1100 W 3 Puma - Jefferies Group · 2015. 6. 11. · Over 3,000 patients treated with neratinib...

Puma Biotechnology

Copyright 2015 Puma Biotechnology

Jefferies 2015 Healthcare Conference

June 2015


This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the anticipated timing of and plans with respect to our regulatory filings, the potential indications of our drug candidates and the development of our drug candidates, including, but not limited to, the anticipated timing for the commencement and completion of various clinical trials and announcement of data relative to these trials. These statements are often, but not always, made through the use of words or phrases such as `ànticipates,'' `èxpects,'' ``plans,'' ``believes,'' `ìntends,'' and similar words or phrases. All forward–looking statements included in this presentation involve risks and uncertainties that could cause our actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors, which include, but are not limited to, the fact that we have no product revenue and no products approved for marketing; our dependence on our lead product candidate PB272, which is still under development and may never receive regulatory approval; the challenges associated with conducting and enrolling clinical trials; the risk that results of clinical trials may not support our drug candidate claims; even if approved, the risk that physicians and patients may not accept or use our products; our reliance on third parties to conduct our clinical trials and to formulate and manufacture our drug candidates; our dependence on licensed intellectual property; and the other risk factors disclosed in our periodic reports filed with the Securities and Exchange Commission from time to time, including our Annual Report on Form 10-K for the fiscal year ended December 31, 2014. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. We assume no obligation to update these forward-looking statements except as required by law.

Forward-Looking Safe Harbor Statement

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Company Highlights In-licensing driven business model – mitigates R&D risk

PB272 (neratinib)- clinical stage candidate targeting multiple oncology indications

HER2+ Metastatic Breast Cancer HER2+ Metastatic Breast Cancer with Brain Metastases HER2+ Neoadjuvant Breast Cancer HER2+ Adjuvant Breast Cancer HER2 Mutated Non-Small Cell Lung Cancer HER2 Mutated Breast Cancer HER2 Mutated Solid Tumors

Retained commercial rights to PB272

Strong Phase II and Phase III data for PB272 (single agent and in combination with chemotherapy)

Potential for multiple clinical trial readouts over next 6-12 months 3


Product Pipeline Drug Indication Pre-clinical I II III Registration

PB272 Single agent

Adjuvant Breast Cancer

PB272 Combination w/ Xeloda

Metastatic Breast Cancer

PB272 Combination w/ Paclitaxel


PB272 Combination w/ Torisel


PB272 Single agent/ combination

Metastatic Breast Cancer with Brain Mets

PB272 Combination w/ chemotherapy

Neoadjuvant Breast Cancer

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Product Pipeline (cont’d.) Drug Indication Pre-clinical I II III Registration PB272 (oral) Combination and Single agent

HER2 Mutated NSCLC

PB272 (oral) Single agent

HER2 Mutated Breast Cancer

PB272 (oral) Single agent

HER2 Mutated Solid Tumors

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Neratinib (PB272) Safety

Over 3,000 patients treated with neratinib prior to Puma licensing drug

Neratinib - Main Grade 3/4 AE-Diarrhea (previously ~30% Grade 3/4)

Typically a first cycle effect (first 28 days) Historically treated with antidiarrheal agents (loperamide)

after diarrhea occurs Treated with dose reductions after diarrhea occurs

Puma introduced diarrhea prophylaxis with loperamide Given Day 1 with neratinib dose for first cycle High dose of loperamide initially (8-16mg) Taper dose during cycle 1

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Neratinib (PB272) Grade 3 Diarrhea Rates Without Prophylaxis with Loperamide

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Neratinib (PB272) Diarrhea Prophylaxis with Loperamide

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- HER2 positive breast cancer

- Lymph node negative, positive or residual invasive disease after

neoadjuvant treatment

Ran

dom

ize

1:1

Neratinib (1 year)

2800 patients total

Placebo (1 year)

- Completed 1 year prior adjuvant treatment with trastuzumab prior to

randomization

Primary endpoint: Invasive Disease Free Survival (IDFS) Secondary endpoints: Disease Free Survival Including Ductal Carcinoma in Situ (DFS-DCIS), Time to Distant Recurrence, Incidence of CNS recurrence, Overall Survival No loperamide prophylaxis used to prevent neratinib related diarrhea

ExteNET Trial - HER2 Positive Extended Adjuvant Breast Cancer

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ExteNET-HER2+ Extended Adjuvant Breast Cancer Announced trial hit primary endpoint (July 2014)

33% Reduction in Risk of Disease Free Survival (DFS) Hazard ratio: 0.67 p= 0.009

37% Reduction in Risk of Disease Free Survival including DCIS (DFS-DCIS)

