Pyxis Oncology, Inc. · NASDAQ:PYXS
Pyxis Oncology — Investor Presentation (March 2024)
33 slides from Pyxis Oncology's investor presentation, Mar 21, 2024
Slide 1: Building a Leading ADC-Focused Company
Building a Leading ADC-Focused Company Nasdaq: PYXS March 2024 Exhibit 99.2
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. These statements are often identified by the use of words such as “anticipate,
Slide 3: PYXS: Building the Next Leading ADC-Focused Company
PYXS: Building the Next Leading ADC-Focused Company ADC-Focused with Opportunistic Bets in I/O Deeply Experienced Team with Proven Track Record in Both Pharma and Biotech Clinical-Stage Portfolio with 2024 Data Catalysts Strong Balance Sheet with $173M in Cash Provides Runway into 2H 2026
Slide 4: Executive Leadership Team
Lara Sullivan, MD CEO Xiaodong Yang, MD, PhD Distinguished Research Fellow Jan Pinkas, PhD CSO Pam Connealy, MBA CFO & COO Balu Balasubramanian, PhD CTO Executive Leadership Team PYXS Team Members Have Collectively Contributed to >60 Oncology Drug Approvals Ken Kobayashi, MD, FACP CMO
Slide 5: Pipeline Focused on Difficult-to-Treat Tumors
Pipeline Focused on Difficult-to-Treat Tumors Program Discovery Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Antibody-Drug Conjugate (ADC) PYX-201 (anti-EDB) Preliminary data in Fall 2024 Immuno-Oncology (I/O) PYX-106 (anti-Siglec-15) Preliminary data in 2H 2024 PYX-107 sotigalimab (CD40 agoni
Slide 6: PYX-201 is a First-in-Concept and First-in-Class ADC Binding EDB+FN
PYX-201 targets an antigen contained within the tumor stroma and releases its payload extracellularly, diffusing into nearby tumor cells PYX-201 is a First-in-Concept and First-in-Class ADC that Binds to EDB+FN within the Tumor Stroma and may Address Multiple Difficult-to-Treat Tumors The stroma pro
Slide 7: Tumor Stroma is an Exciting Opportunity for ADC Modality
Tumor Stroma is an Exciting Opportunity for ADC Modality Many of the proteases found intracellularly in endosomes and lysosome are also found outside the cell and are involved in disease pathologies including cancer* The Tumor Micro-Environment (TME) is acidic (i.e., pH between 6.4 to 7.0) compared
Slide 8: Volume of Stroma is Highly Variable by Tumor Type
Volume of Stroma is Highly Variable by Tumor Type Pyxis Oncology Internal Data. Stromal density analysis of tumors via H&E staining.
Slide 9: IHC Shows EDB+FN Highly Differentially Expressed in Tumor Stroma
Immunohistochemistry (IHC) Analysis Demonstrates EDB+FN Protein is Highly Differentially Expressed in Tumor Stroma Pyxis Oncology Internal Data. EDB+FN protein expression analysis via immunohistochemistry (IHC) of tumor vs. normal stromal tissue. Stromal EDB+FN Protein Expression – IHC Data Normal C
Slide 10: EDB-targeted Radio-Conjugate Selectively Accumulates in Tumor
An EDB-targeted Radio-Conjugate Selectively Accumulates in Tumor with No Accumulation in Normal Tissues Poli GL et al 2013, Cancer Immunol Res; 1(2); 134–43 PET imaging using radiolabeled target-antibody fragment shows selective accumulation in hepatic and CNS lesions A B C D E PET image 24 hours p.
