Slide 1: PDS0101 in HPV16+ Head and Neck Cancer KOL Roundtable
PDS0101 in HPV16+ Head and Neck Cancer KOL Roundtable NASDAQ: PDSB October 3, 2023
Slide 2: Forward Looking Statements
Forward Looking Statements Versamune® and Infectimune® are registered trademarks of PDS Biotechnology Corporation.KEYTRUDA® is a registered trademark of Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Certain information in this presentation may include forward-looking
Slide 3: Disclaimer
Disclaimer PDS Biotech is the sponsor of this roundtable Each panelist is speaking on behalf of PDS Biotech under the terms of a consulting agreement Information presented is consistent with FDA regulations and guidelines
Slide 4: Welcome and Introductions
Welcome and Introductions Dr. Lauren V. Wood
Slide 5: Introducing Our Panel
Dr. John Kaczmar Associate Professor Medical University of South Carolina Dr. Ricard Mesía Head of Medical Oncology Catalan Institute of Oncology Introducing Our Panel Dr. Glenn Hanna Assistant Professor, Harvard University and Medical Oncologist, Dana-Farber Cancer Institute Dr. Katharine Price Ass
Slide 6: Today's Agenda
Today’s Agenda Welcome and Introductions Dr. Lauren V. Wood Current Treatment of HPV16+ HNSCC and Unmet Needs Dr. Ricard Mesía PDS0101 for the Treatment of HPV16+ HNSCC Data to Date Dr. John Kaczmar Plans for Phase 3 Study Dr. Katharine Price Emerging Use of ctDNA in Treatment of HPV+ HNSCC Dr. Glen
Slide 7: Current Treatment of HPV16+ HNSCC and Unmet Needs
Current Treatment of HPV16+ HNSCC and Unmet Needs Dr. Ricard Mesía
Slide 8: Standard-of-Care in Recurrent/Metastatic HNSCC
CPS Tumor burden and growth rate Standard-of-Care in Recurrent/Metastatic HNSCC: ECOG 0-1 Mesia R, Clin Transl Oncol 2021 Ferris RL, et al. NEJM. 2016;375:1856-67 Burtness B et al., Lancet. 2019; 394:1915-1928 OS 12-14 m PFS 3-5 m CT POST-IO OS 8 m PFS 2 m PD-L1 CPS≥1 PD-L1 CPS<1 Performance Score (
Slide 9: What Happened with CPS<1?
What Happened with CPS<1? CT: chemotherapy Burtness B, et al. J Clin Oncol. 2022. Pembrolizumab vs EXTREME Pembrolizumab + CT vs EXTREME CPS < 1: pembrolizumab alone is detrimental and pembrolizumab + CT is not superior
Slide 10: Baseline Characteristics, KEYNOTE-048
Baseline Characteristics, KEYNOTE-048 Burtness B et al., Lancet. 2019; 394:1915-1928 Characteristic, n (%) Pembrolizumab Alone vs EXTREME Pembrolizumab + Chemo vs EXTREME Characteristic, n (%) Pembro N = 301 EXTREME N = 300 Pembro + Chemo N = 281 EXTREME N = 278a Age, median (range), years 62 (22-94
Slide 11: The Actual Goals of Therapy in Recurrent/Metastatic Disease
The Actual Goals of Therapy in Recurrent/Metastatic Disease IO: immuno-oncology therapy 1. Tahara M ESMO 2022 Treatment Goal 5-yr OS: 15-18% with IOsin CPS≥1 Recurrent/Metastatic Improve long-survivors rate The complete cure of the recurrent/metastatic patient? Palliative intent = Only??? ↑ Survival
Slide 12: Treatment After 1st Line Recurrent/Metastatic: Expectations
Treatment After 1st Line Recurrent/Metastatic: Expectations Harrington K. et al. ASCO Annual meeting 2020 Haddad J Clin Oncol 2023 Only 50 to 60% will receive a second line therapy based on what, they received first
Slide 13: Treatment After 1st Line Recurrent/Metastatic: Expectations
