1530 th 1 puma biotechnology, inc - jefferies group · acaria health. accredo. cvs. onco360....

Puma Biotechnology

Copyright 2019 Puma Biotechnology

Jefferies 2019 Healthcare Conference

June 2019


This presentation contains forward-looking statements, including statementsregarding the benefits of NERLYNX® (neratinib) and neratinib, thecommercialization of NERLYNX, the potential indications of our drugcandidates and the development of our drug candidates, including, but notlimited to, the anticipated timing for the commencement and completion ofvarious clinical trials and announcement of data relative to these trials. Allstatements other than historical facts are forward–looking statements and arebased on our current expectations, forecasts and assumptions. Forward–looking statements involve risks and uncertainties that could cause our actualresults to differ materially from the anticipated results and expectationsexpressed in these forward-looking statements. These risk and uncertaintiesare identified in our Annual Report on Form 10-K for the year ended December31, 2018, and any subsequent documents we file with the SEC. Readers arecautioned not to place undue reliance on these forward-looking statements,which speak only as of the date hereof. We assume no obligation to updatethese 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

US: 7/17EU: 9/18

HER2-mutant Breast Cancer/Solid TumorsMetastaticNeratinib (± 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)

CONTROL

ExteNET (Phase III HER2+ EBC)

I-SPY 2

NSABP FB-7

TBCRC-022


EAP/MAP

33

Puma’s Pharmacy and Distributor Network

4

Specialty Distributor Network

Patients

Hub Services

Specialty Pharmacy Network

Acaria HealthAccredo

CVSOnco360DiplomatBiologics

Sites of Care

Academic Hospitals Community Hospitals

Other (VA, DoD)Physician Practices

McKessonASD / Oncology Supply

Cardinal Health


$45.6 Million Net Revenuein Q1 2019

5

6.1

20.1

36.0

50.8 52.6

61.1

45.6

Q 3 2 0 1 7 Q 4 2 0 1 7 Q 1 2 0 1 8 Q 2 2 0 1 8 Q 3 2 0 1 8 Q 4 2 0 1 8 Q 1 2 0 1 9

QUARTERLY NET REVENUE (IN $MM)


6

Bottles Sold By Quarter

• SP = Specialty Pharmacy Network, SD = Specialty Distributor Network

675

2,137

3,517

4,799 4,936

5,538

4,449

1,600

Q3-17 Q4 -1 7 Q1 -1 8 Q2-18 Q3-18 Q4-18 Q1 -19 Q2 -19

BOTTLES SOLD BY QUARTER (SP+SD)

April


Time to First Dispense in Specialty Pharmacy Network

7

74% of patients receive their first dispense within 15 days of a network SP receiving the RX

33%

26%

15%

7% 8%4%

2% 2% 1% 1%

5 O R L E S S 5 T H R O U G H 1 0

1 0 T H R O U G H 1 5

1 5 T H R O U G H 2 0

2 0 T H R O U G H 3 0

3 0 T H R O U G H 4 5

4 5 T H R O U G H 6 0

6 0 T H R O U G H 9 0

9 0 T H R O U G H 1 2 0

1 2 0 A N D G R E A T E R

PERCENT OF PATIENTS TIME TO FIRST DISPENSE


8

74% of Targeted Prescribers Reached

• Reach defined as physician detailed.• Numbers reported for historical quarters may be slightly different from previous statements due to data updates

26%

54%

61%66%

69% 71% 74%

Q 3 - 1 7 Q 4 - 1 7 Q 1 - 1 8 Q 2 - 1 8 Q 3 - 1 8 Q 4 - 1 8 Q 1 - 1 9

CUMULATIVE TARGET WRITER REACH BY QUARTER


Pierre Fabre License for NERLYNX® in EuropeMarch 2019

• Well established oncology commercial/medical infrastructure in breast cancer throughout Europe, based on Navelbine® (vinorelbine)

• Pierre Fabre has commercial and development rights to neratinib in Europe and parts of North and Western Africa

• First anticipated launch is Germany in 2019, with other countries to follow in 2019/2020

• UK NICE submission complete and under review • Major financial terms of the agreement

