Slide 1: SUMMIT Trial: Update on Regulatory Strategy
Puma Biotechnology SUMMIT Trial Update on Regulatory Strategy November 6, 2019 Copyright 2019 Puma Biotechnology
Slide 2: Forward-Looking Safe Harbor Statement
Forward-Looking Safe Harbor Statement This presentation contains forward-looking statements, including statements regarding ongoing clinical studies and potential regulatory approvals for NERLYNX®. All statements other than historical facts are forward–looking statements and are based on the current
Slide 3: Current SUMMIT 'Basket' Trial: Study Design
Current SUMMIT ‘Basket’ Trial: Study Design EGFR exon18- Neratinib mutant tumors Lung monotherapy EGFR, HER2 or HER4 mutations (documented by local testing) Cervical Primary endpoint Neratinib • Objective response rate at first post-baseline Salivary gland tumor assessment (ORRfirst) monotherapy Sec
Slide 4: SUMMIT: Hormone Receptor Positive Breast Cancer Cohort
SUMMIT Hormone Receptor Positive Breast Cancer Cohort Copyright 2019 Puma Biotechnology 4
Slide 5: Somatic Mutations in HER2 (ERBB2) in Hormone Receptor Positive Breast Cancer
Somatic Mutations in HER2 (ERBB2) in Hormone Receptor Positive Breast Cancer • Incidence: HER2 somatic mutations - 7-9%, pre-treated ER+ MBC1 • Tumor characteristics: - usually mutually exclusive to HER2 amplifications • Preclinical evidence of oncogenic activity: - constitutive activation of intrac
Slide 6: Maximal Change in Tumor in RECIST Measurable HR positive/HER2-negative, HER2mut MBC Subjects
Maximal Change in Tumor in RECIST Measurable HR positive/HER2-negative, HER2mut MBC Subjects Receiving Neratinib Monotherapy, N+F, or N+F+T and Grouped by Treatment Type and HER2mut Type Copyright 2019 Puma Biotechnology 6
Slide 7: Kaplan Meier Plot of Progression Free Survival for Breast Cancer Cohorts in SUMMIT
Kaplan Meier Plot of Progression Free Survival for Breast Cancer Cohorts in SUMMIT (Efficacy Evaluable Population - HR positive/HER2-negative, HER2mut MBC Cohort and with RECIST Tumor Assessment) Copyright 2019 Puma Biotechnology 7
Slide 8: Proposed Amendment to Breast Cancer Cohort in SUMMIT to Support Accelerated Approval
Proposed Amendment to Breast Cancer Cohort in SUMMIT for HR positive/HER2-negative, HER2mut MBC Cohort to Support Accelerated Approval HER2 mutations (documented by local testing) Primary endpoint • Objective response rate fulvestrant Secondary endpoints • DOR fulvestrant + trastuzumab Randomized 1:
Slide 9: SUMMIT: Cervical Cancer Cohort
SUMMIT Cervical Cancer Cohort Copyright 2019 Puma Biotechnology 9
Slide 10: Characteristics of HER2 Mutant Cervical Cancer
Characteristics of HER2 Mutant Cervical Cancer Incidence Histology Genomics 5% - Metastatic cervical Enriched in adenocarcinomas Most common HER2mut is cancers High occurrence in HPV+ S310 extracellular domain May be negatively prognostic tumors hotspot mutation for survival Usually exclusive to HER
Slide 11: Neratinib Monotherapy Results Presented at SGO Meeting
Neratinib Monotherapy Results Presented at SGO Meeting Copyright 2019 Puma Biotechnology 11
Slide 12: Neratinib Monotherapy Results Presented at SGO Meeting
Neratinib Monotherapy Results Presented at SGO Meeting Copyright 2019 Puma Biotechnology 12
Slide 13: Path Forward
Path Forward ▪ SUMMIT study to enroll additional patients with HER2 mutated cervical cancer ▪ Monotherapy data can be used to file for accelerated approval ▪ Overall response rate ▪ Duration of response ▪ Puma to schedule pre NDA meeting with FDA (anticipated Q4 2020- Q2 2021) Copyright 2019 Puma Bi
Slide 14: HER-Seq (PUMA-NER-9501): HER2 mutation screening protocol
HER-Seq (PUMA-NER-9501): HER2 mutation screening protocol 14
Slide 15: Why HER-Seq?
Why HER-Seq? 1 Rarity of HER2 mutation warrants an active screening program Lack of access to genomic testing 2 • Ex-US regions 3 Liquid biopsy is non-invasive and convenient • Also facilitates repeat sampling 4 Tracked by Puma from clinical presentation to neratinib trial eligibility HER-Seq fills
Slide 16: HER-Seq (PUMA-NER-9501) Study Protocol
HER-Seq (PUMA-NER-9501) Study Protocol HER-Seq: A Blood-based Screening Study to Identify Patients with HER2 Mutations for Enrollment into SUMMIT (initiated December 2018) HER2 mutation positive Consider screening for neratinib treatment CONSENTFORSCREENING protocol PROTOCOL Retest in 3-6 HER2 month
Slide 17: HER-Seq Trial
HER-Seq Trial ▪ Currently open at ~15 sites ▪ Being expanded to other SUMMIT sites ▪ Utilizes proprietary next generation sequencing assay for HER2 mutations ▪ Screening Goals: Breast cancer: Screen 2500 patients Cervical cancer: Screen 1200 patients ▪ Patients with HER2 mutations identified through
Slide 18: SUMMIT Trial Proposed Registration Pathway
SUMMIT Trial Proposed Registration Pathway ✓ Meet with FDA to discuss registration pathway in HR-positive, HER2 negative HER2 mutated breast cancer and HER2 mutated cervical cancer ▪ Modify SUMMIT trial to expand HER2 mutated breast cancer cohort ▪ Continue to enroll HER2 mutated cervical cancer coh