1. GTX: F ILLING THE GAP A recommendation to Cure on Gastrex drug license opportunities YBPS Marketing Case Competition Richard Hernandez, MBA Liying Jin, MS Statistics Selina Tirtajana, MPH Mike Ran Zou, PhD Pathology * Candidates Biotechnology & Pharmaceutical Solutions

2. P ROBLEM S TATEMENT IBD is a chronic inflammation of the gastrointestinal tract. Two major types of IBD are Crohn’s Disease (CD) and Ulcerative Colitis (UC) – which affect different parts of the GI tract. Currently, there are unmet needs in IBD therapy and Cure has been presented with licensing opportunities (GTX-001 & GTX-002) from Gastrex that can potentially fulfill these needs. Based on pre-clinical studies results and market analysis of these two drugs, we will provide recommendation for Cure.

3. IBD P ATH PHYSIOLOGY Antigen GI Flora 1 1 Antigen Processing & Presentation, Activation of Macrophages Activated Macrophage Activated T-Cell TNFα IFNγ Th1 Cell Th2 Cell IL-4 IL-12 IFNγ IL-10 Endothelium Intestinal Lumen 2 2 Antigen Recognition & Activation of CD4+T Cell Recruitment, Migration, and Adhesion 5 Generation of Th1/Th2 Response 3 3 Production of Proinflammatory Cytokines 4 4 5 Macrophage Monocytes Epithelium Neutrophils TNFα IFNγ IL-10

4. P REVALENCE ESTIMATES OF CD & UC IN 2008

5. GTX-001 SHOWS PROMISING RESULTS IN PRE - CLINICAL STUDIES GTX-001 is a Monoclonal Antibody that targets VLA-1 Blocks immune cell trafficking/activation Pre-clinical (animal studies) results Improved inflammation score within 4-6 wks Dose of 2mg/kg intravenously (IV) every 48 hours Drug tolerated up to 6 mg/kg Good substitute of existing biologics in the market VLA-1 GTX-001

6. GTX-002 SHOWS PROMISING RESULTS IN PRE - CLINICAL STUDIES GTX-002 is a small molecule compound used to induce T-cell death by targeting IκB Kinase Effectiveness confirmed by cell-based assays Pre-clinical (animal studies) results Remodeling of GI commensal flora indicates altered pathology Susceptibility to bacterial infection demonstrates immunosuppresion Improved clinical scores when used in combination with 5-ASA and/or steroids Good remission, but not induction, agent Dosage above threshold limit causes liver and kidney toxicity 50 mg/kg orally or 5 mg/kg IV GTX-002 cell death

7. Type of treatmentPros & Cons 5-ASA (Asacol, Lialda, Pentasa, Colazal, Sulfasalazine) -Reliable & effective for mild CD/UC cases -Relatively affordable -Used to maintain remission in moderate cases (but lack efficacy in more severe cases) Steroids (Budesonide, Prednisone, Methylprednisolone) -Effective for induction of remission -Cheap -Long term side effects make it a poor agent to maintain remission Immunomodulators (Azathioprine, 6-MP) -Effective maintenance therapy for moderate to severe cases (up to 60% response rate) -Slow onset & high rate of toxicity Biologics (Infliximab, Adalimumab, Natalizumab, Certolizumab) -Effective in severe cases -Expensive, relatively inconvenient to administer -Few clinical data in UC cases -Patients don’t respond / lose response to TNF-α inhibitor over time. C URRENT TREATMENT

8. U NMET NEEDS IN IBD THERAPY Mild (5-ASA) Moderate (5-ASA, Steroids, IM) Severe (Steroids, IM, Biologics) Crohn’s Disease/ Ulcerative Colitis NONE1. Induction agent safer than steroid 2. Remission agent that is more effective than 5-ASA and/or has faster onset & safer than IM 3. Substitute to anti-TNF with safer profile 4. Biologics with better sustained remission rates Mild IBD cases are well served by 5-ASA Severe patients failed to respond to anti-TNF therapy, which dominates the current market to treat moderate to severe IBD

9. P OTENTIAL TARGET MARKET FOR GTX001 AND GTX002 Choice of market segments based on pre-clinical findings GTX002 GTX001

10. D RUG VALUATION ON THE MARKET Assess net value at the present day by discounting cash flow of future revenue and subtracting license fees and other associated payouts. GTX-001 in the moderate to severe market is sufficient to provide positive NPV Generic biologics are not competitive Sensitivity analysis shows that NPV is robust across a spread of various growth rates. GTX-002 fails to meet a positive NPV Growth RateNPV (discount rate at 11%) -1% -16.38 -0.9%0 0%105.98 0.6%188.97 3%609.27 5%1099.33 Growth RateNPV (discount rate at 9%) -1.8% 0 -0.9%118.00 0%283.04 1%476.03 3%965.43 5%1633.84

11. R ECOMMENDATION : FILL THE GAP ! Purchase license for GTX-001 There is a demonstrated market need Added advantage of being a biologic in the US because barriers of entry NPV is positive and therefore a profitable drug Do not purchase license for GTX-002 under the current agreements. Market is well served by other available agents 56% of market share is required in order to break even in the licensing investment Consider renegotiating license fee or changing payout structure to delay payment

12. Q&A

14. C ITATION Title slide image http://www.scumdoctor.com/images/How-Much-Does- Enbrel-Suppress-The-Immune-System.jpghttp://www.scumdoctor.com/images/How-Much-Does- Enbrel-Suppress-The-Immune-System.jpg Biologics cannot have generic synthetic http://www.businessweek.com/bwdaily/dnflash/conten t/mar2007/db20070314_175878.htm http://www.businessweek.com/bwdaily/dnflash/conten t/mar2007/db20070314_175878.htm Decision tree for pharmaceutical acquisition. http://www.springerlink.com/content/j28414r31p0 13331/fulltext.pdf http://www.springerlink.com/content/j28414r31p0 13331/fulltext.pdf Sands, Bruce E. Therapy of Inflammatory Bowel Disease, GASTROENTEROLOGY 2000;118:S68– S82

15. I NTERNATIONAL MARKET FOR CD? Prevalence Market SharePotential Market Share

16. I NTERNATIONAL MARKET FOR UC? Prevalence Market SharePotential Market Share