Pyxis Oncology, Inc. · NASDAQ:PYXS
Pyxis Oncology — Society for Immunotherapy of Cancer (SITC) Annual Meeting 2022
25 slides from Pyxis Oncology's conference presentation, Nov 10, 2022
Slide 1: SITC 2022 Annual Meeting
20322 NOVEMBER 8-12 MASSACHUSETTS r he Society for Immuno erapy of Cancer © - am Annual Meeting nd Pre-Conference Progra ms THE LEADING CANCER IMMUNOTHERAPY AND TUMOR IMMUNOLOGY CONFERENCE “#511022
Slide 2: Intratumoral Sotigalimab with Pembrolizumab in First-line Metastatic Melanoma
Intratumoral Sotigalimab with Pembrolizumab Activates Antigen-presenting cells and Induces Local and Distant Anti-tumor Responses in First-line Metastatic Melanoma: Results of a Phase I/II Study Salah-Eddine Bentebibel, PhD The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Slide 3: Presenter Disclosure Information
Presenter Disclosure Information Salah-Eddine Bentebibel I have no financial relationships to disclose.
Slide 4: In Situ Priming of Intratumoral Immunity (Vaccine Effect)
In Situ Priming of Intratumoral Immunity (Vaccine Effect) Local Priming Intra-tumoral injection of immunostimulatory agents to trigger tumor-specific immunity Distant Effects Systemic anti-tumor immunity against non-injected tumor sites
Slide 5: Sotigalimab (APX005M): Harnessing the CD40 Pathway
Sotigalimab (APX005M) : Harnessing the CD40 Pathway to Activate Innate and Adaptive Immunity Innate immunity Adaptive immunity • The use of immune-checkpoint APX005M APX005M CD40 APX005M inhibitors (CPI) is an important DC CD40 CD40 MHC II B cells modality for the treatment of metastatic melanoma IL
Slide 6: Objectives of our Study
Objectives of our Study • Assess the safety and tolerability of the combination of sotigalimab and pembrolizumab. • Define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). • Assess objective response rate (ORR) based on RECIST 1.1. • Measure biomarkers in blood and tumor samp
Slide 7: Dose-Escalation and Recommended Phase 2 Dose Expansion Trial
Dose‐Escalation and Recommended Phase 2 Dose Expansion Trial of Intratumoral Sotigalimab + Pembrolizumab I.V. Pembro 2 mg/kg Phase 1 (N=14) + I.T. Sotigalimab 10mg Pembro 2 mg/kg CPI Treatment-Naïve I.V. Pembro 2 mg/kg + + Sotigalimab 10 mg I.T. Sotigalimab 3 mg • Histologically or cytologically I.V
Slide 8: Patient Demographics and Disease Characteristics
Patient Demographics and Disease Characteristics Characteristic Total n (%) (N=32) Characteristic (N=32) % BRAF status Sex Positive 11 34 Male 27 (84%) Negative 19 59 Female 5 (16%) Unknown 2 7 Age (years) LDH at baseline Median (Range) 64.5 (32-81) < ULN 16 50 > ULN 7 22 ECOG Performance Status ×2
Slide 9: Safety and Tolerability
Safety and Tolerability • The combination of sotigalimab with pembrolizumab is well tolerated. • No study discontinuations or death due to treatment-related adverse events (TRAEs). • Most common TRAEs were injection-site reactions; six patients (18%) experienced grade-3 immune-related adverse events
Slide 10: Best Overall Response by RECIST 1.1
Best Overall Response by RECIST 1.1 as of October 28, 2022 100 Patients (N=32) Change in distant tumor size 80 CR (16%) 60 PR (31%) Total Evaluable 32 SD (22%) 40 ORR (CR+PR) 15 (47%) PD (31%) 20 CR 5 (16%) (%) from baseline 0 -20 PR 10 (31%) -40 SD 7 (22%) -60 DCR -80 22 (69%) (CR+PR+SD) -100 PD 10
Slide 11: Clinical Responses in PD-L1 Negative Tumors and Elevated LDH
Clinical Responses were Observed in Both PD-L1 Negative Tumors and Patients with Elevated LDH Change in distant tumor size (%) 100 100 LDH, [range] 80 80 < ULN [163-222] PDL1 negative 60 60 > ULN [238-426] PDL1 positive > ×2 ULN [466-586] 40 40 PDL1 unknown 20 20 0 0 -20 from baseline -20 -40 -40 -6
Slide 12: Strategy for Biomarker Analysis
Strategy for Biomarker Analysis ✴ Sotigalimab Pre-dose 24 hrs D3 W3 W6 W9 W12 Pembrolizumab Local Distant Local Local Distant Tumor core needle biopsy NanoString gene expression assay Local lesion Opal multiplex immunofluorescence (mIF) and imaging mass cytometry (IMC) Distant TCR repertoire analysi
Slide 13: Sotigalimab Engaged CD40 Activation and Up-regulation of APC Genes
Sotigalimab Engaged CD40 Activation and Up-regulation of Genes Associated with Antigen Presenting Cells (APCs) (NanoString Gene Expression) DE 24 hrs/Baseline (local lesions) Blood Fold-Change 24 hrs/Baseline IL8 MARCO CLEC5 Fold-Change Day 3/Baseline CD40 −Log10 (P-value) 4 IL1B MAP2K2 APCs APCs T-
Slide 14: Sotigalimab Administration Leads to Activation Profile