Slide 11: PYX-201 Believed to Act Via Three Distinct Mechanisms
PYX-201 Believed to Act Via Three Distinct Mechanisms to Deliver Powerful Anti-Tumor Activity Servier medical art: https://smart.servier.com/; CD8+ lymphocyte Dendritic cell PYX-201 Cleaved & active payload (auristatin) Tumor cell Fibroblast EDB+FN Matrix EDB+FN receptor Proteases (e.g., cathepsin)
Slide 12: ADC Technical Improvements of PYX-201 vs Other ADCs
ADC Technical Improvements of PYX-201 vs Other ADCs Conjugation: Engineered cysteine residues allow for a target DAR of 4 without disrupting the inter-chain cysteine bonds that holds the antibody together Linker: Optimized val-cit linker that is more stable in circulation (i.e., reduced carboxyleste
Slide 13: PYX-201 is Designed for Tolerability and Activity
PYX-201 is Designed for Tolerability and Activity Key improvements of PYXS optimized ADC technology: Monoclonal antibody uniquely directed at Extra-domain B of Fibronectin (EDB+FN) in the tumor stroma Designed to reduce off-target effects and improve tolerability Carries four Auristatin 0101, microt
Slide 14: Potential for Improved Technical Profile of PYX-201 vs. Competitors
Potential for Improved Technical Profile of PYX-201 vs. Competitors Graziani, MolCanTher (19) 2020: 2068-78; Hooper, MolCanTher (21) 2022: 1462-72. Enhanced tolerability in NHP at 10–12 mg/kg (preclinical publications for the HER-2 and EDB ADCs) compared to approved older generation val-cit-MMAE ADC
Slide 15: PYX-201-101: Ongoing Open-Label Phase 1 Dose Escalation Study
2022 1Q 2023 2024 PYX-201-101: Ongoing Open-Label Phase 1 Dose Escalation Study with 10 Solid Tumor Types, Enriched for 4 Histologies Preliminary data expected Fall 2024 Part 1 Tumor Types* Part 1 Dose Escalation (Underway) Part 2 Dose Optimization/ Indication Selection Expansion cohort(s) in select
Slide 16: PYX-201 Ongoing Phase 1 Part 1 Dose Escalation Trial Design
Determine MTD using Bayesian optimal interval (BOIN) design Analysis of paired biopsies pre/post treatment (fresh where available) 18 sites - US, Belgium, Spain 37 patients dosed in Cohorts 1-6 as of March 2024 Q3W IV infusion PYX-201 Ongoing Phase 1 Part 1 Dose Escalation Solid Tumor Trial Design F
Slide 17: Anti-Siglec-15 (PYX-106): Potential Best-In-Class Antibody
Anti-Siglec-15 (PYX-106): Potential Best-In-Class, Highly Differentiated Fully Human Antibody in NSCLC and Solid Tumors Higher binding affinity leads to enhanced T cell responses at higher dose levels, empowering the immune system to kill and fend off cancer cells Potential to combine with anti-PD-(
Slide 18: PYX-106 May Address Anti-PD-(L)1 Non-responders
PYX-106 May Address Anti-PD-(L)1 Non-responders in Several Tumor Types Sun et al., Clin Cancer Res 2021; Wang et al., Nat Med 2019; Biosion Corporate Presentation; GlobalData; Citeline Informa Stromal / Epithelial Hematopoietic Tumor cells T cell NF-ĸB/NFAT Tumor Cells Macrophage Tumor Cell Receptor
Slide 19: PYX-106 Targets Siglec-15, Upregulated in Multiple Solid Tumors
PYX-106 Targets Siglec-15, Which is Differentially Upregulated in Multiple Solid Tumors Showing significant t-test results; TCGA normal grouped with GTEx where available Pyxis Oncology data Meaningful Differences in Siglec-15 Expression in Tumor vs. Normal
Slide 20: PYX-106-101: Open-label Multicenter Phase 1 Study
FDA IND approval, Nov ’22 Ph 1 initiation, Q1 ’23 Ph 1 expansion into select tumors Early biomarker data for subject selection First subject dosing Q2 ’23 2022 2023 2024 Preliminary data Select Tumor Types Dose Escalation Analysis Expansion cohort in select tumor type(s) Analysis of paired bio
Slide 21: PYX-107 (Sotigalimab) Potential First- and Best-in-Class CD40 Agonist
PYX-107 (Sotigalimab) is a Potential First- and Best-in-Class CD40 Agonist in Phase 2 that Has Demonstrated Rapid, Deep and Durable Responses Rationally designed with two key modifications for higher potency and improved tolerability Potential applicability across a variety of tumor types with high
