Slide 1: Clinical activity of SD-101 with immune checkpoint inhibition in MUM-LM from PERIO-01
Clinical activity of SD-101 with immune checkpoint inhibition (ICI) in metastatic uveal melanoma liver metastasis (MUM-LM) from the PERIO-01 Phase 1 trial Sapna P. Patel* , Richard Carvajal, Kamaneh Montazeri, Jose Lutzky, Bartosz Chmielowski, Sunil Reddy, Shailander Bhatia, Shaheer Khan, Theresa Me
Slide 2: Presenting Author Disclosures
Presenting Author Disclosures • Advisory board, steering committee, data safety monitoring board, consulting: BMS, Cardinal Health, Castle Biosciences, Delcath, Ideaya, Immatics, Immunocore, MSD, Novartis, OncoSec, Pfizer, Replimune, TriSalus Life Sciences • Clinical trial support (institutional): B
Slide 3: Uveal melanoma
Uveal melanoma • Uveal melanoma is the most common primary eye tumor in adults with an incidence of 6 per million • Half of patients will develop metastatic disease, Tebentafusp Control 90% with liver involvement PFS 3.3 months 2.9 months • One approved immunotherapy treatment for OS 21.7 months 16.
Slide 4: The presence of liver metastases promotes checkpoint inhibitor failure
The presence of liver metastases promotes checkpoint inhibitor failure In cutaneous melanoma patients, liver mets In lung carcinoma patients, the In multiple indications, liver mets predicted ICI predicted inferior presence of liver mets was an failure in association with myeloid cell driven PFS and
Slide 5: Two important barriers to immunotherapy success for liver metastases
Two important barriers to immunotherapy success for liver metastases 1. Pressure Limited Drug High intra-hepatic and intra-tumoral uptake due to pressure produce a mechanical barrier limiting efficient drug delivery via collapsed intravenous or regional hepatic infusion vessel (<1% in some settings
Slide 6: PERIO-01 study addresses these barriers
PERIO-01 study addresses these barriers Overcoming pressure and immune suppression Delivery Strategy Drug Strategy Ø Pressure-enabled drug delivery Ø SD-101 is a Class C toll-like receptor 9 (PEDD) catheter works in sync with agonist the cardiac cycle1 Ø Impacts multiple cell types to prime Ø Optimi
Slide 7: TS-PERIO-01 Trial Design
TS-PERIO-01 Trial Design COHORTS* REGIMEN SD-101 via PEDD Checkpoint via Systemic Infusion Cohort A SD-101 Single Agent Dose Escalation (n=9) SD-101 Cycle 1 SD-101 Off Period SD-101 Cycle 2 Cohort B Weekly x 3 5-week rest Weekly x 3 SD-101 + Anti-PD-1 Dose Escalation (n=6) Checkpoint Inhibitor (12 m
Slide 8: TS-PERIO-01 Patient Characteristics
TS-PERIO-01 Patient Characteristics Patient Characteristics N = 56 (%) Age (median, range) 64 (35-86) N = 56 (%) Gender Cohort A 13 (23) Female 26 (46) 2 mg 4 Male 30 (54) 4 mg 5 LDH 8 mg 4 >ULN 27 (48) Cohort B 26 (46) Normal 27 (48) 2 mg 7 N/A 2 (4) 4 mg 8 Performance Status 8 mg 11 0 45 (80) Coho
Slide 9: Safety Summary
Safety Summary Phase 1: Cohort A N=13 N=4 N=5 N=4 Cohort A Cohort A Cohort A Cohort A 8mg All listed events are related 2mg 4mg Summary to SD-101, ipi, and/or nivo SD-101 SD-101 SD-101 n (%) n (%) n (%) n (%) Treatment-related AEs 5 (38) 0 3 (60) 2 (50) (TRAE) (any grade) DLTs 0 0 0 0 SAEs 1 (8) 0 0
Slide 10: Safety Summary
Safety Summary Phase 1: Cohorts A, B N=13 N=4 N=5 N=4 N=26 N=7 N=8 N=11 Cohort A Cohort A Cohort B Cohort B Cohort B Cohort A Cohort A Cohort B 2mg 4mg 8mg All listed events are related 2mg 4mg 8mg Summary Summary SD-101 + SD-101 + SD-101 + to SD-101, ipi, and/or nivo SD-101 SD-101 SD-101 n (%) n (%
Slide 11: Safety Summary
Safety Summary Phase 1: Cohorts A, B, C N=13 N=4 N=5 N=4 N=26 N=7 N=8 N=11 N=17 N=10 N=7 N=56 Cohort A Cohort A Cohort B Cohort B Cohort B Cohort C Cohort C Cohort A Cohort A Cohort B 2mg 4mg 8mg Cohort C 2mg 4mg All All listed events are related 2mg 4mg 8mg Summary Summary SD-101 + SD-101 + SD-101
Slide 12: SD-101 PK Data
SD-101 PK Data SD-101 Concentrations 8 mg SD-101 Plasma PK Within Liver Tissue Post-Infusion 600 3,000 2,500 400 2,000 ng/mL ng/g 1,500 200 1,000 500 Max plasma level for 8 mg 0 Max plasma level for 4 mg 30m 30m 30m 30m 30m 30m Pre 2h 4h Pre 2h 4h Pre 2h 4h Pre 2h 4h Pre 2h 4h Pre 2h 4h Max plasma l
Slide 13: Increased CD8+ T cell and NK cell infiltration in the tumors
