Puma Biotechnology - Jefferies · 0 12 24 36 48 60 Months after randomization Neratinib Placebo HR...

Puma Biotechnology

Copyright 2017 Puma Biotechnology

Jefferies 2017 Global Healthcare Conference

June 2017


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 potential

approval for a drug candidate, pre-commercial activities, 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, 2016. 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

Product PipelineNeratinib across the breast cancer therapy spectrum

Phase I Phase II Phase III Registration Approval

HER2+ Breast Cancer

Extended adjuvantNeratinib monotherapy

MetastaticMonotherapy or combination therapy

Metastatic w/ brain metsMonotherapy or combination therapy

NeoadjuvantCombination with standard therapy

HER2-mutant Breast Cancer/Solid Tumors

MetastaticNeratinib (± fulvestrant in MBC)

NSABP FB-7

NALA (Phase III 3rd Line HER2+ MBC)

FB-10: T-DM1 + neratinib

NEfERTT (Phase II HER2+MBC)

SUMMIT (Basket Trial)

Phase II trial (WashU)

EAP/MAP

CONTROL

ExteNET (Phase III HER2+ EBC)

I-SPY 2

NSABP FB-7

3

TBCRC-022


NDA filed 07/16MAA filed 06/16


- HER2 positive breast cancer

- Lymph node negative, positive or

residual invasive disease after

neoadjuvant treatment

Ran

do

miz

e 1

:1

Neratinib (1 year)

2840 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

4


Kaplan-Meier Estimates of Disease Free Survival

ITT Population

5

Dis

ea

se-f

ree

su

rviv

al (%

)

Months after randomization

100

70

60

50

80

90

0

Neratinib

Placebo

P-value = 0.009

HR (95% CI) = 0.67 (0.50–0.91)

1420

1420

1291

1367

1260

1324

1229

1292

1189

1243

1150

1209

1108

1163

1033

1090

662

704

No. at risk

Neratinib

Placebo

97.8%

93.9%

91.6%95.6%

0 3 6 9 12 15 18 21 24


0 3 6 9 12 15 18 21 24

Dis

ea

se-f

ree

su

rviv

al (%

)


100

70

60

50

80

90

0

Neratinib

Placebo

741

722

692

706

683

684

672

663

654

641

635

623

610

599

570

561

374

356

No. at risk

Neratinib

Placebo

98.1%

94.9%94.7%

90.6%

Kaplan-Meier Estimates of DFS

Centrally Confirmed HER2 Positive Population

P-value = 0.002

HR (95% CI) = 0.51 (0.33–0.77)

6

Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2017 Puma BiotechnologyCopyright 2017 Puma Biotechnology

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)

7

Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2017 Puma Biotechnology

0 3 6 9 12 15 18 21 24

Dis

ea

se-f

ree

su

rviv

al (%

)


100

70

60

50

80

90

0

Neratinib

Placebo

P-value = 0.001

HR (95% CI) = 0.51 (0.33–0.77)

816

815

737

784

721

761

698

741

677

716

653

699

629

669

591

622

380

401

No. at risk

Neratinib

Placebo

97.9%

96.0%95.4%

91.2%

Kaplan-Meier Estimates of DFS

Hormone Receptor Positive Patients ITT Population

8

Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2017 Puma BiotechnologyCopyright 2017 Puma Biotechnology

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)

9

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

Dis

ea

se-f

ree

su

rviv

al


Neratinib

Placebo

HR (95% CI): 0.73 (0.57-0.92)

Two-sided P=0.008

At risk

Neratinib 1420 1316 1272 1225 1106 978 965 949 938 920 885

Placebo 1420 1354 1298 1248 1142 1029 1011 991 978 958 927

5-year Analysis Shows Durable iDFS BenefitITT Population

97.9%

95.5%

94.3%

91.7% 2.5% Δ

92.2%

90.2%

91.2%

89.1%

(Descriptive P value)

90.2%

87.7%

10

0 12 24 36 48 60


Neratinib

Placebo

HR (95% CI): 0.95 (0.66-1.35)

