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Latest Oncology Developments
Luke Lin, MD
Committed to Oncology: Our Pillars Driving Innovation
Significant Investment
Strong Partnerships
€2.7bn
>50%
devoted to research and
development in 2014
of our early-mid stage pipeline
comes from research partnerships
& licensing agreements
Robust Pipeline
Dedication to Research
20 programs
in Phase I-III trials across a range
of indications, driven by medical
need and scientific innovation
~270 staff at specialized oncology
drug discovery site in Vienna
BI Oncology Drug Discovery
Research Capabilities: Target to Drug Candidate
Commitment to
deliver innovative
differentiated
drugs targeting the
molecular basis of
disease
 Molecular and cell biology
 High-throughput screening
 High-content screening
Cooperation
 Medicinal chemistry
 Structural research
 Computational chemistry
 NBE technologies
 Pharmacological profiling
 ADME
 Translational research
 Coordination and alliance management
ADME = absorption, distribution, metabolism and elimination/excretion.
Note: Micromet is now part of Amgen
…with external partners
BI Oncology Drug Discovery: Leveraging Internal Strengths
and External Partnerships
The science is ready
Cross-TA lead
exchange
Academia1
Internal proposals
Target
identification
 Targeted combinations
TA=therapeutic area.
1 Examples
Note: Micromet is now part of Amgen
Lead
identification
Lead
optimisation
(Pre-) clinical
development
Collaborations1
Technology licensing
New precision medicines
 Impact of cancer genome
sequencing and pathway
mapping
Target/
assay validation
Licensing
Biotech
BI Oncology: Breadth and Depth in Pipeline
From Discovery Research to the Market
Approved
Afatinib#
Nintedanib##






Phase II
BI 836845 * IGF ligand mAb
BI 836826 * CD37 mAb
BI 1361849 * mRNA vaccine
BI1482694 * EGFR targeting agent
Phase I
BI 6727 *
BI 853520 *
BI 836858 *
BI 860585 *
Preclinical Dev.
Several NBEs and NCEs
Discovery Research
Focus areas




First irreversible ErbB Family Blocker
First launched September 2013 (NSCLC)
Clinical development program continuing
Novel triple angiokinase inhibitor
First launched November 2014 (NSCLC)
Clinical development program continuing
PLK inhibitor
FAK inhibitor
CD33 mAb
mTOR (mTORC1/mTORC2) inhibitor
Clinical development to be initiated within
12–18 months
Growth signalling, immunotherapy, apoptosis, epigenetics, protein homeostasis,
angiogenesis, cell-cycle progression
Leveraging capabilities in NBE and NCE development
~ 3 compounds to enter preclinical development per year
NBE = new biological entities; NCE = new chemical entities. # Afatinib is approved in a number of markets, including the EU, Japan, Taiwan and Canada under the brand name
GIOTRIF® and in the U.S. under the brand name GILOTRIF® for use in patients with distinct types of EGFR mutation-positive NSCLC. Registration conditions differ internationally,
please refer to locally approved prescribing information. Afatinib is under regulatory review by health authorities in other countries worldwide. Afatinib is not approved in other
indications.## Nintedanib is approved in the European union (EU) under the brand name VARGATEF® for use in combination with docetaxel in adult patients with locally
advanced, metastatic or locally recurrent NSCLC of adenocarcinoma tumour histology after first-line chemotherapy. Registration conditions differ internationally, please refer to
locally approved prescribing information. Nintedanib is not approved in other indications.
BI Oncology Drug Discovery – Focus on Attractive Areas
Signal transduction
Tumour angiogenesis
Cell-cycle progression
Immunotherapy
Several NBEs and NCEs from
preclinical to Market including
Afatinib#, IGF ligand mAb*, FAK
inhibitor*, mTORC1/2 inhibitor*
Several NBEs and NCEs from
preclinical to Market
including Nintedanib##
Several NCEs from preclinical to
Phase I including BI 6727*
Several NBEs from preclinical to
Phase I
including CD37 mAb*, CD33
mAb*, BI 1361849*
Effector cell
Tumour cell
Regulation of apoptosis
Epigenetic regulation
of gene expression
Protein homeostasis
Tumour Initiating Cells
and Stem Cell Pathways
Several NCEs and NBEs from
discovery to preclinical
Several NCEs from discovery to
Phase I
Several NCE discovery projects
Several NCE and NBE discovery
projects
8
BI Oncology Development Pipeline: Growing More Diverse
Target
Compound