Treatment After 1st Line Recurrent/Metastatic: Expectations Psyrri A. et al. Annals of Oncology, 2023, Harrington K. et al. ASCO Annual meeting 2020 mOS Can Be Predicted by Response to First Line mPFS to 2L May Range Between 3-6m
Slide 14: Unmet Needs in 1st Line Recurrent/Metastatic HPV16+ HNSCC
Unmet Needs in 1st Line Recurrent/Metastatic – HPV16+ HNSCC: Head and neck squamous cell carcinoma IO: Immuno-oncology therapy To improve the rate of long-term survival To reduce the toxicity of the actual treatments, to improve QoL To define the best sequence of treatment for specific HPV-related p
Slide 15: PDS0101 for the Treatment of HPV16+ HNSCC Data to Date
PDS0101 for the Treatment of HPV16+ HNSCC Data to Date Dr. John Kaczmar
Slide 16: VERSATILE-002 Key Goal: Improve Survival with PDS0101
VERSATILE-002 Key Goal: Improve Survival with PDS0101 Targeted Immunotherapy Burtness B et al., Lancet. 2019; 394:1915-1928 Mehra R et al., Br J Cancer 2018; 119:153-159 Overall Survival with KEYTRUDA® or KEYTRUDA® + chemo is only 12–14 months in KEYNOTE-048 24-month survival rate with KEYTRUDA® or
Slide 17: VERSATILE-002 Phase 2 Clinical Trial
VERSATILE-002 Phase 2 Clinical Trial Objective: To Assess the Combination of PDS0101 and KEYTRUDA® in ICI Naïve Subjects with Recurrent or Metastatic HPV-positive HNSCC KEYTRUDA®(pembrolizumab) FDA Approved Standard of Care Partner StudyDesign Open-label, non-randomized, adaptive design study N=54 E
Slide 18: VERSATILE-002 ICI Naive Key Demographics and Treatment Exposure
VERSATILE-002 ICI Naïve Key Demographics and Treatment Exposure Majority of Patients Are CPS 1-19 Demographic ITT Population (N=55) mITT Population (N=52) Age, Median (Min, Max) 64.0 (46, 83) 64.0 (46, 83) Sex, n (%) Male Female 51 (92.7) 4 (7.3) 48 (92.3) 4 (7.7) Race, n (%) American Indian or Alas
Slide 19: PDS0101 and KEYTRUDA Combination Demonstrates Promising Patient Survival
PDS0101 and KEYTRUDA® Combination in ICI Naïve HNSCC Demonstrates Promising Patient Survival to Date Median OS Not Yet Estimable Data on File. 08/02/23 Data Cut. Kaplan-Meier Estimates of Overall Survival (OS) (Intent-to-Treat Population) No. of Subjects at Risk (Events) 55 (0) 53 (2) 50 (3) 42 (5)
Slide 20: Overall Survival Rates vs KEYNOTE-048
PDS0101 and KEYTRUDA® Combination in ICI NaïveHNSCC Demonstrates Promising Patient Survival to Date Overall Survival is Primary Endpoint in Planned Phase 3 Study VERSATILE-003 * No controlled or comparative studies have been conducted between checkpoint inhibitors and PDS0101Data on File. 08/02/23 D
Slide 21: Disease Stabilization or Tumor Reduction in 81% of Patients
Disease Stabilization or Tumor Reduction in 81% of Patients Tumor Shrinkage in 60% (31/52) with Confirmed Objective Response in 27% (14/52) to Date Assessments based on Investigator assessment per RECIST 1.1 Data on File. 08/02/23 Data Cut. Burtness B et al., Lancet. 2019; 394:1915-1928. Best Percen
Slide 22: Safety: Treatment Related Adverse Events (ICI Naive)
No ICI Naïve Subjects Have Grade 4 or 5 Combination Treatment Related Adverse Events (N=62) Safety Population: All enrolled subjects who received at least 1 dose of pembrolizumab or PDS0101. Includes subjects who became ineligible, for example due to lack of central confirmation of HPV16-positivity.
