Pyxis Oncology, Inc. · NASDAQ:PYXS
Pyxis Oncology — AACR Annual Meeting 2019
25 slides from Pyxis Oncology's conference presentation, Mar 31, 2019
Slide 1: Phase 1b Study of CD40 Agonist APX005M in Metastatic PDAC (PRINCE)
A Phase 1b Study of CD40 Agonistic Monoclonal Antibody APX005M Together with Gemcitabine and nab-Paclitaxel with or without Nivolumab in Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Patients PICI0002 (PRINCE) M a r k H . O ’ H a r a , E i l e e n M . O ’ R e i l l y, R o s e m a r i
Slide 2: Disclosure Information
Disclosure Information 2019 AACR Annual Meeting I have the following financial relationships to disclose: Research support: BMS, Lilly, AstraZeneca, Celldex, KaryoPharm Consultant: KaryoPharm, Exelixis I will discuss the following investigational drugs in my presentation: • APX005M • Nivolumab
Slide 3: Trial sponsored and conducted by / In collaboration with
Trial sponsored and conducted by In collaboration with
Slide 4: Background
Background • 1L treatment for metastatic PDAC is composed of combination chemotherapy with modest results Disease Median Regimen N Response Rate Median OS Control Rate PFS FOLFIRINOX1 171 32% 70% 6.4 mos 11.1 mos (24.7 – 39.1) Gemcitabine/nab-paclitaxel2 431 23% 48% 5.5 mos 8.5 mos (19 – 27) • PDAC
Slide 5: Rationale for Combining Chemo/CD40/PD-1
Rationale for Combining Chemo/CD40/PD -1 • Chemotherapy releases tumor antigens, which are then presented on antigen presenting cells, including dendritic cells • Engagement of CD40 primes and activates antigen presenting cells • In preclinical pancreatic cancer models • Gemcitabine, nab-paclitaxel
Slide 6: Study Design
Study Design Phase 1b Phase 2 Cohort B1: 6 Subjects Arm A1: 35 Subjects Gem, NP + Gem, NP + Nivolumab APX005M 0.1 mg/kg Randomization (n=93) Cohort B2: 6 Subjects Cohort C1: 6 Subjects Arm B1: 29 Subjects Arm B2: 29 Subjects Gem, NP + APX005M 0.3 mg/kg Gem, NP + nivo + APX005M 0.1 mg/kg Gem, NP +Rec
Slide 7: Phase 1b Objectives
Phase 1b Objectives Primary • To determine the feasibility, safety and dose-limiting toxicities (DLT) of each treatment cohort • To determine the recommended Phase 2 dose (RP2D) of APX005M when combined with NP/Gem • To determine the RP2D of APX005M when combined with nivolumab/NP/Gem Secondary • To
Slide 8: Key Inclusion and Exclusion Criteria
Key Inclusion and Exclusion Criteria Inclusion • Metastatic pancreatic adenocarcinoma • Measurable disease per RECIST 1.1 • Age > 18 • ECOG status 0 or 1 • Baseline tissue mandatory • Adequate hematologic, hepatic and renal function Exclusion • Previous systemic therapy in the metastatic setting • S
Slide 9: Enrollment Timelines and Minimum Follow-Up
Enrollment Timelines and Minimum Follow -Up Cohort B1: Gem/NP/APX005M 0.1 mg/kg Enrollment 08/2017 – 11/2017 Minimum Follow-Up 15 Months Cohort B2: Gem/NP/APX005M 0.3 mg/kg Cohort C1: Gem/NP/APX005M 0.1 mg/kg + nivo Concurrent Enrollment 01/2018 – 03/2018 Minimum Follow-Up 11 Months Cohort C2: Gem/N
Slide 10: Baseline Subject Characteristics
Baseline Subject Characteristics Safety-evaluable population (N=30): received > 1 dose of any study drug Cohort B1 Cohort B2 Cohort C1 Cohort C2 Gem/NP/ Gem/NP/ Gem/NP/nivo/ Gem/NP/nivo/ Total APX005M 0.1 mg/kg APX005M 0.3 mg/kg APX005M 0.1 mg/kg APX005M 0.3 mg/kg (N=30) (N=7) (N=7) (N=8) (N=8) Age
Slide 11: Time on Treatment
Time on Treatment Cohort B1 Cohort B2 Cohort C1 Cohort C2 Gem/NP/ Gem/NP/ Gem/NP/nivo/ Gem/NP/nivo/ Total APX005M 0.1 mg/kg APX005M 0.3 mg/kg APX005M 0.1 mg/kg APX005M 0.3 mg/kg (N=30) (N=7) (N=7) (N=8) (N=8) Time on Treatment Median (Weeks) 30.3 39.1 19.6 NR 30.3 Min-Max (Weeks) 2.1 – 59.1+ 0.4 – 5
Slide 12: Patient Populations
Patient Populations Safety-evaluable population (N=30) • Received > 1 dose of any study drug DLT-evaluable population (N=24) • Enrolled in Phase 1b • Received at least 2 doses of Gem/NP and 1 dose of APX005M during Cycle 1 • Completed the DLT observation period (Cycle 1) or experienced a DLT event
Slide 13: Dose-Limiting Toxicities and Deaths