EGFR (ErbB1), HER2 (ErbB2),
ErbB3, ErbB4
Afatinib#
NCE po

VEGFR, FGFR, PDGFR
Nintedanib##
NCE po

EGFR M+, ErbB3, ErbB4
BI1482694
NCE po

Innate immune system
lung cancer
BI 1361849*
NBE id


IGF ligand
Solid tumours
BI 836845*
NBE iv

CD37
Hematology
BI 836826*
NBE iv

mTor
Solid tumours
BI 860585*
NCE po


FAK
Solid tumours
BI 853520*
NCE po

CD33
Hematology
BI 836858*
NBE iv


PLK
Hematology
BI 6727*
NCE iv
Multiple products entering broad development
in solid tumours and hematology in 2015
NCDev
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Phase I
Phase II
✓
✓
✓
✓
✓
✓
✓
Phase III
Approved
 SCC NSCLC (submission)  NSCLC 1st line
 HNSCC
EGFR M+#
 Mesoth.
 CRC
 NSCLC EGFR M+
 NSCLC T790M
 NSCLC EGFR M+
 NSCLC stage 3
 NSCLC 2nd
line##
 NSCLC EGFR M+
 NSCLC stage 3
 mBC
 CRPC
 NSCLC
 NHL
 CLL
 Solid tumour
programs
 Solid tumour
programs
Proposed phase 3 trials
HNSCC = head and neck squamous cell carcinoma; CRC = colorectal cancer; RCC = renal cell cancer; HCC = hepatocellular carcinoma; AML =acute myeloid leukaemia; NSCLC = non-small cell lung
cancer; OC = ovarian cancer; TKI = tyrosine kinase inhibitor; Mesoth = mesothelioma; MDS = myelodysplastic syndromes; SCC = squamous cell carcinoma.
8
Chemo
therapy
Gefitinib/
erlotinib
LUX-Lung Clinical Trial Programme
TKI/chemotherapy pretreated patients
EGFR mutation-positive patients
(TKI-naïve)
LUX-Lung 1
Phase IIB/III - Pivotal trial
Completed and reported
LUX-Lung 2
Phase II
Completed and reported
LUX-Lung 4
Phase I/II
Completed and reported
LUX-Lung 3
Phase III - Pivotal trial
Completed and reported
LUX-Lung 5
Phase III
Ccompleted and reported
LUX-Lung 6
Phase III - Pivotal trial
Completed and reported
LUX-Lung 8
Phase III
Completed and reported (vs erlotinib in SCC)
LUX-Lung 7
Phase IIb
Completed; analysis ongoing (vs gefitinib)
Afatinib’s approval in EGFR M+ advanced NSCLC was based on the results of the
pivotal LUX-Lung 3 trial
9
NSCLC: Our Current and Future Footprint
BI1361849
(CV9202)
BI1482694
RNA vaccine
BI 1361849*: Therapeutic mRNA-based vaccine
 A novel investigational therapeutic
mRNA**-based vaccine
developed in collaboration with
CureVac
 Mobilises the patient’s own
immune system to fight the
tumour with a specific immune
response
 Clinical investigation is underway
in lung cancer settings
 Currently in Phase II
Source: http://www.curevac.com/rna-technology/rnactiver/
*This is an investigational compound and has not yet been approved. Its safety and efficacy have not yet been fully established.
** Messenger ribonucleic acid
Source: Boehringer Ingelheim (data on file)
BI ‘694 Background
Dr. Jin-Soo Kim
013
BI1482694 (HM61713) in-licensing
BI1482694 (HM61713): Mechanism of Action
Oral EGFR mutant -specific TKI
-
Potent and irreversible inhibition of sensitizing (Del19, L858R) and
resistance (T790M) EGFR mutations
-
More than 200 fold selectivity over wild type EGFR
In vitro cell growth inhibition in NSCLC
Inhibition concentration (IC50, nM)
H358
HCC827
H1975
EGFR WT
EGFRexon 19 del
EGFRL858R/T790M
Erlotinib
449
3.2
2,253
Afatinib
BI1482694
/HM61713
31
1.8
53
2,225
9.2
10
Park K. et al. J Clin Oncol May 2015
BI1482694 (HM61713): Pre-clinical summary
015