Slide 23: PDS0101 with KEYTRUDA Well Tolerated in VERSATILE-002
PDS0101 with KEYTRUDA® Well Tolerated in VERSATILE-002 to Date Grade 3–5 Treatment Related Adverse Events *No controlled or comparative studies have been conducted between checkpoint inhibitors and PDS0101 Data on File. 08/02/23 Data Cut Burtness B et al. Lancet. 2019;394:1915-1928 ® ® ® VERSATILE-0
Slide 24: Combination Continues to Show Promising Survival Outcomes in ICI Naive Subjects
Combination of PDS0101 & KEYTRUDA® Continues to Show Promising Survival Outcomes in ICI Naïve subjects PDS0101 with KEYTRUDA® Combination Data Shows Potential Of PDS0101 to Safely Modify the Tumor Microenvironment and Target HPV16-positive HNSCC to Promote Survival The 24-month OS rate in the ICI na
Slide 25: Plans for Phase 3 Study
Plans for Phase 3 Study Dr. Katharine Price
Slide 26: VERSATILE-003 Designed to Be Confirmatory Trial
VERSATILE-003 Designed to Be Confirmatory Trial for ICI Naïve Cohort of Phase 2 VERSATILE-002 Study with Overall Survival as Primary Endpoint A Phase 3 Open-Label, Randomized Study of PDS0101 Plus Pembrolizumab vs Pembrolizumab Alone in First Line Treatment of Immune Checkpoint Inhibitor (ICI) Naïve
Slide 27: VERSATILE-003 Phase 3 Study Design
VERSATILE-003 Phase 3 Study Design Global Randomized, Controlled Clinical Study with Estimated 90–100 Sites Overall survival (OS) Primary Endpoint For the treatment of recurrent or metastatic HPV16-positive HNSCC Targeted Indication Randomization 2:1 PDS0101 +KEYTRUDA® PDS0101 + KEYTRUDA® KEYTRUDA®
Slide 28: Primary and Secondary Objectives
Primary and Secondary Objectives Primary Objective Overall survival (OS) between investigational arm (PDS0101 + KEYTRUDA®) vs. control arm (KEYTRUDA®) Secondary Objectives Progression-free survival (PFS) between the investigational arm vs. control arm per RECIST1.1, BICR Objective response rate (ORR
Slide 29: Safety and Exploratory Objectives
Safety and Exploratory Objectives Safety Objective Overall safety between the investigational arm vs control arm Exploratory Objectives Disease Control Rate (DCR) between the investigational arm vs control arm PFS2 between the investigational arm vs control arm iORR, iPFS, and iDOR between the inves
Slide 30: Study Treatment Schedule
Study Treatment Schedule Study Treatments PDS0101 1mL subcutaneous every 3 weeks Pembrolizumab 200mg intravenous every 3 weeks Treatment Schedule Cycles 1-4 Cycles 5-11 Cycles 13-35 Cycle 12 PDS0101 + Pembrolizumab PDS0101 + Pembrolizumab Pembrolizumab monotherapy Pembrolizumab monotherapy Cycles 1-
Slide 31: Key Inclusion Criteria
Key Inclusion Criteria Subject is ≥18 years of age History of histologically- or cytologically-confirmed diagnosis of squamous cell cancer of the head and neck (HNSCC) Unresectable recurrent and/or metastatic measurable disease with confirmation of at least 1 lesion that is considered a target lesio
Slide 32: Key Exclusion Criteria
