bavarian - kapitalmarkedsdag marts 2012
DESCRIPTION
TRANSCRIPT
1 Anders Hedegaard, CEO | 27 March 2012
DELIVERING THE VACCINE PROMISE
Bavarian Nordic
Vaccines for cancer and infectious diseases
• Founded in 1994
• Lead product in Phase 3
• Strong IP position
• Listed on NASDAQ OMX Copenhagen
• Market cap (Mar-2012): DKK 1.3bn
• 450+ employees in Denmark, Germany and USA
2
3
Main strategic business areas
Infectious Diseases
SmallpoxAnthrax
Full value chain
Cancer
Prostate cancerBreast cancer
Partnerships
Major Goals Achieved
PROSTVAC® - Phase 3 initiated• Phase 3 initiated in 4Q 2011• Recruitment currently ongoing at centres across the U.S.• Planned to enrol 1,200 patients at approx. 300 centres in 20 countries
Expanded cancer pipeline through collaboration with NCI• Includes rights to vaccine candidate (CV-301) – applicable in multiple
cancers• Includes Ph1 and Ph2 data and ongoing NCI-funded studies• Offers long-term opportunity to develop cancer portfolio in major cancers
(breast, lung and ovarian)
IMVAMUNE® - producing successfully at 4 batches per week• Delivered 4 million doses as planned• Performance-based milestone of USD 25m received after successful scale up
of production• RFP-3 contract modifications adds USD 8m to total value• Phase 3 clinical protocol approved• Submitted marketing application in Canada and Europe4
2011 Financials Better Than Expected
5
Revenue DKK 524 m
Result (loss) before tax DKK -296 m
Cash preparedness at year-end DKK 704
m
Cancer Vaccines - Highlights
PROSTVAC® • Initiated the pivotal Ph3 trial in mCRPC• Attractive news flow from NCI studies
• Initiated randomized Ph2 combination study with chemotherapy in mCRPC • Presented data at ASCO from Ph1 study in locally recurrent PC by intraprostatic
injection • Presented preliminary data at GU-ASCO from Ph2 combination study (flutamide) in
non-metastatic prostate cancer • Data published from Ph1 combination study with ipilimumab in mCRPC
CV-301• Expanded pipeline through NCI collaboration• Broadly applicable technology platform – targeting major cancers• Off-the-shelf product candidates: PROSTVAC® and CV-301
• Investigated in 1000+ patients in more than 30 clinical studies• Multiple NCI-funded studies – ongoing and future
6
Cancer Vaccines
7
7
Data (1H 2012)
Enrolment (2013)PROSTVAC®
MVA-BN® PRO
Ph1 Ph 1/2 Ph 2 Ph 3 Next milestone
Prostate cancer
Prostate cancer
Data (2H 2012)CV-301 breast Breast cancer
PC
Await CV-301 dataMVA-BN® HER2 Breast cancer
Data update (2012)CV-301 lung Lung cancer
Data update (2012)CV-301 ovarian Ovarian cancer
Therapeutic vaccine platform for major cancers
Prostate cancer – a large unmet medical need
8
• Metastatic disease is incurable
• Common cause of death in men
• >250,000 deaths/year
(WW)1
• Increase in cases (780,000 annually)1
• Treated with chemotherapy (limited life-extension and severe side effects)
• Provenge approved in 2010 as first immunotherapy for this patient population
1) Global Cancer Facts & Figures 2007, American Cancer Society
Driving PROSTVAC® into Early Stage Prostate Cancer
9
Tumor volume
and activity
Hormone dependent Hormone refractory
No pain Pain
DeathStart of chemotherapy
Hormone treatment
Local treatment
Non-metastatic Metastatic
PROSTVAC®
SizeableMarket
10
The PROSTVAC® Opportunity
Prostate cancer therapies market in the US, Japan, and major EU countries of US$3.3 billion (2007), forecasted to grow to US$4.5 billion by 20172
PremiumPrices
Cancer market is occupied by products at premium prices
Shaped Market
Opportunity to enter a vaccine-receptive market shaped by first entrant
Advantageous Product
A standardized therapeutic vaccine with clear advantages to competition
Source: 1 American Cancer Society2 Decision Resources, 2008. Not including primary therapy such as surgery or radiotherapy. Major EU countries include France, Germany, Italy, Spain, and the UK
