Puma Biotechnology Inc · NASDAQ:PBYI
Puma Biotechnology — Investor Presentation (January 2022)
52 slides from Puma Biotechnology's investor presentation, January 2022
Slide 1: Puma Biotechnology Corporate Presentation
Puma Biotechnology Corporate Presentation January 2022
Slide 2: Forward-Looking Safe-Harbor Statement
Forward-Looking Safe-Harbor Statement This presentation contains forward-looking statements, including statements regarding commercialization of NERLYNX® and the potential indications and development of our drug candidates. All forward-looking statements involve risks and uncertainties that could ca
Slide 3: Product Pipeline
Product Pipeline Neratinib across the breast cancer therapy spectrum Phase I Phase II Phase III Registration Approval HER2+ Breast Cancer Extended adjuvant ExteNET (Phase III HER2+ EBC*) Neratinib monotherapy CONTROL Metastatic NALA (Phase III 3rd Line HER2+ MBC**) Monotherapy or combo therapy FB-10
Slide 4: PUMA's Pharmacy and Distributor Network
PUMA’s Pharmacy and Distributor Network Hub Services Specialty Pharmacy Network (SP) Acaria Health Accredo CVS ONCO 360 Patients Optum / Biologics Diplomat Sites of Care Specialty Distributor Network (SD) Academic Hospitals McKesson Community Hospitals ASD/Oncology Supply Physician Practices Cardina
Slide 5: ~$43 Million net NERLYNX revenue in Q3'21
~$43 Million net NERLYNX revenue in Q3’21 Quarterly Net Revenue (in $MM) 61.1 58.7 52.6 53.8 53.5 50.8 50.0 48.6 48.8 49.3 48.9 45.6 45.8 43.4 36.0 20.1 6.1 Copyright 2022 Puma Biotechnology 5
Slide 6: 3,454 Ex-factory bottles were sold in Q4'21
3,454 Ex-factory bottles were sold in Q4’21 Bottles Sold (SP + SD) by Quarter 5,538 4,936 4,935 4,799 4,791 4,696 4,452 4,035 3,728 3,611 3,517 3,585 3,354 3,454 3,247 2,947 2,137 675 Q4’21 bottle count includes ~345 additional bottles due to increase in inventory Includes Commercial SP and SD Copyr
Slide 7: Field Structure Reduced to Adapt to Virtual Environment
Field Structure Reduced to Adapt to Virtual Environment Prior Field Structure Current Field Structure VP, Sales VP, Sales Area Directors (2 total) Regional Business Director (7 total) Regional Manager (10 total) Strategic Account Clinical Specialists Managers (38 total) (4 total) Clinical Specialist
Slide 8: ~57% of patients in Q3'21 started at a reduced dose
~57% of patients in Q3’21 started at a reduced dose* ** % of Patients starting at reduced dose 56.5%** 42.4% 37.7% 38.7% 32.8% 30.4% 30.8% 28.4% 19.0% 12.0% 10.7% 6.3% 6.8% 2.9% 3.8% 1.8% 2.5% *Reduced dose defined as fewer than 6 pills per day ** FDA approved dose-escalation label supplement in Jun
Slide 9: Rest of World Partnerships – Timelines
Rest of World Partnerships – Timelines Region Partner Regulatory Approvals Commercial Launches • 2019 – Ext. Adj. in Australia, Singapore • 2020 – Singapore Australia / SE Asia • 2020 – Ext. Adj. in Brunei, Malaysia, New • Q2 2021 – Malaysia Zealand • Q3 / Q4 2021 – Brunei, New Zealand Israel • 2020
Slide 10: CONTROL Study Design
CONTROL Study Design Phase 2 trial to characterize the incidence and severity of diarrhea in patients with HER2+ early breast cancer treated with neratinib and loperamide prophylaxis ± an investigational agent 1 year of therapy HER2+ early BC Neratinib 240 mg/day (endocrine therapy as indicated) • R
Slide 11: CONTROL Population and Treatment Flowchart