Key Exclusion Criteria Prior therapy with HPV-specific immunotherapy including therapeutic cancer vaccines and cellular immunotherapy. Note: subjects who have received prophylactic HPV vaccines are eligible for enrollment Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an ag
Slide 33: Timeline to Registrational Trial Initiation
Timeline to Registrational Trial Initiation Worldwide Randomized, Controlled Clinical Study to Be Initiated Q4 2023 PDS0101 + KEYTRUDA® in Recurrent or Metastatic HPV16-Positive HNSCC 2Q 2022 3Q 2022 1Q 2023 2Q 2023 3Q 2023 4Q 2023 FDA Fast Track designation for PDS0101 + KEYTRUDA® Successful EOP2 m
Slide 34: Emerging Use of ctDNA in Treatment of HPV+ HNSCC
Emerging Use of ctDNA in Treatment of HPV+ HNSCC Dr. Glenn Hanna
Slide 35: Pre-treatment HPV ctDNA Detection
Pre-treatment HPV ctDNA Detection Rettig EM, et al. JAMA Otolaryngol Head Neck Surg 2022
Slide 36: HPV ctDNA Clearance During Treatment
HPV ctDNA Clearance During Treatment Chera BS, et al. Clin Cancer Res 2019 ctHPV16DNA levels increased after starting CRT and later declined 80% of patients had no detectable ctHPV16DNA by the end of CRT No patients with >95% viral clearance (from baseline) by week 4 demonstrated recurrence * N=87 (
Slide 37: HPV ctDNA Clearance During Treatment
HPV ctDNA Clearance During Treatment Chera BS, et al. Clin Cancer Res 2019 Low baseline ctHPV16DNA (≤200 copies/mL) had lower tumor HPV copy number Those with low tumor HPV copy number (≤5 copies/haploid genome) had HPV integration Low baseline ctHPV16DNA → HPV integration → adverse tumor genomics
Slide 38: HPV ctDNA Clearance During Treatment
HPV ctDNA Clearance During Treatment Chera BS, et al. Clin Cancer Res 2019 Favorable ctHPV16DNA profile: >200 copies/mL baseline and >95% viral clearance by week 4
Slide 39: Risk Stratifying HPV+ Oropharyngeal Cancer
Risk Stratifying HPV+ Oropharyngeal Cancer Ang KK, et al. N Engl J Med 2010 HPV+, ≤10 pack-year smoker 0-1 lymph node Trend towards de-intensificationTORS + Radiation (60 Gy), or lower dose chemoradiation, or induction chemotherapy followed by lower dose radiation Standard chemoradiation in 35 fract
Slide 40: Risk Stratifying HPV+ Oropharyngeal Cancer: Intermediate Risk Group
Risk Stratifying HPV+ Oropharyngeal Cancer What do we do for the intermediate risk group? 63M (former smoker) with HPV+ left tonsil SCC with cT4N1 (stage III, AJCC 2017 8th ed) disease? Standard bolus cisplatin with chemoradiation or can we de-intensify at all? What can we use to risk stratify him b
Slide 41: Risk-adapted Therapy Using ctHPV DNA Profile ReACT Study
Risk-adapted Therapy in HPV+ Oropharyngeal Cancer Using Circulating Tumor (ct)HPV DNA Profile ReACT Study Hanna GJ, Schoenfeld JD, et al. Accruing 2022 Phase II, non-randomized, exploratory study 2-year PFS of 75% from RTOG 1016 for the favorable intermediate-risk group N=45 evaluable pts provides 8
Slide 42: Risk-adapted Therapy Using ctHPV DNA Profile ReACT Study
Risk-adapted Therapy in HPV+ Oropharyngeal Cancer Using Circulating Tumor (ct)HPV DNA Profile ReACT Study Hanna GJ, Schoenfeld JD, et al. Accruing 2022 Failure to clear TTMV-HPV DNA by 95% at week 4-5, no de-escalation (higher risk?)
