Slide 1: PYX-201 Phase 1 Dose Escalation Study Data Disclosure
PYX-201 Phase 1 Dose Escalation Study Data Disclosure November 2024
Slide 2: Forward Looking Statement
Forward Looking Statement 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. All statements other than statements of historical facts contained in this pres
Slide 3: Today's Presenters and Guest Key Opinion Leaders
Today's Presenters and Guest Key Opinion Leaders Lara Sullivan, MD President and CEO Pam Connealy, MBA CFO and COO Jan Pinkas, PhD CSO Pyxis Oncology Senior Management Team Glenn Hanna, MD Director, Center for Cancer Therapeutic Innovation, Medical Oncologist, Center for Head & Neck Oncology Dana-Fa
Slide 4: Today's Discussion will address these five questions
Today’s Discussion will address these five questions What's novel about PYX-201? How stable is it? How is it tolerated? What early response data have we seen? How will it be further tested? 1 2 3 4 5 First-in-concept ADC with non-cellular targeting and extracellular payload cleavage Stable molecule
Slide 5: PYX-201 is the first-in-concept extracellular-cleaving ADC in clinical development
PYX-201 is the first-in-concept extracellular-cleaving ADC in clinical development PYX-201 targets EDB+FN (Extra-domain B of Fibronectin) A splice variant of fibronectin Non-cellular structural component of the extracellular matrix (ECM) Highly overexpressed in several solid tumors PYX-201 has a uni
Slide 6: EDB+FN is highly differentially expressed in tumor Extracellular Matrix
EDB+FN is highly differentially expressed in tumor Extracellular Matrix (ECM) Source: Pyxis Oncology nonclinical data IHC assay demonstrated high baseline EDB in indications of interest EDB expression from Phase 1 patient biopsies consistent with IHC validation data-set No distinct correlation initi
Slide 7: PYX-201 potential to deliver powerful anti-tumor activity in mono and combo regimens
PYX-201 potential to deliver powerful anti-tumor activity in mono and combo regimens PYX-201 designed to bind to EDB and releases payload within tumor ECM CD8+ lymphocyte Dendritic cell PYX-201 Cleaved & active payload (auristatin) Tumor cell Matrix Proteases (e.g., cathepsin) Key 1 2 3 Payload diff
Slide 8: New Clinical Trial Collaboration to Evaluate PYX-201 with KEYTRUDA
New Clinical Trial Collaboration to Evaluate PYX-201 in Combination with KEYTRUDA® (pembrolizumab) PYX-201 disruption of ECM has potential to augment PD-1 anti-tumor effects in early lines of therapy FPFV: First Patient First Visit NOTE: Merck is known as MSD outside of the US and Canada; KEYTRUDA®
Slide 9: PYX-201 ADC construct with site-specific conjugation chemistry and optimized payload
PYX-201 ADC construct with site-specific conjugation chemistry & optimized auristatin payload has shown improved stability and biological potency EDB+FN targeting mAb Aur-0101 payload (x4) Valine Citrulline linker PYX-201 Construct Light chain Heavy chain Engineered cysteine Disulfide bond Key poten
Slide 10: PYX-201 PK profile demonstrates superior stability in circulation
PYX-201 PK profile demonstrates superior stability in circulation compared to approved Val-Cit-MMAE ADCs 1. Based on the corresponding FDA label, shown as ADC half-life MMAE: Monomethyl Auristatin E The site-specific conjugation for PYX-201 delivers two advantages: Lower levels of free payload in ci