– $60M USD upfront upon execution of the license agreement– Additional commercial and regulatory milestones totaling $345M USD– Double digit royalties up to 40% on net sales

9Copyright 2019 Puma Biotechnology

Rest of World Partnerships – Timelines

10

Region Partner Expected Regulatory Approval

Australia / SE Asia • Approved in ITT population –Australia

Israel • Q3 2019

Canada • Q3 2019

Greater China • 1H 2020 – China• Q4 2019 – Hong Kong• 1H 2020 – Taiwan

Latin AmericaSouth America

• 1H 2020 – Mexico• 1H 2020 – Argentina • 1H 2020 – Chile• 1H 2020 – Ecuador• 1H 2020 – Peru• 2H 2020 – Colombia• 1H 2021 – Brazil


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 Neratinib

Paclitaxel + 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

0 4 (57%) of 7

1 (50%) of 2 1 (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


CONTROLStudy Design

STUDY ENDPOINTSPrimary endpoint: Incidence of grade ≥3 diarrheaSecondary 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)


NeratinibLoperamide prophylaxisBudesonide

Budesonide cohort Colestipol cohort Colestipol cohortLoperamide cohort(Original protocol)

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

NeratinibLoperamide prophylaxis

NeratinibLoperamide prophylaxisColestipol

NeratinibColestipol

prophylaxisLoperamide PRN

Sequential investigational cohorts

Popu

latio

nCo

hort

Trea

tmen

tAn

alys

isCONTROL

Study Flowchart

13

Interim analysis(N=137)

Preliminary analysis(N=64)

Preliminary analysis(N=136)

Currently ongoing (N=104)

Dose escalation cohort

Neratinibdose escalation

Currently enrolling


CONTROL1 ExteNET2

LoperamideLoperamide

+ budesonideLoperamide+ colestipol

Loperamideprn + colestipol

Neratinib dose escalation +

loperamide prn

Loperamideprn

N (at data cut-off) 137 64 136 104 60 1408

Any grade 79.6 85.9 83.1 95.2 95.0 95.4

Grade 1 24.1 25.0 27.9 30.8 43.3 22.9

Grade 2 24.8 32.8 34.6 32.7 40.0 32.5

Grade 3 30.7 28.1 20.6 31.7 11.7 39.8

Grade 4 0 0 0 0 0 0.1Median neratinib treatment duration, months 11.6 12.0 11.9 11.9 5.6 11.6Discontinuation due to diarrhea 20.4% 10.9% 4.4% 6.7% 3.3% 16.8%

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

Loperamide prophylaxis reduces incidence and severity of diarrhea

1. Barcenas et al. ASCO 20192. Chan et al. Lancet Oncol 2016 14Copyright 2019 Puma Biotechnology

Copyright 2019 Puma Biotechnology 15

PB272 Extended Adjuvant HER2+ Breast Cancer Market Size

Approximately 28,300 patients (US) with early stage HER2+ breast cancer treated with adjuvant treatment1

Approximately 37,000 patients (EU) with early stage HER2+ breast cancer treated with adjuvant treatment1 Approximately 65–70% of patients have HR-positive disease

1Roche epidemiology slides 09/18


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)

No Prior HER2+ Rx

16

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

Therapy Region / Study Response 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 OBJECTIVESCo-Primary: PFS (central) and OSSecondary: 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

RAN

DOM

IZAT

ION

1831

n=600


Phase III Trial – Third Line HER2+ MBC (NALA): Study ResultsCentrally Confirmed PFS (co-primary endpoint)

307 183 113 69 54 35 20 13 9 7 3 2 2314 183 82 39 24 9 8 3 2 2 2 2 1

N+CL+C

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

00 3 6 9 12 15 18 21 24 27 30 33 36

Time since randomization (months)

PFS

prob

abili

ty

No. at risk:

Saura et al. ASCO 2019 Oral Session: Breast Cancer – Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019.

