HEALTHCARE SECTOR SECONDARY RESEARCH SAMPLE REPORT

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1 HEALTHCARE SECTOR SECONDARY RESEARCH SAMPLE REPORT Market Landscape Assessment: Epidemiology, Current Treatments and Unmet Needs, Clinical and Preclinical Pipeline, Review of Key Trials, Emerging Profile of New Therapies Dan Meichenbaum Will Anlyan

2 Introduction of services Market Research Intelligence: Make More Informed Investment and Management Decisions Dectiva specializes in delivering quantitative and qualitative market research data and analysis to leading investment and business decision makers. By providing access to a a global panel of survey and interview respondents, Dectiva empowers its clients with proprietary knowledge and timely insights in the life sciences industry. Dectiva serves institutional investment, venture capital, private equity, and corporate entities. Clients Use Dectiva's Primary Market Research Platform To:» Survey targeted physician and patient groups to forecast demand and rate of adoption for new products» Test new target product profiles to investigate strengths, weaknesses, opportunities, and positioning relative to the competitive set» Identify unmet therapeutic needs and determine potential barriers to new product adoption» Analyze existing target markets to understand usage rates of competing products where sales information is incomplete» Collect early feedback from physicians, payers, and patients to inform new product design and development of target product profiles» Evaluate key drivers of market share to guide product enhancements and post-marketing efforts Clients Use Dectiva's Secondary Market Research Services To Better Understand:» Disease definition and epidemiology» Current treatments, market size by number of patients and sales volume, and unmet therapeutic needs» Clinical and preclinical pipelines» Status and results of key trials» Emerging profiles of competing new therapies» Pricing, coverage, and reimbursement issues Clinical Trial Recruitment - Investigators and Patients: Leveraging our global network, Dectiva performs custom recruitment campaigns of clinical investigators and patients for enrollment in clinical trials. 2

3 Secondary Research Detailed Overview Secondary Research Extensive literature review:» Scientific publications» Trade journal and databases» Securities analyst reports» Government sponsored databases» Syndicated databases (based on client access) Information distilled to deliver insights, as well as data Completed within 5-7 days Market Landscape Assessment Ideal for companies/investors exploring:»new products in new areas»new applications for existing products Collect and analyze technical data on:»disease classification info»diagnostic algorithm»epidemiology»market drivers»competitive intelligence (detailed pipeline and existing market overviews) Structured and customized reports to support business planning and investment decisions Completed within 3-5 days 3

4 Case Study - Overview SECTOR Life Sciences Thrombocytopenia OBJECTIVES Opportunity assessment» Market size, growth» Current treatments» Unmet needs Competitive landscape analysis» Current treatments, advantages, limitations» Pipeline competitors, trial design and potential positioning Client Background Pharmaceutical client evaluating multiple opportunities for in-licensing Needed preliminary assessment of market attractiveness based on secondary data to prioritize different opportunities Next steps would be to conduct primary research to validate findings and to quantify value of specific asset opportunity Disease Area Thrombocytopenia Diverse patient population Minimal syndicated market data available 4

5 Case Study - Table of Contents Disease Definition and Epidemiology Current Treatments and Unmet Needs Clinical and Preclinical Pipeline Key Trials Conclusions Emerging Profile of New Therapies 5

6 Disease Definition: Diverse Causes Thrombocytopenia is a reduction in platelets (<100,000 platelets/µl), which can lead to excessive bleeding. The condition is caused by: Suppression of megakaryocytes (responsible for platelet production) in the bone marrow. Immune disorders that produce antibodies that destroy platelets. Medications that result in myelosuppression and/or immunological destruction of platelets. THROMBOCYTOPENIA CAUSES Platelet Production Bone marrow diseases (leukemia, lymphoma, MDS, multiple myeloma) Myelosuppressive therapies (e.g., chemotherapy, radiation) Reduced thrombopoietin in the liver due to liver disease (chronic hepatitis C, cirrhosis, liver failure) Systemic viral or bacterial infection HIV, HCV, HCB Dengue fever infects megakaryocytes Sepsis Vitamin B12 or folic acid deficiency Numerous hereditary syndromes Platelet Destruction Immune or idiopathic thrombocytopenic purpura (ITP) Autoimmune disorders (e.g., lupus, rheumatoid arthritis) Disseminated intravascular coagulopathy (DIC) associated with cancer, sepsis or infection Medications: drug-antibody complexes bind and activate platelets Heparin-induced thrombocytopenia is a rare, but serious example of this 6

