puma biotechnology - jefferies - the global investment ... · pdf filecopyright 2014 puma...

Puma Biotechnology

Copyright 2014 Puma Biotechnology

Company Presentation

June 2014


This presentation contains forward-looking statements within the meaning of the Private

Securities Litigation Reform Act of 1995, including statements regarding 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, 2013.

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

2


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 data for PB272 (single agent and in combination with chemotherapy)

Potential for multiple clinical trial readouts during 2014

3


Product Pipeline Drug Indication Pre-clinical I II III Registration

PB272

Combination w/

Xeloda

Metastatic

Breast Cancer

PB272

Combination w/

Torisel

Metastatic

Breast Cancer

PB272

Single agent/

combination

Metastatic

Breast Cancer

with Brain Mets

PB272

Combination w/

chemotherapy

Neoadjuvant

Breast Cancer

PB272

Combination w/

Paclitaxel

Metastatic

Breast Cancer

PB272

Single agent Adjuvant

Breast Cancer

4


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

5


Neratinib (PB272) Safety

Over 3,000 patients treated with neratinib

Neratinib - Main Grade 3/4 AE-Diarrhea (~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

High dose of loperamide initially (8-16mg)

Taper dose during cycle 1

6


Neratinib (PB272)

Diarrhea Prophylaxis w/Loperamide (Q1 2013)

7


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-data expected

2014)

8


HER2+ Metastatic Breast Cancer-Tykerb (Lapatinib)

Tykerb-oral, reversible pan-HER tyrosine kinase inhibitor-

dual inhibitor EGFR/HER2

Single agent activity in second-line HER2+ MBC

Response rate: 5-7%

Progression free survival: 8-9 weeks

Activity in combination with Xeloda (capecitabine) in

second/third line HER2+ MBC (FDA approved regimen)

Response rate (n=399)

23.7 % for Tykerb/Xeloda vs. 13.9% for Xeloda alone

Progression free survival

27.1 weeks for Tykerb/Xeloda vs. 18.6 weeks for Xeloda alone

9


Neratinib (PB272)

Oral irreversible pan-HER tyrosine kinase inhibitor

In-licensed from Pfizer (August 2011)

Irreversible dual inhibitor of EGFR/HER2

Single agent activity in second line metastatic breast cancer (MBC; n=63)

Response rate: 24%

Progression free survival: 22.3 weeks Journal of Clinical Oncology, March 2010

10


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 25% 22.0

Neratinib plus vinorelbine 57% 44.1

Tykerb plus capecitabine 23.7% 27.1

Neratinib plus capecitabine 64% 40.3

11


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)

150 study sites (North America, Europe, Asia-Pacific)

Co-primary endpoint: progression free survival/overall survival

Trial initiated June 2013

12


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

13


Neratinib (PB272) Combination with Torisel

Temsirolimus

Neratinib

14

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

13 of 27 patients showed clinical benefit

12 patients with PR (44%) and 1 patient with

stable disease > 6 months

Enrollment continuing in 2013 (n=34)

Benefit seen in patients previously treated with

Herceptin, Perjeta, Tykerb, TDM-1

Additional data anticipated in H2 2014

15

San Antonio Breast Cancer Symposium 2012


Neratinib (PB272)

Phase II Trial in Combination with Torisel

16

Maxim

um

Chan

ge I

n S

ize

of T

arg

et

Lesio

n

-100%

-80%

-60%

-40%

-20%

0%

20%

40%

60%

PR

PR

PR

PR

PR

PR

PR

PR

PR

PR

PR

PR

SD

SD

SD

SD

SD

SD

SD

SD

SD

SD

PO

D

PO

D


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

17


Neratinib (PB272)

HER2+ MBC with Brain Metastases

Phase II trial of neratinib in MBC patients with brain metastases (Initiated January 2012)

Conducted by Dana Farber Translational Breast Cancer Research Consortium

Patients have been previously treated with Tykerb

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=40)

Patients must be Tykerb naïve

Potential for results over next 6-12 months

18


Neratinib (PB272)

Neoadjuvant Studies in HER2+ MBC

Neo-ALTTO trial (neoadjuvant Tykerb (lapatinib)) Randomized trial of Taxol, Herceptin, Tykerb in neoadjuvant setting

Results presented San Antonio Breast Cancer Symposium (December 2010)

Pathological complete response rate (breast and axillary lymph nodes)

Taxol plus Herceptin – 27.6%

Taxol plus Tykerb (lapatinib) – 20.0%

Taxol plus Herceptin plus Tykerb – 46.8%

19


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

20


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 (probability of improving path CR for biomarker signature)

21


Neratinib-Neoadjuvant HER2+ Breast Cancer I-SPY2 Trial

Neratinib eligible for I-SPY3 (Phase III neoadjuvant trial)

22

Patient

Population

pCR

Taxol/

neratinib

pCR

Taxol/

Herceptin

p

Prob of

superiority

to control

Prob of

superiority

in a 300 pt

Phase III

HER2

positive/HR

negative

55.6%

32.6%

0.051

94.9%

79.1%

HER2 positive

(HR negative

and HR positive)

39.4%

22.8%

0.046

95.4%

72.7%


Neratinib-Neoadjuvant HER2+ Breast Cancer I-SPY2 Trial

MammaPrint UltraHigh patients represented those patients with MammaPrint scores above the median from previous I-SPY1 trial