Market Expansion
Potential application in both early and late-stage prostate cancer
PROSTVAC® - asset with solid data
11
Journal of Clinical OncologyMarch 1, 2010 vol. 28 no. 7 1099-1105
Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer
Published Ongoing/Not yet
published
Phase 1 4 3
Phase 2 8 4
Phase 3 - 1
Total studies
12 8
Total pts. 580 + 1,470 +
Clinical trial overview
PROSTVAC® specifications
Phase 2 results demonstrated extended overall survival of 8.5 months• Decreased risk of death by 44% (HR =
0.56)
Multicenter Phase 21
• Randomized, placebo-controlled • Double-blind• 125 patients enrolled in 43 sites• 83 PROSTVAC® + GM-CSF• 41 placebo
12
• Off-the-shelf vial vaccine
• Sequentially dosed combination of two different Poxviruses
• Targets a unique cancer cell antigen (PSA) and encodes co-stimulatory molecules
• Subcutaneous injectionVaccinia-PSA TRICOM
Fowlpox-PSA-TRICOM
1) Kantoff et al., Journal of Clinical Oncology, January 2010
PROSTVAC® Phase 2 Results
13
p=0.0061
Δ 8.5 months
N Deaths
Median
Control 40
37 16.6
PROSTVAC®
82
65 25.1
Hazard ratio0.56 (95% CI 0.37–0.85)
0 12
24 36 48 60
survival(% of patients)
0
20
40
60
80
100
months
Source: Kantoff et al., Journal of Clinical Oncology, January 2010
Significantly extended overall survival
16.6 months
25.1 months
PROSTVAC® Phase 3 Design and Endpoints Agreed in SPADesign
• Strongly powered, single global, placebo-controlled study
• ~1,200 patients - asymptomatic or minimally symptomatic, metastatic castration-resistant prostate cancer
• Three study arms:• PROSTVAC® • PROSTVAC® + GM-CSF • Placebo
Endpoints
• Primary endpoint is overall survival (OS)• Either one or both of the treatment arms
must be superior to placebo• Each comparison requires 534 deaths
with sensitivity for estimated death hazard ratios of 0.82 or less
• Phase 3 clinical trial costs — US$150m:• CRO cost • Manufacturing cost• BN internal cost
14
SPA allows for broad margin to be successful
Phase 2 results SPA terms for Phase 3
Demonstrated hazard ratio 0.56
44% reduction in risk of death
Required hazard ratio 0.82 or less
18% reduction in risk of death
Ongoing PROSTVAC® Studies
15
Stage Study design Target Endpoint
Ph3n=1,200
Randomized, double-blind, placebo-controlled efficacy trial of PROSTVAC® +/- GM-CSF
Asymptomatic or minimally symptomatic mCRPC
Overall survival
NCI funded studies:Ph2n=144
Comparison of docetaxel (chemo) with/without PROSTVAC®
Metastatic prostate cancer mCRPC
Survival
Ph2n=65
Comparison of flutamide (antihormone) with/without PROSTVAC®
Non-metastatic prostate cancer
Time to progression (TTP)
Ph2n=68
Comparison of samarium (radioactive drug) with/without PROSTVAC®
Metastatic prostate cancer
4 month progression free survival
Ph2n=50
Investigate PROSTVAC® in men with PSA progress
After local therapy (surgery and/or radiation)
PSA progression at 6 months
Ph1n=21
Investigate PROSTVAC® by intraprostatic injection
Progressive or locally recurrent prostate cancer
Safety, PSA and immune responsePROSTVAC® has more clinical data from combination trials and trials in earlier disease
stages than other prostate cancer immunotherapies
CV-301
• Stimulates immune system to destroy tumors by targeting two tumor-associated antigens (TAA):
• CEA: Carcinoembryonic antigen• MUC-1: Mucin 1
• CEA and MUC-1 are over-expressed in multiple cancers
16
Type Incidence Mortality CEA+ MUC-1+
Breast 233,000 40,000 50% >90%
Lung 221,000 157,000 70% >80%
Ovarian 22,000 15,000 15-65%* >90%
*Non-Mucinous: Mucinous
Cancer Facts & Figures 2011, American Cancer Society
Selected cancers – U.S. figures
Broadly applicable technology platform
17
VF Prime-boost: Vaccinia + Fowlpox
TRICOMTRIad of CO-stimulatory Molecules
PSA MUC-1CEA
• Breast, Lung, Ovarian, Gastric, Bladder, Liver and Renal cancer
• Prostate cancer
PROSTVAC® CV-301
LFA-3ICAM-
1B7.1