CONTROL Population Study Flowchart Stage 1–3c HER2+ breast cancer Trastuzumab-based adjuvant therapy completed within 1 year Sequential investigational cohorts Cohort Loperamide cohort Budesonide cohort Colestipol cohort Colestipol cohort Dose-escalation (Original protocol) cohort Neratinib Neratini
Slide 12: CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea Loperamide prophylaxis reduces incidence and severity of diarrhea CONTROL1 ExteNET3 Neratinib dose Budesonide Colestipol Colestipol + escalation + Loperamide Loperamide + loperamide + loperamide loperamide prn loperamide prn prn (n=137) (n=64
Slide 13: NERLYNX Extended Adjuvant HER2+ Breast Cancer Market Size
NERLYNX® Extended Adjuvant HER2+ Breast Cancer Market Size Approximately 28,300 patients (US) with early stage HER2+ breast cancer treated with adjuvant treatment1 Approximately 6,000 patients (US) with HR positive early stage HER2+ breast cancer and no pathological complete response to neoadjuvant
Slide 14: Phase III Trial – Third-Line HER2+ MBC (NALA) Study Design
Phase III Trial – Third-Line HER2+ MBC (NALA) Study Design 3rd- or later-line therapy for patients with HER2+ mBC Patients with asymptomatic CNS metastatic disease are eligible Obtained SPA from FDA and review by EMA in February 2013 1:1 RANDOMIZATION Neratinib + Capecitabine PD HER2+ mBC Received ≥
Slide 15: NALA Study Results: Centrally Confirmed PFS
Phase III Trial – Third-Line HER2+ MBC (NALA): Study Results Centrally Confirmed PFS (co-primary endpoint) 1.0 Hazard ratio Log-rank 0.9 (95% CI) p-value 0.8 Neratinib + Capecitabine 0.76 (0.63–0.93) 0.0059 Lapatinib + Capecitabine 0.7 PFS probability 0.6 0.5 47% 0.4 38% 0.3 29% 0.2 16% 0.1 15% 7% 0
Slide 16: NALA Study Results: Restricted Means PFS
Phase III Trial – Third-Line HER2+ MBC (NALA): Study Results Prespecified restricted means analysis – PFS 1.0 Mean PFS 0.9 (months) p-value 0.8 Neratinib + Capecitabine 8.8 0.0003 Lapatinib + Capecitabine 6.6 0.7 PFS probability 0.6 Restriction: 24 months 0.5 0.4 0.3 0.2 2.2 months 0.1 0 0 3 6 9 12
Slide 17: NALA Study Results: Overall Survival
Phase III Trial – Third-Line HER2+ MBC (NALA): Study Results OS (co-primary endpoint) 1.0 Mean OS Hazard ratio Log-rank 0.9 (months) (95% CI) p-value Neratinib + Capecitabine 24.0 0.8 0.88 (0.72–1.07) 0.2086 Lapatinib + Capecitabine 22.2 0.7 OS probability 0.6 Restriction: 48 months 0.5 0.4 0.3 0.2
Slide 18: NALA: Time to Intervention for CNS Metastases
Phase III Trial – Third-Line HER2+ MBC (NALA): Study Results Time to intervention for CNS metastases 100 Neratinib + Capecitabine Lapatinib + Capecitabine 90 Intervention (n=55/307) (n=75/314) Radiation therapy 11% 15% 80 Surgery/procedure 2% 3% Cumulative incidence (%) 70 Anticancer medication 1% 1
Slide 19: Third-Line HER2+ MBC Market Size
Third-Line HER2+ MBC Market Size Approximately 6,400 patients (US) with third-line HER2+ metastatic breast cancer and 4,700 patients (US) with fourth-line HER2+ metastatic breast cancer1 1Roche epidemiology slides 09/18 Copyright 2022 Puma Biotechnology 19
Slide 20: FB-10 – Phase I/II Trial of Kadcyla + Neratinib
FB-10 – Phase I/II Trial of Kadcyla (T-DM1) + Neratinib HER2+ MBC Neratinib Dose level 1: 120 mg/d Must have received prior Dose level 2: 160 mg/d anti-HER2-based therapy Dose level 3: 200 mg/d with pertuzumab for mBC Dose level 4: 240 mg/d No prior T-DM1 or HER2 T-DM1 TKI allowed 3.6 mg/kg IV d1 Q3
