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Project Valuation
& Deal
AnalysisTheory & Applications in the Pharmaceutical
Industry
Pascale Boyer Barresi, CFAAssociate Director, Business Analysis,
Business Development & Licensing, Debiopharm International,
Lausanne (Switzerland)
March 2015
1
Agenda
Business Development & Financing
Product Fit inside the Company Deals Basics Financing
Product Valuation
Case Study without Risk Case Study with Risks
Basic Understanding
Drug Characteristics Diagnostics Overview Valuation Preparation
Introduction
Drug Industry Landscape Finance – Time Value of Money Basics
2
Speaker’s BackgroundEducation
◦ Master in Economics (Finance & Marketing), University of Fribourg (Switzerland), 1998.◦ Chartered Financial Analyst, CFA Institute, Charlottesville (USA), 2003.◦ Certificate in Pharmaceutical Economics & Policy, University of Lausanne, IEMS, 2008.◦ Health Technology Assessments & Economic Valuations, SDA Bocconi, Milan, Italy, 2012.◦ Diploma of Advanced Studies in Digital Communication, Web Expertise & Social Media,
University of Geneva, 2015 (ongoing).
Professional experience◦ More than 10 years professional experience in Banking Industry (Equity Analyst & Fund Manager).◦ Senior Business Analyst in the Pharma Industry since 2010, responsible for Project Valuations & Health Economics.◦ Various lectures
◦ UNIL / IEMS - Financial Analysis of Pharma Companies; ◦ UNIL / HEC - Financial Analysis for CFA Research Challenge teams; ◦ University of Genova (Italy) – Sales Forecasting Techniques; ◦ HEG Geneva – Communication Strategies of Pharmaceutical Companies.
Contact Details◦ Email: [email protected]◦ Linkedin: http://www.linkedin.com/pub/pascale-boyer-barresi-cfa/0/674/a95
3
Your Expectations?
4
Introduction
5
Business Development & Financing
Product Fit inside the Company Deals Basics Financing
Product Valuation
Case Study without Risk Case Study with Risks
Basic Understanding
Drug Characteristics Diagnostics Overview Valuation Preparation
Introduction
Drug Industry Landscape Finance – Time Value of Money Basics
Agenda
6
IntroductionOur goals for today… you will go home with:
◦ Background information on the pharma industry◦ Basic knowledge in finance (focus on time value of money)◦ Valuation tools◦ Ability to value any product (from chewing-gum to drug and medical device)◦ An understanding of a valuation method: rNPV (risk-adjusted Net Present
Value)◦ Some considerations on how to manage a product portfolio◦ An overview of players in start-up fundraising◦ A check-list for project valuation
You will have the view of a CEO or CFO working for a start-up.
7
Drug Industry Landscape
8
Drug Industry LandscapeSome basic charts and stats about the pharmaceutical industry:
• Rx drug sales• Key players• Key therapeutic areas• 2014 drug approvals• R&D process• R&D spending• R&D efficiency
9
Worldwide Rx Drug Sales
10
Key Players (2020)
11
Key Therapeutic AreasTherapy Area Sales 2013
(USDb)Sales 2020e
(USDb)Growth
(CAGR %)Market Share
2013Market Share
2020e
Oncology 72.8 153.1 11.2% 9.7% 14.4%
Diabetes 38.4 68.9 8.7% 5.1% 6.5%
Rheumatology 44.9 57.1 3.5% 6.0% 5.4%
Virology 27.8 45.6 7.3% 3.7% 4.3%
Vaccines 25.6 41.3 7.1% 3.4% 3.9%
Respiratory 32.6 35.9 1.4% 4.3% 3.4%
Sensory Organs 17.5 28.2 7.1% 2.3% 2.7%
Hypertension 33.7 26.1 -3.6% 4.5% 2.4%
Multiple Sclerosis 16.2 21.8 4.3% 2.2% 2.0%
Dermatology 13.5 19.2 5.1% 1.8% 1.8%
Blood Disorders 8.9 17.8 10.4% 1.2% 1.7%
Infectious Diseases 14.6 17.7 2.8% 1.9% 1.7%
Source: Evaluate Pharma 2014.
12
2014 FDA drug approvals
Source: http://www.nature.com/nrd/journal/v14/n2/full/nrd4545.html
EMA approved 40 drugs in 2014 and 34 in 2013.
13
2014 FDA drug approvals
BCG's analysis looked at peak sales estimates for53 new therapeutic drugs (NTDS) that wereapproved in 2014, including new molecular entities(NMEs) and biologic license applications (BLAs).
Source: http://www.nature.com/nrd/journal/v14/n2/full/nrd4545.html
14
How do we get there?R&D Process
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15
Worldwide R&D Spending
16
Down trend in R&D efficiency
Source: http://www.nature.com/nrd/journal/v11/n3/full/nrd3681.html
a | The number of new drugs approved by the US Food and Drug Administration (FDA) per billion US dollars (inflation-adjusted) spent on research and development (R&D) has halved roughly every 9 years.
b | The rate of decline in the approval of new drugs per billion US dollars spent is fairly similar over different 10-year periods.
c | The pattern is robust to different assumptions about average delay between R&D spending and drug approval.
17
Time Value of Money Basics
18
Time Value of MoneyThe time value of money impacts business finance, consumer finance, and government finance.
Time value of money results from the concept of interest.
What we will cover here:
- simple interest - present value
- compounding interest - present value table
- compounding formula
- future value table
Future Value Concept Present Value Concept
19
Simple InterestSimple interest is a topic that most people cover in elementary school. Interest may be thought of as rent paid on borrowed money.
Simple interest is calculated only on the beginning principal (meaning the interest amount doesn’t change).
Continuing to receive 5% interest on the original $100 amount, over five years the growth of the original investment would look like
Year Principal Interest (5%) Total amount1 100 5 1052 105 5 1103 110 5 1154 115 5 1205 120 5 125
20
Compound InterestWith compound interest, interest is calculated not only on the beginning interest, but on any interest accumulated in the meantime.