Hazard ratio: 0.63 p = 0.002

Presentation and publication of data in 2015

Anticipate Filing for Regulatory Approval (US/Europe) in Q1 2016

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Copyright 2012 Puma Biotechnology Copyright 2014 Puma Biotechnology Copyright 2014 Puma Biotechnology Copyright 2014 Puma Biotechnology

Kaplan-Meier Estimates of Disease Free Survival ITT Population

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Kaplan-Meier Estimates of DFS Centrally Confirmed HER2 Positive Population

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Comparator Adjuvant Registration Studies Study

Design

DFS

DFS-DCIS

Reduction in risk of disease

recurrence

Absolute reduction in risk of disease

recurrence HR p HR p DFS DFS-

DCIS DFS DFS-

DCIS ‘Extended’ adjuvant HER2+ BC ExteNET Local HER2 0.67* 0.009 0.63 0.002 33% 37% 2.3%

(24 mo) 2.9%

(24 mo) Central HER2 0.51 0.002 0.49 <0.001 49% 51%

4.1%

(24 mo) 4.5%

(24 mo) HERA 2 years

Central HER2 0.99 0.86 ND 2.4% (24 mo)

Extended adjuvant HR+ EBC post tamoxifen Rx (HER2+ and HER2-) MA.17 Letrozole

(post 5yrs tamoxifen)

0.62* <0.001 2.8% (24 mo)

Adjuvant treatment HR+ EBC (HER2+ and HER2-) Arimidex 5 yrs Rx 0.83 0.0049 17% 2.8%

(5 yrs)

Aromasin 2-3 yrs tamoxifen → Aromasin

0.69 <0.001 31% 3.4% (5 yrs)

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Kaplan-Meier Estimates of DFS Hormone Receptor Positive Patients ITT Population

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Crosstalk between ER and HER2 Signaling Pathways: Rationale for Dual Neratinib and Hormonal Therapy

Source: Prat and Baselga. Nat Clin Practice Onc 2008;5:531–42

*Inhibition of cross talk not seen in extended adjuvant trials of Herceptin (HERA 2 year) or Tykerb (TEACH)


Phase II Trial of Neratinib in HER2+ Extended Adjuvant Breast Cancer using Loperamide

Prophylaxis Open label Phase II trial of neratinib monotherapy in patients

who have completed trastuzumab in adjuvant setting (n=70)

Patients will be given high dose loperamide prophylaxis (no loperamide prophylaxis used in ExteNET)

Trial initiated in Q1 2015

Primary endpoint: Incidence and severity of diarrhea

Data anticipated in late 2015

Anticipate results will be including in NDA/MAA filings to support ability of high dose loperamide to reduce neratinib related diarrhea in extended adjuvant HER+ breast cancer

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Surgery

Early HER2-positive Breast Cancer, Adjuvant

AC Herceptin + Taxol (NCCTG N9831 + NSABP B-31)

ExteNET Neratinib vs Placebo

AC Taxotere + Herceptin (BCIRG)

Approved APHINITY

Perjeta + Herceptin + Chemotherapy vs Placebo+ Herceptin + Chemotherapy

KAITLIN AC Trastuzumab + Pertuzumab + Taxane vs

AC TDM1 + Pertuzumab

Ongoing

ALTTO Herceptin+/- taxane

Herceptin +/- taxane Tykerb

Tykerb + Herceptin +/- taxane

Chemo

Herceptin (HERA 2 yrs Rx Arm)

Adjuvant (for up to 52 weeks post surgery) Extended adjuvant

Failed

Chemotherapy Herceptin (HERA 1 yr)

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PB272 Extended Adjuvant HER2+ Breast Cancer Market Size

Approximately 36,000 patients (US) with early stage HER2+ breast cancer

Approximately 34,000 patients (EU) with early stage HER2+ breast cancer

Treatment duration: 12 months

Current WW Herceptin adjuvant revenue (year 1) : $4.3 billion Neratinib would be used in year 2 after adjuvant Herceptin

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Treatment Paradigm for HER2+ Metastatic Breast Cancer

Prior HER2+ MBC Rx

T-DM1 (EMILIA)

Tykerb (lapatinib) + Xeloda (capecitabine)

Herceptin + other Chemo Rx

Herceptin + Tykerb

Herceptin (trastuzumab) + Perjeta (pertuzumab)

+docetaxel

Neratinib + Xeloda (capecitabine)

