1. GTX: An Opportunity Not to be Missed? Team Veritas Reuben Estrada MBA Candidate Fang Fang PhD Candidate Stan Guthrie PhD Candidate Minlee Kim PhD Candidate Hiromi Yoshida MD/MBA Candidate

2. Crohn’s Disease Targets small intestine and colon Extensive transmural inflammation and ulceration “Skip lesions” Abdominal pain, diarrhea, and rectal bleeding Ulcerative Colitis Targets colon and rectum Inflammation and ulceration in mucosal and submucosal layer of the colon and rectum Continuous involvement Abdominal pain, diarrhea, and blood stools Two IBD diseases Symptoms

3. Ulcerative Colitis (UC) Prevalence and incidence peak in the 20-29 year age group Prevalence highest in the US, and Northern Europe Crohn’s Disease (CD) Prevalence and incidence peak in two groups: 15-30 and 55-80 year of age Prevalence highest in the US and UK affect many people Market Analysis

4. Crohn’s DiseaseUlcerative Colitis Primary Goals Induce remission of acute flares Maintain remission Try to substitute steroids Treatment Progression Current Market Share No Treatment Topical 5-ASA 5-ASA/Sulfasalazine Antibiotics Oral Corticosteroids IV Corticosteroids 6-Mercaptopurine/Azathioprine Methotrexate Cyclosporine Infliximab Experimental Therapies… (20% UC received colectomy) Severe Mild who have some options Market Analysis

5. Crohn’s Disease SeverityUnmet Need Mild (46%) Oral agent for maintenance Moderate (38%) Maintenance drug with better side- effect profile Severe (16%) Maintenance drug different from anti- TNF-α therapy RemissionMaintenance drug Ulcerative Colitis SeverityUnmet Need Mild (55%) Current therapies effective Moderate (30%) Maintenance drug that is fast-acting and safe Severe (15%) Maintenance drug with better response rates RemissionMaintenance drug Minimal side effects Different from anti-TNF-α therapy but not many Unmet Needs

6. Longer acting Convenient delivery mechanism Minimal side effects Humanized drug Excellent value Faster onset of action Synergy with existing drugs Attacks disease through a different pathway We can address this need Ideal Drug Profile

7. GTX-001 Biologic IV (6mg/kg) in vivo Significantly reduces inflammation with 2mg/kg, every other day, after 4-6 weeks GTX-002 Immunomodulator Oral (50mg/kg) or IV (5mg/kg) Liver/kidney toxicities Bacterial infection Synergistic if combined with 5- ASA/steroid Inhibits activation of pro-survival pathway and induces T-cell apoptosis Inhibits leukocyte migration and accumulation in gut mucosa collagen VLA-1 MEKK3 IKKs TNF- α and have two ways to do it GTX-001 and GTX-002

8. Phase 1 ($42MM) Initial Safety Dosing and delivery Phase 2 ($67MM) Safety and efficacy Phase 3 ($241MM) New Drug vs. Existing Drug Phase 4 Long-term safety and effectiveness Post-marketing surveillance Clinical R&D ($350MM)Preclinical R&D ($50MM) Dosing Efficacy Toxicity Pharmacokinetics Synergies with existing drugs Effects on refractory IBD cases Long-term side effects The process requires Drug Trials

9. DISEASE CD UC X 206,400 5ASA 40,000 Steroid 122,000 IM MARKET SIZE PROFIT GTX-002 GTX-001 147.36MM X Annual Figures UC disease Synergies 100% of market Price of $400 159MM + 10% Sales DISEASE CD UC MARKET SIZE PROFIT 159MM + 10% Sales 32,500 Refractory ? Biologic 20,000 Refractory ? Biologic 1.522B Annual Figures CD and UC disease Refractory 50% of market Price of $21,000 1.21B making a choice Drug Selection

10. Revenue1,522,500,000 Cost of Sales: Selling, informational and administrative expenses100,000,000 Acquisition-related in-process R&D charges: Licensing Fee833,333 Late stage development costs25,000,000 R&D Milestone33,333,333 Royalty Costs152,250,000 Net Income1,211,083,334 INCOME STATEMENT: Phase 1 70% Phase 2 33% Phase 3 30% Growth rate- 3% Discounting rate- 10% Price- $21,000 52.5 thousand people 13 year period EXPECTED VALUE 7% - success rate Total Actual Value: 20.1B Total Actual Value: 1.4B Total Present Value: 10.5B Total Present Value: 738MM Costs: 710MM Project Value: 9.83B Project Value: 28MM IF SUCCESSFUL ADJUSTING FOR RISK running with the numbers Calculations