Two-sided P=0.762

604 559 541 520 464 407 400 391 384 376 362

605 575 548 529 495 448 444 435 427 416 402

97.5%

94.7%92.8%

91.8%

90.8%

90.4%89.9%

89.3% 88.8%

88.9%

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

Dis

ea

se

-fre

e s

urv

iva

l


Neratinib

Placebo

HR (95% CI): 0.60 (0.43-0.83)

Two-sided P=0.002

At risk

Neratinib 816 757 731 705 642 571 565 558 554 544 523

Placebo 815 779 750 719 647 581 567 556 551 542 525

iDFS by Hormone Receptor Status5-Year Analysis

98.1%

96.1%95.4%

91.7% 4.4% Δ

93.6%

89.8%

92.6%

88.5%

91.2%

86.8%

Hormone receptor positive Hormone receptor negative

(Descriptive P value)


ExteNET-HER2+ Extended Adjuvant Breast Cancer

Filed NDA for US FDA approval (July 2016)

Filed MAA for EU approval (June 2016)

Label revised to include patients treated up to one year from

completion of adjuvant Herceptin (March 2017)

Managed Access Program (MAP) launched Q4 16

Expanded Access Program (EAP) launched Q1 17

FDA Oncologic Drugs Advisory Committee voted to recommend approval (May 24, 2017)

Anticipated PDUFA Date (July 2017)

12


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

13

Ustaris et al. Am J Hematol Oncol 2015

No prophylaxis Loperamide prophylaxis

Targetpopulation

HER2+MBC

HER2+ MBC

HER2+MBC

HER2+ EBC

(ExteNET)

HER2+MBC

HER2+MBC

HER2 mutated

NSCLC

HER2 mutated

NSCLC

HER2 mutatedtumors

Protocol-directedtherapy

Paclitaxel + Herceptin

+ Neratinib

Neratinib + Torisel

Neratinib NeratinibPaclitaxel + Herceptin + Neratinib

Neratinib + Torisel

Neratinib + Torisel

Neratinib Neratinib

Loperamide prophylaxis

None 16 mg → 6 mg during cycle 1

Total patients (N)

15 37 66 1408 6 41 14 13 81

Grade 3 diarrhea

8 (53%) 12 (32%) 20 (30%)1 562 (40%)1 0 7 (17%) 2 (14%) 1 (8%) 10 (12%)

Noncompliantwith Loperamide

04 (57%)

of 71 (50%)

of 21 (100%)

Duration of TE diarrhea(days)

‒ 14 14 ‒ ‒ 2 2 2 2

Loperamide Prophylaxis Reduces Duration and Incidence of Neratinib-induced Diarrhea

1. Includes 1 grade 4 event

14Copyright 2017 Puma Biotechnology

CONTROLStudy Design

STUDY ENDPOINTS

Primary endpoint: Incidence of grade ≥3 diarrhea

Secondary endpoints: Frequency distribution of maximum-grade diarrhea; incidence and severity of diarrhea by loperamide exposure

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• Received up to 1 year of

adjuvant trastuzumab• Stage I–3c• HR (ER/PR) +/–

Neratinib 240 mg/day(endocrine therapy as indicated)

As needed

Cycle 1-2

Loperamideprophylaxis

Day 57 onwardsAnti-inflammatory agent or bile acid sequestrant (Cycle 1)


CONTROLStudy Flowchart

NeratinibLoperamide prophylaxis

Budesonide

Budesonide cohort n=40 planned(Amendment 3)

Colestipol cohortn=40 planned(Amendment 4)

Investigational cohortn=40 planned(Amendment 4)

Loperamide cohortn~120 planned

(Original protocolAmendment 1 and 2)

Stage 1-3c HER2+ breast cancerTrastuzumab-based adjuvant therapy completed within 1 year



Colestipol


To be decided

Sequential investigational cohorts

Po

pu

lati

on

Co

ho

rtTr

eatm

en

tA

nal

ysis


Planned enrollmentstart date: 2017

Interim analysis(N=137)