Year Principal Interest (5%) Cumulatedamount
1 100.00 5.00 105.002 105.00 5.25 110.253 110.25 5.50 115.754 115.75 5.75 121.505 121.50 6.00 127.506 127.50 6.25 133.757 133.75 6.50 140.258 140.25 6.75 147.009 147.00 7.00 154.00
10 154.00 7.25 161.25
21
Simple vs. Compound
0
50
100
150
200
250
300
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Tota
l Am
ount
Year
Simple Interest vs. Compound Interest
Simple Interest Compound Interest
When you compare the growth of simple and compound interest, investments with simple interest grow in a linearfashion and compound interest in a geometric one.
22
Compound Interest Formula
𝑷𝑷𝒏𝒏 = 𝑷𝑷𝟎𝟎 ∗ (𝟏𝟏 + 𝒊𝒊)𝒏𝒏
𝑃𝑃0 = Beginning value𝑃𝑃𝑛𝑛 = End value after n time periods i = interest rate n = number of years
23
Compound Interest Example𝑷𝑷𝒏𝒏 = 𝑷𝑷𝟎𝟎 ∗ (𝟏𝟏 + 𝒊𝒊)𝒏𝒏
𝑷𝑷𝒏𝒏 = 𝟏𝟏𝟎𝟎𝟎𝟎 ∗ (𝟏𝟏 + 𝟎𝟎.𝟎𝟎𝟎𝟎)𝟏𝟏𝟎𝟎= 162.89
𝑃𝑃0 = Beginning value𝑃𝑃𝑛𝑛 = End value after n time periods i = interest rate n = number of years
Year Principal Interest (5%) Cumulated amount
1 100.00 5.00 105.002 105.00 5.25 110.253 110.25 5.50 115.754 115.75 5.75 121.505 121.50 6.00 127.506 127.50 6.25 133.757 133.75 6.50 140.258 140.25 6.75 147.009 147.00 7.00 154.00
10 154.00 7.25 161.25
24
Why the results are not the same?The formula is based on continuous compounding, meaning that eachday the calculation is done.
In the table, the calculation is done once a year yielding a smalleramount.
25
Future Value TablesHow to use them?
𝑷𝑷𝒏𝒏 = 𝑷𝑷𝟎𝟎 ∗ (𝟏𝟏 + 𝒊𝒊)𝒏𝒏 Future Value Factor
i
n
To find the future value of a present amount, locate the appropriate number of years and the appropriate interest rate, take the resulting factor and multiply it times the present value.
26
Future Value ExercisesUse the formula
What is the future value of USD 600 in 5 years with an interestrate of 3%?
◦ 696◦ 730◦ 540
Let’s check!
Use the Future Value Table
What is the future value of USD 1600 in 7 years with an interestrate of 6%?
◦ 2406◦ 3025◦ 1530
𝑷𝑷𝒏𝒏 = 𝑷𝑷𝟎𝟎 ∗ (𝟏𝟏 + 𝒊𝒊)𝒏𝒏
27
Present ValuePresent value is simply the reciprocal of compound interest.
Another way to think of present value is to adopt a stance out on the time line in the future and look back toward time 0 to see what was the beginning amount.
28
Present Value Formula
𝑷𝑷𝟎𝟎 =𝑷𝑷𝒏𝒏
(𝟏𝟏 + 𝒊𝒊)𝒏𝒏
𝑃𝑃0 = Beginning value𝑃𝑃𝑛𝑛 = End value after n time periods i = interest rate n = number of years
29
Present Value Tables
𝑷𝑷𝟎𝟎 = 𝑷𝑷𝒏𝒏 ∗𝟏𝟏
(𝟏𝟏 + 𝒊𝒊)𝒏𝒏
How to use them?
Present Value Factor
To find the present value of a future amount, locate the appropriate number of years and the appropriate interest rate, take the resulting factor and multiply it times the future value.
30
Present Value TablePresent Value Factors are all less than one.
Therefore, when multiplying a future value by these factors, the future value is discounted down to present value.
𝑃𝑃0 < 𝑃𝑃𝑛𝑛The Present Value is always inferior to the Future Value.
31
Present Value ExercisesUse the formula
What is the present value of USD 7500 where n is 7 years and the interest rate is 2%?
◦ 7625◦ 6529◦ 6551
Use the Present Value Table
What is the present value of USD 200’000 where n is 3 years and the interest rate is 6%?
◦ 150’872◦ 195’637◦ 167’920
Let’s check!
𝑷𝑷𝟎𝟎 =𝑷𝑷𝒏𝒏
(𝟏𝟏 + 𝒊𝒊)𝒏𝒏
32
Agenda
Business Development & Financing
Product Fit inside the Company Deals Basics Financing
Product Valuation
Case Study without Risk Case Study with Risks
Basic Understanding
Drug Characteristics Diagnostics Overview Valuation Preparation
Introduction
Drug Industry Landscape Finance – Time Value of Money Basics
33
Drug Characteristics
34
Drug CharacteristicsTopics covered in this section:
◦ Process overview◦ Development costs◦ Drivers of R&D costs◦ Trends in R&D costs◦ Success rates, timing◦ Market access issues◦ Execution
35
OverviewTo estimate the total cost per successful new drug emerging from R&D pipelines accurately, both
◦ the costs of lines of research that ultimately fail and ◦ the cost of capital must be included.
Out-of pocket costs are merely one part of the total cost.
Capitalized costs are real costs as investors require a return that reflects alternative potential uses of their investment. These are the opportunity costs, i.e. the expense of investing in drug research rather than alternative types of investment.
36
OverviewClinical stages
Source: The R&D Cost of a New Medicine, J. Mestre-Ferrandiz, Office of Health Economics, December 2012.
Cumulative probability to reach the market when you start In Target-to-hit: 4.1% In Phase I: 11.7% In Phase II: 21.7% In Phase III: 63.7%
Probability of success of the current phase
Number of productsneeded in R&D to have 1 product on the market
Cost per product in R&D per phase
Duration of eachphase
WIP needed for 1 launch* Cost per WIP per phase e.g. (24.3*1) TTH or (19.4*2.5) HTL
See next slide
37
Focus - CapitalizationThe cost of capitalizing R&D expenditures has to be included in the calculation because it is an opportunity cost as we said earlier. Capitalized costs are real costs as investors require a return that reflects alternative potential uses of their investment.