7 Epidemiology: 200,000+ US Cases Per Year Medication induced thrombocytopenia has increased with introduction of new therapies that cause hematological complications (e.g., antiinflammatories, cardiac & ulcer drugs, antibiotics). Reduced thrombopoietin production in the liver results in thrombocytopenia in patients with chronic HCV infection and liver disease. Other forms of thrombocytopenia are more rare; congenital thrombocytopenia, though quite varied, accounts for <X% of all cases. US INCIDENCE OF THROMBOCYTOPENIA Cause Comments Est. US 2008 Incidence Annual Growth ITP 1 Scientific references cite incidence of X/100,000 in adults and X/1MM in children Non-scientific references cite X/1MM. XXXXX But may be as high as XXXXX +X% Chemotherapy induced Based on Decision Resources estimates and projections XXXXX +X% thrombocytopenia 2 Heparin induced thrombocytopenia (HIT) 3 XX% of patients treated with unfractionated heparin XX% develop HIT with thrombosis Estimates based only on cardiovascular patients XXXXX +X% Myelodysplatic syndromes (MDS) 4 MDS est 2008 incidence = XXXXX Thrombocytopenia occurs in ~XX% of patients XXXXX +X% Chronic hepatitis C infection 5 XX M Americans chronically infected XX% of chronic HCV patients affected XXXXX +X% HIV/AIDS 6 XXXXX diagnosed cases of AIDS in US in 200X 1 yr incidence is XX% in patients with AIDS XXXXX +X% Source: 1. ITP: Frederiksen H, Schmidt K, 1999; 2. Decision Resources, 2007; 3. HIT: Ohman EM, et al, 2005; 4. MDS: Ma X, et al, 2007 (est MDS incidence rate of 3.56/100,000 applied to 2008 US population); Hagop K, et al, 2007; 5. HCV: Armstrong GL, et al, 2006; Chong- Shan W, et al, 2004; 6. HIV: CDC, HIV/AIDS Surveillance Report, 2005; Moore R, 7

8 Current Treatment Approach: Disrupt antibody-mediated destruction ITP treatment guidelines established by American Society of Hematology (ASH) in 1996 are still in place today. Following acute situations, many patients experience spontaneous remission. Patients whose symptoms persist require further treatment; ~X% of patients become refractory. ITP TREATMENT APPROACH 1 st Line 2 nd Line / 3 rd Line Platelets >30,000/µL, asymptomatic or minor purpura Observation Platelets <30,000/µL after 4-6 weeks of treatment Consider Splenectomy Cylcophosphamide / Chemo Comb. Dx Platelets 20,000-30,000/µL and/or significant mucous membrane bleeding Drug Tx Glucocorticoids Rituximab Off-Label Other Experimental Tx Platelets <20,000/µL and/or significant mucous membrane bleeding Hospitalization & Drug Tx High dose IV glucocorticoids, IVIG, platelet transfusions Source: George JN, et al, ITP: A Practice Guideline Developed by Explicit Methods for the American Society of Hematology, Blood,

9 Current Treatment Approaches: Treat Underlying Cause In other forms of thrombocytopenia, physicians must assess underlying disease or risk-benefit of treatments causing reduced platelet levels. TREATMENT APPROACH FOR OTHER FORMS OF THROMBOCYTOPENIA Chemotherapy Induced Thrombocytopenia Heparin Induced Thrombocytopenia Chronic Hepatitis C / Cirrhosis HIV Platelet transfusion Neumega (oprelvekin, IL-11) Direct Thrombin Inhibitors (argatroban, lepirudin) Interferon Therapy Liver Transplant Antiretroviral Therapy (AZT, ART) 9

