1、Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,June 4-8,2004,*,Click to edit Master title style,Click to edit M
2、aster text styles,Second level,Third level,Fourth level,Fifth level,June 4-8,2004,*,From Pipelines To Portfolios,Min Ding,Pennsylvania State University,Jehoshua Eliashberg,University of Pennsylvania,Choice Symposium,June 4-8,医药公司产品组合优化,第1页,Outline,Optimizing New Drug Pipeline,one business opportunit
3、y,Ding and Eliashberg,Management Science,From Pipelines to Portfolios,many business opportunities,Some theoretical insights,An empirical demonstration-GlaxoSmithKline,June 4-8,2,医药公司产品组合优化,第2页,Terms Used in Presentation,Indications,Also known as disease,Each indication is considered as one business
4、opportunity,e.g.,AIDS,We use the terms“,pipeline or project,”to represent the NPD structure for a given indication,We use“,approach,”to represent a specific way(e.g.,a compound,a biological molecule)of drug development tailored for a given indication.,Therapeutical,Classes,Also known as therapeutica
5、l,areas,groups,or categories,e.g.,Anti-infective products,Each class has many different indications,We use the term“,portfolio,”to represent the NPD structure for many different indications,within or across different therapeutical classes.A portfolio has many different pipelines(or projects).,June 4
6、-8,3,医药公司产品组合优化,第3页,Optimizing New Drug Pipeline,An Example,Bristol-Myers Squibb wants to develop a preventive HIV vaccine.,NPD in Pharmaceutical Industry,Alternative approaches:,subunit vaccine,recombinant vector vaccine,peptide vaccine,virus-like particle vaccine,plasmid DNA vaccine,“naked DNA”vac
7、cine,whole-inactivated virus vaccine,live-attenuated virus,etc.,Question:How many alternative approaches should the firm pursue at each NPD stage?,Pre-clinical,trial,Clinical,Phase I,Clinical,Phase II,Clinical,Phase III,launch,1,June 4-8,4,医药公司产品组合优化,第4页,Optimizing New Drug Pipeline,Model Output,For
8、 each phase in development,we derived the expected reward,variance,and likelihood of having a successful drug candidate.For example,for Phase III,they are,respectively,We solve for the optimal number of approaches to be supported at each phase in development,June 4-8,5,医药公司产品组合优化,第5页,Optimizing New
9、Drug Pipeline,One Key Insight-A Pattern of Underspending?(Ding and Eliashberg,Management Science,),June 4-8,6,医药公司产品组合优化,第6页,Firms Target Multiple Business Opportunities,a survey of new drug portfolios in 1450 firms on 12/31/,Most firms work on multiple indications.,June 4-8,7,医药公司产品组合优化,第7页,From Pi
10、pelines to Portfolios,A conventional approach to portfolio construction,Portfolio construction is the sum of pipelines.,Process:,Develop a(not necessarily optimal)pipeline for each business opportunity independently and calculate the expected value,Rank order each business opportunity,Build a portfo
11、lio by supporting those business opportunities whose expected values are above a threshold(e.g.,marginal return,IRR),Example:SmithKline in mid-1990s(HBR,1998),June 4-8,8,医药公司产品组合优化,第8页,From Pipelines to Portfolios,State of Art Practice GlaxoSmithKline,Cardiovascular and Urogenital,Metabolic and Vira
12、l Diseases,Microbial,Musculoskeletal and Proliferative Diseases,Neurology and Gastrointestinal,Psychiatry,Respiratory and Inflammation,Six,Centers of Excellence(Therapeutic Class)for Drug Discovery(CEDDs),Indications Supported,In Each CEDD,9(,Stroke)and 3(ED),5(,Obesity)and 7(HIV),7(,Sepsis),2(osteo
13、porosis)and 9(cancers),11(,Alzheimers)and 5(Irritable bowel synd.),9(,Depression),4(,Asthma)and 3(Rheumatoid arthritis),June 4-8,9,医药公司产品组合优化,第9页,From Pipelines to Portfolios,Where does the state of the art practice succeed and fail?,Succeeded:,Correctly recognized the importance of cross-project ef
14、fects in structuring portfolio,Developed the necessary organizational structure(e.g.,3 tier structure at GSK),Failed:,Risk has not received sufficient attention,ENPV is the most commonly used metric.,No rigorous portfolio evaluation process and optimization model exist.,June 4-8,10,医药公司产品组合优化,第10页,F
15、rom Pipelines to Portfolios,Research Objectives,Understand how risk and expected reward change as the nature of a pipeline changes.,Today:How Phase III variance and expected reward change as the degree of correlation changes,Indication level,Area level,Develop optimal portfolio,given a certain manag