The cost of capital is used in the calculation.
It should be measured as the expected return that is foregone, i.e. the return that would be expected from investing in an equally riskyportfolio of other investments.
Several studies estimated it between 11 and 14%.NB: The cost of capital for biotechnology companies, heavily focused on discovery and earlystage development, has in the past been observed to be higher than the cost of capital for more traditional pharmaceutical companies, which have projects through all stages of R&D up to regulatory approval.
38
How to calculate capitalizedR&D?
Total processduration: 13 years
We will use the concept we learntbefore: Present Value & Future Value
In this case, the present value is the Cost per launch: $24The number of years is the total process duration: 13.5The cost of capital used as i is 11%
So we calculate the Future Value for TTH by applying the formula:FV TTH = 24*(1+11%)13=$94
For the next phases, you have to reduce the duration as youprogressed along the wholeprocess.FV HTL = 49*(1+11%)(13-1)=171
The amount differences are due to rounding in duration
39
Drivers of R&D Costs
Out-of-Pocket Costs
Success Rates
Development Times
Cost of Capital
Average Cost of a New Molecular
Entity
But there are differences due to:◦ Therapy areas◦ Compound origin (in-house vs.
in-licensed)◦ Firm size (big vs. small)◦ Small molecules vs. biologics
Source: The R&D Cost of a New Medicine, J. Mestre-Ferrandiz, Office of Health Economics, December 2012.
40
Therapeutic Areas & Compound Origin
TherapeuticArea
Cost per NME
(USDm) 2011
Respiratory 1'457 Cancer 1'339 Neurological 1'306 Musculoskeletal 1'216 Blood disorders 1'164 Cardiovascular 1'140 Dermatological 870 Genito-urinary 816 HIV/AIDS 694 Anti-parasitic 583
Phase transition probabilities and clinical approval success probabilities bysource of compound, for compounds first tested in humans from 1993 to 2004
Cumulative probability
to reach the market
Source: The R&D Cost of a New Medicine, J. Mestre-Ferrandiz, Office of Health Economics, December 2012.
41
Firm Size & Molecule TypeFirm Size:
◦ An important variable explored in the literature is the effect of firm size on R&D productivity and whether R&D costs per approved drug vary with firm size.
◦ Results of research on the impact of firm size on R&D productivity and R&D costs are mixed. It remains unclear, however, whether R&D productivity is greater for smaller companies than for traditional “big pharma”.
Molecule Type:
◦ Studies found generally that the overall clinical success rate for biotech products is higher than for traditional pharmaceutical products (30.2% vs. 21.5%).
◦ Total clinical plus approval time is 8% longer for biopharmaceuticals than for traditional pharmaceuticals, with nearly all the difference being in Phase I.
◦ Comparisons between biologics and other pharmaceuticals should be treated with caution because the sample size for biologics still is small.
42
Trends in R&D Costs over Time
Source: The R&D Cost of a New Medicine, J. Mestre-Ferrandiz, Office of Health Economics, December 2012.
43
Success RatesNot all the projects started in discovery end up on the market.
Remember this figure shown at the beginning of the presentation?
44
Success RatesSuccess rates differ by therapeutic area. Here are some benchmarks:
Therapeutic Area Phase 1 Phase 2 Phase 3 Approval CumulativeArthritis & Pain 77% 38% 78% 89% 20%Central Nervous System 66% 46% 62% 78% 15%Cardiovascular 63% 43% 76% 84% 17%Gastrointestinal 67% 49% 71% 86% 20%Immunology 65% 45% 65% 82% 15%Infectious Diseases 71% 51% 80% 97% 28%Metabolism 48% 52% 79% 93% 18%Oncology 77% 44% 62% 85% 18%Respiratory Diseases 63% 41% 60% 77% 12%
Source: Tufts University, 2010; Villiger, 2012.
45
Study from Nature Biotechnology (January 2014)A wide study has been done recently and published in Nature Biotechnology*. It was included in pre-readings.
Key Points:◦ More relevant study (including all types of companies)◦ More recent (time frame: 2003-2011)◦ Inclusion of all development paths (example: if an antibody is developed
for 4 indications and only 1 reach the market, in some studies, the successrate is 100%, in reality it is a 25% success rate)
◦ Main statistic: 10.4% of all indication development paths in phase 1 wereapproved by the FDA (n = 5820)
* Nature Biotechnology, January 2014, Volume 32, Number 1, «Clinical development success rates for investigational drugs», M. Hay, D. Thomas, J. Craighead, C. economides, J. Rosenthal.
46
Study from Nature Biotechnology (January 2014)
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, Vol
ume
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Clin
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inve
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rugs
», M
. Hay
, D. T
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. Cr
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. Ros
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47
Market AccessMarket access ≠ marketing
Market access is linked to the anticipation of whether the payer will reimburse your drug and at what price…
Budget pressure + increase of health expenditures = more scrutiny from payers
48
Market Access Clinical trials
Filing
Approval
Market access
Market access means negotiation with payers (pricing authorities (Europe) or health plans or governmental organizations (USA)).
Payer evidence ≠ Regulatory evidence
Health system, payer requirements and drug pricing are different in each country.
49
Market Access
Source: Bridgehead, Oncology Workshop, London, 2012.
50
Market Access Stakeholders
51
Market Access Planning
Source: Bridgehead, Oncology Workshop, London, 2012.
52
ExecutionThe characteristics of a drug (low success rates, long developmenttimes, challenging commercialization,…) require anticipation and strategic thinking.
It is important to take a external view(why would I purchase this idea/product?).
