Slide 1: SPRINT Phase 2 Study of EDP-235: Topline Results & Additional Analyses
SPRINT Phase 2 Study of EDP-235: Topline Results & Additional Analyses June 7, 2023
Slide 2: Forward Looking Statements Disclaimer
Forward Looking Statements Disclaimer This presentation contains forward-looking statements concerning our business, operations and financial performance and condition, as well as our plans, objectives and expectations for our research and development programs, our business and the industry in which
Slide 3: Enanta Pipeline
Enanta Pipeline PRODUCT CANDIDATE DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MARKET HCV Protease Inhibitor Glecaprevir* Virology: Liver HBV Core Inhibitor EDP-514 EDP-938 RSVPEDs N-Protein Inhibitor EDP-938 RSVTx RSV EDP-938 RSVHR Virology: L-Protein Inhibitor EDP-323 Respiratory Dual Non-Fusion
Slide 4: EDP-235: Oral Protease Inhibitor Designed for COVID-19
EDP-235: Oral Protease Inhibitor Designed for COVID-19 • Novel, oral, direct-acting antiviral specifically designed to target the SARS-CoV-2 3CL protease • Potent and selective inhibition of SARS-CoV-2 3CLpro enzyme – Potent inhibition in multiple cellular models • Potent against SARS-CoV-2 variants
Slide 5: EDP-235 Profile Suggests Potential for Best-in-Class Antiviral Treatment for SARS-CoV-2 Infection
EDP-235 Profile Suggests Potential for Best-in-Class Antiviral Treatment for SARS-CoV-2 Infection Preclinical Properties EDP-2351 Nirmatrelvir2 Pomotrelvir3 Ensitrelvir4 Molnupiravir5 Bemnifosbuvir6 Mechanism Protease Protease Protease Protease Polymerase Polymerase Enzyme IC50 5.8 19 24 13 n/a n/a
Slide 6: SPRINT Phase 2 Study of EDP-235: Topline Results & Additional Analyses
SPRINT Phase 2 Study of EDP-235: Topline Results & Additional Analyses A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Effects of EDP-235 in Non-hospitalized Adults with Mild or Moderate COVID-19
Slide 7: SPRINT Phase 2 Results: Conclusions
SPRINT Phase 2 Results: Conclusions Safety • EDP-235 was generally safe and well tolerated • Low frequency of adverse events; most were mild in severity – 1.3%, 6.4%, and 2.6% in the EDP-235 200mg, 400mg and placebo arms • No serious adverse events or discontinuations due to adverse events Clinical
Slide 8: SPRINT: SARS-CoV-2 PRotease INhibitor Treatment Phase 2 Study
SPRINT: SARS-CoV-2 PRotease INhibitor Treatment Phase 2 Study for EDP-235 in Non-hospitalized Standard Risk Patients Double Blinded Treatment Phase 5 days • Primary Objective: Evaluation of safety and Placebo (QD) tolerability ~200 patients* 1:1:1 EDP-235 200mg (QD) 28 Day Follow-up • Secondary Obje
Slide 9: Patient Disposition
SPRINT: Patient Disposition Screening (N=262) Did not meet inclusion & exclusion criteria (n=31) Randomization (N=231) EDP-235 200mg EDP-235 400mg Placebo Safety Population (N=77) (N=78) (N=76) Early discontinued: 2 Early discontinued: 4 Early discontinued: 2 Completed Day 33 Visit 75 (97%) 74 (95%)
Slide 10: Demographics and Baseline Characteristics
SPRINT: Demographics and Baseline Characteristics Safety Population • Demographics and baseline characteristics were well balanced between the arms. • Majority were White, Hispanic, young, enrolled within 3 days of symptom onset, and seropositive EDP-235 200mg EDP-235 400mg Placebo Parameter (N=77)
Slide 11: Summary of Treatment Emergent Adverse Events (TEAEs)
SPRINT: Summary of Treatment Emergent Adverse Events (TEAEs) Safety Population • Low frequency of treatment emergent adverse events; most were mild in severity • No serious adverse events or discontinuations due to adverse events EDP-235 200mg EDP-235 400mg Placebo (N=77) (N=78) (N=76) n (%) n (%) n
Slide 12: Treatment-Emergent Adverse Events
SPRINT: Treatment-Emergent Adverse Events Safety Population • No specific pattern of treatment-emergent adverse events was identified EDP-235 200mg EDP-235 400mg Placebo (N=77) (N=78) (N=76) n (%) n (%) n (%) Total Number of Treatment-Emergent Adverse Events 1 6 3 Number of Subjects With At Least On
Slide 13: Laboratory Values
SPRINT: Laboratory Values • Laboratory values were generally unremarkable – One subject receiving EDP-235 400mg who had concomitant use of alcohol and acetaminophen, experienced asymptomatic, transient elevation of ALT (grade 4), AST (grade 3) and GGT with normal bilirubin and alkaline phosphatase –
Slide 14: Safety Summary
SPRINT: Safety Summary • EDP-235 was generally safe and well tolerated • Low frequency of adverse events; most were mild in severity – 1.3% in EDP-235 200mg – 6.4% in EDP-235 400mg – 2.6% in Placebo • No serious adverse events or discontinuations due to adverse events • Laboratory values were genera
Slide 15: Pharmacokinetics Summary
SPRINT: Pharmacokinetics Summary • EDP-235 target exposures were achieved and consistent with Phase 1 • Plasma drug levels were 7x and 12x higher than the protein-adjusted EC90 of Omicron for 200mg and 400mg, respectively EDP-235 Predose Concentration on Day 5 (ng/mL) Dose n Mean Median % CV 200mg 6