10 Current Treatments: Most Drugs are Immunomodulators MOA / Rationale Dosing / Admin Duration of Therapy Prednisone Prevents bleeding Raises platelet count quickly Begin 1mg/kg IV for 3 days; taper to <10-15 mg/d IV Gamma Globulin (IVIG) Interrupts antibody mediated platelet destruction 6 months Can be intermittent for 18 months Efficacy Platelet recovery within 4 days vs 16 days in untreated Safety Adverse events associated with longterm steroid use (hyperglycemia, hypertension, weight gain, growth retardation) Rho(D) Immune Glubulin (Anti-D) Approved for prevention of Rh immunization but also shown to interrupt platelet destruction Splenectomy Spleen is site for antiplatelet antibody production and destruction of opsonized platelets Neumega (Oprelvekin) IL-11 enhances growth and maturation of IL-3 dependent megakaryocytic progenitors 1g/kg/d IV for 2 d 75µg/kg IM injection Surgical procedure 50µg/kg/d SC injection Platelet increase in 75% of pts within 3-4 weeks 50% achieved normal levels 15-75% of patients have mild headache, backache, nausea, fever Some risk of aseptic meningitis, alloimmune hemolysis Can be intermittent for 18 months 68% response Transiently increases platelet counts for 2-3 weeks Risk of alloimmune hemolysis Potential for renal failure N/A Given in 10 and 21 day courses 75-85% of patients have initial response 25-40% relapse within 5-10 years Risks of infection (lifelong use of antibiotics recommended by UK guidelines but not US) 28-65% of patients did not require platelet transfusions, vs 7-41% in placebo arms Boxed warning for allergic reactions Constitutional toxicities, peri-pheral edema Low incidence of atrial arrhythmias and syncope Rituximab Eliminate B- lymphocytes needed for autoantibody production May contribute to Fc receptor blockade 375mg/m2 four times at weekly intervals TBD 40-46% CRs 63% overall response 2-48 months duration 22% mild/mod adverse events 4% severe events Source: George JN, et al, 1996; Cines DB, et al, Congenital and Acquired Thrombocytopenia, Hematology, 2004; Beardsley DS, ITP in the 21 st Century, Hematology, 2006; Panzer S, New Therapeutic Options for Adult Chronic ITP, Vox Sanguinis,

11 Unmet Needs: Safer Treatments and Options for Refractory Cases Current treatment options present risks of significant side effects and efficacy typically achieve 70% response rates or less. Even splenectomy, considered a cure for ITP, has efficacy of up to XX% but XX% may relapse within 5-10 years. UNMET NEEDS Safer therapies for patients at risk of bleeding or overt bleeding tendency, to postpone splenectomy Drugs with more rapid onset of action Effective therapies for refractory patients Drugs for patients scheduled for minor or major surgery, who can not take steroids or IVIG Diagnostics to more quickly and effectively identify patients with ITP versus other conditions Source: Panzer S, 2008; Decision Resources, Managing the Side Effects of Chemotherapy,

12 Clinical Pipeline: Focus is on TPO receptor Even when the cause of thrombocytopenia is platelet destruction, patients may also be subject to decreased platelet production due to: Antiplatelet antibodies binding to megakaryocytes Apoptosis of megakaryocytes Low thrombopoietin (TPO) levels 1 st generation TPO growth factors were recombinant megakaryocyte growth factors. These agents tended to be immunogenic and were discontinued. 2 nd generation agents are TPO peptide and non-peptide mimetics and TPO agonist antibodies. All bind to TPO receptor but in different ways. Potential concerns with new TPO agents are thrombosis, development of cancer/leukemia, antibody production, marrow fibrosis and rebound effects when treatment is stopped. Of the 11 clinical and 8 preclinical compounds in development for thrombocytopenia, at least 6 target the TPO receptor. Two compounds are awaiting FDA approval: Nplate (Romiplostim/AMG 531) and Promacta (Eltrombopag) Both will receive fast track or priority review, with launch expected by 20XX 12