Key questions:
Imagine the needs• Of the patient• Of the patient’s
family• Of the insurance
company• Of the doctor &
doctor’s office staff
Understand all the possible outcomes• Best case• Worst case
Regulatory risks
Challenges in patient practice• How the disease is
treated• Every aspect of
therapy delivery• Specific need of
patient population• Referral patterns
Clinical risks(enrollment, drugavailability,…)
Reimbursement
53
Diagnostics Overview
54
DiagnosticsMedical Devices
Diagnosis
IVD – In Vitro Diagnostics
Collect, prepare, analyze samples
from human body
MolecularMedicine - In Vivo
Diagnostics
Measure anatomy& patient function
(imaging,…)
Therapy Monitoring Telemedicine
55
DiagnosticsIn this part of the lecture, we will focus only on IVD (in-vitro diagnostics) and its applications in Personalized Medicine.
56
Personalized Medicine
Have a look at this video - http://www.pfizer.ie/personal_med_video.cfm Sour
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Personalized Medicine
Source: http://www.pfizer.ie/personalized_med.cfm
58
Market Size of IVD
Source: Roche.
59
From genediscovery to healthapplication•Analytical validation•Clinical validation
From healthapplication to evidence-basedguideline•Clinical utility•CE & CU studies•Meta-analyses•Systematic reviews•HTA•Guideline
development
From guideline to healthpractice•Dissemination
research•Implementation
research•Diffusion research
From practice to health impact•Outcomes research
IVD Development Path
Source: adapted from http://www.cihr-irsc.gc.ca/e/46872.html
60
IVD Development Costs & Success Rates
StageProbability to do this
stage
CumulatedProbability
EstimatedDuration (years)
EstimatedCosts (USD)
Analytical validation 100% 100.0% 2 600'000 Clinical validation 90% 90.0% 1 1'000'000 Regulatory approval 40% 36.0% 1 500'000 Clinical utility 90% 32.4% 2 6'000'000 Final assay 50% 16.2% 1 100'000 Market 90% 14.6% 0 1'000'000 Total 7 -9'200'000 Source: internal estimates
61
What is the Biggest Challenge in Development?
Source: http://fr.slideshare.net/eInfochips_Solution/designer-pulse-medical-device-developers-survey (2014)
3.2%
3.2%
3.2%
6.5%
6.5%
9.7%
12.9%
19.4%
35.5%
0% 5% 10% 15% 20% 25% 30% 35% 40%
Well defined architecture
UI Development
Hardware design
Software based control
Other
Software development
Design verification test development
Replicating all use case scenarios
Regulatory compliance
The biggest challenge in completing development of a new medical device:
62
What is the Most Critical Success Factor?
3.2%
4.2%
8.7%
9.7%
12.9%
19.4%
41.9%
0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0% 45.0%
Transitioning to products tailored for mHealth era
Other
Improving quality
Lowering development costs to compete globally
Reducing time to market
Lowering product costs to compete globally
Continuing to out-innovate the competition
The most critical success factor in design:
Source: http://fr.slideshare.net/eInfochips_Solution/designer-pulse-medical-device-developers-survey (2014)
63
Opportunities & Challenges Opportunities:
• Aging populations• Increasing incidence of diseases• Focus to disease prevention• Increasing insured population
(USA)• Increased demand for devices
with connectivity solutions (point of care), remote monitoring & data management
• Next Generation Sequencing (all in one test) – Personalizedmedicine
• Emerging countries
Challenges:• Regulatory requirements• Increasing buying power• Switching costs as product
lifecycles are shorter than in the drug industry
• Sensitivity to buying patterns & formulary listings
Trends:• Customer care• Continuous improvements• Automation• Increasing competition, even from
smaller companies
64
Regulatory PathwaysCompare & Contrast… between• Drugs• Medical Devices• IVD
65
Regulatory Pathway - Drugs
Source: https://regulatory.usc.edu/consulting/resources/drugs/
66
Regulatory Pathway –Medical Devices
Source: https://regulatory.usc.edu/consulting/resources/medical-devices/
67
Regulatory Pathway – IVD
Source: https://regulatory.usc.edu/consulting/resources/in-vitro-diagnostics/
68
Valuation Preparation
69
Valuation PreparationTopics covered in this section:
◦ Commercial & Marketing Phase◦ Sales Forecasts
70
Commercial & Marketing PhaseOnce approved by regulatory authorities and reimbursed by payers, patients can start drug treatment and pharma companies will generate sales.
Marketing basics:◦ Building and maintaining a strong, differentiated brand◦ Solidifying and leveraging physician relationships◦ Increasing customer engagement, responsiveness, and loyalty◦ Communicating quality and value◦ Improving the patient experience
71
Sales ForecastsBefore reaching the market and generating sales, the pharma company has to know early whether it is worth developing the project and what is the peak sales potential.
Sales forecasting is an unavoidable step.
72
Sales ForecastsWhat is forecasting?
◦ a planning tool
◦ relying on data from the past, present and trend analysis.
◦ start with assumptions based on experience, knowledge, judgment
◦ build estimates
•Everybody in the organization shouldcommit
Need definition
•Data transparency•Excel is sufficient for
modelling purposes•Adapt to product
evolution
Methodologyselection •Simulations
•Scenarii•Sensitivity analysis•Break-even analysis
Results analysis & Scenario definition
•Garbage in garbage out•Use ranges or scenarios•Keep asking yourself
about the impact on decision making
Presentation
73
Sales Forecasts
Market
EpidemiologyPatient population (diagnosed, treatable, eligible,…)Market access (insurancetypology by patients) Patient awareness
Product
Competitive landscapeMarket share estimationAdoptionCannibalization
Conversion
DosingCompliancePricing (according to product positioning)Benchmark pricing
Sales Forecasts
74
Sales Forecasts - Market
Population• Epidemiology• Growth rate• Symptomatic• Diagnosed
PotentialPatients• Treatable• Eligible• Patient awareness
Treated Patients• Patient access• Insurance types• Patient action
75
Sales Forecasts - Product
Treated patients• Patient access• Insurance types• Patient action
Patients treated withyour product• Competitive landscape• Market share estimation• Adoption curves• Cannibalization
76
Sales Forecasts - Conversion
Patient treatedwith your product• Competitive landscape• Market share
estimation• Adoption curves• Cannibalization
Volume forecast• Dosing• Compliance• Persistence
Sales forecast• Benchmark pricing• Positioning• Target pricing• Discount & rebates• Price erosion/inflation
77
Market Share EstimationLimited data available for benchmarking…
Order of entry1 2 3 4 5 6 7 8 9 10
Number of
products
1 100%2 58% 42%3 43% 31% 26%4 35% 25% 21% 19%5 30% 22% 18% 16% 14%6 26% 19% 16% 14% 13% 12%7 24% 17% 14% 13% 11% 11% 10%8 22% 16% 13% 12% 10% 10% 9% 8%9 20% 15% 12% 11% 10% 9% 8% 8% 7%
10 19% 14% 11% 10% 9% 8% 8% 7% 7% 7%
Source: The order of entry effect in prescription (Rx) and over-the-counter (OTC) pharmaceutical drugs, G. Kalyanaram, International Journal of Pharmaceutical Healthcare Marketing, Volume 2, Numero 1, 2008, pp. 35-46.
