Slide 1: Virtual KOL Investor Event
FEBRUARY 27, 2025 VIRTUAL KOL INVESTOR EVENT Exhibit 99.1
Slide 2: Forward-Looking Statements and Topline Data Disclaimer
Forward-Looking Statements and Topline Data Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “should,” “expect,” “believe”, “plan” and similar expressions (as well as other words
Slide 3: Agenda and Speakers
Christopher J. Kirk, PhD Chief Executive Officer, Co-founder Zung To Senior Vice President, Head of Clinical Development Rachel Peterson, MD Head of Clinical Immunology Aparna Goel, MD Associate Professor of Medicine, Stanford University Agenda 4:00 PM – 4:05 PM Opening Remarks Christopher J. Kirk,
Slide 4: Zetomipzomib: Immunomodulation Across the Immune System
Zetomipzomib: Immunomodulation Across the Immune System *Some preclinical studies were conducted with ONX 0914, a first-generation selective immunoproteasome inhibitor. Rituxan®/Gazyva® Benlysta® Atacicept IVIg/FcRn Inhibitor Humira®, et al Actemra® Skyrizi®/Stelara® Saphnelo® Orencia® Lupkynis® Xel
Slide 5: Selective Inhibition of the Immunoproteasome Impacts Multiple Drivers of AIH
Selective Inhibition of the Immunoproteasome Impacts Multiple Drivers of Autoimmune Hepatitis (AIH) Zetomipzomib Targets Multiple Immune Effector Cells Involved in AutoimmunityBroad Immunomodulatory Activity • Reduction of multiple inflammatory cytokines from APC • Reduced inflammatory T-cell activi
Slide 6: Update from the PALIZADE Trial for Lupus Nephritis
Rachel Peterson, MD Head of Clinical Immunology UPDATE FROM THE PALIZADE TRIAL FOR LUPUS NEPHRITIS (LN)
Slide 7: Safety and Clinical Activity of Zetomipzomib in the PALIZADE Trial
Safety and Clinical Activity of Zetomipzomib in the PALIZADE Trial • Phase 2b global clinical trial tested 2 zetomipzomib dose levels (30 and 60 mg) vs. placebo in patients with lupus nephritis (LN) and enrolled 84 patients prior to study termination • In patients reaching 6 months of treatment, zet
Slide 8: MISSION Trial Results Supported Design of PALIZADE Study
MISSION Trial Results Supported Design of PALIZADE Study MISSION LN Trial • Open-label Phase 2 trial enrolled 21 participants with active Class III or IV ± V LN in the US, Australia, Eastern Europe and Latin America who had an inadequate response to standard of care • Weekly administration of zetomi
Slide 9: PALIZADE: Phase 2b Placebo-Controlled Trial Design in Active LN
PALIZADE: Phase 2b Placebo-Controlled Trial Evaluating the Efficacy and Safety of Zetomipzomib in Participants with Active LN Primary Endpoint: Proportion of participants achieving CRR (UPCR ≤0.5 and eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease of >20% from baseline eGFR) at week 37. Abbreviatio
Slide 10: Lupus Nephritis Mortality and Steroid Risks
• Nephritis is the most severe manifestation of lupus and in those diagnosed before 40 years of age, there is a 12x higher standardized mortality vs. the general population, with infection as the leading cause of death1 • High dose and intravenous (IV) corticosteroids (induction therapy) are commonl
Slide 11: PALIZADE Enrollment Metrics and Trial Termination
PALIZADE Enrollment Metrics and Trial Termination • 84 patients enrolled at the time of termination (October 2024) with 56% of patients enrolled in APAC region – All enrolled participants were included in the safety analysis – Prior to termination, the discontinuation rate was less than 15% • Indepe