Neratinib + Torisel

No Prior HER2+ Rx

T-DM1 +/- Perjeta (MARIANNE-trial did not

achieve primary endpoint December 2014)

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Neratinib (PB272) Activity in second-line/third-line HER2+ MBC

Response Rate

PFS (weeks)

Tykerb (single agent) 5-7% 8-9

Neratinib (single agent) 24% 22.3

Herceptin plus vinorelbine 37% 24.6

Neratinib plus vinorelbine 57% 44.1

Tykerb plus capecitabine 23.7% 27.1

Neratinib plus capecitabine 64% 40.3

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PB272 Phase III Trial-Third Line HER2+ MBC (PUMA-NER-1301)

Obtained SPA from FDA and review by EMA in February 2013

Performed in patients with HER2+ Metastatic Breast Cancer (MBC) who have been treated with two or more prior treatments (third-line disease)

Trial Design PB272 plus Xeloda (capecitabine) versus Tykerb plus Xeloda

(N=600, 1:1 randomization) Study conducted in North America, Europe, Asia-Pacific Co-primary endpoint: progression free survival/overall survival

Trial initiated June 2013

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PB272 Third-Line HER2+ MBC Market Size

Approximately 5,000-6,000 patients (US) with third-line HER2+ metastatic breast cancer

Tykerb 2013 WW sales - ~$325 M (~$86 M US, ~$239M ex US) Approved in combination with Xeloda In US, Herceptin often substituted for Tykerb in combination with

Xeloda

Opportunity to gain market share from both Xeloda-Tykerb patients and Xeloda-Herceptin patients

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-No Prior Treatment for Metastatic Disease

-Prior taxane/trastuzumab in adjuvant setting allowed R

ando

miz

e 1:

1

Paclitaxel plus Neratinib

Paclitaxel plus Trastuzumab

Primary endpoint: Progression free survival (PFS)

Secondary endpoints: Overall response rate, clinical benefit rate, safety, time to CNS mets

No loperamide prophylaxis used to prevent neratinib related diarrhea �

480 patients total

NEfERTT Trial-First Line HER2 Positive Metastatic Breast Cancer

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PB272 First-Line HER2+ Metastatic Breast Cancer Trial (NEfERTT)

Progression Free Survival: Paclitaxel-Neratinib: 12.9 months Paclitaxel-Herceptin: 12.9 months (p=0.777)

Objective Response Rate: Paclitaxel-Neratinib: 74.8% Paclitaxel-Herceptin: 77.2% (p=0.595)

Incidence of CNS Metastases: Paclitaxel-Neratinib: 7.9% Paclitaxel-Herceptin: 16.0% (p=0.004)

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Comparison of Incidence of CNS Metastases

CLEOPATRA (first line metastatic breast cancer) Taxotere-Herceptin-Perjeta: 13.7% Taxotere-Herceptin: 12.6% (p=NS)

EMILIA (second line metastatic breast cancer) Kadcyla: 2.0% Xeloda-Tykerb: 0.7% (p=NS)

NEfERTT (first line metastatic breast cancer) Taxol-Neratinib: 7.9% Taxol-Herceptin: 16.0% (p=0.004)

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Kaplan Meier Estimates of Incidence of CNS Metastases

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Neratinib (PB272) Combination with Torisel

Temsirolimus

Neratinib

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Source: Company


Neratinib (PB272) Phase II Trial in Combination with Torisel

Neratinib (240 mg) in combination with Torisel (8 mg/wk) Fourth-Line (and Later) HER2+ Metastatic Breast

Cancer 11 of 37 patients with PR (30%) Median duration of response = 7.4 months Progression free survival not yet mature Benefit seen in patients previously treated with

Herceptin, Perjeta, Tykerb, TDM-1 Potential to initiate Phase III trial in 2015

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San Antonio Breast Cancer Symposium 2014


Neratinib (PB272) HER 2+ MBC with Brain Metastases

33% of HER2+ advanced metastatic breast cancer patients develop brain metastases

Phase II trial of Tykerb (lapatinib) in MBC patients with CNS metastases (n=39)

2.6% response rate in CNS metastases (Tykerb naïve)

Phase II trial of Tykerb (lapatinib) in MBC patients with CNS metastases (n=242)

6% response rate in CNS metastases (Tykerb naïve)

Phase II extension trial of Tykerb (lapatinib) plus Xeloda in MBC patients with CNS metastases (n=50) 20% response rate in CNS metastases

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Neratinib (PB272) HER2+ MBC with Brain Metastases

Phase II trial of neratinib in MBC patients with brain metastases

Conducted by Dana Farber Translational Breast Cancer Research

Two cohorts of patients:

Single agent neratinib (n=40) 85% of patients are Tykerb refractory 7.5% response rate in CNS metastases (ASCO, 2014)

Xeloda plus neratinib (n=60) Patients who are Tykerb naïve (n=30) Patients who are Tykerb refractory (n=30)

Potential for results over next 6-12 months

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Neratinib - Neoadjuvant Trials Comparison

pCR rate (breast & lymph)

NeoALTTO Taxol + Herceptin 27.6%

Taxol plus Tykerb 20.0%

Taxol plus Herceptin plus Tykerb 46.8%

NeoSphere

Taxotere plus Herceptin 21.5% Taxotere plus Perjeta 17.7%

Taxotere plus Herceptin plus Perjeta 39.3%

-No doublet (Tax plus single HER2 agent) outperformed Tax plus Herceptin

-Herceptin added ~22-27% to pCR rate for Tax plus single HER2 agent doublet

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Neratinib (PB272)-Neoadjuvant HER2+ Breast Cancer I-SPY2 Trial (Investigation of Serial Studies to Predict Your

Therapeutic Response with Imaging And moLecular Analysis 2)

NIH Funded Trial (n=20 (min) - 120 (max) per arm)

Enrolls patients with higher risk of recurrence (MammaPrint 70 gene signature assay)

Adaptive trial design using Bayesian predictive probability Taxol plus Herceptin Taxol plus Neratinib

Extensive Biomarker analysis (signatures) being performed

Endpoint: pathological complete response (path CR) rate (breast and lymph nodes)

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I-SPY 2 Trial: Neoadjuvant Therapy

AACR 2014

• 80.5% of MammaPrint UltraHigh patients were HER2 negative • Neratinib now eligible for I-SPY3 (Phase III)

(p=0.089)

(p=0.067)

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Neratinib (PB272) Neoadjuvant Studies in HER2+ Breast Cancer NSABP Trial (FB-7) - Neoadjuvant randomized trial of neratinib, Taxol, Herceptin

Funded by NSABP (National Surgical Adjuvant Breast and Bowel Project) Taxol plus Herceptin (n=43) Taxol plus Neratinib (n=43) Taxol plus Herceptin plus Neratinib (n=43)

Endpoint: pathological complete response (path CR) rate (breast and axillary lymph nodes)

Results anticipated H1 2015

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PB272 Neoadjuvant HER2+ Breast Cancer Market Size

Approximately 36,000 patients (US) with newly diagnosed HER2+ breast cancer

Approximately 34,000 patients (EU) with newly diagnosed HER2+ breast cancer

Treatment duration: 3 months

Market opportunity: $1.0 - 2.0 billion

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HER2 Mutated Non-Small Cell Lung Cancer (NSCLC)

Approximately 2-4% of NSCLC have HER2 kinase domain mutation at exon 20 (~4,500-9,000 patients US)

Most common in adenocarcinoma, non-smokers

Mutation narrows ATP binding cleft resulting in increased tyrosine kinase activity

HER2 mutation also results in increased PI3K/mTOR activation

Data suggests patients with HER2 mutated NSCLC do not respond to platinum based chemotherapy or EGFR inhibitors

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Phase II HER2 mutant NSCLC: Study Schema

Prior 1st or subsequent line Stage

IIIb/IV NSCLC w/ documented

ERBB2 mutation

Enroll n = 13 each arm

-expand one arm to 39 total

Neratinib 240mg daily

Neratinib 240mg daily + Temsirolimus 8mg iv weekly

Interim results (ESMO 2014): Neratinib monotherapy (n=13): 4 (31%) patients with clinical benefit Neratinib plus Torisel (n=14): 3 (21%) patients with partial response, 9 (64%) patients with clinical benefit

1:1

PD

PD

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HER2 Negative Breast Cancer with HER2 Mutation

Approximately 2% of all breast cancer patients have mutation in HER2 kinase (~4000-5000 patients US)

Identified in patients with HER2 negative disease

Mutation results in increased HER2 kinase activity

Data first presented at 2012 San Antonio Breast Cancer Symposium and published in Cancer Discovery (December 2012)

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Phase II HER2 mutant MBC: Study Schema

Enroll up to 29 patients

Neratinib 240mg daily

STUDY OBJECTIVES: 1o endpoint: Clinical Benefit Rate (CR + PR + SD ≥ 6 months) 2o endpoints: Correlate HER2 mutations with histology, Grade, Stage, PFS

PD

HER2 mutant, non-HER2 amplified

Stage IV MBC w/ documented

ERBB2 mutation

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Phase II Basket Trial: Study Schema