Slide 11: PYX-201 Dose linear PK demonstrated no antigen sink
PYX-201 Dose linear PK demonstrated no antigen sink Consistent with differentiated EDB target expression in tumor ECM and negligible expression in normal tissue Nominal time after dose (d) Median plasma concentration (µg/mL) 0.3 mg/kg 0.6 mg/kg 1.2 mg/kg 2.4 mg/kg 3.6 mg/kg 5.4 mg/kg 6.6 mg/kg 8 mg/
Slide 12: PYX-201 Ph1 Dose Escalation Study design
PYX-201 Ph1 Dose Escalation Study with 10 solid tumor types *No patient was dosed in this Phase 1 study for Renal Cancer HNSCC: Head and neck squamous cell carcinomas NSCLC: Non-small cell lung cancer; PDAC: Pancreatic ductal adenocarcinoma TNBC: Triple negative breast cancer HCC: Hepatocellular Car
Slide 13: Ph1 Dose Escalation Study identified range of potentially effective doses
PYX-201 Ph1 Dose Escalation Study identified range of potentially effective doses 0.3 mg/kg 0.6 mg/kg 1.2 mg/kg 2.4 mg/kg 3.6 mg/kg 4.4 mg/kg 5.4 mg/kg 6.6 mg/kg 8.0 mg/kg N=3 N=3 N=3 N=8 N=11 N=42 N=3 N=3 N=4 3.6 - 5.4 mg/kg focus of Phase 1 Part 1 recruitment Observed dose-dependent responses star
Slide 14: Phase 1 Trial Patient Demographics
Phase 1 Trial Patient Demographics show heavily pretreated heterogeneous population 1. Safety evaluable population 2. Include Trodelvy, Enhertu, IMG-151(FRα ADC ), I-DXd, ELU001 (FRα ADC), ASN004 (5T4 ADC) HNSCC: head and neck squamous cell carcinomas NSCLC: Non-small cell lung cancer; PDAC: Pancrea
Slide 15: Treatment-related adverse events summary
TRAEs N 3 3 3 8 11 3 39 4 3 771 All TRAEs 1 (33%) 1 (33%) 3 (100%) 6 (75%) 9 (82%) 3 (100%) 36 (92%) 4 (100%) 3 (100%) 66 (86%) Grade 1/2 TRAEs 1 (33%) 1 (33%) 3 (100%) 4 (50%) 8 (73%) 2 (67%) 22 (56%) 1 (25%) 2 (67%) 44 (57%) Grade 3/4 TRAEs 0 0 0 2 (25%) 1 (9%) 1 (33%) 14 (36%) 3 (75%) 1 (33%) 22
Slide 16: Grade 1/2 TRAE profile
N 3 3 3 8 11 3 39 4 3 771 MMAE-Payload-related Toxicity Cutaneous2 0 0 1 (33%) 3 (38%) 4 (36%) 1 (33%) 19 (49%) 2 (50%) 3 (100%) 33 (43%) Neuropathy 0 0 1 (33%) 2 (25%) 1 (9%) 0 8 (21%) 0 2 (66%) 14 (18%) Neutropenia 0 0 0 0 0 0 1 (3%) 0 0 1 (1%) Ocular 1 (33%) 0 0 3 (38%) 3 (27%) 0 5 (13%) 1 (25%)
Slide 17: Grade 3/4 TRAE profile
N 3 3 3 8 11 3 39 4 3 771 MMAE-Payload-related Toxicity Cutaneous2 0 0 0 0 0 0 3 (8%) 0 0 3 (4%) Neuropathy 0 0 0 1 (13%) 0 0 0 1 (25%) 0 2 (3%) Neutropenia 0 0 0 0 0 0 3 (8%) 1 (25%) 1 (33%) 5 (6%) Ocular 0 0 0 0 0 0 0 0 0 0 Non-Payload-related Toxicity Anemia3 0 0 0 0 0 0 2 (5%) 2 (50%) 0 4 (5%) P
Slide 18: PYX-201 safety compares favorably to other approved ADCs
PYX-201 safety and tolerability data compares favorably to data from third party studies of other approved ADCs ADC Target Payload Ocular Neuropathy Neutropenia Cutaneous Pneumonitis PYX-201 EDB+FN Auristatin 0101 (Auristatin) Padcev Nectin-4 Vedotin (MMAE) Tivdak TF Vedotin (MMAE) Elahere FRa DM4 m
Slide 19: PYX-201 Phase 1 Part 1 RECIST 1.1 responses across all dose levels
Best % change from baseline PR CR PD PD PD PD PD PD PD PD PD PD PD SD SD SD SD SD PD PD PD SD PD SD SD PD PD SD SD SD SD SD PD PD SD SD SD SD SD PD PD SD SD SD SD PD SD SD SD SD SD SD SD SD SD PR SD PR #PR PR ##PR *PR PR PR *PR *PR *CR PR PYX-201 Phase 1 Part 1 RECIST 1.1 responses across all dose l