Slide 12: Baseline Co-Morbidities Observed in Fatal Events
Significant Baseline Co-Morbidities Including Infections, Adrenal Insufficiency, and Severe Disease Characteristics Were Observed in Fatal Events • Trial enrolled at 1:1:1 randomization of zetomipzomib (30 and 60 mg) to placebo − Fatalities observed across cohorts: 1 placebo, 2 at 30 mg, 1 at 60 mg*
Slide 13: Baseline Co-Morbidities Observed in Fatal Events (continued)
Significant Baseline Co-Morbidities Including Infections and Adrenal Insufficiency Were Observed in Fatal Events • Patient 3 (30 mg) – Cause of Death: Acute respiratory distress – Baseline feature: Adrenal insufficiency – Day of first dose: C reactive protein (CRP) levels more than 20-fold higher th
Slide 14: Demographic and Baseline Characteristics (Safety Population)
Demographic and Baseline Characteristics (Safety Population) 14 Placebo N=28 n (%) Zetomipzomib 30 mg N=27 n (%) Zetomipzomib 60 mg N=29 n (%) All participants N=84 n (%) Age, mean (SD), years 32.8 (9.1) 31.0 (10.5) 32.5 (9.4) 32.1 (9.6) Female, n (%) 25 (89.3) 25 (92.6) 28 (96.6) 78 (92.9) Race, n
Slide 15: Demographic and Baseline Characteristics, Cont'd
Demographic and Baseline Characteristics (Safety Population), Cont’d 15 Placebo N=28 n (%) Zetomipzomib 30 mg N=27 n (%) Zetomipzomib 60 mg N=29 n (%) All participants N=84 n (%) 24-hour UPCR, mean (SD), mg/mg 3.1 (1.6) 3.7 (2.0) 3.6 (2.1) 3.5 (1.9) SLEDAI-2K, mean (SD) 10.5 (5.0) 11.8 (5.3) 11.7 (5
Slide 16: PALIZADE Safety Overview: Adverse Events
Adverse Events Placebo N=28 n (%) Zetomipzomib 30 mg N=27 n (%) Zetomipzomib 60 mg N=29 n (%) Participants with at least 1 Treatment Emergent Adverse Event (TEAE) 17 (60.7) 23 (85.2) 25 (86.2) Deaths 1 (3.6) 2 (7.4) 1‡ (3.4) Most common TEAEs: Systemic injection reaction (SIR) Injection site reactio
Slide 17: PALIZADE Safety: Infectious TEAEs
PALIZADE Safety: Infectious TEAEs 17 Mean immune cell counts or immunoglobulin levels were not reduced to below lower limit of normal in either zetomipzomib treatment arm Adverse Events Placebo N=28 n (%) Zetomipzomib 30 mg N=27 n (%) Zetomipzomib 60 mg N=29 n (%) Infectious TEAE 13 (46.4) 13 (48.1)
Slide 18: Safety Comparison Across MISSION, PALIZADE and PRESIDIO
Trial/Treatment arm/Dose (N) MISSION Ph 2 Zetomipzomib 60 mg N=21 n (%) PALIZADE Placebo N=28 n (%) PALIZADE Zetomipzomib 30 mg N=27 n (%) PALIZADE Zetomipzomib 60 mg N=29 n (%) Indication Lupus Nephritis Treatment Period (Weeks) 24 52* At least one TEAE, n (%) 21 (100.0) 17 (60.7) 23 (85.2) 25 (86.
Slide 19: Efficacy Analysis Indicates Clinical Activity of Zetomipzomib in LN
*One Class IV patient in the placebo arm was incorrectly classified as Class V. Efficacy Analysis Indicates Clinical Activity of Zetomipzomib in LN • Planned enrollment was 279 patients, including 249 with proliferative LN (Class III or IV ± V) with a planned duration of 52 weeks of treatment and a
Slide 20: Demographic and Baseline Characteristics of Class III/IV ± V LN Patients
Demographic and Baseline Characteristics of Class III/IV ± V LN Patients 20 Placebo N=24* n (%) Zetomipzomib 30 mg N=23 n (%) Zetomipzomib 60 mg N=26 n (%) All participants N=73 n (%) 24-hour UPCR, mean (SD), mg/mg 2.9 (1.5) 3.6 (2.2) 3.5 (2.1) 3.3 (2.0) SLEDAI-2K, mean (SD) 9.9 (4.8) 12.2 (5.6) 12.