15%

29%38%

47%

7%

16%

Hazard ratio(95% CI)

Log-rank p-value

0.76 (0.63–0.93) 0.0059Neratinib + Capecitabine


ASCO 201919


Phase III Trial – Third Line HER2+ MBC (NALA): Study Results Prespecified restricted means analysis – PFS


1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

00 3 6 9 12 15 18 21 24 27 30 33 36


PFS

prob

abili

ty

No. at risk:

Mean PFS(months) p-value

8.80.0003

6.6



Restriction: 24 months

2.2 months

307 183 113 69 54 35 20 13 9 7 3 2 2314 183 82 39 24 9 8 3 2 2 2 2 1

N+CL+C


20ASCO 2019

Phase III Trial – Third Line HER2+ MBC (NALA): Study Results OS (co-primary endpoint)



307 294 275 244 220 182 142 112 82 13 6 2 1314 303 273 240 208 170 132 107 84 12 8 3 1

6467

4747

1822

1517

44

3436

2827

OS

prob

abili

ty

No. at risk:N+CL+C

Restriction: 48 months

3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57

1.7 months



Mean OS(months)

Hazard ratio(95% CI)

Log-rank p-value

24.00.88 (0.72–1.07) 0.2086

22.2

21ASCO 2019


1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

00

Phase III Trial – Third Line HER2+ MBC (NALA): Study Results Time to intervention for CNS metastases



22ASCO 2019

100

90

80

70

60

50

40

30

20

10

00 6 12 18 24 30 36 42 48 54 60




Overall cumulative incidence (Gray’s test): 22.8% vs 29.2%; p=0.043

InterventionNeratinib + Capecitabine

(n=55/307)Lapatinib + Capecitabine

(n=75/314)

Radiation therapy 11% 15%

Surgery/procedure 2% 3%

Anticancer medication 1% 1%

Cum

ulat

ive

inci

denc

e (%

)


PB272 Third-Line HER2+ MBCMarket Size

Approximately 6,400 patients (US) with third-line HER2+ metastatic breast cancer and 4,700 patients (US) with fourth line HER2 positive metastatic breast cancer1

Tykerb 2017 US sales - $68 M ($118M 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

23


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

24

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

25

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


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


0 100 200 300 400 500 600 700 800

120120120120120160160160160160160160160200200200200200240240

Days on Treatment

Dos

e m

g/d

+

CRPRSDPD

*

*

*

*

*

*Off TX, AE/withdrawn + On treatment

ORR (CR/PR): 12 of 20 (60%)

ASCO 2018

DS-8201: Rationale of Neratinib Combo*

Research collaboration with Puma and Memorial Sloan Kettering Cancer Center (Dec 2017)

HER2-ADC

HER2

Degradation

Endosome

InternalizationEndolysosome

HER2 positive Cancer CellLysosome

Drug release

DS-8201Neratinib

ADC

Will confirm synergetic effect hypothesis in non-clinical study HER2 dual blockage by combination of DS-8201 and neratinib Increase of internalization rate of DS-8201 by neratinib (increase uptake rate of DS-8201 into tumor)

27

HER2 Signal Cell proliferationCell survival

NeratinibTyrosine kinase inhibitorIrreversibly inhibit HER2,

EGFR, HER4 and suppress cell proliferation

HER2-TKI

* Daiichi Sankyo FY2017 Q3 Financial Results Presentation Material


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

28

TBCRC 022: A Phase II Trial of HKI-272 (Neratinib) and Capecitabine for Patients with Human Epidermal Growth Factor Receptor 2

(HER2)-Positive Breast Cancer and Brain Metastases


HER2+ mBC

w/ Brain Mets

Neratinib (240 mg/day)

Primary endpoint: ORR in CNS: Cohort 1 >5 pts (12.5%), Cohort 3a >9 pts (25.7%), Cohort 3b >2 pts (8%); Cohort 2: PFS

Secondary endpoints: ORR in non-CNS, PFS, OS

(Tre

at u

ntil

PD o

r tox

icity

; if n

on-C

NS

PD, t

rast

uzum

ab m

ay b

e ad

ded)

Cohort 1 (n = 40 pts)

Neratinib (240 mg/day) X 1 cycle, Surgical resection, then Neratinib (240 mg/day)

Cohort 2 (n = 5 pts)

Cohort 3a (n = 39 pts)Neratinib (240 mg/day)