13 Clinical Pipeline: Two Near-Term Entrants; Very Crowded Post-20XX Discontinued Discontinued Mechanism of Action TPO Receptor MOA2 MOA3 MOA4 13

14 Clinical Pipeline Source: Panzer S, 2008; ADIS R&D Insight; Amgen Press Release Jan 31,

15 Clinical Pipeline Source: Panzer S, 2008; ADIS R&D Insight; GSK Press Release Dec 10,

16 Clinical Pipeline Three additional TPO agonists are in clinical development the XXX compounds are follow-up candidates to Promacta. Immunomodulators have also generated interest. CD20 antibodies affect the immune system s ability to make autoantibodies. Drug Developer MOA Phase Indication ROA XXXXX XXXXX Thrombopoietin receptor agonist XXXXX XXXXX Thrombopoietin receptor agonist XXXXX XXXXX Syk tyrosine kinase inhibitor XXXXX XXXXX CD20 antigen antagonist XXXXX XXXXX CD20 antigen antagonist XXXXX XXXXX Platelet activating factor agonist XXXXX XXXXX CD16 antigen antagonist XXXXX XXXXX Anti-RhD immunoglobulin antagonist XXXXX XXXXX Thrombopoietin receptor agonist X ITP Oral X ITP Oral X ITP Oral X ITP IV X ITP IV X ITP IV X ITP IV X ITP IV X Thrombocytopenia Oral Source: ADIS R&D Insight; IDDB3 16

17 Preclinical Pipeline Several companies have active research programs targeting thrombocytopenia, but very little data are available to assess activity. Drug Developer MOA Phase Indication ROA XXXXX XXXXX IL-1 agonists X Thrombocytopenia Injectable XXXXX XXXXX ADAM protein stimulants XXXXX XXXXX Thrombopoietin receptor agonist XXXXX XXXXX VPAC1 receptor antagonist XXXXX XXXXX LG543 growth factor agonist XXXXX XXXXX Anti-RhD immunoglobulin antagonist XXXXX XXXXX Staphylococcal protein A down regulates human B-lymphocyte and macrophage activation XXXXX XXXXX Platelet activating factor agonist X TTP Injectable X Chemo-induced Injectable thrombocytopenia X Thrombocytopenia IV X Thrombocytopenia Injectable X ITP IV X ITP Injectable X Thrombocytopenia IV Source: ADIS R&D Insight; IDDB3 17

18 Key Trials Overview Most pipeline competitors have focused on ITP as their lead indication for registration. GSK fielded two phase III studies (up to 200 subjects) and Amgen s phase III had 210 subjects. Most trials involve patients who are relapsed after at least one standard therapy or are refractory. Thrombocytopenia related to hepatitis C or chronic liver disease is another area of investment, where trial sizes are much larger (up to 750 patients). HCV related studies aim to address thrombocytopenia such that patients can initiate and/or stay on antiviral therapy. Other thrombocytopenia studies in late phases address MDS and chemotherapy patients. 18