Preliminary analysis(N=64)

Preliminary analysis(N=26)

CONTROL1 ExteNET2


(original + modified)


+ budesonide


+ colestipol

Loperamide

prn

N (at data cut-off) 137 64 26 1408

Any grade 77.4 79.7 57.7 95.4

Grade 1 24.1 26.6 30.8 22.9

Grade 2 22.6 29.7 15.4 32.5

Grade 3 30.7 23.4 11.5 39.8

Grade 4 0 0 0 0.1

Median duration of

neratinib treatment,

months 10.6 5.1 1.7 11.6

Characteristics of treatment-emergent diarrheaCONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea

Loperamide prophylaxis reduces incidence and severity of diarrhea

1. Ibrahim et al. AACR 2017

2. Chan et.al. Lancet Oncol 2016 17Copyright 2017 Puma Biotechnology

CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea

Significant improvement seen with CONTROL prophylaxis

Ibrahim et al. AACR 2017

18


Loperamide prophylaxis reduces diarrhea duration

Median cumulative duration per patient, days

CONTROL 1 ExteNET 2

Loperamide prophylaxis (original + modified)


+ budesonide


+ colestipol

Loperamide

prn

(n=127) (n=64) (n=26) (n=1408)

Any grade 12.0 10.0 8.0 59.0

Grade ≥ 2 4.0 3.0 2.0 10.0

Grade ≥ 3a 3.0 2.0 2.0 5.0

Treatment

duration, months

Median 10.6 5.1 1.7 11.6


a No grade 4 events in the CONTROL study;

one grade 4 event in the ExteNET study

1. Ibrahim et.al. AACR 2017

2. Chan et.al. Lancet Oncol 2016

Median diarrhea episodes per patient

CONTROL1 ExteNET2

Loperamide

prophylaxis

(original + modified)

Loperamide

prophylaxis +

budesonide

Loperamide

prophylaxis +

colestipol

Loperamide

prn

(n=137) (n=64) (n=26) (n=1408)

Any grade 2 4 3 8

Grade ≥ 2 2 2 2 3

Grade ≥ 3a 1 1 2 2

• Loperamide prophylaxis with or without the addition of budesonide reduces the

number of diarrhea episodes experienced by patients

a No grade 4 events in the CONTROL study;

one grade 4 event in the ExteNET study.


Loperamide prophylaxis reduces diarrhea episodes

20Copyright 2017 Puma Biotechnology 1. Ibrahim et.al. AACR 2017


Loperamide Prophylaxis in CONTROL Decreases

Neratinib Dose Reductions and Dose Holds

1. Ibrahim et al. AACR 2017


Actions required due to diarrhea, %

CONTROL 1 ExteNET 2

Loperamide

prophylaxis

(original +

modified)

Loperamide

prophylaxis +

budesonide

Loperamide

prophylaxis +

colestipol

Loperamide

prn

(n=137) (n=64) (n=26) (n=1408)

Dose reduction 7.3 1.6 3.8 26.4

Dose hold 14.6 14.1 7.7 33.9

Discontinued treatment 20.4 9.4 0 16.8

Hospitalization 1.5 0 0 1.4


CONTROLPrior pertuzumab exposure affects diarrhea incidence

Prior pertuzumab exposure

Loperamide prophylaxis Loperamide prophylaxis + budesonide

Yes(n=55)

No(n=82)

Yes(n=39)

No(n=25)

Grade 3 diarrhea, % 38.2 25.6 10.3 36.0

22

• Prior pertuzumab may result in a higher incidence of grade 3 diarrhea that is not prevented/reduced with loperamide prophylaxis alone

• Adding budesonide may reduce grade 3 diarrhea

Ibrahim et.al. AACR 2017Copyright 2017 Puma Biotechnology

Antidiarrheal Prophylaxis Reduces the Incidence and Severity of DiarrheaExteNET and CONTROL (Updated May 2017)