Additional biomarker analyses ongoing

23

Patient

Population

pCR

Taxol/

neratinib

pCR

Taxol

(alone or w

Herceptin)

p

Prob of

superiority

to control

Prob of

superiority

in a 300 pt

Phase III

MammaPrint

UltraHigh (MP+)*

47.5%

29.4%

0.067

93.3%

71.8%

*80.5% of MammaPrint UltraHigh patients were HER2 negative


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 2014

24


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

25


-No Prior Treatment for

Metastatic Disease

-Prior taxane/trastuzumab

in adjuvant setting Ra

nd

om

ize 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

Results anticipated H1 2014 •

480 patients total

First Line HER2 Positive

Metastatic Breast Cancer

26


- HER2 positive breast cancer

- Lymph node negative, positive or

residual invasive disease after

neoadjuvant treatment

Ran

do

miz

e 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

Results anticipated H1 2014

HER2 Positive Adjuvant

Breast Cancer

27



(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

28


HER2 Mutated Non-Small Cell Lung

Cancer (NSCLC)

Phase I dose ranging study of neratinib plus Torisel (3X3

design, 12 dose combinations, n=59)

Enrolled patients with multiple solid tumors

7 patients with HER2 mutated NSCLC were enrolled

Patients had received a median of 3 prior treatments

Data presented ASCO 2011 and International Association

for Study of Lung Cancer (IASLC) 2012

29


Phase I Dose Ranging Trial of Neratinib Plus

Torisel-HER2 Mutated NSCLC Cohort

-80

-60

-40

-20

0

20

40

% c

ha

nge

fro

m b

ase

lin

e

160 mg neratinib (N)/ 75 mg torisel (T) 160 N/ 50 T

200 N/ 15 T 120 N/ 75 T

240 N/ 15 T 200 N/ 25 T

30

Copyright 2014 Puma Biotechnology 31

Time on Study

*still on study

* SD

SD

PR

PD

SD

PR

NE

Phase I Dose Ranging Trial of Neratinib Plus

Torisel-HER2 Mutated NSCLC Cohort

Time on Study

PR=partial response SD=stable disease

PD=progressive disease NE=not evaluable


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

STUDY OBJECTIVES:

1o endpoint: Objective Response Rate (ORR)

2o endpoints: Clinical Benefit Rate, Duration of Response, PFS, OS

Results anticipated in 2014

1:1

PD

PD

32


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)

33


Cell Growth Inhibition by Neratinib and

Lapatinib

34

IC50 (nM)

Neratinib Lapatinib

MCF10A - Her2 WT <2 400 ± 60

G309A <2 470 ± 50

V777L <2 1,040 ± 570

D769H <2 980 ± 950

V842I <2 650 ± 210

Del755-759 2.1 ± 0.2 660 ± 90

L755S 15 ± 6 > 10,000

BT474 cells <2 31 ± 2

MCF7 cells > 3,000 > 10,000


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

Results anticipated in 2014

PD

HER2 mutant,

non-HER2

amplified

Stage IV MBC w/ documented

ERBB2 mutation

35


HER2 Mutation Phase II Basket Study

Approximately 2-10% of solid tumors have mutation in

HER2 kinase

Bladder: ~7,000-7,500 patients (US)

Colorectal: 4,000-4,500 patients (US)

Glioblastoma: ~1,500-2,000 patients (US)

Melanoma: ~1,000 patients (US)

Prostate: ~4,000-5,000 patients (US)

Stomach: ~1,000 patients (US)

Uterine: ~1,000-2000 patients (US)

Phase II “basket” trial of neratinib in patients with solid

tumors that have a HER2 kinase mutation initiated Q4 2013

Potential to present initial data in 2014

36


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*

37

* Planned expansion in H1 2014


Phase II Basket Study-Breast Cohort

Expansion

Expanded cohort that included HER2 negative breast

cancer with HER2 mutations (May 2014)

Enrolled in “other tumor” basket

Basket expanded to 18 patients

Anticipate announcing additional cohort expansions during

2014

Potential to present initial data in 2014

38


Puma-Expected Milestones

Initiate Phase III neratinib plus Xeloda randomized trials in third line

MBC (Q2 2013)

Initiate Phase II trial of neratinib in HER2 mutated NSCLC (Q1

2013)

Initiate Phase II trial of neratinib in HER2 negative mutated MBC

(Q1 2013)

Potential to report data from 1) Phase II neoadjuvant studies (I-

SPY2 and NSABP); 2) Phase II trial in MBC patients with brain

metastases; 3) Phase II HER 2 mutated NSCLC trial; 4) Phase II

HER2 mutated MBC trial; 5) Phase II mutation basket trial; 6) Phase

II first line HER2 positive MBC trial; and 7) Phase III HER2 positive

adjuvant trial during 2014

40


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

41


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

42


Experienced Management Team

Alan H. Auerbach

Chairman, Chief Executive Officer, President, Founder

-Chief Executive Officer, President, Founder, Cougar Biotechnology, Inc.

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

Richard B. Phillips, Ph.D.

Senior VP Regulatory Affairs, Quality Assurance, Pharmacovigilance

-Cougar Biotechnology, Johnson & Johnson

43


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, Wellspring Biosciences, CEO Avidity Nanomedicines

Former CEO, President, Intellikine

44


Currently Trading on NYSE: PBYI

Cash position at March 31, 2014: ~$196.1 million

Payment due from licensor in Q2 2014: ~$13.3 million

Net loss Q1 2014 (non-GAAP): ~$14.6 million

Completed $138.0 million Public Offering (February 2014)

Issued 1,126,530 shares at $122.50 per share

Shares issued and outstanding: 30,117,819

Puma Biotechnology-Financial

45


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 Breast Cancer

HER2 Mutated Solid Tumors

Retained commercial rights to PB272

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

Potential for multiple clinical trial readouts during 2014

46

Puma Biotechnology


Company Presentation

June 2014

puma biotechnology - jefferies - the global investment ... · pdf filecopyright 2014 puma...

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