Slide 21: FB-10 – Phase I/II Trial of Kadcyla + Neratinib Results
FB-10 – Phase I/II Trial of Kadcyla (T-DM1) + Neratinib 240 * 240 *Off TX, AE/withdrawn + On treatment 200 200 200 200 * 200 ORR (CR/PR): 12 of 20 (60%) 160 Dose mg/d 160 CR 160 PR 160 SD 160 PD 160 160 * 160 + 120 * 120 120 120 * 120 0 100 200 300 400 500 600 700 800 Days on Treatment Copyright 202
Slide 22: TBCRC 022: Phase II Trial in HER2+ Breast Cancer with Brain Metastases
TBCRC 022: Phase II Trial of HKI-272 (Neratinib) for Patients with HER2+ Breast Cancer and Brain Metastases Progressive Cohort 1 (n = 40 pts) (Treat until PD or toxicity; if non-CNS PD, Neratinib (240 mg/day) brain mets trastuzumab may be added) Craniotomy candidates Cohort 2 (n = 5 pts) Neratinib (
Slide 23: TBCRC-022 Cohort 3a CNS Response
TBCRC-022 Cohort 3a CNS Response Best Volumetric Response (n=31)* Best Volumetric CNS response (n=31 evaluable pts) 100 % reduction in volume of CNS lesions 80 CNS ORR = 49% (95% CI 32–66%) 60 40 20 0 -20 -40 -60 -80 18 responses -100 Copyright 2022 Puma Biotechnology * ASCO 2017 23
Slide 24: Neratinib Included in NCCN Guidelines for CNS Metastases
Neratinib Recently Included as a Treatment Option for Recurrent Breast Cancer CNS Metastases By NCCN® Guidelines1 Guidelines updated March 2020 Category 2A: Category 2B: Neratinib + Capecitabine Neratinib + Paclitaxel TBCRC 0222 NEfERT-T3,4 A Phase II Trial of Neratinib and Randomized, Multi-Center,
Slide 25: Current SUMMIT 'Basket' Trial: Study Design
Current SUMMIT ‘Basket’ Trial: Study Design EGFR exon18- Neratinib EGFR, HER2 or HER4 mutations mutant tumors Lung monotherapy (documented by local testing) Cervical Primary endpoint • Objective response rate at first post-baseline tumor assessment (ORRfirst) Neratinib Salivary gland Secondary endpo
Slide 26: SUMMIT: Breast Cancer Cohort
SUMMIT Breast Cancer Cohort
Slide 27: Characteristics of HER2-mutant breast cancer
Characteristics of HER2-mutant breast cancer1–8 Incidence Histology Genomics 2% Primary breast cancers Predominantly in hormone Occur across multiple domains receptor-positive (luminal-A) of the protein (KD, ECD, TMD) 2–4% MBC and HER2-negative tumors Most common variants: 8% ER+ MBC Represented in
Slide 28: Current SUMMIT breast cancer cohorts
Current SUMMIT breast cancer cohorts • Added inclusion criteria for HR+ cohort to reflect current standard of care: prior CDK4/6 inhibitor therapy HER2-mutant MBC MBC cohort Treatment assignment HR+/HER2-negative MBC Neratinib + Fulvestrant (with prior CDK4/6i) + Trastuzumab Non-randomized Neratinib
Slide 29: HR+ non-randomized N+F+T w prior CDK4/6i: Efficacy findings
HR+ non-randomized N+F+T w prior CDK4/6i: Efficacy findings Non-randomized Characteristics (N+F+T, n=26) Objective response (confirmed CR/PR)a, n (%) 12 (46.2) CR 0 PR 12 (46.2) Best overall response 15 (57.7) (confirmed or unconfirmed PR or CR), n (%) Median DORb, months (95% CI) 14.4 (6.4–NE) Clin
Slide 30: HR+ randomized cohorts: Efficacy findings
HR+ randomized cohorts: Efficacy findings Neratinib appears to be critical for inhibition of HER2 mutations Randomized cohort Characteristics (N+F+T, n=7) (F+T, n=7) (F, n=7) Objective response (confirmed CR/PR)a, n (%) 2 (28.6) 0 0 CR 1 (14.3) 0 0 PR 1 (14.3) 0 0 Best overall response 3 (42.9) 0 0