High selectivity for mutant EGFR over wild type EGFR

Potent growth inhibition EGFR M+ NSCLC cell lines

Antitumor activity in EGFR M+ NSCLC xenograft models including
T790M

Clear correlation between in vitro MOA and in vivo POC as an
irreversible EGFR mutant-specific TKI
Lee KO, et al. AACR 2014; Abstract # LB-100
EMSI-101 Phase I/II Trial
016
• Study conducted in 16 centres in Korea
• Delineated 800 mg as RP2D
Arm A (N=42)
failure of prior TKI
within 4 weeks
Arm B (N=41)
failure of prior TKI
at least 4 weeks or
more
Park K. et al. J Clin Oncol May 2015
EMSI-101 Trial: Patient Population
017
Key inclusion criteria
a. <Dose escalation part> Malignancy that has progressed after at least two prior
chemotherapy regimens, including EGFR TKI
b. <Expansion part 1> Patients with disease progression despite anticancer
therapy with EGFR TKI Arm A: failure of prior TKI within 4 weeks Arm B: failure of
prior TKI at least 4 weeks and more
c. <Expansion part 2 & Phase II> Patients with disease progression despite
anticancer therapy with EGFR TKI Confirmed T790M mutation in tissue
Key exclusion criteria
a. Symptomatic or uncontrolled central nervous system metastases
b. Patients with lung diseases including pulmonary fibrosis and interstitial lung
disease
Park K. et al. J Clin Oncol May 2015
EMSI-101 Trial: Activity in T790M+ Patients at 800 mg
018
Expansion Part 2 and Phase II
N=62
ORR (%)
DCR (%)
Median PFS
54.8
95.2
Not reached
>70% of responders still continue on treatment
Park K. et al. J Clin Oncol May 2015
BI1482694 (HM61713): Summary
019
• BI1482694 is an oral EGFR mutant-specific TKI with selective activity
against sensitizing and T790M resistance mutation over wild type EGFR
• BI1482694 induces durable responses in patients with T790M positive
NSCLC following failure of EGFR TKI (ORR=55%) at the RP2D of 800 mg
• Treatment is well tolerated and the vast majority of adverse events having
mild-to-moderate intensity
• Registration program of BI1482694 is underway
Park K. et al. J Clin Oncol May 2015
020
BI’694: Clinical Trial Program
Completed
Phase I/II dose escalation study in ≥ 2 line patients with EGFR M+ NSCLC
Completed
Phase I study in healthy volunteers in Korea
Recruiting
Phase II Korean study in 1st line patients with EGFR M+ NSCLC
Recruiting
Planned
Planned
Phase II global study in ≥ 2 line patients with EGFR T790M positive NSCLC
Phase III randomized trial of BI1482694 in patients with EGFRT790M NSCLC
Phase III randomized trial of BI1482694 as 1st line treatment in EGFR M+ NSCLC
Hanmi
Pharmaceuticals
Keunchil Park, M.D. Ph.D
Boehringer
Ingelheim