Puma Biotechnology Inc · NASDAQ:PBYI
Puma Biotechnology — Corporate Update (September 2022)
42 slides from Puma Biotechnology's corporate update, Sep 20, 2022
Slide 1: Alisertib Exclusive License Agreement
Puma Biotechnology Alisertib Exclusive License Agreement September 20, 2022 1
Slide 2: Forward-Looking Safe-Harbor Statement
Forward-Looking Safe-Harbor Statement This presentation contains forward-looking statements, including statements regarding the potential indications and development of our drug candidates. All forward-looking statements involve risks and uncertainties that could cause our actual results to differ m
Slide 3: Alisertib (MLN 8237) Aurora Kinase A (AURKA) inhibitor
Alisertib (MLN 8237) Orally Bioavailable Aurora Kinase A Drug Class: Benzazepine (AURKA) inhibitor • Single-agent and combinational clinical activity in solid tumors including hormone receptor-positive breast cancer (HR+ MBC), triple negative breast cancer (TNBC), small cell lung cancer (SCLC), and
Slide 4: Alisertib Mechanism of Action
Alisertib Mechanism of Action Inhibits Aurora Kinase A (AURKA), a serine/threonine protein kinase and transcription factor Leads to: – Disruption of mitotic spindle apparatus assembly – Disruption of chromosome segregation – Inhibition of cell proliferation Highly selective, reversible ATP competiti
Slide 5: Aurora Kinase A and Epithelial to Mesenchymal Transition
Aurora Kinase A and Epithelial to Mesenchymal Transition • AURKA promotes epithelial to mesenchymal transition in breast cancer cells Aurora Kinase A overexpression • AURKA overexpression leads to the transition from an epithelial phenotype to a mesenchymal phenotype, leading to decreased ERα and CD
Slide 6: Prognostic Implications of High Aurora Kinase A Expression
Prognostic Implications of High Aurora Kinase A Expression High AURKA expression is correlated with worse overall survival in multiple solid tumor types Hazard Ratio Hazard Ratio Study/Subgroup Log Hazard Ratio SE Weight IV, Random, 95% CI IV, Random, 95% CI Lung cancer Lung Lung Colorectal cancer M
Slide 7: Alisertib in Breast Cancer Cell Lines
Alisertib in Breast Cancer Cell Lines Alisertib inhibits proliferation and induces G2/M cell cycle arrest, apoptosis, and autophagy Alisertib induces G2/M cell cycle arrest Alisertib induces apoptosis (HR+, HER2-) (TNBC) Alisertib inhibits CDK1 and Cyclin B1 and induces Alisertib induces autophagy p
Slide 8: Synthetic Lethality of AURKA and Rb1
Synthetic Lethality of AURKA and Rb1 Cancers with a hypersensitive spindle assembly checkpoint (SAC) depend on AURKA for mitotic exit and survival1 • Loss of function of Rb1 is a common event in cancer and can emerge as a mechanism of resistance to EGFR, CDK4, and ER-targeted therapies in breast and
Slide 9: RB1-mutant Cell Lines are Sensitive to Alisertib
RB1-mutant Cell Lines are Sensitive to Alisertib Alisertib inhibits Rb1 deficient small-cell lung cancer Alisertib inhibits RB1-mutant TNBC cell line (green) cell line models to a much greater degree than wild- but not when transfected with wild-type RB1 (blue) type Gong X Cancer Discov 2019, Lyu J
Slide 10: AURKA and c-Myc Co-regulate Each Other
AURKA and c-Myc Co-regulate Each Other Nuclear AURKA exerts kinase-independent functions by acting as a transcription factor AURKA c-Myc Genomic instability & • AURKA and c-Myc transcriptionally upregulate each other, tumor development suggesting the existence of a positive feedback loop E2F1 cyclin
Slide 11: Alisertib in c-MYC-amplified Cancer Models
Alisertib in c-MYC-amplified Cancer Models c-Myc, AURKA, and p-AURKA protein levels trend together in a panel of thyroid cancer cell lines Alisertib inhibits tumor growth in xenograft models of thyroid cancer with high c-Myc expression, but not low c- Myc expression Alisertib inhibits growth of cell
Slide 12: Clinical Experience in Small-Cell Lung Cancer
Clinical Experience in Small-Cell Lung Cancer
Slide 13: Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts Study design: • Pts had to have undergone ≤ 2 previous cytotoxic regimens, not including adjuvant or neoadjuvant treatments • Alisertib administration: orally in 21-day cycles at 50 mg twice daily for 7 days followed by a break of
Slide 14: Phase 2 Alisertib Monotherapy - SCLC Response
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts 10 (21%; 95% CI 10–35) of 48 patients had an objective response; all responders achieved a partial response Change in target lesion size and best response (investigator assessed response) PD=progressive disease. SD=stable disease.