22%

24%23%

31%

5%

23%

32%

40%

None

Grade 1

Grade 2

Grade 3

25%

28%27%

20%

ExteNET

n=1408

Loperamide

n=137

Loperamide + budesonide

n=64

46%

26%

20%

8%

Colestipol + loperamide

n=39

23

Copyright 2012 Puma BiotechnologyCopyright 2017 Puma Biotechnology

Commercial Launch Initiatives

2016 Q1 2017 Q2 2017 Q3 2017

Market Research (Physician & Patient)

Commercial Operations (3PL, Distribution, Specialty Pharmacy, Reimbursement Hub)

Patient Advocacy Partnerships; Oncology Congress Presence

Marketing : Message and Market Development

Market Access : Payer Education, AMCP Dossier, NCCN

Field Team Sizing

Disease Awareness Campaigns

Key examples (not full list of initiatives)

Sales Force

EU : Physician & Payer Research

L

A

U

N

C

H

Pricing

Managed Access, Global Value Dossiers

24

Copyright 2017 Puma Biotechnology 25

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

Estimated 2015 WW Herceptin adjuvant revenue (year 1) :

$4.5-$5.0 billion

Neratinib would be used in year 2 after adjuvant Herceptin


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)

26

Phase III Trial – Third Line HER2+ MBC (NALA):

Study Rationale

Therapy Region / StudyResponse Rate (%)

Median PFS (weeks)

Tykerb (lapatinib) Phase II 5-7 8-9

lapatinib + capecitabine USA (USPI) 24 27.1

lapatinib + capecitabine EMILIA 31 27.8

neratinib Phase II 24 22.3

neratinib + capecitabine Phase II 64 40.3


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

STUDY OBJECTIVES

Co-Primary: PFS (central) and OS

Secondary: PFS (local), ORR, DoR, CBR, time to intervention for CNS metastases, safety, health outcomes

HER2+ mBCReceived ≥2 prior

lines of HER2-directed therapy

PD

PD

Neratinib + Capecitabine

Lapatinib + Capecitabine

Follow-up (Survival)

1:1

RA

ND

OM

IZA

TIO

N

2831

n=600



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

29

NEfERTT Trial – First-Line HER2 Positive

Metastatic Breast Cancer

30

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

Awada et al. JAMA Oncol 2016

Previously untreated HER2+ locally recurrent or mBC• No evidence of primary disease

refractory to trastuzumab or paclitaxel

• No prior therapy for locally recurrent or mBC

Trastuzumab +Paclitaxel

Neratinib + Paclitaxel

PD

PD

1:1

RA

ND

OM

IZA

TIO

N

n=479



PB272 First-Line HER2+

Metastatic Breast Cancer Trial (NEfERTT)

Progression Free Survival:

Paclitaxel-Neratinib: 12.9 months

Paclitaxel-Herceptin: 12.9 months (p=0.89)

Objective Response Rate:

Paclitaxel-Neratinib: 74.8%

Paclitaxel-Herceptin: 77.6% (p=0.52)

Incidence of CNS Metastases:

Paclitaxel-Neratinib: 8.3%

Paclitaxel-Herceptin: 17.3% (p=0.002)

31

CNS ProgressionNeratinib-Paclitaxel Delayed Onset of CNS Metastases

Time (months)

242237

191196

141144

10296

7370

5753

4544

3835

00

3533

3227

2223

1414

106

33

GroupNeratinib + paclitaxel

Trastuzumab + paclitaxel

N242237

Event2041

Median (95% CI)Not estimableNot estimable

Hazard ratio (95% CI) = 0.48 (0.29, 0.79)Log-rank test P-value = 0.002

0 4 8 12 16 20 24 28 5632 36 40 44 48 52

Free

of

CN

S p

rogr

essi

on

(%

)1.0

0.6

0.5

0.8

0.9

0.0

0.7

0.2

0.1

0.4

0.3

Neratinib + paclitaxel

Trastuzumab + paclitaxel

No. at riskNeratinib + paclitaxelTrastuzumab + paclitaxel

323Awada et al. JAMA Oncol 201632Copyright 2017 Puma Biotechnology


NSABP FB-10 Phase I/II Trial Kadcyla (T-DM1)

plus Neratinib

Kadcyla (T-DM1)