GM-CSF can be used as adjuvant in both PROSTVAC® and CV-301
CV-301 breast cancer – ongoing trial
• NCI-funded, open-label Ph2 study (n=48) in metastatic breast cancer
• Docetaxel naïve• Treatment with Docetaxel with/without CV-301• Primary endpoint: Time to progression (TTP)• Enrolment has been completed• Data expected in 2H 2012
18
RANDOMIZE
Arm A: Weekly Docetaxel + CV-301
Arm B: Weekly Docetaxel alone
Study Protocol ID: NCT00179309, NCI-6977
Cancer Vaccines - Short Term Objectives• Complete enrolment in the PROSTVAC® Phase 3 trial • Establish PROSTVAC® partnership before market commercialisation • Report preliminary data from five NCI-funded Phase 1 and 2 studies
with PROSTVAC®
• Report breast cancer data from CV-301 studies and determine future development strategy
19
Infectious Diseases - highlights
• Delivered 4 million IMVAMUNE® doses to the US Strategic National Stockpile as planned
• Received a USD 25 million milestone payment under the RFP-3 contract after a successful scale-up of production
• Extended the contract for development of a freeze-dried version to a total value of USD 94 million
• Clinical Phase 3 trial plan agreed with the FDA• Marketing Authorization Application submitted in Canada and
Europe• If found acceptable, IMVAMUNE® (IMVANEX® in Europe) will be indicated for active
immunization against smallpox in persons aged 18 and older, including immune compromised individuals
2020
Infectious Diseases
2121
Phase 1 (1H 2012)
Phase 3 (2H 2012)IMVAMUNE®
MVA-BN® Anthrax
Next milestone
Smallpox
Anthrax
Phase 1 (2013)MVA-BN® RSV RSV
New Phase 2 (1H 2013)IMVAMUNE® freeze-dried Smallpox
MarketPh1 Ph 1/2 Ph 2 Ph 3PC
Sold to government stockpiles under national emergency rules
Leading supplier of vaccines for biodefense
IMVAMUNE® US Government Contracts
22
RFP-1RFP-2
Early clinical and technical development500,000 doses of IMVAMUNE® deliveredClinical studies will support Emergency Use
RFP-3 Base contract
Option
20 million doses of IMVAMUNE®
Licensing for at-risk individualsDevelopment for immune compromised
RFP Freeze-dried
Validation of production processPreclinical and clinical studies to support advanced development
>US$144m
US$513m
>US$751m
>US$1,100
m
Secured Optional
60 million doses of IMVAMUNE®>US$1,100
m
US$94m
IMVAMUNE® Delivery Status
2010
2011
2012
2013
Deliveries to the US Strategic National Stockpile
Delivered in 2010 2m doses
Delivered in 2011 4m doses
Planned deliveries in 2012 7m doses
Planned deliveries in 2013 7m doses
IMVAMUNE® Freeze-dried
• Contract expanded from USD 40m to USD 94m• Validation of production process• Preclinical and clinical studies to support advanced development
• New Ph2 study planned for 1H 2013 to support emergency use
• Anticipated data availability for stockpiling in 2016
24
IMVAMUNE® - Anticipated Developments
2012 2013 2014-
25
Maintenance orders (LF), Replacement (FD)
Deliver RFP-3 base
LF: Liquid-frozenFD: freeze-dried
Approval
Approval
Infectious Diseases - Short Term Objectives• Deliver 14 million doses of IMVAMUNE® to the US Strategic National
Stockpile in 2012-2013 (7 million in 2012)• Obtain profitability in division • Secure new IMVAMUNE® orders in the USA• Initiate pivotal Phase 3 trial of IMVAMUNE®
• Obtain marketing authorisation for IMVAMUNE® in Canada• Obtain marketing authorisation for IMVANEX® (IMVAMUNE®) in the
EU
26
2012Revenue DKK 850m
Result (loss) before tax DKK -200m
Cash preparedness at year-end
DKK 350m
Assumptions:Deliver and revenue recognize 7 million doses of IMVAMUNE®
R&D costs - GROUP DKK 400m *
Infectious Disease Division, EBITbefore allocation of internal charges
DKK 110m to 130m
Cancer Vaccines Division, EBITbefore allocation of internal charges
DKK -250m to -270m
All numbers are approximate
* R&D costs include approximately DKK 100 million in contract expenses (stated under production costs in the profit and loss statement).