11. GTX 001 Maintenance drug for both CD and UC Product $21,000 Price Refractory patients Moderate and severe patients Target Market Expansion into international markets Development and commercialization for other diseases Extension of patent – orphan drug patent Re-negotiation of contract License exclusivity Decrease production costs Future Direction and developing a plan Proposal

12. Acknowledgements

13. J.A. DiMasi et al. “The Price of Innovation: New Estimates of Drug Development Costs.” Journal of Health Economics 22 (2003): 151-185. Marianne Moody Jennings. Business Ethics: Case Studies and Selected Readings. Mason: South-Western Cengage Learning. 2009. P.M. Matthews. “The Long, Sometimes Bumpy Road of Drug Development.” The Dana Foundation. 2006.. John Hopkins Medicine Gastroenterology & Hepatology Additional Information References

14. Current Treatment Crohn’s DiseaseUlcerative Colitis Goals - Induce remission of acute flares - Maintain remission -Try to substitute steroid Market Share US EU 5-ASA - Pros: Oral; Cheap - Cons: Few have robust efficacy data - Pros: Oral; Cheap; Lower dosing; Well developed - Cons: Ineffective for severe form; Poor retention Steroids - Pros: Effective; Rapid-acting for acute flares - Cons: Long-term side effects - Pros: Oral; Effective induction; Rapid onset - Cons: Long-term side effects; Infection; Immuno- modulator - Pros: Oral; Effective for severe condition; Cheaper than biologic - Cons: Harmful when combine with TNF-a - Pros: Oral; Highly effective - Cons: Toxic; Potential tremors/infections; Slow onset; Not for pregnant women Biologic - Pros: Robust clinical data (eg. Infliximab) Higher comfort level; Possibility of SC Choice of non-anti-TNF-a approach -Cons: IV; Not fully humanized; Infections - Pros: Effective; Reduce surgery -Cons: IV; Can’t stop once started; Infection Long-term safety Others No treatment or Refractory20% undergoes Colectomy

15. Population Predictions CD Population USEU PrevalenceIncidenceBiologicRefractoryOther TreatPrevalenceIncidenceBiologicRefractoryOther Treat 2007479,00020,212101,54043,831307,864355,20014,98851,27124,618260,464 2008481,52620,327102,07744,063309,493357,07415,07351,54224,748261,842 2017505,87321,246107,21646,281325,074375,12715,75454,13725,994275,024 2020 516,897 21,590 109,528 47,279 332,085 383,303 16,010 55,305 26,554 280,956 2021 520,802 21,705 110,346 47,632 334,564 386,198 16,095 55,718 26,752 283,053 2022 524,821 21,820 111,187 47,995 337,114 389,179 16,180 56,142 26,956 285,211 2023 528,956 21,935 112,051 48,368 339,734 392,244 16,265 56,579 27,166 287,427 2024 533,205 22,049 112,939 48,751 342,425 395,395 16,351 57,027 27,381 289,704 2025 537,569 22,164 113,850 49,145 345,187 398,631 16,436 57,487 27,602 292,041 2026 542,047 22,279 114,784 49,548 348,020 401,953 16,521 57,959 27,828 294,438 2027 546,641 22,394 115,742 49,961 350,924 405,359 16,606 58,442 28,061 296,895 2028 551,350 22,509 116,723 50,385 353,898 408,850 16,691 58,938 28,299 299,411 2029 556,173 22,624 117,727 50,818 356,944 412,427 16,776 59,445 28,542 301,988 2030 561,111 22,738 118,755 51,262 360,060 416,089 16,862 59,964 28,791 304,624 2031 566,164 22,853 119,806 51,716 363,247 419,836 16,947 60,494 29,046 307,320 2032 571,332 22,968 120,881 52,180 366,505 423,668 17,032 61,037 29,307 310,077 UCPrevalenceIncidenceBiologicRefractoryOther TreatPrevalenceIncidenceBiologicRefractoryOther Treat Every year525,00021,00067,25319,793403,410442,50017,70032,74521,107248,154 - For CD, prevalence and incidence increase linearly every year. - For UC, prevalence remain stable through out the whole period; incidence and death rate balance out. Assumptions: -Consider a 4% constant death rate. - using the market segment provided predict each medicine sector.