Slide 1: Dual CD39 and PD-L1 inhibition: Interim results from the phase 2 MATISSE trial
Dual CD39 and PD-L1 inhibition: Interim results from the phase 2 MATISSE trial of IPH5201 plus durvalumab and platinum-based chemotherapy in patients with resectable NSCLC Fabrice Barlesi1, Tibor Csoszi2, Renata Duchnowska3, Thomas Egenod4, Laurent Greillier5, Amanda Psyrri6, Maurice Perol7, Herve L
Slide 2: Disclosure information
Disclosure information Professor Fabrice BARLESI, MD, PhD Personal financial interests: None Institutional financial interests: Abbvie, ACEA, Amgen, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate
Slide 3: MATISSE study background and rationale
MATISSE study background and rationale ▪ Approximately 25% of patients with Non-Small Cell Lung Cancer (NSCLC) are diagnosed at a resectable early-stage and potentially curable ▪ Neoadjuvant chemo-immunotherapy (PD-(L)1) has become the new standard of care (NCCN V5.2026*, ESMO 2025 guidelines**) ▪ I
Slide 4: IPH5201 CD39 inhibitor MoA
IPH5201 CD39 inhibitor MoA Adenosine pathway ✓ CD39 is an extracellular enzyme over-expressed in the tumor microenvironment. Upstream CD39 degrades immunostimulatory extracellular ATP released by dying cells into AMP, which is further degraded into immunosuppressive adenosine by downstream CD73* *Al
Slide 5: IPH5201 CD39 inhibitor MoA
IPH5201 CD39 inhibitor MoA Adenosine pathway IPH5201 blocking CD39 antibody • IPH5201 is a humanized Fc-silent IgG1 inhibiting both membrane and soluble CD39 IPH5201 • IPH5201 improves antitumor activity of durvalumab+chemo in preclinical models, turning anti-PD-(L)1 resistant into sensitive tumors*
Slide 6: MATISSE study design
MATISSE study design MATISSE is an open-label, single-arm phase 2 study evaluating IPH5201 in combination with neoadjuvant CT and perioperative durvalumab in resectable, early-stage NSCLC Key eligibility criteria Neoadjuvant part Adjuvant part FollowUp ~18 months Patients with early-stage NSCLC IPH5
Slide 7: Patient baseline characteristics & disposition
Patient baseline characteristics & disposition Baseline characteristics (N=40) N (%) Median age (range) 64.7 (48, 83) Screened (n=75) Females/Males 13 (32.5) / 27 (67.5) ECOG 0/1 32 (80.0) / 8 (20.0) Enrolled PD-L1 ≥1% / PD-L1 <1% 28 (70.0) / 12 (30.0) (n=40) Clinical Preoperative Stage (TNM 8th) St
Slide 8: Safety
Safety Safety overview N (%) TEAE ≥ 15% N (%) TEAE (any grade) 39 (97.5) Patients with at least one TEAE 39 (97.5) related to any drug 36 (90.0) Asthenia 16 (40.0) related to chemotherapy 32 (80.0) Constipation 12 (30.0) related to IPH5201 29 (72.5) Nausea 12 (30.0) related to durvalumab 29 (72.5) A
Slide 9: Efficacy
Efficacy Radiological Response Surgery to systemic treatment Radiological response Surgery N (%) % [95% CI] or N (%) per RECIST V1.1 Surgery ORR, % [95% CI] 62.5 [45.8, 77.3] Subjects underwent surgery 35 (87.5) CR, n (%) 3 (7.5) Subjects underwent surgery within 40 days 28 (75.7) PR, n (%) 22 (55.0
Slide 10: Efficacy
Efficacy Whole population Pathological response, N=40* % [95% CI] Overall pCR, % [95% CI] 27.5 [14.6, 43.9] MPR, % [95% CI] 32.5 [18.6, 49.1] pCR by PD-L1 expression PD-L1 <1% (N=12) 8.3 [0.2, 38.5] PDL1 ≥ 1% population PD-L1 ≥ 1% (N=28) 35.7 [18.6, 55.9] PD-L1 ≥ 50% (N=14) 50.0 [23.0, 77.0] *includ
Slide 11: Tumor CD39+ cell density as an emerging biomarker
Tumor CD39+ cell density as an emerging biomarker CD39 expression profiles Representative images of the MATISSE study CD39+ cell density in CD39+ cell density in tumor CD39+ cell density in tumor =126 cells/mm² =466 cells/mm² tumor =2124 cells/mm² • In treatment naive early-stage NSCLC patients, CD3
Slide 12: Tumor CD39+ cell density as an emerging biomarker
Tumor CD39+ cell density as an emerging biomarker CD39 expression profiles Higher baseline CD39+ and CD8+ cell density Representative images of the MATISSE study in tumor of patients with mPR/pCR CD39+ cell density in tumor (baseline) CD8+ cell density in tumor (baseline) CD39+ cell density in tumor
Slide 13: Conclusions
Conclusions • MATISSE is the first clinical study to show feasibility and preliminary activity of preoperative CD39 blockade by IPH5201 in combination with platinum-based chemotherapy and PD-L1 inhibition for patients with resectable early stage NSCLC with: • The majority of patients reaching surger
Slide 14: Acknowledgments
Acknowledgments ▪ FRANCE ▪ POLAND BARLESI Fabrice, Paris DUCHNOWSKA Renata, Warsaw Thank you to all the patients and their families, EGENOD Thomas, Limoges LOWCZAK Anna, Prabuty investigators, experts, and site staff MANDZIUK Slawomir , Lublin GREILLIER Laurent, Marseille MROZ Robert, Bialystok PERO