Slide 1: PN-943 Phase 2 Study Data Readout
1 PN - 943 Phase 2 Study Data Readout Dinesh V. Patel, PhD | President & CEO April 25, 2022
Slide 2: Today's Agenda
Today’s Agenda 2 Introduction: Dinesh V. Patel, PhD, President & CEO Data readout from the Phase 2 IDEAL Study of PN - 943 in Ulcerative Colitis (UC): Scott Plevy, MD, Executive Vice President & Therapeutic Head, Gastroenterology Reflections on the data and the unmet need in UC : Bruce Sands, MD, MS
Slide 3: Forward-looking Statements
Forward - looking Statements 2 This presentation and the accompanying oral presentation contain forward - looking statements made pursuant to the safe harbor pro visions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in thi
Slide 4: Phase 2 UC IDEAL Study Topline Results and Next Steps
PN - 943 Phase 2 UC IDEAL Study Topline Results and Next Steps 4 • PN - 943 is an oral, gut - restricted a4b7 - integrin antagonist – ‘Oral Entyvio’ equivalent • Achieved clinical proof - of - concept and validation for oral, gut - restricted approach for ulcerative colitis via blockade of the a4b7
Slide 5: PTG-100 Phase 2A Efficacy Similar to Other IBD Targeted Therapy Drugs
PTG - 100 Ph2A Efficacy Similar to Other IBD Targeted Therapy Drugs 5 *Anti - MadCam mAb * No central read endoscopy ( Entyvio ) PTG - 100, 900 mg q.d . dose showed 44% histological remission (RHI)
Slide 6: The Outcome of Phase 2 IDEAL Study will Inform Phase 3 Decisions
The Outcome of Phase 2 IDEAL Study will Inform Phase 3 Decisions • Phase 2 data in UC with various candidates spanning different mechanism of actions – Large confidence intervals, influenced by study design, duration, size, demographics, & criteria – Phase 2 outcomes has generally predicted efficacy
Slide 7: IDEAL: Phase 2 UC Study Design
IDEAL: PN - 943 Phase 2 UC Study Design 7 Part - 1: Induction Part - 2: Extended Treatment Period 5 weeks 12 weeks 40 Weeks Week 52 Randomize (n=150) Placebo BID (n=55) Active Drug 450 mg BID (n=53) Active Drug 150 mg BID (n=51) PN - 943 Adult Patients with UC N≈169 ( mITT = 159) Eligibility: • Mode
Slide 8: Enrollment by Country
Enrollment by Country 8 Percentages are based on the total number of subjects in each column Country Subjects Screened (N=338) n (%) Subjects Randomized (N=169) n(%) Poland 163 (48.2) 97 (57.4) Russia 45 (13.3) 24 (14.2) United States 60 (17.8) 13 ( 7.7) Georgia 20 ( 5.9) 10 ( 5.9) Ukraine 15 ( 4.4)
Slide 9: Demographic and Disease Characteristics at Baseline
9 Placebo (N=55) PN - 943 150mg bid (N=51) PN - 943 450mg bid (N=53) Age yrs , mean (SD) 38 (10.6) 42 (12.6) 38 (13.3) Male sex, n (%) 35 (63.6) 26 (51.0) 33 (62.3) Weight (kg), mean (SD) 71.7(17.39) 74.3 (15.61) 74.4 (15.18) BMI, mean (SD) 24.2 (4.80) 25.7 (5.11) 24.6 (4.18) Duration of UC, months
Slide 10: Clinical Remission
30.2% 13/43 17 .0% 8/47 14 % 6/43 0 5 10 15 20 25 30 35 150 mg BID 450 mg BID Placebo Clinical Remission (%) mITT Bio - Naïve ( Δ 16%) 27.5 % 14/51 15.1 % 8/53 14.5 % 8/55 0 5 10 15 20 25 30 150 mg BID 450 mg BID Placebo Clinical Remission (%) mITT ALL ( Δ 13%) CONFIDENTIAL 10 P=0.035 Clinical Remis
Slide 11: Histologic Remission and Improvement
37.2 % 16/43 23.4 % 11/47 14.3 % 7/49 0 5 10 15 20 25 30 35 40 150 mg BID 450 mg BID Placebo Histologic Remission (%) (RHI≤6) 36.4 % 16/44 20.8 % 10/48 16 .0% 8/50 0 5 10 15 20 25 30 35 40 150 mg BID 450 mg BID Placebo Histologic Improvement ( Geboes <3.1) CONFIDENTIAL 11 P=0.0107 P=0.0213 Histologi
Slide 12: Endoscopic Remission and Improvement