Slide 20: Responses by tumor type
30 60 90 120 150 180 210 240 270 300 330 360 390 420 HR+ BC Sarcoma HNSCC NSCLC Ovarian Cancer Sarcoma Pancreatic Cancer Sarcoma NSCLC TNBC Ovarian Cancer Pancreatic Cancer TNBC Pancreatic Cancer Pancreatic Cancer HNSCC Sarcoma NSCLC NSCLC TNBC HCC HNSCC Pancreatic Cancer HNSCC Sarcoma Thyroid Cance
Slide 21: PYX-201 demonstrated strong signal in HNSCC patients
PYX-201 demonstrated strong signal in HNSCC patients Identified dose range of 3.6 – 5.4 mg/kg (n=6) 100% DCR Confirmed by RECIST 1.1 ORR 50% & 2 PRs 1 CR
Slide 22: Durable responses in HNSCC patients
1 confirmed CR 50% ORR Participants Days since first dose PR PD CR SD EOT Death Median 115 days (16 weeks)1 Durable responses for 6 evaluable patients in 3.6 - 5.4 mg/kg Identified Dose Range Patient Ongoing -100 -80 -60 -40 -20 0 20 40 60 80 100 3.6 mg/kg 5.4 mg/kg + / - / UNK: HPV positive / negat
Slide 23: HNSCC monotherapy patient responses
Confirmed CR in HPV+ PD-L1 negative patient Confirmed PR in HPV- patient heavily treated with Taxanes and IO Confirmed PR in HPV+ patient who progressed on multi lines of IO therapy Best Observed Response per RECIST 1.1: -100% CR 16.3 mm tumor completely resolved 66 y/o male; HPV positive; PD-L1 neg
Slide 24: Current HNSCC market expanding and innovating
Current HNSCC market expanding and innovating HNSCC market growing at 10.6% CAGR1 >606K1 new cases annually worldwide Current SOC Current SOC lacking in long term survival Current innovation in development Next generation EGFR assets 1. Source: DRG; 2. Source: Barsouk, A., Aluru, J. S., Rawla, P., S
Slide 25: Early PYX-201 monotherapy data compares favorably with emerging competitors in HNSCC
Early PYX-201 Phase 1 Part 1 monotherapy data compares favorably with emerging competitors in HNSCC 1. Merus Company Presentation, 17Apr2023; 2. Philippe L. Bedard et al.,; A phase 1 trial of the bifunctional EGFR/TGFβ fusion protein BCA101 alone and in combination with pembrolizumab in patients wit
Slide 26: PYX-201 potential for early line in combo with PD-1
PYX-201 potential for early line in combo with PD-1 PYX-201 Mono Merus combo with PD-1 Bicara combo with PD-1 (HPV-) ORR% (N evaluable in HNSCC) 50%1 (N=6) 67%3 (N=24) 64%2 (N=28) Bicara combo with PD-1 (HPV+/-) Bicara Merus PYXS 1.. PYX-201 Phase 1 data 2. Bicara Press Release, 27June2024 3. Merus
Slide 27: HNSCC Clinical Studies starting in 1Q25 will deliver catalysts
3 HNSCC Clinical Studies starting in 1Q25 will deliver 3 catalysts 2H25-1H26 2/3L Monotherapy in PD-1 and EGFR experienced patients Potential Opportunity: Limited next set of options for these patients beyond chemo 1/2L Combo therapy PYX-201 + KEYTRUDA® Potential Opportunity: Improved tolerability a
Slide 28: RECIST 1.1 responses in Ovarian, NSCLC, HR+ BC, TNBC and Sarcoma
PD PD SD SD SD PD PD Best % change from baseline SD SD SD SD SD SD SD SD SD SD PR PR ##PR PR *PR PD PYX-201 RECIST 1.1 responses seen in 3.6 - 5.4 mg/kg Identified Dose Range Ovarian Cancer, NSCLC, HR+ BC, TNBC and Sarcoma * = Confirmed Response as of Oct 4th cut-off ## Confirmed Response after Oct