Slide 15: Phase 2 Alisertib Monotherapy - SCLC Adverse Events
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts All-cause adverse events in safety evaluable SCLC cohort (n=60) Table adapted from Melichar B Lancet Oncol 2015. Data are number of patients with AE (%) for AEs of any grade in at least 10% of patients overall. NA = not applicable
Slide 16: Grade 3-4 AEs Present in ≥ 10% of SCLC Patients
Grade 3-4 AEs Present in ≥ 10% of SCLC Patients - alisertib monotherapy compared to lurbinectedin monotherapy Alisertib (n=60)1 Lurbinectedin (n=105)2 AE All grade, n (%) Grade 3-4, n (%) All grade, n (%) Grade 3-4, n (%) Neutropenia 27 (45%) 22 (37%) 75 (71%) 48 (46%) Anemia 19 (32%) 10 (17%) 100 (
Slide 17: Randomized Phase 2 Paclitaxel plus Alisertib in Second-Line SCLC: Primary Analysis
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Primary Analysis Study design: • Patients with relapsed or refractory SCLC stratified by relapse type (sensitive vs resistant or refractory) • Randomized 1:1 to alisertib + paclitaxel or placebo + p
Slide 18: Paclitaxel plus Alisertib SCLC: c-Myc Biomarker Analysis
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Correlative Biomarker Analysis Improved PFS observed among patients positive versus negative for c-Myc expression PFS in patients positive for c-Myc expression Median PFS 4.64 mo w/ paclitaxel + ali
Slide 19: Paclitaxel plus Alisertib SCLC: Cell Cycle Gene Alterations
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Correlative Biomarker Analysis Improved outcomes among pts with genetic alternations in cell cycle genes CDK6, RBL1, RBL2, and RB1 (collectively referred to as “mutant”) Owonikoko J Thorac Oncol 202
Slide 20: Paclitaxel plus Alisertib SCLC: Safety
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Safety AE, adverse event Owonikoko J Thorac Oncol 2020 20
Slide 21: Clinical Studies of Alisertib in Breast Cancer
Clinical Studies of Alisertib in Breast Cancer
Slide 22: Phase 2 Alisertib Monotherapy - Breast Cancer Cohorts
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts Study design: • Pts had to have undergone ≤ 2 previous cytotoxic regimens, not including adjuvant or neoadjuvant treatments • Alisertib administered orally in 21-day cycles at 50 mg twice daily for 7 days followed by a br
Slide 23: Phase 2 Alisertib Monotherapy - Breast Cancer Response
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts 9 / 49 patients (18%; 95% CI 9–32) had an objective response; all responders achieved a partial response Change in target lesion size and best response (investigator assessed response) PD=progressive disease. SD=stable di
Slide 24: Phase 2 Alisertib Monotherapy - Breast Cancer Adverse Events
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts All-cause adverse events in safety evaluable breast cancer cohort (n=53) Table adapted from Melichar B Lancet Oncol 2015. Data are number of patients with AE (%) for AEs of any grade in at least 10% of patients overall. N
Slide 25: Phase 2 Alisertib + Fulvestrant vs Alisertib in HR+ Breast Cancer
Phase 2 Randomized Trial of Alisertib + Fulvestrant vs Alisertib in Advanced HR+ Breast Cancer Patients (n=96) Regimen & Schedule Patients Inclusion (n=96) Criteria • Alisertib + Fulvestrant: Alisertib 50 mg PO • Post-menopausal women BID on days 1-3, 8-10, 15-17 q 28-day cycle • Histologically-prov
Slide 26: Phase 2 Alisertib + Fulvestrant vs Alisertib in HR+ Breast Cancer
Phase 2 Randomized Trial of Alisertib + Fulvestrant vs Alisertib in Advanced HR+ Breast Cancer Haddad TC SABCS 2020 PD2-05 26
Slide 27: Paclitaxel + Alisertib vs Paclitaxel - Efficacy in ER+/HER2- MBC
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Efficacy in ER+/HER2- MBC Cohort PFS in ER+/HER2- ITT Study design: Median PFS: 10.2 (3.8-15.7) mo for • Patients with ER+/HER2- or triple negative metastatic paclitaxel + alisertib vs 7.1 (3.8-10.6) breast cancer stratified by
Slide 28: Efficacy in ER+/HER2- MBC Pretreated with Palbociclib
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Efficacy in ER+/HER2- MBC Cohort Pretreated with Palbociclib Efficacy in patients pretreated with palbociclib (n=30) • Median PFS: 13.9 (5.6-15.6) mo (14 pts) w/ paclitaxel + alisertib vs 5.6 (3.0-10.6) mo (16 pts) w/ paclitaxe
Slide 29: Rb1 Loss and c-Myc Upregulation Correlate with Palbociclib Resistance
Rb1 Loss and c-Myc Upregulation Correlate with Palbociclib Resistance Both RB1 loss and MYC upregulation were observed in palbociclib-resistant HR+ breast cancer cell lines, supporting a role for alisertib in this setting RB1 Loss C-Myc Upregulation Pandey Cancers 2020 29
Slide 30: Paclitaxel + Alisertib vs Paclitaxel - Efficacy in TNBC Cohort
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Efficacy in TNBC Cohort PFS in TNBC ITT Median PFS 9.6 (6.1-22.6) mo w/ paclitaxel + alisertib vs 5.7 (2.9-8.2) mo w/ paclitaxel HR = 0.35, 95% CI: 0.14-0.89, p=0.022 Median OS: 16 (9.6-34.0) mo w/ paclitaxel + alisertib vs 12.