Slide 31: TNBC cohort: baseline characteristics and efficacy
TNBC cohort: baseline characteristics and efficacy TNBC TNBC Baseline characteristics (N+T, n=18) Efficacy (N+T, n=18) ECOG performance status, n (%) Objective response (confirmed CR/PR)a, n (%) 6 (33.3) 0 9 (50.0) CR 1 (5.6) 1 9 (50.0) PR 5 (27.8) Best overall response Histological type, n (%) 7 (3
Slide 32: Change in tumor size (target lesion) and characteristics
Change in tumor size (target lesion) and characteristics Non-randomized Randomized Randomized Randomized HR+ HR+ HR+ HR+ Prior CDK4/6i Prior CDK4/6i Prior CDK4/6i Prior CDK4/6i TNBC N+F+T N+F+T F+T F N+T Best overall response CR PR SD 100 HER2 mutation category PD Kinase domain hotspot Kinase domain
Slide 33: Change in tumor size (target lesion) and characteristics
Change in tumor size (target lesion) and characteristics Non-randomized Randomized Randomized Randomized HR+ HR+ HR+ HR+ Prior CDK4/6i Prior CDK4/6i Prior CDK4/6i Prior CDK4/6i TNBC N+F+T N+F+T F+T F N+T Best overall response CR PR SD 100 HER2 mutation category PD Kinase domain hotspot Kinase domain
Slide 34: Conclusions/Next Steps
Conclusions/Next Steps The combination of N+F+T demonstrated encouraging clinical activity in patients with heavily pretreated HR+, HER2-negative, HER2-mutant MBC who had previously received CDK4/6: – Objective response rate 42.4% (1 CR and 13 PRs); median PFS 7.0 months, n=33 Following guidance fro
Slide 35: SUMMIT: Cervical Cancer Cohort
SUMMIT Cervical Cancer Cohort
Slide 36: Characteristics of HER2-Mutant Cervical Cancer
Characteristics of HER2-Mutant Cervical Cancer Incidence Histology Genomics 5% metastatic cervical cancers Enriched in adenocarcinomas Most common HER2mut is S310 May be negatively prognostic for High occurrence in HPV+ tumors extracellular domain hotspot mutation survival Usually exclusive to HER2
Slide 37: Neratinib Monotherapy Results Published in Gynecologic Oncology
Neratinib Monotherapy Results Published in Gynecologic Oncology Best response Histology PIK3CA co-mutation KRAS co-mutation TP53 co-mutation Gynecologic Oncology, 2020 Copyright 2022 Puma Biotechnology 37
Slide 38: Neratinib Monotherapy Results Published in Gynecologic Oncology
Neratinib Monotherapy Results Published in Gynecologic Oncology Gynecologic Oncology, 2020 Copyright 2022 Puma Biotechnology 38
Slide 39: SUMMIT Basket Trial: EGFR exon 18 lung cancer cohort update
SUMMIT (PUMA-NER-5201) Basket Trial EGFR exon 18 lung cancer cohort update
Slide 40: EGFR Exon 18 Lung Cohort: Baseline Demographics
EGFR Exon 18-Mutant Lung Cancer Cohort Receiving Neratinib Monotherapy: Baseline Demographics and Patient Characteristics Patient characteristics Safety/Efficacy evaluable patients (n=11) Median (range), years 67 (56-83) <65 years, n (%) 4 (36) ≥65 years, n (%) 7 (64) Gender, n (%) Female 5 (45) Mal
Slide 41: EGFR Exon 18 Lung Cohort: Efficacy Summary
EGFR Exon 18-Mutant Lung Cancer Cohort Receiving Neratinib Monotherapy: Efficacy Summary Efficacy evaluable patients TKI Pre-Treated Parameter (n=11) (n=10) Objective response (confirmed),a n 4 4 CR 0 0 PR 4 4 Objective response rate, % (95% CI) 36 (11–69) 40 (12–74) Best overall response, n 6 6 CR
Slide 42: EGFR Exon 18 Cohort: Treatment Duration, Best Response and Tumor Change
