A Tale of Two(?) IBDs CYMMBiosis for Cure Colleen Feriod, PhD candidate Yujie Wang, MBA candidate Matthew Fleming, PhD candidate Michael Coggins, PhD Brian Cope, MBA/MEM candidate
The CYMMBiosis Team Recommends: Executive Summary The CYMMBiosis Team Recommends: High Unmet Need: For patients with severe conditions, roughly 50% fail to respond to current biologics. High Revenue Potential: Annual Price of Biologics = $10,000 - $15,000 Barren Competitive Landscape, especially in the EU where few biologics are approved Greater Market Size, but Higher Consumer Elasticity Small Molecule: Lower Science and Safety Risks Ultimately Unprofitable due to Lower Willingness-to-Pay; Negative Expected Value Breakeven Price Exceeds Market Potential License GTX-001 “Gastrolux” Pass on GTX-002
IBD Landscape Crohn’s Disease Ulcerative Colitis Disease mechanism unknown: genetic, environment, pathogenic factors Highest incidence and prevalence in age group 20-29 Ulcerative Colitis Disease mechanism unknown: genetic, environment, pathogenic factors Highest incidence and prevalence in age group 15-30
Current Treatment Crohn’s Disease Ulcerative Colitis Lines of Therapy % of Patient Population Current treatment 5-ASA Only 37.05% Effective induction and maintenance for mild to moderate UC; considered safest Steroids + 5-ASA 14.21% Steroids are the most rapid-acting therapies; NOT suitable for long-term use because safety concerns Steroids + IM 26.74% IMs are primary choice for maintenance because lower cost than biologics; HIGH toxicity for long-term use Biologics 10.42% More doctors prescribe biologics as first-line treatment. Infliximab is the only biologics approved for UC Treatment Refractory 4.21% 50-60% patients lose response over time to Infliximab Crohn’s Disease Lines of Therapy % of Patient Population Current treatment 5-ASA Only 16.69% 5-ASAs are rarely effective, mainly for very mild cases Steroids + 5-ASA 18.21% Steroids are the most effective, rapid-acting therapies; NOT suitable for long-term use because safety concerns Steroids + IM 28.79% IMs are first-line choice for maintenance because lower cost than biologics; high toxicity for long-term use Biologics 17.04% More doctors prescribe biologics as first-line treatment. Infliximab most prescribed, high efficacy but high side effects. Treatment Refractory 10.34% 45-70% patients lose response over time to anti-TNF biologics therapy
Target product profile Criteria Is it medically plausible? Is there a penetrable market? Is this financially viable? Is it safe? Does it perform better than SOC? Gastrolux GTX-002
Pathophysiology of IBD Crohn’s Disease Ulcerative Colitis Unknown (genetic, environment, pathogenic) Initiation Visible and invisible symptoms Immune response Diagnosis of severity: Mild, moderate, severe Treatment depends on: Incident vs. recurrent Severity of diagnosis Unknown (genetic, environment, pathogenic) Initiation11111 Visible and invisible symptoms Immune 1111 Response1111 Diagnosis of severity: Mild, moderate,111 severe111 Treatment depends on: Incident vs. recurrent111 Severity of diagnosis111
Market Analysis GTX-002 Gastrolux Competitors Crohn’s Disease Ulcerative Colitis GTX-002 Gastrolux Competitors
Key Assumptions of Financial Modeling Discount Rate: 10% Average WACC for comparable Pharma Cos = 7.2% Probability of Regulatory Success: 12% Science and Safety Risks based on historical drug approval data. Individual Phase hurdles based on professional experience. Cost of Goods Sold: 20% Industry Average = 15% Annual Price: $12,000 Based on Comparable Drug Costs: Infliximab, Natalizumab, Adalimumab, etc Rx Price Growth: 3% Roughly the rate of inflation: very conservative estimate. Potential Customers (treatment population) Growth Stable Relative to National Expected Population Growth Low Initial Market Penetrations 1-2% depending on relevance in treatment category. Growth Plateau Market Share capped at levels previously discussed. Shift in Treatment Modeled trend of earlier ‘top-down’ maintenance regime.