78
Distribution Chain in PharmaA small word on pricing in pharma
Manufacturer Wholesaler Pharmacist PayerPatient
Government
Ex-Factory
Price
WholsalePrice
PharmacyPrice
RetailPrice
Tax
Out of pocket
AgreedPrice
COGS
Used to calculate
sales forecasts
About Drug PricesThe manufacturer won’t sell its medicine directly. It will go through a wholesaler, which will sell to a pharmacist and then to the patients. The state can also apply some tax on drugs.In one word, the manufacturer won’t receive the retail price but the exFactoryprice, which is what will be used in sales forecasts.The breakdown between the manufacturer, the wholesaler, the pharmacist and the state will vary country by country.
79
Retail Price Breakdown
0% 20% 40% 60% 80% 100%
Austria (2008)Belgium (2008)
Denmark (2007)Finland (2007)France (2011)
Germany (2008)Italy (2007)
Portugal (2008)Spain (2010)
Sweden (2007)Switzerland (2011)
AverageMedian
ExFactory Margin Wholesale Margin Pharmacy Margin VAT
Main source: http://whocc.goeg.at/Publications/CountryReports & internal calculations
80
Case StudyExcel spreadsheet structure
81
ExerciseNow you have all the tools to try alone.
82
Business Development & Financing
Product Fit inside the Company Deals Basics Financing
Product Valuation
Case Study without Risk Case Study with Risks
Basic Understanding
Drug Characteristics Diagnostics Overview Valuation Preparation
Introduction
Drug Industry Landscape Finance – Time Value of Money Basics
Agenda
83
Net Present Value
84
NPV – Net Present ValueIn finance, the net present value (NPV) of a time series of cash flows, both incoming and outgoing, is defined as the sum of the present values (PVs) of the individual cash flows of the same entity.
NPV is a standard method for using the time value of money to appraise long-term projects.
Used for capital budgeting and widely used throughout economics, finance, and accounting, it measures the excess or shortfall of cash flows, in present value terms, above the cost of funds.
It compares the present value of money today to the present value of money in the future, taking inflation and returns into account
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NPV – Context
Time
InvestmentUSD -2000
0
1 32 4
CashflowYear 1
USD 1000
CashflowYear 2
USD 1000
CashflowYear 3
USD 1000
CashflowYear 4
USD 1000
Cash inflows
Cash outflows
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NPV – What is the value today?
Time
InvestmentUSD -2000
0
1 32 4
CashflowYear 1
USD 1000
CashflowYear 2
USD 1000
CashflowYear 3
USD 1000
CashflowYear 4
USD 1000
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NPV – PV FormulaRemember?
𝑷𝑷𝟎𝟎 =𝑷𝑷𝒏𝒏
(𝟏𝟏 + 𝒊𝒊)𝒏𝒏
𝑃𝑃0 = Beginning value𝑃𝑃𝑛𝑛 = End value after n time periods i = interest rate n = number of years
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NPV – Transformation of Future Values in Present Values
Time
InvestmentUSD -2000
0
1 32 4
CashflowYear 1
USD 1000
CashflowYear 2
USD 1000
CashflowYear 3
USD 1000
CashflowYear 4
USD 1000
Let’s take a 10% discount rate
𝑷𝑷𝟏𝟏 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟏𝟏
= 909
𝑷𝑷𝟐𝟐 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟐𝟐
= 826𝑷𝑷𝟑𝟑 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎
(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟑𝟑= 751
𝑷𝑷𝟒𝟒 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟒𝟒
= 683
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NPV CalculationIt is the sum of the initial investment (negative cashflow) and all the present value of the positive cash flows:
InvestmentUSD -2000
𝑷𝑷𝟏𝟏 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟏𝟏
= 909 𝑷𝑷𝟐𝟐 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟐𝟐
= 826 𝑷𝑷𝟑𝟑 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟑𝟑
= 751 𝑷𝑷𝟒𝟒 = 𝟏𝟏𝟎𝟎𝟎𝟎𝟎𝟎(𝟏𝟏+𝟎𝟎.𝟏𝟏)𝟒𝟒
= 683++ + +
= 1169
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Exercise – Project ValuationYou are the project manager of a well-established brand of cakes and youwould like to launch a new flavor. You already tested the market withseveral panels that decided on almond and strawberry new cake.◦ Start-up costs (year 0): USD 5 million
◦ Launch costs (year 1): USD 1 million
◦ Sales (year 1): USD 1.5 million◦ Sales (year 2): USD 2 million
◦ Sales (year 3): USD 3.2 million
◦ Sales (year 4): USD 4 million◦ Discount rate: 9%
What’s the present value of the project?
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Focus on the Discount RateThe discount rate consists of 2 elements:
Remember that the discount rate reflects your view.
It will not be the same if your are:◦ the founder of the company◦ a partner looking for a project◦ an investor (VC, business angel,…)
Time value of money•Risk-free rate of return•Return on a US Treasury security withthe same time horizon
•~ 3.5%
Risk premium - standard•All the risks faced by the company(management, currency, market, country, legal, manufacturing)
•~ 5.5-6.5%
Total Discount rate: ~ 9.3%-10.3%
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20-year US Treasury Yield
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Risk-adjustedNet Present Value
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rNPV IntroductionDeveloping a cake is less risky than developing a drug.