EGFR Exon 18-Mutant Lung Cancer Cohort Receiving Neratinib Monotherapy: Treatment Duration, Best Response and Best Change in Tumor 100 0902 (G719A) 0711 (G719X) 7902 (G719C; E709K) 50 0758 (G719X) % Change in Tumor 0712 (G719X; S768I) 1910 (G719C; S768I; T790M) 0 7904 (G719X; S768I) 1900 (G719A; E70
Slide 43: Historical Response Rates of Afatinib in EGFR Exon 18 NSCLC
Historical Response Rates of Afatinib in NSCLC Patients With EGFR Exon 18 Mutations (G719X) TKI-naïve patients TKI-pre-treated patients Yang et al. Journal of Thoracic Oncology (2020) 15(5): 803-815 Copyright 2022 Puma Biotechnology 43
Slide 44: Milestones for Neratinib in EGFR Exon 18-Mutant Lung Cancer
Milestones for Neratinib in EGFR Exon 18-Mutant Lung Cancer Cohort in SUMMIT Study The success criteria for the 1st stage and 2nd stage of the Simon’s 2-stage design has been met – Enrollment in the 2nd stage is continuing up to a total of 30 patients Anticipate presentation of additional data from
Slide 45: Puma – Expected Milestones
Puma – Expected Milestones Conduct pre-NDA meeting with the FDA to discuss accelerated approval of neratinib in HER2-mutated HR+ breast cancer (H1 2022) Report Phase II data from cohort of patients in SUMMIT basket trial of neratinib in non-small cell lung cancer patients with EGFR exon 18 mutations
Slide 46: Intellectual Property
Intellectual Property Composition of matter patent issued (expires 2030) – Extended by USPTO in November 2021 per Hatch/Waxman Use in the treatment of cancer issued (expires 2025) Two polymorph patents issued (both expire 2028) Combination with capecitabine (expires 2031) Use in extended adjuvant br
Slide 47: Intellectual Property on EGFR T790M Mutations
Intellectual Property on EGFR T790M Mutations Issued claims in Europe, Asia, Australia (expires 2026) – Possibility to extend up to 5 years Issued claims in United States (expires 2026) Patent claims upheld after European Opposition Hearing (February 2014) Patent claims upheld after Appeal to Europe
Slide 48: Experienced Management Team
Experienced Management Team Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder – Chief Executive Officer, President, Founder, Cougar Biotechnology Jeff Ludwig Chief Commercial Officer – Eli Lilly, Astellas, Amgen Maximo F. Nougues Chief Financial Officer – Getinge AB, Boston Scie
Slide 49: Board of Directors
Board of Directors Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder, Puma Biotechnology, Inc. Allison Dorval CFO, Verve Therapeutics; Former CFO Voyager Therapeutics, Inc.; VP and Controller, Juniper Pharmaceuticals, Inc. Michael Miller Former EVP U.S. Commercial, Jazz Pharmace
Slide 50: Puma Biotechnology – Financial
Puma Biotechnology – Financial Currently trading on NASDAQ: PBYI Cash, cash equivalents and marketable securities at September 30, 2021: ~$87.5 million Cash burn in Q3 2021: ~$21.4million Note purchase agreement (July 2021) – Fund managed by Athyrium Capital Management – New agreement for $125 milli
Slide 51: Company Highlights
Company Highlights NERLYNX® – first HER2-directed drug approved by FDA for extended adjuvant treatment of early-stage HER2+ breast cancer in patients who have received prior trastuzumab NERLYNX® – first HER2-directed tyrosine kinase inhibitor approved in both early stage and metastatic HER2+ breast
Slide 52: Puma Biotechnology
Puma Biotechnology Corporate Presentation January 2022
Puma Biotechnology — Investor Presentation (January 2022) on 6ix