19 Key Trials: Promacta (Eltrombopag) in ITP Compound Cancer Sponsor Phase Patients Design Primary Endpoints Promacta ITP GSK III 200 EXTEND: Open-label, dose-adjustment, extension to evaluate safety and efficacy of eltrombopag for treatment of subjects with ITP previously enrolled in an eltrombopag trial. Study allows individualized dose and schedule for each subject. Ability to reduce the dose of concomitant ITP medications in the presence of eltrombopag, while maintaining platelet counts = 50,000/microL will be investigated. Promacta ITP GSK III 189 RAISE: Randomized, double-blind, placebocontrolled study, to evaluate efficacy, safety and tolerability of eltrombopag, initially administered as 50 mg oral tablets once daily for six months in adult subjects with previously treated chronic ITP. Subjects randomized 2:1, eltrombopag to placebo, and will be stratified based upon splenectomy status, use of ITP medication at baseline and baseline platelet count less than or equal to 15,000/µL. Safety and tolerability, clinical lab tests, ocular exams and frequency of all AEs Pts w/ platelet counts between 50,000/uL and 400,000/uL during the 6 month treatment period Promacta ITP GSK II 99 Randomized, double blind trial to assess efficacy, safety, tolerability in adults with refractory, chronic ITP. Entry platelet counts <30,000/microL for 6 mos who have failed at Pts achieving platelet counts =50,000/microL after 42 days of least one treatment; also included pts receiving treatment chronic maintenance steroids. Source: ClinicalTrials.gov Secondary Endpoints Timing Proportion of Start Jun 2006; patients achieving end Jul 2010 target platelet counts and duration of count elevation; signs and symptoms of ITP; QOL Duration of count elevation; frequency of AEs; need for rescue treatment or ITP med; ITP symptoms; safety & tolerability Safety & tolerability; PK; PD; ITP symptoms, QOL Start Nov 2006; end Jul 2008 Start Apr 2005; complete 19

20 Key Trials: Promacta (Eltrombopag) in HCV-related Thrombocytopenia Compound Cancer Sponsor Phase Patients Design Primary Endpoints Secondary Endpoints Promacta HCV GSK III 750 Randomized, placebo controlled study in pts w/ SVR rate defined chronic HCV to assess ability of eltrombopag to as percentage of Pts with a shift in platelet count from maintain a platelet count sufficient to facilitate initiation of antiviral therapy (Peg IFN alfasubjects with nondetectable HCV- <75,000/µL to >/=90,000/µL; 2a+ribavirin), to minimize antiviral therapy dose RNA at 24 weeks AEs, laboratory reductions and to avoid permanent post-completion of abnormalities, discontinuation of antiviral therapy. The clinical the planned benefit of eltrombopag will be measured by the treatment period ocular examinations, 12- proportion of subjects who are able to achieve a Sustained Virological Response (SVR). Entry platelet count of <75,000/microL. (i.e., Week 48 for genotype 2/3 or Week 72 for nongenotype 2/3) lead ECGs Promacta HCV GSK III 500 Randomized, double blind trial to assess platelet elevation to reduce need for platelet transfusions in chronic liver disease patients with thrombocytopenia undergoing elective invasive procedures; includes patients with HCV, HBV, HIV, non-alcoholic steatohepatitis, NASH. Patients with model of end stage liver disease score (MELD) of 24 or less; entry platelet count <50,000/microL Source: ClinicalTrials.gov Need for platelet transfusion prior to, during and up to seven days following elective invasive procedures Bleeding; AEs, lab abnormalities, ocular exams, ECGmb Timing Start Oct 2007; end Aug 2011 Start May

21 Key Trials: Promacta (Eltrombopag) in HCV and Chemo-related Thrombocytopenia Compound Cancer Sponsor Phase Patients Design Primary Endpoints Promacta HCV GSK II 422 Randomized, double blind dose ranging study (30, 50, 75 QD for 12 weeks) in chronic HCV related thrombocytopenia who are potential candidates for antiviral therapy. Promacta CIT GSK II 183 Randomized, double blind dose ranging study to assess efficacy, safety, PK in patients receiving multiple cycles of chemo. Included pts with advanced solid tumors scheduled to receive 1st line carboplatin/paclitaxel; subjects had no history of platelet or bleeding disorders. Change in Source: ClinicalTrials.gov Secondary Endpoints Pts shifting from Mean increase in baseline counts to platelet counts; 100,000/microL safety & after 4 weeks tolerability; population PK; PD; effect of antiviral outcome measures baseline platelet count from 1st day of 2nd cycle to lowest count observed in the cycle Safety & tolerability; PD; platelet count change; dose intensity of carbo/paclitaxel Timing Start Feb 2005; complete Start Apr 2005; end Feb