NPVs are perfect for normally risky activities but not for valuing drugprojects because of clinical risks.
If you put clinical risks into the risk premium, you end up with very high discount rates (see next slide).
It is better to consider clinical risk separately and leave the riskpremium unchanged (and by doing so the discount rate is reasonableand the global value is automatically adjusted with the success rates).
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NPV vs rNPVNPV rNPVo The discount rate is a “black box”
containing all the riskso The investors’ preferred method
(which are looking for a common ground for the valuation of their holdings)
o Less preciseo Discount rates to use according to
the stage of development:• Preclinical: 55%• After Phase 1: 45%• After Phase 2: 30%• After Phase 3: 20%• Approved: 15%
o The discount rate is separated from the success rate. The cashflows are impacted more precisely.
o The pharma & biotech industries’ preferred method
o More preciseo Discount rates to use according to
the stage of development:• Preclinical: 18-20%• After Phase 1: 17-18%• After Phase 2: 15-17%• After Phase 3: 13-14%• Approved: 10%
Source: Avance.
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ExampleWe would like to know the value of a drug project today (2014):
◦ disease: rheumatoid arthritis (arthritis & pain category)◦ stage: Phase 1◦ clinical costs: Phase 1: USD 15m; Phase 2: USD 40m; Phase 3: USD 150m;
submission: USD 40m. Each phase lasts one year.◦ annual cashflows (net sales): launch year USD 5m; next year: USD 398m;
the year after: USD 740m; then you can apply a growth rate of 10% per year
◦ discount rate: 13%
Source: Tufts University, 2010; Villiger, 2012.
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ExerciseNow use the success rates given by Nature Biotechnology(Neurology therapeutic area – All indications because classification isnot the same as the previous one).
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rNPV – Methology SummaryGoal: provide a range of financial values for a project or a deal
Methodology: ◦ Collect all datapoints from costs to sales forecasts
◦ Estimate probability of success at each phase and calculate the cumulative probability at each phase.
◦ Choose the discount rate
◦ Build the model & sum to reach rNPV
◦ Stress your model by changing assumptions and build a summary of scenarii and sensitivities
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Business Development & Financing
Product Fit inside the Company Deals Basics Financing
Product Valuation
Case Study without Risk Case Study with Risks
Basic Understanding
Drug Characteristics Diagnostics Overview Valuation Preparation
Introduction
Drug Industry Landscape Finance – Time Value of Money Basics
Agenda
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Product Strategic Fit
101
Product Strategic FitDoes the project fit in your portfolio?
How to analyze it?
How to manage several projects?
How to allocate resources?
Common sense is crucial.
102
Challenging Context◦ Deal with future events and opportunities (where much of the
information is uncertain)
◦ Very dynamic decision environment (status and prospects for projects are ever changing, as new info becomes available)
◦ Projects in the portfolio are at different stages of completion (all projects compete against each other for resources)
◦ Resources to be allocated are limited and resources transfers between projects are not totally seamless (choices have to be made)
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Goals
Value Maximization Balance
StrategicDirection
Right Number of
Projects
104
Goals
Value Maximization Balance
StrategicDirection
Right Number of
Projects
Tools: financial models (NPV, rNPV) & scoring modelsResult: rank-ordered list of “Go” and “Hold” projects
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Goals
Value Maximization Balance
StrategicDirection
Right Number of
Projects
Tools: visual charts, portfolio maps(bubble diagrams with the choice of the dimensions will have to fit your company objectives and it will depend on the stage of the company, the product types, the targeted markets,…The bubble size is very often representing the resources used)
Result: vision of balance
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Goals
Value Maximization Balance
StrategicDirection
Right Number of
Projects
Tools: questionsAre all your projects consistent with your business’strategy? Are they in or out the bounds of the defined focus areas (markets and/or technologies)?Does the breakdown of your spending reflect your strategic priorities?
Result: gap analysis between “what should be” and “what is”.
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Goals
Value Maximization Balance
StrategicDirection
Right Number of
Projects
Tools: resource capacity analysisResult: allocation of resourcesDo you have enough of the right resources to handle projects currently in your pipeline?Do you have enough resources to achieve your new product goals (% of your business sales coming from new products)?
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Deal Basics
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Deal Introduction◦ Pharmaceutical alliances have been a critical driver of growth in the
biotech industry.◦ An important point for biotech companies is to manage the alliance
in order to get enough funding to sustain the operating activities.◦ What are the key characteristics of a biotech company that can
attract a potential partner?◦ Innovation & new technology – something that represents a material change in the
treatment paradigm◦ Broad application of the technology – the broader the better◦ Effective and productive collaboration with academics – value of the access to KOL
(key opinion leaders)◦ Experienced team with the right skill sets – relationships are key. A cultural fit is
always a good complement to the technical fit◦ Financial health to pursue key programs
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Deal Basic Questions
Lice
nsin
gSt
rate
gy What are the gaps?What can we offer?
Opp
ortu
nity
Iden
tific
atio
n What do we need?Where will we find it?
Lice
nsin
gEv
alua
tion What is the
value to us?
Deal
-Mak
ing
& A
gree
men
t What are my target acceptable risks, returns and responsibilities?
Post
-Dea
l Ana
lysi
s What could be done better next time?
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Deal Types◦ In-licensing◦ Out-licensing◦ Co-development◦ Co-promotion◦ Asset purchase / Acquisition◦ Collaboration◦ Joint-venture◦ Sublicense◦ Option◦ Alliance◦ Merger ◦ …
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Deal Due DilligenceEnvironmental Partnering Pressure
EnvironmentalUncertaintyGlobal Competition
Partnering Antecedents
InterdependenceConflictTrustCommitmentOrganizationalCompatibilityTop Management Vision
Partnering Orientation
StrategicOperational
Partnering Implementation
Information SharingTechnology UtilizationStrategic Interface TeamsOrganizational IssuesJoint ProgramsAsset SpecificityJoint Performance Measures
CompetitiveAttainment
Competitive AdvantageCompetitive ParityCompetitiveDisadvantage
BUSINESS PERFORMANCE OUTCOME• Economic
Performance• Patient
Satisfaction • Prescriptor’s
Loyalty• Relationship
Effectiveness
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Deal StructureAn perfect deal structure should:
◦ Compensate the licensee for taking on the risk◦ Generate payments representative of the value of the product for the
licensor
Inputs for the model should be realistic, understandable and transparent.