Current second line standard of care in second line HER2 positive

metastatic breast cancer

Phase III EMILIA Trial (Perjeta naïve):

Objective Response Rate: 43.6%

Median Progression Free Survival: 9.6 months

JCO 2016: Patients previously treated with Perjeta

ORR (second line): 23.1%

Median duration of therapy: 4.0 months

33

FB-10 - Phase I/II trial of Kadcyla (T-DM1) plus

Neratinib

34

Primary endpoint: Phase I: Recommended dose of neratinib when given with T-DM1; Phase 2: Objective response rate (CR/PR)Secondary endpoint: Clinical benefit rate (CR/PR/SD), PFS, PK, tumor biopsy for PDX model (optional)

HER2+ MBC

Must have received prior anti-HER2-based

therapy with pertuzumab for mBC

No prior T-DM1 or HER2 TKI allowed

Neratinib Dose level 1: 120 mg/d Dose level 2: 160 mg/d Dose level 3: 200 mg/d Dose level 4: 240 mg/d

T-DM13.6 mg/kg IV d1 Q3W


-100%

-80%

-60%

-40%

-20%

0%

20%

40%

60%

80%

100%

FB-10-Phase I/II trial of Kadcyla (T-DM1) plus

Neratinib

PD

SD

CR/PR

ORR (CR/PR): 9 of 16 (56%)

Abraham et.al. AACR 2017

35


Neratinib (PB272)

HER2+ 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

36

Ongoing Neratinib Studies Investigating

CNS Metastases

TBCRC -022

37

Cohort 1 (neratinib monotherapy): 7.5% ORR in CNS (ASCO 2014)-85% Tykerb refractory

Cohort 3: Results anticipated Q2 17


TBCRC-022 Cohort 3a– CNS Response %

re

du

cti

on

in

vo

lum

e o

f C

NS

le

sio

ns

* ASCO 2017

-100

-80

-60

-40

-20

0

20

40

60

80

100

Best Volumetric CNS response (n=31 evaluable pts)Best Volumetric Response (n=31)*

CNS ORR = 49% (95% CI 32-66%)

18 responses

Open-label, multinational, phase 2 study of neratinib as monotherapy or in combination in patients with tumors harboring ERBB2 mutations

Primary endpoint: ORR

Secondary endpoints: ORR (confirmed), CBR, PFS, safety, biomarkers

Simon 2-stage design: If threshold response rate hit in first evaluable 7 patients expand cohort

HER

2m

uta

nt*

M

on

oth

era

py

Breast cancer HR (–)

Biliary tract

Endometrial

Gastro-esophageal

Ovarian

Solid tumors (Other)

HER

2m

uta

nt*

C

om

bin

ati

on Breast cancer HR (+)

Neratinib + fulvestrant

Bladder/urinary tractNeratinib + paclitaxel

*Documented mutations based on local testing

PD

NeratinibMonotherapy or

combination therapy in HER2-mutant bladder or

HR+ breast cohort*

3939

Phase II HER2 Mutation Basket Trial (SUMMIT)

Study Design


Neratinib Monotherapy Efficacy in HER2-mutant Patients by Tumor Type

40* no target lesion measurement

Hyman et.al. AACR 2017

Somatic Mutations in HER2 (ERBB2) Are a New Class of

Oncogenic Drivers in Breast Cancer and Other Solid Tumors

1TCGA; 2 Ma et al, ASCO 2016; 3Wagle et al, ASCO 2016; 4Desmedt et al, JCO 2016, 5Deniziaut et al, Oncotargets 2016; 6Bose et al, Cancer Disc. 2013