Capecitabine (1500 mg/m2, d1-14, q3w)Cohort 3b (n = 12 pts)

Progressive brain mets

Craniotomy candidates

Progressive brain mets:

3a: No prior lapatinib3b: Prior lapatinib

4a: Untreated CNS disease; no prior T-

DM14b: Progressive CNS disease; no prior T-

DM14c: Progressive CNS disease; prior T-DM1

Cohort 4a (n = 20 pts)

Cohort 4b (n = 20 pts)Cohort 4c (n = 23 pts)

Neratinib (160 mg/day) T-DM1 (3.6 mg/kg IV q21d)

TBCRC-022 Cohort 3a– CNS Response %

redu

ctio

n in

vol

ume

of C

NS

lesi

ons

* ASCO 2017

-100

-80

-60

-40

-20

0

20

40

60

80

100

Best Volumetric Response (n=31)*

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

18 responses


Neratinib Recently Included as a Treatment Option for Recurrent Breast Cancer CNS Metastases By NCCN® Guidelines1

1. NCCN Guidelines v 1.2018. Central Nervous System Cancers.2. Freedman RA, et al. Presented at ASCO Annual Meeting, 2017. Abstract 10053. Awada A, et al. Poster Presentation at ASCO Annual Meeting, 2015. #610.4. Awada A, et al. JAMA Oncol. 2016;2:1557-1564.

Category 2B: Neratinib + Capecitabine

Category 2B: Neratinib + Paclitaxel

Guidelines updated March 20, 2018

TBCRC 0222 NEfERT-T3,4

A Phase II Trial of Neratinib and Capecitabine for Patients with

HER2+ Breast Cancer Brain Metastases (NCT01494662)

Randomized, Multi-Center, International Study of

HER2-Directed Therapy in 1st-line mBC (NCT00915018)

31

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed [March 20, 2018]. To view the most recent and complete version of the guideline, go online to NCCN.org

SUMMIT Study Design

EGFR, HER2 or HER4 mutations(documented by local testing)

Primary endpoint• Objective response rate at first post-baseline

tumor assessment (ORRfirst)

Secondary endpoints• ORR (confirmed)• Clinical benefit rate (CBR)• Progression-free survival (PFS)• Safety• Biomarkers

Simon 2-stage design• If ≥1 response in first evaluable 7 patients,

expand cohort to Stage 2 (N=18)• If ≥4 responses in Stage 2, expand or breakout

Tumor assessments• RECIST v1.1 (primary criteria)• PET response criteria (RECIST non-evaluable)

Statistical methods• ORRfirst, ORR, CBR: associated 95% CI• Median PFS: Kaplan-Meier estimate with 95% CI

Breast HRc-positive*

Breast HRc-negative

Lung

Colorectal (KRAS/NRAS/BRAF wild-type)

HER2-mutanttumors

Neratinib monotherapy

Biliary tract

Cervical

Salivary

Solid tumors (NOS)

Neratinib* + Trastuzumab#

*plus fulvestrant (in ER+ breast)#biosimilar may be used if available

Bladder Neratinib + Paclitaxel

Lung Neratinibmonotherapy

Solid tumors (NOS) NeratinibmonotherapyHER4-mutant

tumors

EGFR exon18-mutant tumors


Cohorts expanded based on above stated criteria

Neratinib Monotherapy Efficacy in HER2-mutant Patients by Tumor Type

33* no target lesion measurement

Hyman et.al. AACR 2017Hyman et al, Nature 2018

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 PathwayRAS

RAF

MEK

ERK

PI3K

AKT

mTOR

Nucleus↑ Cell cycle control and proliferation↑ Cell survival and decreased apoptosis↑ Cellular migration and metastasis↑ Angiogenesis


Neratinib + Fulvestrant for HER2-mutant HR+ Metastatic Breast Cancers: Updated Results from SUMMIT Trial

L. Smyth et al SABCS 2018 Abstract PD3-06

Chan

ge fr

om b

aseli

ne (%

) 50

0

–50

–100

100

* * * * * *

= PET responses*

Prior CDK4/6 inhibitor

Prior fulvestrant

Not shown: 5 patients in whom no % change in tumor size could be calculated (n=1 died before first post-baseline assessment; n=1 ended treatment due to AEs before first post-baseline assessment; n=3 non-target lesions only)