Slide 31: Paclitaxel + Alisertib vs Paclitaxel - Safety in MBC
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Safety for ER+/HER2- MBC & TNBC (both cohorts combined) One pt receiving paclitaxel + alisertib died of sepsis O’Shaughnessy J JAMA Netw Open 2021 31
Slide 32: Summary of Alisertib Efficacy in Metastatic Breast Cancer
Summary of Alisertib Efficacy in Metastatic Breast Cancer Tumor Type Active Regimen Comparator Reference Regimen (N) N Median PFS Regimen (N) N Median PFS (mo, 95% CI) (mo, 95% CI) HR+/HER2- alisertib 50 mg BID1 26 7.9 (4.2-12.2) NA NA Melichar B Lancet Oncol 2015 ER+/HER2- alisertib 50 mg BID2 45 5
Slide 33: Study-related Neutropenia in Metastatic Breast Cancer
Study-related Neutropenia in Metastatic Breast Cancer - Alisertib compared to other agents Regimen All-grade Neutropenia (%) Grade 3/4 Neutropenia (%) Febrile Neutropenia (%) Alisertib monotherapy 50 mg BID1 63%1 57%1 4%1 Alisertib monotherapy 50 mg BID2 Not reported2 42%2 Not reported2 Alisertib 50
Slide 34: Overview of Alisertib Clinical Development Plan
Overview of Alisertib Clinical Development Plan Target Patient Population(s) Rationale for Selected Indication Potential Biomarker-defined Subgroups HR+/HER2- metastatic breast • Prior Clinical Data cancer (MBC) • Puma experience in breast cancer • c-Myc amplification Small Cell Lung Cancer • Prior
Slide 35: Clinical Milestones
Clinical Milestones Biomarker data from Phase 2 randomized trial of alisertib plus fulvestrant vs alisertib alone in hormone receptor-positive, HER2-negative advanced breast cancer (Q4 2022) Biomarker data from Phase 2 randomized trial of paclitaxel plus alisertib vs paclitaxel alone in patients wit
Slide 36: Treatment Landscape
Treatment Landscape
Slide 37: HR-positive HER2-negative Breast Cancer in US
HR-positive HER2-negative Breast Cancer in US US Incidence: ~40,000 patients1 US Deaths: ~29,7702 Estimated approximately 50% of HR-positive breast cancer patients have elevated c-Myc levels Estimated approximately 2%-9% of HR-positive HER2-negative patients have RB1 mutations at the time of the dev
Slide 38: Proposed Schema of Management of HR+/HER2- MBC
Proposed Schema of Management of HR+/HER2- MBC HR+ / HER2- HR+ / HER2- Biomarker identified, PIK3CA WT Alisertib plus fulvestrant Biomarker identified Alisertib plus paclitaxel 38
Slide 39: Small Cell Lung Cancer Market in US
Small Cell Lung Cancer Market in US US Incidence: ~31,000-33,000 patients1 US Deaths: ~17,000-18,0002 Estimated approximately 72% small cell lung patients have elevated c-Myc levels3 Estimated approximately 60-80% of small cell lung cancer patients have RB1 mutations3 1. Assumes 236,740 newly diagno
Slide 40: Limited Agents Currently Under P2/3 Development for SCLC
Limited Agents Currently Under P2/3 Development for SCLC Most recent immunotherapies and ADCs for the treatment of SCLC have either failed their confirmatory study or failed to show improvement in OS (e.g., nivolumab, ipilimumab, pembrolizumab, rovalpituzumab tesirine, tremelimumab) Only 2 immunothe
Slide 41: Licensing Agreement Terms
Licensing Agreement Terms $7 million up front $287.3 million upon Puma’s achievement of certain regulatory and commercial milestones – No milestone payments during clinical development Tiered royalty payments for any sales of alisertib No Impact to Puma’s R&D budget or expense guidance for 2022 41
Slide 42: Alisertib Summary
Alisertib Summary Clinical activity demonstrated in Phase 2 clinical trials in HR-positive, HER2-negative breast cancer, Triple Negative Breast Cancer (TNBC), Small Cell Lung Cancer (SCLC) Synergy with Puma’s existing Nerlynx franchise Large potential addressable market Differentiated mechanism of a
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