Increased CD8+ T cell and NK cell infiltration in the tumors CD8+ T cells NK cells Baseline D57 Baseline D57 111-025 B 4mg 111-025 B 4mg Baseline D57 Baseline D57 102-023 B 4mg 102-023 B 4mg CD4 CD8 CD56+ Change in CD8+ T cells Change in CD4+ T cells Change in NK cells 200 600 60 Cohort A (n=5) Coho
Slide 14: Increased immune cell activation within liver metastases
Increased immune cell activation within liver metastases Change in Tumor Pathway Scores 2 Th1 activation Th2 activation 1 TLR signaling Interferon signaling Cytokine signaling 0 Chemokine signaling Lymphocyte activation -1 T cell activation and checkpoint signaling Differentiation and maintenance of
Slide 15: Peripheral immune signatures in PBMC
Peripheral immune signatures in PBMC Change in PBMC Pathway Scores 1.0 Th1 activation Th2 activation 0.5 TLR signaling Interferon signaling Cytokine signaling 0 Chemokine signaling Lymphocyte activation -0.5 T cell activation and checkpoint signaling Differentiation and maintenance of myeloid cells
Slide 16: Optimal dose selection guided by clinical and immune signals
Optimal dose selection guided by clinical and immune signals Dose within predicted range elicits expected immune signals within liver metastases from phase 1 Treg (similar trend for CCL2) M-MDSC 40 10 SD-101 2mg (n=9) 0 SD-101 2mg (n=9) At 2 mg SD-101 via PEDD + nivolumab: SD-101 4mg (n=5) SD-101 4m
Slide 17: Peripheral immune signatures induced by SD-101 delivered via PEDD
Peripheral immune signatures induced by SD-101 delivered via PEDD CXCL10 (IP-10) IFNγ TNFα 10 8 8 SD101 2mg (n=18) 8 SD101 4mg (n=12) 6 6 SD101 8mg (n=12) Δpg/ml Δpg/ml Δpg/ml 6 4 4 4 2 2 2 0 0 0 ↑Systemic immune activation despite IL-2R IL-15 IL-18 limited SD-101 systemic exposure 1500 15 200 SD101
Slide 18: RECIST 1.1 assessment consistent with disease control
RECIST 1.1 assessment consistent with disease control Potential for favorable clinical outcomes in absence of tumor shrinkage Best On-Treatment RECIST Response for Patients Treated with SD-101 + Nivolumab or • 58% DCR across all SD-101 doses in SD-101 + Ipilimumab + Nivolumab * combination with ICI
Slide 19: Decreased ctDNA observed in heavily pretreated patients
Decreased ctDNA observed in heavily pretreated patients Best Reduction in ctDNA MAF from Baseline 150 Cohort B (n=17) Best Molecular Reduction (%) Cohort C (n=5) 100 γ Ø 59% ctDNA clearance 50 Ø 86% reduction of any rate ζ 0 * * Ø At 2 mg + nivo: Ø 5 of 7 with >50% -50 decrease in ctDNA Ø 2 patients
Slide 20: Progression-free survival (PFS) and durable disease control
Progression-free survival (PFS) and durable disease control Median PFS 11.7 Months 71% 2L and beyond, including 4L and 6L patients 59% ctDNA clearance in naïve + pre-treated patients Prolonged PFS in the setting of mainly SD objective responses suggests imaging underestimates clinical activity of th
Slide 21: Overall survival (OS) by cohort and dose level
Overall survival (OS) by cohort and dose level Overall survival proportions Overall survival proportions Cohort B 100 100 Probability of Survival Probability of Survival * Cohort A (n=13) Cohort B 2mg (n=7) Cohort B (n=26) Cohort B 4mg (n=8) Cohort C (n=17) Cohort B 8mg (n=11) 50 50 0 0 0 20 40 60 8
Slide 22: Comprehensive review of biologic effects points to 2 mg SD-101 + nivolumab
Comprehensive review of biologic effects points to 2 mg SD-101 + nivolumab • ↓Treg in liver metastases • ↓Monocytic MDSC in liver metastases • Median PFS 11.7 months • 1 year OS 86% • 5 of 7 with >50% decrease in ctDNA • No Grade 3/4 TRAEs Presented by Sapna P. Patel, M.D. 22
Slide 23: TS-PERIO-01 Summary
TS-PERIO-01 Summary • Promising approach for addressing barriers to success in treating liver metastasis in uveal melanoma • SD-101 in combination with ICI well tolerated with limited peripheral exposure • Expected immune effects, including liver MDSC depletion consistent with SD-101 mechanism of ac
Slide 24: Acknowledgements
Acknowledgements Abstract: 647: PERIO-03: Pancreatic adenoca Massachusetts General Hospital (Kamaneh Montazeri) University of Pittsburgh Medical Center (Diwakar Davar) Abstract 1123: University of Miami (Jose Lutzky) SD-101 with subcutaneous ICI Stanford Cancer Center (Sunil Reddy) Columbia Universi