 15: Case example - Patient with PR following separate lines of prior PD-1 blockade
Case example 2 - Patient with PR following 2 separate lines of prior PD-1 blockade Tumor images, 3 of 3 injected lesions Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Stage IIIC at Lesion 1 of 3 enrollment, 7 lesions in total 3 non-target lesions injected Prior therapies: - Surgery Lesion 2 of 3 - Ni
Slide 16: Evidence of systemic (abscopal) effect – responses observed in several non-injected lesions
Evidence of systemic (abscopal) effect – responses observed in several non-injected lesions Conservative definition of abscopal effect per lesion: o ≥30% tumor reduction from baseline o ≥ 5mm absolute reduction Abscopal effect observed in 4 / 20 patients (20%) o 1 / 8 patients in Part 1 (12.5%) o 3
Slide 17: ONCOS-102 and the combination with pembrolizumab is safe and well tolerated
ONCOS-102 and the combination with pembrolizumab is safe and well tolerated Adverse Event, Preferred term Subjects, n Events, n Grade 1 / 2 events Grade 3 Grade 4 AEs related to ONCOS-102 +/- CPO Pyrexia 10 24 24 - - Chills 9 23 23 - - Nausea 6 10 10 - - Injection site pain 4 6 6 - - Myalgia 3 6 6 -
Slide 18: Broad and persistent modulation of immune-related gene expression observed in Part 2 of the trial
Broad and persistent modulation of immune-related gene expression observed in Part 2 of the trial Modulation of gene expression following ONCOS-102 treatment; % modulated genes 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) Bas
Slide 19: ONCOS-102 + Keytruda data compares well to previous reports in PD-1 refractory melanoma
ONCOS-102 + Keytruda data compares well to previous reports in PD-1 refractory melanoma Company Comment CR PR 5% 30% 35% ORR o Adenovirus expressing GM-CSF ONCOS-102 (7/20 pts.) 31% ORR o Herpes virus expressing GM-CSF RP1 6% 25% retreatment (5/16 pts.) and GALV Anti-PD1 30% ORR o IL-12, DNA plasmid
Slide 20: Successful ONCOS-102 phase I trial warrants further development of PD1 combination
Successful ONCOS-102 phase I trial warrants further development of PD1 combination Safety - ONCOS-102 is well-tolerated, with no safety concerns - Combines well with pembrolizumab, including concomitant dosing - Broad and general immune activation pattern observed in Immune ONCOS-102 injected lesion
Slide 21: Melanoma: Small indication, but influential
Melanoma: Small indication, but influential o We usually set trends followed by the bigger histologies o Easily accessible tissue o Relatively aggressive disease o Hot (cutaneous) vs cold (uveal) vs mixed (mucosal) models o Patient buy-in for biomarker heavy trials 21
Slide 22: What is next in melanoma? Ongoing trials and new combinations to watch
What is next in melanoma? Ongoing trials and new combinations to watch Example compounds Trials to watch o LAG-3 relatimab in combination with Nivolumab in stage IV Novel immune Anti-LAG-3, TIM-3, IO naïve melanoma checkpoint inhibitors TIGIT o TIM-3 mono and in combination with anti-PD-1 in IO pret
Slide 23: First Line Trials in Melanoma: Big Ones
First Line Trials in Melanoma: Big Ones Randomized, PD-1 +/- XYZ o LAG-3: Nivolumab +/- Relatlimab (NCT03470922) o IL-2 directed: Nivolumab +/- BEMPEG (NCT03635983) o VEGF: Pembrolizumab +/- Lenvatinib (NCT03820986) BRAF-MEK +/- PD-1: Enco-Bini-Spartalizumab (NCT02967692) T-VEC: Pembrolizumab +/- T-
Slide 24: First Line Trials in Melanoma: Big Ones – Overall Survival (OS), not just PFS
First Line Trials in Melanoma: Big Ones o Large, randomized trials, 500-700+ patients o What do we need for a new standard? – Overall Survival (OS), not just PFS and ORR – Tolerability – Schedule / ease of use o We are a few years away from making a new frontline standard o Existing frontline treatm
Slide 25: Post PD-1 Trials: Trends
Post PD-1 Trials: Trends o Critical need to develop new treatments, but it’s getting harder to do it well o Rigidly defining “PD-1 resistance” o Slowly relaxing prior toxicity requirements (…too slowly) o Highly selective trials (e.g. lifileucel) o The specter of ipilimumab: 20% ORR, durability o Si
Slide 26: Thanks!
Thanks! 2020 MSKCC Melanoma Disease Management Group