Dose-Limiting Toxicities and Deaths • 2 DLTs were observed, unrelated to APX005M or nivolumab Cohort Treatment Severity Event SAE? Recovered? B2 Gem/NP/APX005M 0.3 mg/kg Grade 3 Febrile neutropenia Yes Yes C1 Gem/NP/APX005M 0.1 mg/kg + nivo Grade 4 Febrile neutropenia No Yes • 1 treatment-related de
Slide 14: Grade 3/4 Treatment-Related AEs
Grade 3/4 Treatment -Related AEs Occurring in ≥ 20% of N=30 Subjects Cohort B1 Cohort B2 Cohort C1 Cohort C2 Gem/NP/ Gem/NP/ Gem/NP/nivo/ Gem/NP/nivo/ Total MedDRA Preferred Term APX005M 0.1 mg/kg APX005M 0.3 mg/kg APX005M 0.1 mg/kg APX005M 0.3 mg/kg (N=30) (N=7) (N=7) (N=8) (N=8) Lymphocyte count d
Slide 15: Best Overall Response
Best Overall Response D e t e r m i n e d b y R E C I S T 1 . 1 i n D LT- E v a l u a b l e P o p u l a t i o n Cohort B1 Cohort B2 Cohort C1 Cohort C2 Gem/NP/ Gem/NP/ Gem/NP/nivo/ Gem/NP/nivo/ Totals APX005M 0.1 mg/kg APX005M 0.3 mg/kg APX005M 0.1 mg/kg APX005M 0.3 mg/kg (N=24) (N=6) (N=6) (N=6) (N
Slide 16: Percent Change in Sum of Target Lesions (Best Response)
Percent Change in Sum of Target Lesions (Best Response) Cohort B1: Gem/NP/APX005M 0.1 mg/kg Cohort B2: Gem/NP/APX005M 0.3 mg/kg Cohort C1: Gem/NP/APX005M 0.1 mg/kg + nivo Cohort C2: Gem/NP/APX005M 0.3 mg/kg + nivo Clinical Snapshot date: 05MAR19 Safety-evaluable Population
Slide 17: Time on Treatment and Time to First Response
Time on Treatment and Time to First Response Cohort B1: Gem/NP/APX005M 0.1 mg/kg Cohort B2: Gem/NP/APX005M 0.3 mg/kg Cohort C1: Gem/NP/APX005M 0.1 mg/kg + nivo Cohort C2: Gem/NP/APX005M 0.3 mg/kg + nivo Treatment ongoing Clinical Snapshot date: 05MAR19 Safety-evaluable Population
Slide 18: Percent Change in Sum of Target Lesions
Percent Change in Sum of Target Lesions Cohort B1: Gem/NP/APX005M 0.1 mg/kg Cohort B2: Gem/NP/APX005M 0.3 mg/kg Cohort C1: Gem/NP/APX005M 0.1 mg/kg + nivo Cohort C2: Gem/NP/APX005M 0.3 mg/kg + nivo = New lesion Clinical Snapshot date: 05MAR19 Safety-evaluable Population
Slide 19: Deep Immune Profiling
Deep Immune Profiling Biomarker Germline WES HLA Determination (MHC Class I and II) Samples Tumor WES Neo-epitope Prediction RNAseq TME Gene Patient Samples (tumor & blood) Expression Signature Harmonized methods of Tumor Genome/TMB Multiparameter collection and processing Tumor Imaging at a central
Slide 20: Collaboration Enables Cutting-Edge Science
Collaboration Enables Cutting -Edge Science Biomarker Sample Collection High-Dimensional Multiplex IHC Tissue Imaging panels and imaging Tumor & Immune Monitoring FACS Symphony flow panel ctDNA-mutant KRAS CyTOF panels Bioinformatics and Data Science
Slide 21: Tumor Immune Profiling with High-Dimensional Imaging
Tumor Immune Profiling with High-Dimensional Imaging CD68 • Low overall immune infiltrate CD8 Ki67 • High macrophages and low CD8 T Cells PD-L1 Fraction of nucleated cells FoxP3 panCK, DAPI Imaging of baseline tumors with two technologies: • Vectra and 30-marker • OHSU mIHC
Slide 22: Circulating Tumor DNA: Mutant KRAS
Circulating Tumor DNA: Mutant KRAS PR SD PR KRAS G12V, D, R mutations KRAS Variant Allelic Fraction Tumor Sum Diameter (cm) • Digital droplet PCR assay to detect KRAS mutations in cell- free DNA from plasma PR PR PR • KRAS variant allelic fraction decrease is associated with tumor shrinkage PR SD KR
Slide 23: High-Dimensional Cytometry for Profiling of Immune Dynamics in Blood
High-Dimensional Cytometry for Profiling of Immune Dynamics in Blood CyTOF FACS Symphony Immune phenotyping (37 markers) T cell panel (28 markers) CD4 EM Treg B2: Gem/NP + APX005M 0.3mg/kg C2: Gem/NP + APX005M 0.3mg/kg + nivo Memory B cells Plasmablasts (CD19+ CD27+ CD38-) (CD19+ CD27-) CD4 Central
Slide 24: Summary
Summary • Gem/NP/APX005M (0.1 or 0.3 mg/kg) ± nivolumab combination is manageable • APX005M 0.3 mg/kg was selected for Phase 2 portion • Preliminary results demonstrate encouraging clinical activity, across cohorts in 1L metastatic PDAC • State-of-the-art deep immune profiling is feasible • Randomiz
Slide 25: Acknowledgements
Acknowledgements We thank the patients, their families and our research teams for making this trial happen! * *Recruiting Phase 2