Financial deal terms are sometimes given. Some databases like Deloitte Recap and Medtrack are trying to guess the terms. They give you trends and comparables usable to draft a first proposal.
Today, deals are much more back-end loaded than before, meaning by that you will get small upfront but double-digit royalties and commercial milestones.
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Deal Trends◦ Pharmaceutical trends of reducing internal R&D and increasing the in-
licensing of early clinical stage candidates is leading to active competition in the field of spotting the best biotech opportunities.
◦ Information on the movements of big pharma is valuable for the business development of biotech startups.
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Big Pharma PartneringInterest by Therapeutic Area
Source: Nature Biotechnology, Building for Big Pharma, A. Giniatullina, M. Boorsma & al., March 2013.
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M&A Deal Statistics(January 2005-June 2012)
Therapeutic Area Total spent(USDm)
Average total deal value (USDm)
Number of deals
Oncology 6576 387 18Infectious diseases 6432 643 10Cardiovascular diseases 3367 561 6Chronic inflammation 3339 477 7Mixed 2470 618 4Injury 1787 596 4Endocrine and metabolic diseases 1710 428 4Platforms 1526 218 8Ophthalmology 1067 534 2Genitourinary diseases 745 373 2CNS 715 358 4Respiratory diseases 540 270 3Blood disorders 445 223 2
Source: Nature Biotechnology, Building for Big Pharma, A. Giniatullina, M. Boorsma & al., March 2013.
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Up-to-date information◦ Interesting information on: www.currentpartnering.com select the
Scorecard tab (for deals over USD 500m).
◦ Ernst & Young, PWC, Deloitte,… are also very active in publishingannual reports on the current state of the industry. Check theirwebsite or subscribe to their newsletter.
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Transaction Total Value per Year
a | Mergers and acquisitions. The chart includes full-company acquisitions and purchases of majority stakes. The 'number of deals' total includes deals that did not have a disclosed value. b | Partnerships. c | Break-down of partnerships by therapeutic area. Deals involving more than one therapy area may be counted multiple times, if applicable. Source: Medtrack.Source: http://www.nature.com/nrd/journal/v14/n2/full/nrd4536.html
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Biggest Deals of 2014
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A deal is a starting point◦ Pharmaceutical alliances = critical driver of growth in the biotech
industry
◦ Over 50% of drugs approved are originated from alliances
◦ Effective alliance management = balance of…
• Risk taking• Discipline• Good relationships
◦ By having enough cash through collaboration, you gain credibility and reputation to attract additional partners
Regular stream of cash fromsuccessfully completed milestones
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Financing
122
IntroductionCapital raised by Life Sciences Companies (USDm)
2014 2013 2012Change
2013-2014 (%)
Global Venture Capital 16’489 12'662 12'419 30.2%Global IPOs (Initial Public Offering) 11’039 7'570 2'126 45.8%Global PIPE (Private Investment in Public Equity) 5’711 4'775 5'382 19.6%
Global Follow-ons 13’836 14'327 7'109 -3.4%Global Other Equity 813 1'545 2'256 -47.4%Global Debt Offerings 40’013 44'359 49'869 -9.8%Global Other Debt 16’249 10'521 13'389 -54.4%
Global Public Financing 87’661 83'097 80'131 5.5%Global Partnering 53’139 43‘049 38'178 23.4%Global M&A 355’309 131‘908 108'865 169.4%
Source: Burrill & Company: http://www.burrillreport.com/article-biotech_industry_shatters_fundraising_records_in_2014.html
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IntroductionFinancing & Acquisition Activity in Lifesciences in 2013
Global Venture Capital5%
Global Public Financing
30%
Global Partnering
16%
Global Mergers &
Acquisitions49%
Global IPOs (Initial Public
Offering)9% Global PIPE
(Private Investment
in Public Equity)
6%Global
Follow-ons17%
Global Other Equity
2%
Global Debt Offerings
53%
Global Other Debt13%
Source: Burrill & Company, Biotech Stocks Win Big In 2013, January 2nd, 2014..
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Global IPOs (Initial Public
Offering)13%
Global PIPE (Private
Investment in Public Equity)
6%
Global Follow-ons16%
Global Other Equity
1%Global Debt
Offerings46%
Global Other Debt18%
IntroductionFinancing & Acquisition Activity in Lifesciences in 2014
Source: Burrill & Company: http://www.burrillreport.com/article-biotech_industry_shatters_fundraising_records_in_2014.html
Global Public Financing
17%
Global Venture Capital
3%
Global Partnering11%
Global M&A69%
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Funding Landscape◦ In the past = Venture capital funds were well capitalized (by
institutional investors) and had assets under management from USD 100m up to USD 1b
◦ Economic downturn 2008-2011
◦ Returns from venture capital funds have not outperformed the public market since the late 1990s (Ewing Marion Kaufmann Foundationstats)
◦ Lack of transparency and long lockup periods turned many funds intocapital trap
◦ A lot of institutional investors withdrew their capital and startedtheir own alternative investing => new players in the field
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Funding Landscape
Source: Nature Biotechnology, The view beyond venture capital, D. ford & B. Nelsen, January 2014..
127
Types of Investors◦ Fundraising is an integral part of almost every young biotech’s
business strategy
◦ It is key to identify and prioritize potential investors
◦ You have 2 types of investors: private and public
Private Investors Public Investors
• Angels & Super Angels• Corporate Venture Capital• Family & Friends• Family Offices & Private Wealth• Foundations, Nonprofit and Patient
Advocacy Groups
• Federal Government• Regional Economic Development
Agencies• Stock Markets
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IPOor Initial Public Offering.