16、erial objective,Today:An application for Glaxo-Smith-Kline(GKS)s Phase III subportfolio,June 4-8,11,医药公司产品组合优化,第11页,From Pipelines to Portfolios,Indication Level-Scenario,Scenario:One indication with two approaches,whose success is conditional on overcoming a common obstacle,Indication 1,Approach 12
17、,Approach 11,p,1,:joint probability of overcoming the common obstacle in Phase III AND other obstacles related to Phase III,p,1i,:probability of overcoming the common obstacle related to Phase III,June 4-8,12,医药公司产品组合优化,第12页,From Pipelines to Portfolios,Indication Level Some Insights(Risk-Reward),Va
18、riance,Expected Reward,Variance,Expected Reward,Case 1.Low p,1,Case 2.High p,1,As p,1i,increases,both variance and expected reward at Phase III increase,As p,1i,increases,variance decreases and expected reward increases,at Phase III,June 4-8,13,医药公司产品组合优化,第13页,From Pipelines to Portfolios,Area Level
19、-Scenario,Scenario:One area with two indications,each indication with two approaches.The success of any approach is conditional on overcoming common obstacles at both area and indication level.,Indication 1,Area,Indication 2,Approach 22,Approach 21,Approach 12,Approach 11,June 4-8,14,医药公司产品组合优化,第14页
20、,From Pipelines to Portfolios,Area Level Some Insights(Risk-Reward),Case.Low p,1,high p,1a,Variance,Expected Reward,As p,1i,increases,both variance and expected reward at Phase III increase.,We have also characterized situations where higher p,1i,leads to lower variance and higher expected reward at
21、 Phase III,June 4-8,15,医药公司产品组合优化,第15页,Work-In-Progress:Evaluating Portfolios Based on other Risk Metrics(Perspectives from Financial Literature),Value-at-Risk(VaR),Measures the likelihood that a given portfolios losses will exceed a certain amount.,Examples,Expected tail loss(expected shortfall),Se
22、mi-variance,June 4-8,16,医药公司产品组合优化,第16页,From Pipelines to Portfolios,Accommodating Richer Environment,Managers want/need to know the entire distribution of reward;,Managers want/need to optimize,in addition to evaluate portfolio;,Managers need to relax assumptions used earlier,for example,Allow each
23、 approach in each indication to have unique probability of success,Solution:A general model,June 4-8,17,医药公司产品组合优化,第17页,From Pipelines to Portfolios,An Application of the General Model,What we show here,An optimization exercise based on GlaxoSmithKline Phase III Subportfolio(December),The predicted
24、distribution of market payoffs of its current portfolio based on our portfolio model,If GSK were interested in licensing two additional Phase III compounds,which compounds it should add to its existing portfolio,under 3 different 2-tier objectives,What we do not show here(but could be done similarly
25、),Optimization of earlier stage subportfolios,Optimization based on other types of strategic objectives,e.g.,Discontinuing some current projects(portfolio audit),Optimal budget(determine budget based on strategic objectives),June 4-8,18,医药公司产品组合优化,第18页,GSK Phase III Subportfolio,From GSK Website,A,B
26、,J only denote the sequence of indications in a given area,the same letter represents different indication in different area.,June 4-8,19,医药公司产品组合优化,第19页,GSK Phase III Subportfolio,A Numeric Matrix Representation,A,B,J only denote the sequence of indications in a given area,the same letter represent
27、s different indication in different area.,The number in a cell represents the number of approaches supported targeting that particular indication,June 4-8,20,医药公司产品组合优化,第20页,Distribution of Market Payoff Given GSKs Current Phase III Subportfolio,June 4-8,21,医药公司产品组合优化,第21页,Optimization Scenarios,GSK
28、 wants to license in two compounds to add to its existing Phase III subportfolio,which compounds should be licensed under each of the three different 2-tier strategic objectives:,Maximize expected NPV,conditional on it will obtain$35b or above with a minimum of 35%chance,Maximize the probability of
29、obtaining more than$50b,conditional on it will obtain$35b or above with a minimum of 31%chance,Minimize the probability of obtaining less than$15b,conditional on it will obtain$35b or above with a minimum of 27%chance,June 4-8,22,医药公司产品组合优化,第22页,Optimization Output,Red(max(ENPV),Blue(max($50b),Orang
30、e(min($15b),Shaded area were searched for optimal portfolio,June 4-8,23,医药公司产品组合优化,第23页,Conclusions,Formal models that link directly the pipeline to the portfolio metrics are needed.,Risk and reward for a given portfolio must be evaluated carefully,Different strategic objectives lead to different optimal portfolios,June 4-8,24,医药公司产品组合优化,第24页,
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