• Incidence:- 1.6%, newly diagnosed breast cancer1

- 2.4%, heavily pre-treated MBC2

- 7-9%, pre-treated ER+ MBC3

- 5-15%, invasive lobular carcinomas4,5

• Tumor characteristics:- usually mutually exclusive to HER2 amplifications- predominantly in ER-positive disease (85-90%)- enriched in invasive lobular subtype

• Preclinical evidence of oncogenic activity:

- constitutive activation of intracellular kinase and downstream signaling pathways6

- increased cell proliferation and tumor growth6

- Cross-talk occurs between ER and HER2 mutation (modified clinical trial to add fulvestrant to ER positive patients)

HER2 somatic mutations

P PP P P

MAPK PathwayPI3K Pathway

RAS

RAF

MEK

ERK

PI3K

AKT

mTOR

Nucleus

↑ Cell cycle control and proliferation

↑ Cell survival and decreased apoptosis

↑ Cellular migration and metastasis

↑ Angiogenesis


Best Change in Tumor Burden: Neratinib Monotherapy (n=25)

SABCS 2016

Still on treatment

Objective

response

rate: 33%

Best Change in Tumor Burden: Neratinib + Fulvestrant

(n=17)

SABCS 2016

Objective

response

rate: 58.3%


Phase II HER2 mutant MBC: Investigator Sponsored

Study

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

44


Phase II HER2 mutant MBC: Investigator Sponsored

Study

Interim data presented at 2016 ASCO Annual Meeting

Neratinib monotherapy (n=14)

Clinical benefit rate: 36% (1 CR, 1 PR, 3 stable disease> 6 months)

PFS: 5.0 months

94% of patients were HR positive

Preclinical data shows cross talk between HER2 mutation and ER

Protocol amended to treat with combination of neratinib

plus fulvestrant

Additional data anticipated 2017

45


Puma-Expected Milestones

Report additional data from Phase II CONTROL trial (loperamide +

budesonide prophylaxis (Q2 17)

Report Interim Phase I/II data from neratinib plus Kadcyla (T-DM1) in

HER2-positive metastatic breast cancer trial (Q2 17)

Report Phase II data from SUMMIT basket trial of neratinib in patients

with HER2 mutations (Q2 17)

Report Phase II trial in MBC patients with brain metastases (Q2 17)

Report final 5-year DFS data from ExteNET (Q2 17)

Report Phase III trial in third-line MBC patients (Q2 17)

Regulatory decision in US/EU on neratinib in extended adjuvant HER2

positive early stage breast cancer (Q3 17)

46


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)

Combination with capecitabine (expires 2031)

Use in extended adjuvant breast cancer (expires 2030)

Composition of specific salt of neratinib (recently issued)

Additional use patents filed

47


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

48


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

Steven LoChief Commercial Officer

-Corcept Therapeutics, Genentech

49


Board of Directors

Alan H. Auerbach

Chairman, Chief Executive Officer, President, Founder

Puma Biotechnology, Inc.

Jay Moyes

Former CFO, Myriad Genetics

Adrian Senderowicz, M.D.

Chief Medical Officer, Cerulean; Former Chief Medical Officer and SVP, Clinical and Regulatory, Ignyta, Inc.; Sanofi, Astrazeneca; FDA (Division of Oncology Drug Products)

Troy Wilson, PhD, JD

CEO, Kura Oncology; CEO, Wellspring Biosciences; CEO Avidity

Nanomedicines; Former CEO, President, Intellikine

Frank Zavrl

Former Partner, Adage Capital Management

50


Currently Trading on NASDAQ: PBYI

Cash position at March 31, 2017: $194.0 million

Net cash used in operating activities (burn) in Q1 2017: $36.0 million

Completed $172.5 million Public Offering (October 2016)

Issued 4,312,500 shares at $40.00 per share

Shares issued and outstanding: 37.0 million

Puma Biotechnology-Financial

51


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

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

HER2+ Extended Adjuvant Breast Cancer

HER2+ Metastatic Breast Cancer

HER2+ Metastatic Breast Cancer with Brain Metastases

HER2+ Neoadjuvant 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 and regulatory milestones over next 6-12 months