Slide 22: Sotigalimab-Nivolumab Activity in PD-1 Refractory Melanoma
Sotigalimab-Nivolumab Demonstrated Activity and Prolonged Responses in PD-1 Blockade Refractory Melanoma Patients in Phase 2 Trial Change in Tumor Size (%) Time from Baseline Assessment (Months) 5 PRs (15%) PR DoR (months): 4.2+ | 11+ | 13.3+ | 18.7 | 24.7+ SD DoR (months): Up to 14+ 10 SDs (30%) 18
Slide 23: Upcoming Meetings
Upcoming Meetings RBCCM Global Healthcare Conference in New York, May 14-15, 2024 BTIG Virtual Biotechnology Conference on August 5-6, 2024 Wells Fargo Healthcare Conference in Boston, September 4-6, 2024 4 AACR Abstracts: PYX-201 (anti-EDB), PYX-106 (anti-Siglec-15), PYX-102 (anti-KLRG1) in San Die
Slide 24: Appendix
APPENDIX PYX-201 & ADC Toolkit PYX-106 APXiMAB Platform & Sotigalimab
Slide 25: PYX-201 Highly Active in PDX Models of NSCLC and Pancreatic Cancer
PYX-201 is Highly Active in Patient-derived Xenograft (PDX) Models of NSCLC and Pancreatic Cancer PYX-201 Induces Immunogenic Cell Death & T cell Infiltration (CD3) PDX Models Demonstrate Dose Dependent Anti-Tumor Activity of PYX-201 Source: Mol Cancer Ther, 2022 Sep 6;21(9):1462-1472. PYX201 PYX201
Slide 26: Pyxis ADC Platform Demonstrates Superior Therapeutic Index
Therapeutic Index† Relative to Kadcyla Technology Pyxis Oncology’s ADC Platform Demonstrates Superior Therapeutic Index (TI) to Currently Marketed Auristatin Based ADC Products *FACT=Flexible Antibody Conjugation Technology; † TI minimally effective dose vs monkey highest non severe toxic dose (HNST
Slide 27: Advancing ADC Technology for More Active, Better Tolerated Therapies
Pyxis Oncology is Advancing ADC Technology to Create More Active, Better Tolerated Therapies DAR: Drug:antibody ratio Limitations of First-Generation ADCs PYXS ADC ToolKit Improvements Less stable linkers can result in higher levels of free payload in circulation and off-target payload deposition Li
Slide 28: PYX-106: A Data Driven Anti-Siglec-15 Therapy
PYX-106: A Data Driven Anti-Siglec-15 Therapy Clinical strategy entrenched in the in-depth understanding of the dynamics between the drug candidate, the tumor microenvironment (TME) and patient impact DIFFERENTIATED DRUG CANDIDATE FROM COMPETITOR Fully Human which may limit ADA formation and improve
Slide 29: PYX-106 Reverses Siglec-15 Mediated T-Cell Suppression
PYX-106 Reverses Siglec-15 Mediated T-Cell Suppression and Increases IFNg Release to Reinvigorate the Immune System Biosion AACR 2022 poster CD8+ T cells CD4+ T cells IFNg Release Anti-CD3 – + + + + + Siglec-15-Fc – – + + + + Isotype control – – – + – – PYX-106 – – – – + – NC318 Analog – – – – – + C
Slide 30: APXiMAB Platform Facilitates In-House Antibody Development
APXiMAB Platform Facilitates In-House Development of Antibodies to Support Novel ADC Generation via FACT Platform
Slide 31: Case Study: Durable Partial Response on Sotigalimab-Nivolumab
Case Study: Patient Achieved a Durable Partial Response (PR) and Resolution of All Lesions on Sotigalimab-Nivolumab PI: principal investigator 2 months Baseline Sotigalimab-Nivo Strong activity: patient responded only 2 months after starting sotigalimab-nivolumab (3 cycles of treatment) Good tolerab
Slide 32: Favorable Tolerability Profile of Sotigalimab
Results Demonstrate Favorable Tolerability Profile of Sotigalimab Abbreviations: C = cohort, DL = dose level, N = number of subjects enrolled, SAE= serious adverse event: TEAE = treatment-emergent adverse event a Regardless of the relatedness to nivolumab b All 3 subjects from DL3 from phase 1b were
Slide 33: Sotigalimab vs. Other Advanced Clinical Stage CD40 Agonists
Sotigalimab vs. Other Advanced Clinical Stage CD40 Agonists (Not Exhaustive) sotigalimab1 CDX-11402 selicrelumab3 ABBV-9271 SEA-CD404 dacetuzumab BNT-3125 (GEN1042) mitazalimab1 ADC-1013 YH0036 (Biocytogen) Format IgG1 humanized mAB IgG2 fully human mAB IgG2 fully human mAB IgG1 IgG1 DuoBody-CD40x4-