Financial Analysis NPV most sensitive to changes in discount rate and price growth The breakeven values: discount rate = 13.9%; price = $7,554 Expected Value of Average Scenario = $46,793, 384
Critical Signals in Development Pre-Clinical Phase I -In vitro and in vivo studies on animal IBD models -Dosage -Gastrolux vs. SOC -Safety assessment -Single ascending dose and/or multiple ascending dose studies -Food effect study Specifics Phase III Phase II -IIA: Assess dosing requirements -IIB: Study drug efficacy -Gastrolux efficacy vs. SOC -Submit for approval to FDA and EMEA *Efficacy is defined as decrease in symptom severity, increase in time between flares, reduction in disease severity progression, and/or inducing remission during acute flares
Evaluation Signal Risks Reward > Risk? Medical Market Financial Safety Improved treatment Legislative Long-term surveillance Gastrolux is a viable target product High unmet need High revenue potential Barren competitive landscape GTX-002 is not viable Greater market size but higher consumer elasticity Breakeven price exceeds market potential
Biological Risk Gastrolux GTX-002 General Able to safely and effectively block VLA-1 in humans and in appropriate patient subset? Is VLA-1 present on T2 cells allowing UC as viable market? GTX-002 Able to safely and effectively block NFκB in appropriate T cells only? General Recent science suggests T17 cells are a point of convergence for CD and UC. Is VLA-1 present on T17 cells? Can NFκB be targeted in this T cell subset?
Realized Market Potential Scenario Assumptions Realized Market Potential NPV US EU 2032 Best 100% 3.29E+09 Ave 50% 33% 9.98E+08 Worse 0% 4.09E+07 Failure -3.4E+08
Expected Project Value Sensitivity Analysis Expected Project Value Sensitivity Analysis Price Growth Rate 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 Discount Rate 2.02E+08 3.04E+08 4.27E+08 5.73E+08 7.48E+08 9.56E+08 1.2E+09 1.5E+09 1.85E+09 2.26E+09 1.39E+08 2.25E+08 3.27E+08 4.49E+08 5.95E+08 7.68E+08 9.74E+08 1.22E+09 1.51E+09 1.86E+09 87757403 1.6E+08 2.45E+08 3.48E+08 4.69E+08 6.14E+08 7.86E+08 9.9E+08 1.23E+09 1.52E+09 46060423 1.06E+08 1.79E+08 2.64E+08 3.66E+08 4.87E+08 6.31E+08 8.02E+08 1E+09 1.25E+09 12097160 63012009 1.24E+08 1.96E+08 2.81E+08 3.83E+08 5.04E+08 6.47E+08 8.17E+08 1.02E+09 0.1 -1.6E+07 27447034 78583167 2.12E+08 2.97E+08 3.99E+08 5.19E+08 6.62E+08 8.3E+08 0.11 -3.8E+07 -1634442 41613078 92963031 1.54E+08 2.26E+08 3.12E+08 4.13E+08 5.33E+08 6.75E+08 0.12 -5.6E+07 -2.5E+07 11263152 54753681 1.67E+08 2.4E+08 3.25E+08 4.26E+08 5.46E+08 0.13 -7.1E+07 -4.5E+07 -1.4E+07 23275185 67002090 1.19E+08 1.8E+08 2.52E+08 3.38E+08 4.39E+08 0.14 -8.3E+07 -6.1E+07 -3.4E+07 -2655676 34514043 78470813 1.3E+08 1.92E+08 3.5E+08 0.15 -9.3E+07 -7.3E+07 -5.1E+07 -2.4E+07 7659580 45074943 89255193 1.41E+08 2.03E+08 2.75E+08 0.16 -1E+08 -8.4E+07 -6.4E+07 -4.2E+07 -1.5E+07 17383517 55038850 99436317 1.52E+08 2.13E+08