Slide 21: Rapid Improvement in Proteinuria in Treatment Evaluable Patients
0 5 10 15 20 25 30 35 40 45 n=21* n=18 n=18 n=14 n=13 n=12 Week 13 Week 25 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 Rapid Improvement in Proteinuria in Treatment Evaluable Patients with Zetomipzomib Data from the PALIZADE clinical trial are preliminary and require further confirmation and analysis. The
Slide 22: Improvements in Serologic Markers of SLE Were Observed
Improvements in Serologic Markers of SLE Were Observed in Both Zetomipzomib Treatment Arms 22 Serologic Biomarkers* Placebo N=25† Zetomipzomib 30 mg N=23 Zetomipzomib 60 mg N=26 Anti-dsDNA Number of patients with elevated anti-dsDNA at baseline Mean % change from baseline at Week 25 21 33.0% 17 -38.
Slide 23: Takeaways From PALIZADE Trial and Impacts on Development Program
Takeaways From PALIZADE Trial and Impacts on Zetomipzomib Development Program 23 • Encouraging clinical activity in patients reaching Week 25, including >40% of patients achieving a UPCR ≤0.5 and improved serologic markers in the patients receiving 60 mg dose of zetomipzomib • Evidence of significan
Slide 24: PORTOLA Clinical Trial Design: Zetomipzomib in Autoimmune Hepatitis
PORTOLA CLINICAL TRIAL DESIGN: ZETOMIPZOMIB IN AUTOIMMUNE HEPATITIS (AIH) Zung To Senior Vice President, Head of Clinical Development
Slide 25: PORTOLA: Placebo-Controlled Trial in Relapsed or Insufficient Responding AIH
PORTOLA: Phase 2 Placebo-Controlled Trial Evaluating the Safety and Efficacy of Zetomipzomib in Relapsed or Insufficient Responding Autoimmune Hepatitis Adult patients with AIH* (N=24) *Clinical diagnosis of AIH + Evidence of active disease despite SOC therapy for ≥ 3 months (insufficient responders
Slide 26: PORTOLA: Key Selection Criteria
PORTOLA: Key Selection Criteria • Clinical diagnosis of AIH and signs of active disease despite standard-of-care therapy for ≥3 months or disease flare after experiencing complete response induced by standard-of-care treatment • Screening ALT values that are 1.25 to 10 times ULN • Liver biopsy resul
Slide 27: PORTOLA: Key Efficacy Endpoints
PORTOLA: Key Efficacy Endpoints Primary efficacy endpoint: • Proportion of patients who achieve complete response (CR) Other efficacy endpoints: • Duration of response and time to response • Proportion of patients who are treatment failures • Proportion of patients who achieve response with successf
Slide 28: PORTOLA: Definitions Related to Biochemical Efficacy Endpoints
PORTOLA: Definitions Related to Biochemical Efficacy Endpoints Normal ALT, AST and IgG values (if IgG is elevated at Baseline) with glucocorticoid dose not higher than starting doseComplete Response (CR) ALT or AST level worsened ≥2x above Baseline and sustained for ≥1 weekTreatment Failure Predniso
Slide 29: PORTOLA Study Status
PORTOLA Study Status • The Independent Data Monitoring Committee (IDMC) overseeing the AIH PORTOLA trial recommended that the trial may proceed without modification following its third scheduled meeting – The IDMC examined safety data from all patients who completed the blinded treatment period and
Slide 30: Next Steps & Closing Remarks
NEXT STEPS & CLOSING REMARKS Christopher J, Kirk, PhD Chief Executive Officer, Co-Founder
Slide 31: Next Steps in the Zetomipzomib Development Program in Autoimmune Hepatitis
Next Steps in the Zetomipzomib Development Program in Autoimmune Hepatitis • AIH is a serious medical condition affecting ~100,000 people in the U.S. alone with limited treatment options and few novel agents in development • Encouraging clinical and serologic activity and biomarker data from clinica
Slide 32: Question & Answer Session
QUESTION & ANSWER SESSION
Slide 33: Contact Us
4000 Shoreline Court Suite 300 South San Francisco, CA 94080 CONTACT US