22 Key Trials: Nplate (Romiplostim) in ITP Compound Cancer Sponsor Phase Patients Design Primary Endpoints Nplate ITP Amgen II 100 Open label study in refractory ITP patients. Entry platelet count <=20,000/microL; failed at least 3 conventional treatments; on anticoagulant medication if pt has AF history. AEs; clinically significant changes in lab values and incidence of antibody formation Nplate ITP Amgen III 210 3b, randomized, SOC-controlled, open-label, Number of pts 52-week treatment study to compare AMG 531 undergoing to medical SOC for ITP, with a 6-month Safety splenectomy; Follow-up. Non-splenectomized subjects who number of are 18 years or older, are diagnosed with ITP treatment failures according to the American Society of Hematology (ASH) guidelines, and who have received at least 1 prior therapy for ITP will be eligible to screen for this study. Eligible subjects will be randomized to AMG 531 or medical SOC for ITP if their platelet count is < 50,000 or their platelet count falls to < 50,000 during or after a clinically-indicated taper or discontinuation of current ITP therapy. After the completion or discontinuation of the study treatment period, any subject who does not transfer in to another AMG 531 study will complete a 6-month Safety Follow-up period. Source: ClinicalTrials.gov Secondary Endpoints Platelet response; transfusions Time to splenectomy; platelet response; change in ITP patient reported outcomes Timing Start Feb 2005; end Dec 2010 Start Nov 2006; end Jan

23 Key Trials: Nplate (Romiplostim) in MDS Compound Cancer Sponsor Phase Patients Design Primary Endpoints Nplate MDS Amgen II 240 Randomized, double blind, placebo controlled Efficacy study evaluating efficacy and safety of treatment of thrombocytopenia in pts w/ low or intermediate-1 risk MDS. Starting dose of 750mcg up to 1000mcg or reduced to min of 250 mcg. Nplate MDS Amgen N/A 200 Open label extension study to evaluate safety of long term dosing in MDS. Patients with IPSS low or intermediate-1 risk MDS. AEs Secondary Timing Endpoints Number of platelet Start May 2008; transfusions, end Jan 2011 bleeding events; platelet hematological improvement; overall survival; disease progression to AML; neutralizing antibodies versus drug; all AEs Platelet response; transfusions; bleeding events Start Jun 2007; end Sep 2010 Source: ClinicalTrials.gov 23

24 Key Trials: Nplate (Romiplostim) in MDSKey Trials: Other Phase II Compounds Compound Cancer Sponsor Phase Patients Design Primary Endpoints XXXXX ITP XXXXX II 106 Open label, single arm study will evaluate the Overall response efficacy and safety of rituximab monotherapy in rate patients with refractory, relapsing or chronic idiopathic thrombocytopenic purpura (ITP). Patients will receive infusions of 1000mg i.v. on days 1 and 15. The anticipated time on study treatment is 3-12 months. XXXXX ITP XXXXX II 65 Double-blind, randomized, placebo-controlled, dose-ranging, parallel-group study will assess the efficacy, safety and tolerability. Once daily oral doses of 2.5, 5, 10, 20 mg or placebo for 28 days. Patients are refractory or relapsed after at least one prior therapy; entry platelet counts <50,000/mm3. XXXXX ITP XXXXX II 24 Randomized, double blind placebo controlled study in ITP with open label extension. Patients dosed 7.5 mg/day for 6 weeks. Includes patients with platelet counts <50,000/microL who have been treated with at least 1 ITP therapy. XXXXX ITP XXXXX II 66 Phase I/II, non-randomized, open label dose comparison study. Includes adults with chronic IPT that have failed at least one therapy. Entry platelet counts <30,000/microL and platelet levels <150,000/microL for >6 mos. Drug dosed twice, two weeks apart. Source: ClinicalTrials.gov Platelet response Secondary Endpoints Time to CR and PR; duration of response and time to new therapy; AEs; hematological toxicity; infections; infusion reactions PK; PK/PD relationship Timing Start May 2007; end Nov 2009 Platelet counts Start Mar 2008; end May 2009 Start Nov