This is the first sale of stock by a private company to the public.
IPOs are often issued by smaller, younger companies seeking the capital to expand, but can also be done by large privately owned companieslooking to become publicly traded.
In an IPO, the issuer obtains the assistance of an underwriting firm, which helps it to determine what type of security to issue (common, preferred,…), the best offering price and the time to bring it to the market.
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IPO Pros & ConsPros Cons
• Access to capital to fund operations• Exit strategy for venture capitalists• Liquidity for management and employees• Stock options to attact employees• Greater public awareness of the company
and its products• Use of the stock for acquisitions
• Compliance and regulatory disclosuresimposed by stock market regulators
• Reporting for sales of securities• Quarterly or half-year financial
statements reporting• Risk of potential liabilities if the company
or its directors do not comply withregulations
• IPO cost: approximately USD 2.5m first year, between USD 0.1 and 1m the yearsafter
• Trading volume and valuation issues if the market capitalization is below a threshold
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Lifesciences IPOs in 2014 –What happened?Key points:
◦ History:◦ 11 in 2012◦ 37 in 2013◦ 79 in 2014
◦ This robust activity, combined with substantial deal-making in the private venture-backed M&A arena, resulted in spectacular returns that were double those of 2012 and more than 25 percent higher than the previous record year of 2013.
◦ Early-stage biotechs accounted for 41% (preclinical and Phase I companies) ◦ Corporate venture arms helped support private venture groups in driving a
big increase in the amount of Series A cash flowing to early-stage ventures.
Source: http://www.fiercebiotech.com/story/record-year-biotech-inspires-some-great-expectations-2015/2015-01-06
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Raising Start-up Capital in Switzerland
◦ Swiss Venture Guide 2013, 5th Edition.
◦ Financing your start-up in Switzerland, Seminar «The practice of Entrepreneurship», 2009, Zurich University, J. Fülscher, www.jan.fuelscher.ch
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Conclusion133
Conclusion –Valuation & Deals Wrap-upValuation check-list to get the most value from your potential partnerby presenting a well-constructed methodology for valuation:
• Revenue (Sales Forecasting Process)• Credible epidemiology (never use 100% diagnostic rate, 100% treatment
rate, 100% compliance or 100% reimbursement rate)• Build an understanding of the complex series of payments and product
flows in the pharmaceutical supply chain. • The price paid to a drug manufacturer is on an exFactory basis (after
discounts and rebates)• Anticipate strategies with payers and reflect program supports in the
valuation• Show realistic expectations about the competitive environment• Always explain the drivers you consider when formulating the
assumptions
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Conclusion –Valuation & Deals Wrap-up
• Costs• Development costs:
• Use average cost per subject costs• These costs will depend on the
therapeutic area
• Commercial costs: • Cost of the salesforce, marketing and
distribution; • Test the ratio of prescribing physicians to
sales reps (often 100:1)• At least 10% of peak revenue annually is
spent on the combination of sales and marketing
• Manufacturing costs• Costs for materials used in clinical
development (will probably be high because lacking of optimization)
Source: Cutting Edge Report, Clinical Development and Trial Operations, Protocol Design and Cost per Patient Benchmarks, November 2013.
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Conclusion –Valuation & Deals Wrap-up
• Discount rate• As indicated before in the lecture, you need a discount rate in order to
discount your cashflows• Each cash flow (revenue – cost) is discounted for time by multiplying by
1/(1+k)n
• Lower discount rate = Higher valuation• It is often to your benefit as an out-licensor to use the discounte rate
appropriate for your partner (a survey found that in-licensors tend to use as discount rate 2% lower than used by precommercial companies)
• Risk-adjustment• With benchmark success rates (publicly available, different sources)
136
Conclusion –Valuation & Deals Wrap-up
• Allocation of value• After completing the valuation and obtaining a range of rNPVs, the next
step is to determine how that value will be shared between the parties• This leads to deal structuring with upfront, milestones and royalties
negotiations• Each partner is entering the agreement because each expects to gain more
value from their share of a partnership than could be obtained by pursuing the opportunity independently
• Rule of thumb: in phase 2, the value allocation for an out-licensor isaround 40-60%.
• It will depend on the risk taken by the party and its financial implications.
137
Conclusion –Valuation & Deals Wrap-up
• Special case – dealing with a VC• VC relies often on comparable analysis• VC is interested in what your company is going to be worth when they can
sell an equity stake• The key steps to be prepared for comparable analysis are:
• Ask industry experts about pre- and post-money valuations => benchmarks for the samedevelopment stage
• Look for companies having achieved a liquidity event recently (acquisition or IPO)• The closer you match the comparable (therapeutic area, development stage, region) to where
your project hopes to be at liquidity, the more credible the comparable analysis• Check exit multiples of VCs, if available
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Conclusion –Valuation & Deals Wrap-upDeals and valuation are closely linked.
You cannot do a deal without a value (and a valuation).
Make sure you control the whole valuation process and you can justifyeach step in order to gain credibility in the eyes of your potentialpartner.
No one knows as much about your asset as you do.
You are in the best position to substantiatethat value.
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Thanks for yourattentionAny feedback?
What you liked?
What you don’t like?
What was too long?
What was too short?
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Non-exhaustive list of references
• Excellent website on bioentrepreneurship: http://www.nature.com/bioent/index.html
• Phrma 2012 profile: http://www.phrma.org/sites/default/files/159/phrma_industry_profile.pdf
• Valuation in LifeScience, 3rd edition, B. Bogdan, R. Villiger, 2010.
• Forecasting for the Pharmaceutical Industry, A. Cook, 2006.
• Valuation for M&A – Building Value in Private Companies, F.C. Evans, 2001.
• Creating Strategic Advantage in the Negotiation of Life Science Deals, Luis Pareras, 2011.
• Managing Your Innovation Portfolio, Harvard Business Review, May 2012, p. 67-74.
• Deloitte Recap LLC, Deal Drafting Guidelines, May 2009.
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