52

Puma Biotechnology



June 2017

Puma Biotechnology



APPENDIX

June 2017

Neratinib / Placebo treatment

0 3 6 9 12 15 18 21 24

Dis

ease

-fre

e su

rviv

al (

%)


11521145

10471100

10231063

10021035

971997

936964

899929

833865

No. at riskNeratinibPlacebo

100

60

50

80

90

0

70Two sided P-value = 0.006HR (95% CI) = 0.63 (0.45–0.88)

97.9%

95.2%93.8%

90.9%

Neratinib

Placebo

Intention-to-treat population

DFS in patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab

55

526554

* p-value descriptive


Interim 5-year DFS in patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab

0 6 12 18 24 36 42 48 6030 54

Dis

ease

-fre

e su

rviv

al (

%)


11521145

10541080

10171034

976982

855894

728770

717753

684724


301321

615644

465504

100

60

50

80

90

0

70

97.8%

95.2% 89.9%

86.8%

Neratinib

Placebo

93.8%

91.0%

92.0%

89.5%

90.8%

88.3%

Two sided P-value = 0.014HR (95% CI) = 0.72 (0.55–0.94)

Neratinib /Placebo

treatment

Intention-to-treat population

56




0 3 6 9 12 15 18 21 24

Dis

ease

-fre

e su

rviv

al (

%)


670664

605638

593619

577602

559580

538563

516541

485501


100

60

50

80

90

0


98.1%

96.0%95.3%

90.8%

Neratinib

Placebo

HR+ patients

DFS in HR+ patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab

57

307326



0 6 12 18 24 36 42 48 6030 54

Dis

ease

-fre

e su

rviv

al (

%)


670664

614630

589604

567575

501520

436447

432434

416417


181171

375370

283284

100

60

50

80

90

0

70

98.0%

96.1% 91.4%

85.9%

Neratinib

Placebo

94.9%

91.3%

93.5%

89.3%

92.6%

87.8%


Neratinib /Placebo

treatment

HR+ patients

58



Interim 5-year DFS in HR+ patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab


0 3 6 9 12 15 18 21 24

Dis

ease

-fre

e su

rviv

al (

%)


482481

442462

430444

425433

412417

398401

383388

348364


100

60

50

80

90

0


97.7%

94.1%91.7%91.1%

Neratinib

Placebo

HR– patients

DFS in HR– patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab

59

219228



0 6 12 18 24 36 42 48 6030 54

Dis

ease

-fre

e su

rviv

al (

%)


482481

440450

428430

409407

354374

292323

285319

268307


120150

240274

182220

100

60

50

80

90

0

70

97.5%

94.0% 87.9%87.8%

Neratinib

Placebo

92.3%

90.6% 89.8%

89.9%

88.2%

88.9%


Neratinib /Placebo

treatment

HR– patients

60



Interim 5-year DFS in HR– patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab

DFS in centrally confirmed HER2+ (ccHER2+) patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab

61


0 3 6 9 12 15 18 21 24

Dis

ease

-fre

e su

rviv

al (

%)


743703

697684

685658

675638

658617

635596

609574

557536


100

60

50

80

90

0

70Two sided P-value <0.001HR (95% CI) = 0.49 (0.32–0.74)

98.1%

94.1%94.5%

89.9%

Neratinib

Placebo

ccHER2+ patients

352336



Interim 5-year DFS in ccHER2+ patients initiating neratinibtreatment less than 1 year after completing adjuvant trastuzumab

0 6 12 18 24 36 42 48 6030 54

Dis

ease

-fre

e su

rviv

al (

%)


743703

698667

683638

660606

583554

493481

484472

459451


195196

410397

312315

100

60

50

80

90

0

70

97.9%

94.1%90.6%

86.7%

Neratinib

Placebo

94.3%

90.0%

92.2%

89.0%

91.1%

87.5%


Neratinib /Placebo

treatment

ccHER2+ patients

62



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