STUDY OBJECTIVES: 1o endpoint: Objective Response Rate (ORR) 2o endpoints: Clinical Benefit Rate, PFS, Duration of Response

For each cohort: • Enroll n=7 per cohort • If threshold response rate hit

then expand cohort

Bladder & GU carcinoma

Colorectal carcinoma

Gastro-Esoph carcinoma

Ovarian carcinoma

Endometrial carcinoma

Other tumor types

Neratinib 240mg daily PD

ERBB2 mutations

Primary brain tumors EGFR mutation

All tumor types ERBB3 mutation

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Phase II Basket Study - Cohort Expansions

Expanded cohort that included HER2 negative breast cancer with HER2 mutations (May 2014) Enrolled in “other tumor” basket Basket expanded to 18 patients

Expanded cohort that included metastatic non-small cell lung cancer with HER2 mutations (April 2015)

Anticipate announcing additional cohort expansions during 2015

Potential to present initial data in next 6-12 months

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Baseline 4 Months

ERBB2 L755S Non-Small Cell Lung Cancer


Puma-Expected Milestones

Present/Publish Phase III trial results from ExteNET Trial (extended adjuvant treatment HER2 positive early stage breast cancer) (mid 2015)

Present/publish Phase II results from NEfERTT Trial (first-line HER2 positive metastatic breast cancer) (mid 2015)

Report Phase II neoadjuvant HER2 positive breast cancer trial (H1

2015)

Expand additional cohorts in basket trial (H2 2015) Report Phase II trial in MBC patients with brain metastases (H2 2015) Report Phase II data in patients with HER2 non-amplified breast cancer

that has a HER2 mutation (H2 2015)

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Intellectual Property

Composition of matter patent issued (expires 2025) Can be extended w/ Hatch/Waxman

Use in the treatment of cancer issued (expires 2025)

Two polymorph patents issued (both expire 2028)

Formulation patent allowed (expires 2030)

Additional use patents filed

Covers entire family of in-licensed candidates

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Intellectual Property on EGFR T790M Mutations

Issued claims in Europe, Asia, Australia (expires 2026) Possibility to extend up to 5 years

Pending claims in United States

Patent claims upheld after European Opposition Hearing (February 2014)

Claims for the pharmaceutical composition comprising an irreversible EGFR inhibitor for use in treating cancer having a T790M mutation

Claims for the pharmaceutical composition for use in the treatment of cancer including lung cancer and non-small cell lung cancer

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Experienced Management Team

Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder

-Chief Executive Officer, President, Founder, Cougar Biotechnology Richard Bryce, MD Senior Vice President Clinical Research and Development -Onyx, Roche, ICON Clinical Research Charles R. Eyler Senior Vice President, Finance and Treasurer -Cougar Biotechnology, Hayes Medical Erin Jones Vice President Regulatory Affairs -Genentech, Biomarin

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Board of Directors

Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder Puma Biotechnology, Inc. Tom Malley Portfolio Manager (retired) Janus Global Life Sciences Fund Jay Moyes Former CFO Myriad Genetics Troy Wilson, PhD, JD CEO, Kura Oncology; CEO, Wellspring Biosciences; CEO Avidity

Nanomedicines; Former CEO, President, Intellikine

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Currently Trading on NYSE: PBYI Cash position at March 31, 2015: $310.4 million Adjusted net loss in Q1 2015: $32.4 million Completed $218.5 million Public Offering (January 2015)

Issued 1,150,000 shares at $190.00 per share Shares issued and outstanding: 32.1 million

Puma Biotechnology-Financial

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Company Highlights In licensing driven business model – mitigates R&D risk

PB272 (neratinib)- clinical stage candidate targeting multiple oncology indications

HER2+ Metastatic Breast Cancer HER2+ Metastatic Breast Cancer with Brain Metastases HER2+ Neoadjuvant Breast Cancer HER2+ Adjuvant Breast Cancer HER2 Mutated Non-Small Cell Lung Cancer HER2 Mutated Breast Cancer HER2 Mutated Solid Tumors

Retained commercial rights to PB272

Strong Phase II and Phase III data for PB272 (single agent and in combination with chemotherapy)

Potential for multiple clinical trial readouts over next 6-12 months 51

Puma Biotechnology


Jefferies 2015 Healthcare Conference

June 2015

1100 W 3 Puma - Jefferies Group · 2015. 6. 11. · Over 3,000 patients treated with neratinib...

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Transcript of 1100 W 3 Puma - Jefferies Group · 2015. 6. 11. · Over 3,000 patients treated with neratinib...