Pyxis Oncology, Inc. · NASDAQ:PYXS
Pyxis Oncology — Technical Presentation (April 2022)
21 slides from Pyxis Oncology's technical presentation, April 2022
Slide 1: Intratumoral CD40 Agonist Sotigalimab with Pembrolizumab in Metastatic Melanoma
Intratumoral CD40 Agonist Sotigalimab (APX005M) with Pembrolizumab Induces Broad Innate and Adaptive Immune Activation in Local and Distant Tumors in Metastatic Melanoma Salah-Eddine Bentebibel, PhD The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Slide 2: Presenter Disclosure Information
Presenter Disclosure Information Salah-Eddine Bentebibel I have no financial relationships to disclose.
Slide 3: 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 4: Sotigalimab (APX005M): Harnessing the CD40 Pathway
Sotigalimab (APX005M) : Harnessing the CD40 Pathway to Activate Innate and Adaptive Immunity Innate immunity Adaptive immunity APX005M APX005M APX005M • The use of immune-checkpoint CD40 DC CD40 inhibitors (CPI) is an important B cells CD40 MHC II IL-12 modality for the treatment of Macrophage B cel
Slide 5: 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 6: Dose-Escalation and Recommended Phase 2 Dose Expansion
Dose‐Escalation and Recommended Phase 2 Dose Expansion Phase 1 (N=14) I.V. Pembro 2 mg/kg + 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. Pembro 2 mg/kg Recommended confirmed cutaneous o
Slide 7: Patient Demographics and Disease Characteristics
Patient Demographics and Disease Characteristics Characteristic Total n (%) (N=30) Characteristic (N=30) % BRAF status Sex Positive 10 38 Male 26 (87%) Negative 18 54 Female 4 (13%) Unknown 2 8 Age (years) LDH at baseline Median (Range) 65 (32-81) < ULN 14 47 > ULN 7 23 ×2 ULN 9 30 ECOG Performance
Slide 8: 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; 6 patients (20%) experienced grade-3 immune-related adverse events.
Slide 9: Best Overall Response by RECIST 1.1
Best Overall Response by RECIST 1.1 as of December 30, 2021 100 CR (17%) 80 PR (33%) Patients (N=30) 60 SD (17%) Total Evaluable 30 40 PD (33%) ORR (CR+PR) 15 (50%) 20 CR 5 (17%) 0 PR 10 (33%) -20 SD 5 (17%) -40 DCR -60 20 (67%) (CR+PR+SD) -80 PD 10 (33%) -100 Response rate at the RP2D (10 mg= 12/22
Slide 10: 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 (%) from 100 100 80 80 DH, [range] PDL1 negative < ULN [163-222] 60 60 PDL1 positive > ULN [238-426] 40 40 20 PDL1 unknown > ×2 ULN [466-586] 20 0 0 -20 -20 -40 -40 -60 -60 base
Slide 11: 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 Distant TCR repertoire analysis using immunoSEQ lesion Collection of tumor biopsy Collection of PBMCs L
Slide 12: 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) CD40 Signaling Pathway (NanoString Gene Expression) Fold-Change 24 hrs/Baseline IL8 MARCO DE 24 hrs/Baseline CLEC5 CD40 4 (local lesions) IL1B MAP2K2 −Log10 (P-value) HLA-DRA CD163 CCL2 CCL
Slide 13: Early Up-regulation of APC Genes Followed by T Cell Activation
Early Up-regulation of Genes Associated with APCs Followed by Genes Associated with T Cell Activation (NanoString gene expression in blood samples) Fold-Change Day 3/Baseline Fold-Change Day 21/Baseline APCs T-B cells APCs T-B cells 2.5 Pt#1 Pt#2 2.0 Pt#3 Pt#4 1.5 Pt#5 Pt#6 ITGAX CTLA4 ZAP70 TBX21 N
Slide 14: Up-regulation of Genes Associated with APCs and T cells
Sotigalimab with Pembrolizumab Induced the Up-regulation of Genes Associated with APCs and T cells (NanoString Gene Expression) Local Lesions GZMH GZMB GZMK DE Week 6/Baseline GZMA CD3D T cells CD8A 4 LAG3 −Log10 (P-value) CTLA4 TIGIT CD4 TBX21 CXCR3 HLA-DPA1 CD74 2 HLA-DPB1 HLA-DMA MARCO CD163 PECA
Slide 15: On-treatment Increase in Macrophage, T cell and Cytotoxic Signatures
On-treatment Increase in Macrophage, T cells, CD8+ T and Cytotoxic Gene Signatures in Responding Patients (NanoString Gene Expression) Local Lesions Cell Type Scores (Log2) Macrophage T cells CD8 T cel ✱✱ 12 ✱✱✱ 12 ✱✱ 12 12 ✱✱ 10 8 8 8 8 6 4 4 4 R 0 0 0 N.S. 12 12 12 12 10 8 8 8 8 4 4 4 NR 6 4 0 0 0
Slide 16: On-treatment Increase in Th1 Gene Signature and TGF-B1
On-treatment Increase in Th1 Gene Signature and TGF-B1 in Responding Patients Th17 Inhibitory cytokines GATA3 IL4 RORC IL17A IL10 TGFB1 TGFB2 Pre-Tx On-Tx Pre On Pre On Pre On Pre On Pre On Pre On Pre On Pretreatment/On- treatment (Week 6)
Slide 17: On-treatment Increase in T cells and Cytotoxic Signatures, Distant Lesions
On-treatment Increase in T cells, CD8+ T and Cytotoxic Gene Signatures in Responding Patients (NanoString Gene Expression) Distant Lesions Macrophage Cell Type Scores (Log2) ✱ ✱ ✱ 12 10 12 10 8 6 8 8 4 4 5 R 2 4 0 0 0 N.S. 12 10 10 10 8 8 6 6 8 4 4 5 NR 2 2 4 0 0 0 Pretreatment/On- Tx Tx Tx Tx Tx Tx
Slide 18: 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 Distant Lesions T Cell Fraction 0.4 0.20 0.20 0.4 0.3 0.15 0.15 0.3 0.2 0.2 0.10 0.10 0.1 0.1 0.05 0.05 0 Pre-Tx On-Tx Pre-Tx On-Tx Pre-Tx On-Tx Pre-Tx On-Tx
Slide 19: 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 R NR TCRB % R NR Number of Shared Clones Expanded Shared Clones with R Higher Abundance in Distant Distant, On-Tx D
Slide 20: Conclusions
Conclusions • Sotigalimab in combination with pembrolizumab is well tolerated. • Sotigalimab in combination with pembrolizumab showed encouraging anti-tumor activity. • Biomarker analysis demonstrates that combination therapy can induce broad innate and adaptive immune activation in both local and d
Slide 21: Acknowledgments
Acknowledgments A special thank you is extended to the patients and their families MD Anderson Cancer Center Apexigen Adi Diab Collaborators Rodabe Amaria Chantale Bernatchez Xiaodong Yang Sapna Patel Cara Haymaker Frank Hsu Michael A. Davies Khalida Wani Susan Owen Patrick Hwu Dzifa Yawa Duose Greg