–30%

HER2 mutation typeKinase domain hotspotExtracellular domain hotspotTransmembrane hotspotNon-hotspot

− + + + + +− − − + + − − − − − − + − + − − + − − + − − + − − + + + − − − − − − +−− + + +− + + − + + − − +− − +−− + − − + − − − − +− − + + + ++ + + + − − + + +

Histology

HistologyDuctalLobularOther/unknown

− + + + + +− − − + + − − − − − − + − + − − + − − + − − + − − + + + − − − − − − +−

Objective responseCR or PRSD ≥24 weeksPD

= Treatment ongoing= (duration on N+F)/(duration on prior CDK4/6 inhibitor or fulvestrant) ≥1= (duration on N+F)/(duration on prior CDK4/6 inhibitor or fulvestrant) <1= no prior CDK4/6 inhibitor or no prior fulvestrant

− + + +− + + − + + − − +− − +−− + − − + − − − − +− − + + + ++ + + + − − + + +Objective response − + + + + +− − − + + − − − − − − + − + − − + − − + − − + − − + + + − − − − − − +−4.5 9.2 3.9 7.3 14.8 9.0 5.4 11.2 9.2 11.0 16.6 7.2 7.4 9.3 Duration of PRs and CRs (months)

Copyright 2019 Puma Biotechnology35


Puma - Expected Milestones Present data from Phase III trial in third-line MBC patients (Q2 19)

Report additional data from Phase II CONTROL trial (Q2 19)

File NDA for neratinib based on results of the Phase III trial in third-line metastatic breast cancer (Q3 19)

Meet with FDA to discuss clinical development and regulatory strategy for SUMMIT trial (Q3 19)

Regulatory decision on neratinib for extended adjuvant HER2 positive early stage breast cancer indication in other countries (H2 19)

Report Phase II data from the SUMMIT basket trial of neratinib in patients with HER2 mutations (H2 19)

36


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

37


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

38


Experienced Management TeamAlan H. AuerbachChairman, Chief Executive Officer, President, Founder

- Chief Executive Officer, President, Founder, Cougar Biotechnology

Steven LoChief Commercial Officer

- Corcept Therapeutics, Genentech

Richard Bryce, MDChief Medical and Scientific Officer

- Onyx, Roche, ICON Clinical Research

Maximo F. NouguesChief Financial Officer

- Getinge AB, Boston Scientific, The Clorox Company

Douglas HuntSenior Vice President, Regulatory Affairs

- ArmaGen, Baxter Healthcare, Amgen

39


Board of DirectorsAlan H. AuerbachChairman, Chief Executive Officer, President, FounderPuma Biotechnology, Inc.

Michael MillerEVP U.S. Commercial, Jazz Pharmaceuticals; Former SVP & Chief Commercial Officer, Vivus; VP, Sales & Marketing, Genentech; Connetics; Alza; Syntex

Jay MoyesFormer CFO, Myriad Genetics

Adrian Senderowicz, M.D.SVP & Chief Medical Officer, Constellation Pharmaceuticals; Former Chief Medical Officer, Cerulean; Chief Medical Officer & SVP, Clinical and Regulatory, Ignyta; Sanofi, Astrazeneca; FDA (Division of Oncology Drug Products)

Troy Wilson, PhD, JDCEO, Kura Oncology; CEO, Wellspring Biosciences; CEO Avidity Nanomedicines;Former CEO, President, Intellikine

Frank ZavrlFormer Partner, Adage Capital Management

40


Currently trading on NASDAQ: PBYI

Cash, cash equivalents and marketable securities at March 31, 2019: $150 million

Cash burn in Q1 2019: ~$15 million

Amended term loan agreement (May 2018) New term loan of $155 million replaces loan of $100 million $125 million drawn down Silicon Valley Bank and Oxford Finance

Shares issued and outstanding: 38.6 million

Puma Biotechnology - Financial

41


Company Highlights NERLYNX® - First HER2 directed drug approved by FDA

for extended adjuvant treatment of early stage HER2-positive breast cancer in patients who have received prior trastuzumab