Slide 43: HPV ctDNA and Response to Induction
HPV ctDNA and Response to Induction 39M (Never Smoker) with de novo Metastatic HPV+ BOT SCC with Lung Metastases, After 1-Cycle of Chemoimmunotherapy TTMV-HPV DNA Nearly Clears…Completed 3-cycles, Now on to Consolidative CRT… Hanna GJ, patient example
Slide 44: HPV ctDNA and Response to Surgery
HPV ctDNA and Response to Surgery Routman DM, et al. Int J Radiat Oncol Biol Phys 2022
Slide 45: HPV ctDNA During Surveillance
HPV ctDNA During Surveillance Chera BS, et al. J Clin Oncol 2020 Worse outcomes for those with two consecutively positive ctHPVDNA results post-treatment Among patients with recurrence, ctHPVDNA positivity often predated detection of recurrence on imaging or biopsy
Slide 46: HPV ctDNA During Surveillance
HPV ctDNA During Surveillance Berger B, Hanna GJ, et al. Clin Cancer Res 2021 In follow-up, PPV is 97% with further cancer events identified
Slide 47: HPV ctDNA During Surveillance
HPV ctDNA During Surveillance Hanna GJ, et al. Clin Cancer Res 2023
Slide 48: HPV ctDNA During Surveillance
HPV ctDNA During Surveillance Rettig EM, Hanna GJ, et al. Accrual completed in 2022
Slide 49: HPV ctDNA Conclusions (or More Questions)
HPV ctDNA Conclusions (or More Questions)… Rettig EM, Hanna GJ, et al. Accrual completed in 2022 Should HPV ctDNA be incorporated into routine surveillance for all HPV-positive oropharyngeal cancer patients? Is this ready for inclusion in the NCCN® guidelines? Can HPV ctDNA results guide the choice
Slide 50: PDS0101 + KEYTRUDA in ICI Refractory Subjects
PDS0101 + KEYTRUDA® in ICI Refractory Subjects Dr. Lauren V. Wood
Slide 51: Assessing the Role of PDS0101 in Extending Survival
Assessing the Role of PDS0101 in Extending Survival in the Absence of a VERSATILE-002 KEYTRUDA® Control Arm Strauss J, et al. Journal for ImmunoTherapy of Cancer. 2020;8:e001395. Evaluation of the combination of PDS0101 and KEYTRUDA in patients who have failed KEYTRUDA therapy provides an “internal
Slide 52: Methods and Limitations: ICI Refractory Cohort
Methods and Limitations VERSATILE-002 ICI Refractory Cohort Phase 2, Open-Label, Non-Randomized, Adaptive Design Study Evaluating the Combination of PDS0101 and KEYTRUDA® Data on File. 08/02/23 Data Cut Population, Treatment Exposure, and Primary Endpoint Limitations: This study presents data from a
Slide 53: Survival Rates Demonstrate Potential Contribution of PDS0101
Survival Rates Demonstrate Potential Contribution of PDS0101 to Survival in Advanced Head and Neck Cancer PDS0101 + KEYTRUDA Shows Promising Survival Benefit even in ICI Refractory Patients * No controlled or comparative studies have been conducted between checkpoint inhibitors and PDS0101 Data on F
Slide 54: Safety in ICI Refractory Subjects
No ICI Refractory Subjects Have Grade 4 or 5 Combination Treatment Related Adverse Events (N=25) 4% (1/25) Subjects Have Grade 3 Combination Treatment Related Adverse Events Data on File. 08/02/23 Data Cut Preferred Term n (%) Any Combination-TRAE 21 (84.0) Injection site pain 12 (48.0) Injection si
Slide 55: VERSATILE-002 Results Support Initiation of Phase 3 Trial
VERSATILE-002 Study Results To-Date Support Initiation of Phase 3 Clinical Trial in ICI Naïve R/M HNSCC Data on File. 08/02/23 Data Cut Burtness B et al., Lancet. 2019;394:1915-1928 Promising survival data in target population for phase 3 study 24-month survival rate of 74% in HPV16-positive ICI naï
Slide 56: Panel Discussion
Panel Discussion CONFIDENTIAL
Slide 57: Closing Remarks
Closing Remarks Dr. Lauren V. Wood