Download A Tale of Two(?) IBDs

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
Executive Summary
The CYMMBiosis Team Recommends:
License GTX001
“Gastrolux”
Pass on GTX002
• 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
IBD Landscape
Crohn’s Disease
Ulcerative Colitis
• Disease mechanism unknown:
genetic, environment, pathogenic
factors
• Highest incidence and prevalence
in age group 20-29
• Disease mechanism unknown:
genetic, environment, pathogenic
factors
• Highest incidence and prevalence
in age group 15-30
Patient Population Growth
Disease Severity
Disease Severity
2008
2020
2032
Mild
Moderate
Mild
Moderate
1,305,000
1,220,000
Severe
16%
15%
1,065,000
46%
896,300
957,500
830,000
30%
38%
CD
Severe
UC
55%
Current Treatment
Crohn’s Disease
Ulcerative
Colitis
Lines of
Therapy
%
% of
of Patient
Patient
Current treatment
Population
Population
5-ASA Only
16.69%
37.05%
Steroids + 5-ASA
18.21%
14.21%
Steroids + IM
28.79%
26.74%
Biologics
Biologics
10.42%
17.04%
Treatment
Treatment
Refractory
Refractory
4.21%
10.34%
Effective
induction
and maintenance
mild
to cases
5-ASAs are
rarely effective,
mainly forfor
very
mild
moderate UC; considered safest
rapid-acting
Steroids are the most effective,
rapid-acting
therapies;therapies;
NOT
NOT
suitable
for long-term
use because
concerns
suitable
for long-term
use because
safetysafety
concerns
IMs are first-line
choice for
for maintenance
maintenance because
because lower
lower
primary choice
high toxicity
cost than biologics; HIGH
toxicityfor
forlong-term
long-termuse
use
More doctors prescribe biologics as first-line treatment.
Infliximab most
high
efficacy for
butUC
high side
is the prescribed,
only biologics
approved
effects.
50-60%
Infliximab
45-70% patients
patients lose
lose response
response over
over time
time to
to anti-TNF
biologics therapy
Target product profile
•
•
•
•
•
Criteria
Gastrolux GTX-002
Is it medically plausible?
Is there a penetrable
market?
Is this financially viable?
Is it safe?
Does it perform better
than SOC?
Pathophysiology of IBD
Crohn’s Disease
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
Ulcerative Colitis
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
Crohn’s Disease
Disease
Crohn’s
300,000
250,000
200,000
200,000
150,000
100,000
100,000
50,000
00
Ulcerative Colitis
Ulcerative Colitis
400,000
400,000
300,000
200,000
200,000
100,000
00
GTX-002
Gastrolux
Competitors
Key Assumptions of Financial Modeling
Discount Rate: 10%
Average WACC for comparable Pharma Cos = 7.2%
Probability of Regulatory Science and Safety Risks based on historical drug approval
Success: 12%
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
Market NPV Scenarios
4.E+09
Best
3.E+09
Ave
2.E+09
Worse
5.E+08
Failure
-5.E+082009
2014
2019
2024
2029
2034
• 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
NPV vs. Price
NPV vs. Discount Rate
4.0E+08
3.5E+08
1.0E+08
3.0E+08
2.5E+08
5.0E+07
2.0E+08
1.5E+08
0.0E+00
1.0E+08
6,000 8,000 10,000 12,000 14,000 16,000
5.0E+07
-5.0E+07
0.0E+00
-5.0E+07 0%
-1.0E+08
-1.0E+08
Sales Price
NPV vs. Price Growth
1.5E+08
8.0E+08
7.0E+08
6.0E+08
5.0E+08
4.0E+08
3.0E+08
2.0E+08
1.0E+08
5%
10%
15%
Discount Rate (WACC)
20%
0.0E+00
-1.0E+08 0%
2%
4%
6%
8%
Price Growth Rate
10%
12%
Critical Signals in Development
Pre-Clinical
-In vitro and in vivo studies
on animal IBD models
Specifics
Phase I
-Safety assessment
-Dosage
-Single ascending dose and/or
multiple ascending dose studies
-Gastrolux vs. SOC
-Food effect study
Phase III
Phase II
-Gastrolux efficacy vs. SOC
-IIA: Assess dosing
requirements
-Submit for approval to FDA
and EMEA
-IIB: Study drug efficacy
*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
Medical
Market
Financial
Safety
Improved treatment
Legislative
Long-term surveillance
Reward > Risk?
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
– 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?
Scenario Assumptions
Realized Market Potential
NPV
US
EU
2032
Best
100%
100%
3.29E+09
Ave
50%
33%
9.98E+08
Worse
33%
0%
4.09E+07
Failure
0%
0%
-3.4E+08
Sensitivity Analysis
Expected Project Value Sensitivity Analysis
Price Growth Rate
Discount Rate
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.05
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
0.06
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
0.07
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
0.08
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
0.09
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
1.39E+08
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
1.06E+08
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
2.64E+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