25 Conclusions Populations are small to moderate More than 200,000 patients in the US experience thrombocytopenia. Drug-induced thrombocytopenia (heparin, chemo or other drugs) are most common. Thrombocytopenia resulting from compromised liver function (chronic HCV infection and cirrhosis) is also a significant contributor to incidence. Estimates of ITP incidence span a large range (XXXX-XXXX/year), but condition is still considered rare. Small population allows for orphan designation and fast track or priority review Unmet need qualifies for fast tract or priority review Competition is poised to intensify Treatment aims to address the underlying cause of thrombocytopenia (e.g., withdrawal of myelosuppressive therapy; antiviral therapy, liver transplant etc.). In ITP, most treatments are immunomodulators targeting production or interaction of autoantibodies targeting platelets (e.g., IVIG, anti-d, rituximab). New TPO mimetics are poised to enter the market in 20XX. Amgen and GSK will specifically address thrombopoiesis with new oral and injectable therapies which have reported high (>75%) response rates in restoring platelets to safe levels. Both will significantly change competitive landscape with investments in advertising, promotion and sales to create share of voice. 25

26 Conclusions Clinical pipeline is limited Only 11 compounds have entered the clinic and 8 appear to be in preclinical development. Several are focused on the TPO receptor, while others are immunomodulators or other MOAs. TPO agents hold the most promise at this time, with Amgen and GSK in the lead. Most competitors have focused on ITP as their lead indication for registration, due to potential for fast track or priority review. Phase II and III studies require patients Clinical trials focus on ITP, but also HCV Companies have also fielded several studies in patients with chronic HCV infection and liver disease and Amgen has a large trial in MDS. Phase III studies with HCV patients are larger (~ patients) Amgen, GSK and others are looking at chemotherapy induced thrombocytopenia, but investigation appears to be in phase II to date. Based on additional safety studies being fielded, long-term use and safety are significant concerns. Specific studies are evaluating ocular effects. 26

27 Emerging Profile New agents must be effective, with relatively low toxicity Emerging Profile based on Clinical Pipeline MOA Target TPO receptor or autoantibody activity Indication(s) ITP (lead) Thrombocytopenia related to chronic HCV or liver disease Chemotherapy-induced thrombocytopenia (CIT) ROA and Dosing Oral or subcutaneous dosing QD Efficacy 75-90% response, measured by achievement of platelet counts 50,000/µL Duration of response 15 weeks Reduced need for platelet infusions Safety Well tolerated; similar to placebo Mild headaches and fatigue Rare grade 3 or 4 toxicities (e.g., bleeding / thrombosis) Ocular effects TBD 27

28 Key References Armstrong GL, et al, Prevalence of Hepatitis C Virus Infection in the United States, , Ann Intern Med, 2006 Beardsley DS, ITP in the 21 st Century, Hematology, 2006 CDC, HIV/AIDS Surveillance Report, 2005 Chong-Shan W, et al, Strong Association of Hepatitis C Virus Infection and Thrombocytopenia, Clinical Infectious Diseases, 2004 Cines DB, et al, Congenital and Acquired Thrombocytopenia, Hematology, 2004 Frederiksen H, Schmidt K, Incidence of Idiopathic Thrombocytopenic Purpura in Adults Increases with Age, Blood, 1999 Decision Resources, Managing the Side Effects of Chemotherapy, 2007 George JN, et al, ITP: A Practice Guideline Developed by Explicit Methods for the American Society of Hematology, Blood, 1996 Hagop K, et al, Incidence and Impact of Thrombocytopenia in Myelodysplastic Syndromes, Cancer, 2007 Ma X, et al, Myelodysplastic Syndromes: Incidence and Survival in the US, Cancer, 2007 Moore R, Ohman EM, et al, Identification, Diagnosis and Treatment of HIT and Thrombosis (CATCH Registry), J Thromb Thrombolysis, 2005 Panzer S, New Therapeutic Options for Adult Chronic ITP, Vox Sanguinis,

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