Financial Outlook
Anticipated Future Milestones
CANCER VACCINES• PROSTVAC® Ph3 complete enrolment
(2013)• Data from PROSTVAC ® NCI studies
• Phase 1 recurrent PC• Phase 2 PSA progression• Phase 2 non-metastatic PC• Phase 2 metastatic PC• Phase 2 mCRPC
• CV-301 Ph2 data in metastatic breast cancer (2H 2012)
• MVA-BN® PRO final Ph1/2 data (1H 2012)
INFECTIOUS DISEASES• Deliver 14m doses of IMVAMUNE® to US
government in 2012-2013• IMVAMUNE® Ph3 initiation (2H 2012)• IMVAMUNE® licensure in Canada (2H 2012)• IMVANEX® (IMVAMUNE®) licensure in
Europe (2013)• Anthrax Ph1 funding and initiation (1H
2012)• RSV Ph1 initiation (2013)• Government funding opportunities, current
and future projects
28
29
This presentation includes "forward-looking statements" that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.
APPENDIX
30
Financial Statements
31
DKK million FY 2011 FY 2010
RevenueProduction costs
Gross profit
524403
120
314444
(130)Research and development costsDistribution and administrative costs
Total operating costs
262167
428
189155
344
Income before interest and taxes (308) (474)Financial income/loss
Income before company tax12
(296)(9)
(483)
Tax 28 94
Net profit for the period (268) (390)
Cash preparedness (end of period) 704 460
RFP-3 Contract as of 31 December 2011
USD million P&L Cash Flow
Contract value
Revenue recognise
d
To be recognise
dReceived
To be received
Upfront & Milestone 183 109 74 181 2
Deliveries 2010-2013
270 85 185 56 214
Hold-back 50 - 50 - 50
Security 10 7 3 7 3
TOTAL 513 201 312 244 269
32
Based on 6.048 million doses delivered
Overview of USG IMVAMUNE® Contractsas of 31 December 2011
USD million P&L Cash Flow
Contract value
Revenue recognise
d
To be recognise
dReceived
To be received
RFP-3 513 201 312 244 269
RFP-2 116 113 3 112 4
RFP Freeze-dried 95 13 82 11 84
TOTAL 724 327 397 367 357
33
PROSTVAC® Extends Survival in Patients with Less Advanced Disease
Open-Label Phase 2 in 32 mCRPC patients
34
Median survival (months)
All patients Patients with Halabi-predicted
survival <18 months
Patients with Halabi-predicted
survival ≥18 months
Predicted by Halabi model
17.4 12.3 20.9
With PROSTVAC® (n=32)
26.6 14.6 ≥37.3 (not yet reached)
Δ 9.2 months Δ 2.3 months Δ ≥16.4 months
Patients surviving longer than predicted
22 of 32 (69%) 10 of 17 (59%) 12 of 15 (80%)
Gulley et al. Cancer Immunol Immunother 2009 Nov 5 (Epub ahead of print)