Additional potential indications 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

Retain full U.S. commercial rights to NERLYNX®

Large initial market opportunity with additional label expansion potential

42

Puma Biotechnology


Jefferies 2019 Healthcare Conference

June 2019

Puma Biotechnology


Jefferies 2019 Healthcare ConferenceAPPENDIXJune 2019


- HER2 positive breast cancer

- Lymph node negative, positive or residual invasive disease after

neoadjuvant treatment

Ran

dom

ize

1:1

Neratinib (1 year)

2840 patients total

Placebo (1 year)

- Completed 1 year prior adjuvanttreatment 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

45


Kaplan-Meier Estimates of Disease Free SurvivalITT Population

46

Dis

ease

-free

sur

viva

l (%

)

Months after randomization

100

70

60

50

80

90

0

NeratinibPlacebo

P-value = 0.009HR (95% CI) = 0.67 (0.50–0.91)

14201420

12911367

12601324

12291292

11891243

11501209

11081163

10331090

662704

No. at riskNeratinibPlacebo

97.8%

93.9%

91.6%95.6%

0 3 6 9 12 15 18 21 24

Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2019 Puma Biotechnology

0 3 6 9 12 15 18 21 24

Dis

ease

-free

sur

viva

l (%

)


100

70

60

50

80

90

0

NeratinibPlacebo

P-value = 0.001HR (95% CI) = 0.51 (0.33–0.77)

816815

737784

721761

698741

677716

653699

629669

591622

380401

No. at riskNeratinibPlacebo

97.9%

96.0% 95.4%91.2%

Kaplan-Meier Estimates of DFSHormone Receptor Positive Patients ITT Population

47

Rationale for efficacy in HR+ subgroup

membrane

HER2 HER1/2/3

ERE

nucleus

Cytoplasm

ER-regulatedgenetranscription

ER ER X

FOXO3a

MEK

ErK1/2

PI3-K

AKT

RAS

FOXO3a

HER2 signalling decreasesER-regulated gene transcription

Cytoplasm

membrane

HER2 HER1/2/3

ERE

RAS

nucleus ER-regulatedgenetranscription

ER ER

Neratinib

MEK

ErK1/2

PI3-K

AKT

RAS

FOXO3a

XX

HER2 inhibition upregulates ER-regulated gene transcription

ER ER

membrane

HER2 HER1/2/3

ERE

RAS

nucleus

Cytoplasm

ER-regulatedgenetranscription

ER ER

Neratinib

MEK

ErK1/2

PI3-K

AKT

RAS

FOXO3a

XX

Inhibition of HER2 and ER is required for effective blockage in HER2+/HR+ tumors

X

Endocrine therapy

ER ERER

Adapted from: Paplomata et al. Cancer 2015

48

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 12 24 36 48 60

Dis

ease

-free

sur

viva

l


Neratinib Placebo

HR (95% CI): 0.73 (0.57-0.92)Two-sided P=0.008

At riskNeratinib 1420 1316 1272 1225 1106 978 965 949 938 920 885Placebo 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% Δ92.2%

90.2%91.2%

89.1%

(Descriptive P value)

90.2%

87.7%

49

0 12 24 36 48 60Months after randomization

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 362605 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

ease

-free

sur

viva

l


Neratinib Placebo

HR (95% CI): 0.60 (0.43-0.83)Two-sided P=0.002

At riskNeratinib 816 757 731 705 642 571 565 558 554 544 523Placebo 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)

iDFS for HR+ patients completing prior trastuzumab ≤1 year from randomization (2-year and 5-year Analyses)

EC Approved Indication

51% relative reduction in risk of recurrence


Gnant M, et al. SABCS 2018, poster #P2-13-01 51

2-year (primary) analysis 5-year analysis

DDFS for HR+ patients completing prior trastuzumab ≤1 year from randomization (2-year and 5-year Analyses)

EC Approved Indication





iDFS for HR+ patients completing prior trastuzumab ≤1 year from randomization (2-year and 5-year Analyses)

who had prior neoadjuvant therapy with no pCR





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