Slide 29: Time on study in Identified Dose Range
30 60 90 120 150 180 210 240 270 Sarcoma NSCLC Ovarian Cancer Sarcoma TNBC NSCLC Sarcoma TNBC Sarcoma HR+ BC NSCLC TNBC Ovarian Cancer NSCLC NSCLC Sarcoma NSCLC NSCLC TNBC Ovarian Cancer Sarcoma Sarcoma Ovarian Cancer Ovarian Cancer PR SD SD SD PR PD SD SD PD PR Ovarian Cancer SD SD SD PD SD SD SD P
Slide 30: Patient case examples with tumor shrinkage
Ovarian cancer patient with platinum resistance had rapid tumor shrinkage TNBC patient post Trodelvy and IO completely resolved skin lesions in 4 wks NSCLC patient progressed on multiple prior lines had ~42% tumor shrinkage Week 6: -49% PR; Week 12: -72.6% PR (scan after data cutoff of Oct 4th) Elim
Slide 31: Program areas, indications and next milestones
Program Area Potential Indications Preclinical Phase 1 FPFV1 Next Milestone Head & Neck Squamous Cell Carcinoma (HNSCC) HNSCC – PYX-201 with KEYTRUDA® 1/2L Q1 ‘25 Preliminary data in 2H25 HNSCC – PYX-201 Mono 2/3L Platinum & PD-1 Experienced Q1 ‘25 Preliminary data in 2H25 HNSCC – PYX-201 Mono 2/3L
Slide 32: KOL Perspectives: Panel Discussion
KOL Perspectives: Panel Discussion Lara Sullivan, MD President and CEO Moderated by Glenn Hanna, MD Director, Center for Cancer Therapeutic Innovation, Medical Oncologist, Center for Head & Neck Oncology, Dana Farber Cancer Institute Guest Key Opinion Leaders Anthony Tolcher, MD, FRCPC Founder and C
Slide 33: NEXT Oncology Case Example: Serous ovarian cancer patient (1 of 2)
NEXT Oncology Case Example: Serous ovarian cancer patient (1 out of 2 pgs) November 2023 November 2023 Baseline scan 29.5 mm x 23.2 mm 1st scan (Unscheduled) after Cycle 1 (1 dose PYX-201)
Slide 34: NEXT Oncology Case Example: Serous ovarian cancer patient (2 of 2)
NEXT Oncology Case Example: Serous ovarian cancer patient (2 out of 2 pgs) December 2023
Slide 35: KOL Perspectives: Panel Discussion
KOL Perspectives: Panel Discussion Lara Sullivan, MD President and CEO Moderated by Glenn Hanna, MD Director, Center for Cancer Therapeutic Innovation, Medical Oncologist, Center for Head & Neck Oncology, Dana Farber Cancer Institute Guest Key Opinion Leaders Anthony Tolcher, MD, FRCPC Founder and C
Slide 36: $146M in cash provides runway into 2H 2026
As of Q3 2024, $146M in cash provides runway into 2H 2026 Multiple Clinical Catalysts for PYX-201 over next 6-18 months Building a Leading ADC Focused Company
Slide 37: Q&A
Q&A PYAIS
Slide 38: Appendix
APPENDIX PYAIS
Slide 39: PYX-201-101 Phase 1 Part 1 tumor types and total patient numbers
PYX-201-101 Phase 1 Part 1 tumor types total patient numbers 80 Patients Dosed in Phase 1 Part 1 0.3 1 1 1 3 0.6 1 2 3 1.2 1 1 1 3 2.4 3 2 1 1 1 8 3.6 3 3 1 2 1 1 11 4.4 1 2 3 5.4 7 6 5 5 5 5 4 4 1 42 6.6 1 1 2 4 8.0 1 1 1 3 Total 17 14 12 9 9 8 6 4 1 0 80 NSCLC TNBC Sarcoma HNSCC Ovarian Cancer PDA
Slide 40: Summary of all responses in PYX-201 Phase 1 Part 1 trial
Summary of all responses in PYX-201 Phase 1 Part 1 trial observed Note: Efficacy population defined by dose received; dose level for patients who escalated or de-escalated = starting dose 1. N=65; 3 patients dosed after 10/4 data cutoff and do not yet have scans; 12 patients of the 77 patients inclu