Slide 16: Total Symptom Score (TSS): Change from Baseline
Total Symptom Score (TSS): Change from Baseline (ITT-c population within 5 days of symptom onset; all 14 FDA defined symptoms1) • Dose-dependent improvement in TSS for all 14 symptoms, with statistical significance achieved at multiple timepoints for EDP-235 400mg compared to placebo 1COVID-19 Sympt
Slide 17: Total Symptom Score (TSS): Change from Baseline
Total Symptom Score (TSS): Change from Baseline (Population within 5 days of symptom onset) SPRINT Phase 2 EDP-235 Shionogi Phase 2b Ensitrelvir* N=190, 14 symptoms N=341, 12 symptoms Study Symptoms: Days: 1 2 3 4 5 6 Respiratory: Cough, Shortness of Breath, Sore Throat, Stuffy or Runny Nose Systemi
Slide 18: Total Symptoms Score (TSS): Change from Baseline
Total Symptoms Score (TSS): Change from Baseline (ITT-c population within 3 days of symptom onset; all 14 FDA defined symptoms1) • Prespecified population enrolled within 3 days of symptom onset showed a statistically significant improvement in TSS for all 14 symptoms for EDP-235 400mg compared to p
Slide 19: Subtotal Symptom Score: Change from Baseline
Subtotal Symptom Score: Change from Baseline (ITT-c population within 3 days of symptom onset; 6 selected symptoms1) • Prespecified population enrolled within 3 days of symptom onset showed a statistically significant improvement in a subset of 6 symptoms for EDP-235 400mg compared to placebo at all
Slide 20: Subtotal Symptom Score: Change from Baseline
Subtotal Symptom Score: Change from Baseline (ITT-c population within 3 days of symptom onset; 6 selected symptoms1) • EDP-235 400mg significantly reduced duration of 6 symptom subset by 2-days compared to placebo in patients enrolled within 3 days of symptom onset 1COVID-19 Selected Symptoms: Respi
Slide 21: Symptom Summary
SPRINT: Symptom Summary • Improvement in 14 symptom TSS for 400mg EDP-235 compared to placebo: – Statistical significance achieved at multiple timepoints in full ITT-c population – Statistical significance at all time points in a prespecified population enrolled within 3 days of symptom onset – Effe
Slide 22: Viral RNA Change from Baseline
SPRINT: Viral RNA Change from Baseline Intent-to-Treat-c Population • No difference between treatment arms and placebo for viral RNA decline (ITTc) • Additional analysis of patients with a baseline viral load greater than 5 log (~50% of patients) – Day 3: viral RNA decline of 0.4 log in both EDP-235
Slide 23: Viral RNA Change from Baseline
SPRINT: Viral RNA Change from Baseline ITT-c population within 3 days of symptom onset and nucleocapsid negative • Seropositive: presence of antibodies to COVID, generated by prior natural infection and/or vaccination (≥1) – Natural infection produces antibodies to both nucleocapsid and spike viral
Slide 24: COVID Trial Placebo Arms: Change in Viral RNA from Baseline
COVID Trial Placebo Arms: Change in Viral RNA from Baseline • Rapid decline in viral RNA from nasal swabs in placebo arm of SPRINT was more robust than in placebo arms from other trials of antivirals published to date, indicating this highly immune population rapidly cleared virus from the nose 1 2
Slide 25: Virology Summary
SPRINT: Virology Summary • High degree of nucleocapsid positivity and rapid decline in viral RNA from nasal swabs in placebo arm indicate a highly immune population that quickly cleared virus from the nose • No difference between treatment arms and placebo for viral RNA decline (ITTc) • Additional a
Slide 26: SPRINT Phase 2 Results: Conclusions
SPRINT Phase 2 Results: Conclusions Safety • EDP-235 was generally safe and well tolerated • Low frequency of adverse events; most were mild in severity – 1.3%, 6.4%, and 2.6% in the EDP-235 200mg, 400mg and placebo arms • No serious adverse events or discontinuations due to adverse events Clinical
Slide 27: Reference Slides
Reference Slides fi: Enanta Pharmaceuticals
Slide 28: Seroprevalence by Natural Infection: CDC US Nationwide Blood Donor Survey
Seroprevalence by Natural Infection CDC US Nationwide Blood Donor Survey Background • Seroprevalence: % of a population who have antibodies to an infectious agent – Indicates past infection and/or vaccination • Natural infection produces antibodies to both Nucleocapsid and Spike viral proteins • Vac
Slide 29: Seroprevalence by Natural Infection (Jul – Sep 2022)
Seroprevalence by Natural Infection (Jul – Sep 2022) CDC US Nationwide Blood Donor Survey Majority of people in the US are seropositive for COVID-19 (as of Sept 2022) through either vaccination, natural infection, or both. Majority of people in the US have been naturally infected with COVID-19 (as o
Slide 30: www.enanta.com
Ei: Enanta Pharmaceuticals www.enanta.com