11.8 % 6/51 1.9 % 1/53 3.6 % 2/55 0 2 4 6 8 10 12 14 150 mg BID 450 mg BID Placebo Endoscopic Remission* (%) (ESS=0) 43.1 % 22/51 20.8 % 11/53 16.4 % 9/55 0 5 10 15 20 25 30 35 40 45 50 150 mg BID 450 mg BID Placebo Endoscopic Improvement** ( ESS= 0 or 1) 12 P=0.0023 Endoscopic Remission and Improve
Slide 13: Clinical Remission Comparison in Bio-Naive Vs Vedolizumab
23% 7% 0% 5% 10% 15% 20% 25% Vedo Placebo Clinical Remission (%) Vedolizumab* 30.2 % 14 % 0 5 10 15 20 25 30 35 150 mg BID Placebo Clinical Remission (%) PN943 13 Clinical Remission Comparison in Bio - Naive PN - 943 Vs Vedolizumab efficacy in Phase 2 Studies Δ 16.3% Δ 15.5% * Feagan 2017; Clin. Gas
Slide 14: Safety Summary
Safety Summary 14 • Generally well tolerated • No drug discontinuation from AEs • No drug related SAEs • Safety analysis similar for the 150 mg BID dose versus the placebo group * pre - existing, not drug related System Organ Class Preferred Term Placebo (N=57) n(%) PN-943 150mg (N=55) n(%) PN-943 4
Slide 15: Trough Concentrations and Receptor Occupancy
15 PN - 943 Trough Concentrations and Receptor Occupancy 0 4 8 12 0 3 6 9 12 Weeks P N - 9 4 3 ( n g / m L ) 0 4 8 12 0 20 40 60 80 100 120 Weeks R e c e p t o r O c c u p a n c y ( % )
Slide 16: Inverse Dose Response
Inverse D ose R esponse 16 • A bell - shaped dose response in Phase 2 UC studies is a frequent occurrence across multiple therapies that block the a4b7 integrin/ MAdCAM pathway – Observed since 1997 but still not fully understood – Decisions made to move into Phase 3 trials based on identification o
Slide 17: Clinical Evidence of Bell Shaped Dose Response in UC Studies
Clinical Evidence of Bell Shaped Dose Response in UC Studies 17 Anti - a4b7 Integrin Antibody Vedolizumab (VDZ) Ph3 Exposure - Response for Clinical Remission with VDZ Treatment* *Becker, Gut, 2021
Slide 18: Clinical Evidence of Bell Shaped Dose Response in UC Studies
Clinical Evidence of Bell Shaped Dose Response in UC Studies 18 Anti - MAdCAM - 1 Antibody Ontamalimab (SHP647/PF - 00547659) Ph2 Clinical Remission at Week 12 By Anti - MAdCAM Treatment * * Vermeire , Lancet, 2017
Slide 19: Clinical Evidence of Bell Shaped Dose Response in UC Study
Clinical Evidence of Bell Shaped Dose Response in UC Study 19 Anti - IL - 23 Antibody - Mirikizumab 4.8 15.9 22.6 11.5 0 5 10 15 20 25 30 Mirikizumab Clinical Remission (%) Placebo 50 mg (N=63) 200 mg (N=62) 600 mg (N=61) * Sandborn, Gastroenterology, 2020 Ph2 Clinical Remission by Mirikizumab IL -
Slide 20: Summary of Phase 2 Findings
• PN - 943 150 mg BID appears to be a safe & effective dose – 27.5% Clinical remission vs 14.5% in placebo (delta 13%, p = 0.08) for mITT analysis ▪ 16% delta in BIO - naïve population (p = 0.04) – Strong concordance with efficacy across multiple key secondary endpoints with statistically significan
Slide 21: Phase 2 UC IDEAL Study Topline Results and Next Steps
PN - 943 Phase 2 UC IDEAL Study Topline Results and Next Steps 21 • PN - 943 is an oral, gut - restricted a4b7 - integrin antagonist – ‘Oral Entyvio’ equivalent • Achieved clinical proof - of - concept and validation for oral, gut - restricted approach for ulcerative colitis via blockade of the a4b7
Slide 22: Product Portfolio
Programs Candidates Study Phase 1 Phase 2 Phase 3 Key Milestones HEMATOLOGY & BLOOD DISORDERS Hepcidin Mimetic Rusfertide (PTG - 300) s.c. POLYCYTHEMIA VERA (PV) VERIFY 300 - 11 • Patient screening underway REVIVE 300 - 04 • Enrollment completed • Updates at 2022 conferences PACIFIC 300 - 08 • All p
Slide 23: Thank you
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