Sotigalimab Administration Leads to Activation Profile Distinct from TLR9 agonist IFNa gene signature after i.t IFNa gene signature after i.t TLR9 agonist (IMO-2125) CD40 agonist (Sotigalimab) Differential ISG15 IFIT1 IFITM1 expression 6000 N.S. 6000 N.S. 30000 N.S. Total Normalized Reads 24 hrs/Bas
Slide 15: Sotigalimab Induced Rapid DC and Macrophage Activation
Sotigalimab induced Rapid DC and Macrophage Activation (mIF and IMC) Local Lesions SOX10 Baseline 24 hr CD11c+DC-LAMP+CD40+ CD40+ Macrophage (counts/mm2) CD40+ Macrophage Sotigalimab Dose Level (mg) CD40 CD68 0.1 CD11c CD11c CD40 CD11cCD68 24 hr 0.3 40 1 3 CD40 CD40 CD40 20 10 0 merged CD40+CD11c+ D
Slide 16: Clinical Response Does Not Require Pre-existing IFN-g Activation
The Clinical Response to the Combination Therapy Does not Require Pre-existing IFN-g Mediated Immune Activation at Baseline • The clinical response to anti-PD1 is associated with Pre-existing IFN-g Mediated Immune Activation (Rodig, Science Translational Medicine 2018 Ayers, J. Clin. Invest 2017, Gi
Slide 17: Responding Patients Have Higher Pre-existing CD11c+ Myeloid and DC Cells
Responding Patients Appear to Have Higher Pre-existing CD11c+ Myeloid cells and CD11c+DC-LAMP+ DC (mIF) Local Lesions at Baseline CD11c+ myeloid (SOX10-CD8-CD11C+) CD11c+DC-LAMP+ (Sox10-CD8-CD11c+DC-LAMP+) CD8+ (SOX10-CD8+) CD11c+ myeloid CD11c+DC-LAMP+ CD8+ T cells 400 150 600 Counts/mm2 300 100 40
Slide 18: Combination Activated DC and Increased Macrophage Signature
The Combination Treatment Activated DC and Increases Macrophage Signature in Local and Distant Tumors (NanoString Gene Expression) Distant lesions (mIF) Distant lesions Local Lesions Macrophage Distant T Macrophage Lesions cells CD8 + TLocal T cells cellsLesions CD8 Distant + T cells Lesions Cytotox
Slide 19: On-treatment Increase in CD8+ T, Cytotoxic and Th1 Scores (Local)
On-treatment Increase in CD8+ T, Cytotoxic and Th1 Scores in Tumor Observed in Responding Patients (NanoString Gene Expression) Local Lesions Totalnormalized Total normalized reads reads cells CD8+ T cells Cytotoxic cells Non-responders Responders Th2 Th2 Th17 Th17 cells ✱✱ 12 CD8+ ✱✱T cells 12 Cyto
Slide 20: On-treatment Increase in CD8+ T, Cytotoxic and Th1 Scores (Distant)
On-treatment Increase in CD8+ T, Cytotoxic and Th1 Scores in Tumor Observed in Responding Patients (NanoString Gene Expression) Distant Lesions Totalnormalized Total normalizedreads reads CD8+ T cells Cytotoxic cells Th2 Th17 CD8+ T cells Cytotoxic cells Th1 Score (Linear) Non-responders Responders
Slide 21: Increase in CD8+ T cell Proliferation in Responding Patients
The Combination Treatment Can Lead to an Increase in CD8+ T cell proliferation in Responding Patients Pretreatment (IMC) Responders Non-responders Local Lesions Distant Lesions Local Lesions Distant Lesions 100 (Density/mm2) Ki-67 CD8 CD8+Ki-67+ 80 On-treatment (Week 6) 60 40 20 0 Ki-67 CD8 Pre-Tx W
Slide 22: Increase in T cell Infiltration and Clonality
The Combination Treatment Can Lead to an Increase in T cell Infiltration and Clonality (TCR Sequencing in Tumor Samples) Local lesions LocalLocal lesions Lesions DistantDistant lesions Distant lesions Lesions T Cell Fraction T Cell Clonality T Cell Fraction T Cell Clonality T Cell Fraction T Cell Cl
Slide 23: Expansion of New Clones Shared between Local and Distal Lesions
The Combination Treatment Can Lead to an Expansion of New Clones Shared between Local and Distal Lesions Assessment of Shared Clones between Local and Distant Lesions by TCR Sequencing TCRB % Expanded in Distant Number of Shared Clones with higher Abundance Distant, On-Tx Distant, Pre-Tx 400 Pre-TX
Slide 24: Lessons and Take Home Messages
Lessons and Take Home Messages • Sotigalimab in combination with pembrolizumab is well tolerated. • Sotigalimab in combination with pembrolizumab showed encouraging anti-tumor activity. • Biomarker analysis demonstrates that combination of sotigalimab with pembrolizumab can induce broad innate and a
Slide 25: A special thank you is extended to the patients and their families
A special thank you is extended to the patients and their families MD Anderson Cancer Center Apexigen Collaborators Adi Diab Jared Burks Xiaodong Yang Rodabe Amaria Cho Sungnam Frank Hsu Sapna Patel Javier Gomes Michael A. Davies Cara Haymaker Ravi Murthy Dzifa Yawa Duose Khaled M. Elsayes Khalida W
Pyxis Oncology — Society for Immunotherapy of Cancer (SITC) Annual Meeting 2022 on 6ix