MIGSYS Ian Evans, Genetics Max Musicant, SOM Grant Patterson, EPH Jia Kang, Med Informatics Colin Shaw, Nursing YBPS Case Competition November 20, 2009

Patient Population Market Landscape Steroids Immunomodulators 5-ASAs Biologics 5-ASAs Steroids Immunomodulators Biologics

Target Market Drug Usage By Disease Severity MildModerateSevere Disease Severity MildModerateSevere Disease Severity GTX-001 Biologic GTX-002 Immunomodulator CD78,000 (20%) UC76,000 (14%) CD117,000 (37%) UC108,000 (37%) CD50,000 (37%) UC70,000 (48%) CD87,000 (27%) UC52,000 (18%) CD58,000 (43%) UC47,000 (32%)

Opportunity 1: Science Behind GTX-002 Identification Computational Design In Vitro Kinase Assays in two T- Cell Lines In Vivo Oral toxicity at 50mg/kg Altered GI flora Combo Therapy most effective

Finances GTX-002

Opportunity 2: Science Behind GTX-001 Mechanism of Action: mAb against  1  1 integrin Identification High Throughput Screening Target expression is more T H 1 specific (question of use in UC patients) In Vitro Abolished Interaction with Collagen In Vivo IV toxicity at 6mg/kg Effective at 2mg/kg every other day Reduced inflammation at 4-6 weeks

Released in 2004 for MS, Tysabri was then removed from market in 2005 due to cases of PML Reintroduced in 2005 and since restricted to smaller patient segment – To date 24 cases of PML found in Tysabri users GTX-001 is in the same class as Tysabri – mAb against  4-integrin – Decreases extravasation PML (Progressive Mulitfocal Leukoencephalopathy): a rare neurological disease Due Diligence

Finances GTX-001

Recommendation: GTX-002 Pros – A new class of kinase inhibitor Cons – Existing market well served by many products – Low market prices for immunomodulators – Signs of side effects in pre-clinical studies – Financial models show inviability Recommendation: NO GO

Recommendation: GTX-001 Pros – Large moderate and severe segments are underserved – Biologics command high prices in market – Large therapeutic window – Financial model shows significant profitability Cons – Similar mechanism to existing treatment (Tysabri) Significant medical risk associated with this class of molecules Recommendation: NO GO

Thank You from MIGSYS Ian Evans, Genetics Max Musicant, SOM Grant Patterson, EPH Jia Kang, Med Informatics Colin Shaw, Nursing

Tysabri, A Risky Proposition PML in patients who have received at least 24 infusions ranges from 0.4 to 1.3 per 1,000 in MS patients CD patients make up only 2% of the Tysabri users EMEA rejected Tysabri twice in 2007 Approved for the indication of CD in 2008 Strong warnings not to use Tysabri with PML in family history Case Report: N Engl J Med 2005;353: Previous FDA Alert: [issued 2/2006] The FDA has lifted the clinical hold on Biogen-IDEC's trials of natalizumab for patients with multiple sclerosis (MS). Biogen-IDEC can now resume administration of natalizumab to patients with relapsing-remitting MS who had previously been treated with the drug in clinical trials. Biogen-IDEC had previously suspended marketing of natalizumab and all further dosing of patients in on-going clinical trials. This decision was made after confirmation of one fatal case and one additional case of severely disabling progressive multifocal leukoencephalopathy (PML) in patients receiving natalizumab for MS. A third case of PML, this one fatal, in a patient with Crohn's Disease had been identified shortly thereafter.

Pro Forma GTX-001

Best and Worst Case GTX-001

GTX-002 Pro Forma

Best Case GTX-002