CLN1/CLN2 Gene Therapy
Business Plan
Objectives
Introduce a therapy to CLN1 and CLN2
children for treatment of their disorder.
 Develop a model for other AAV gene
therapy clinical trials. Gaining vital
information to be leveraged in future gene
transfer applications.

Keys to Success

Clinical Trial Sponsor
– Interest in or knowledge of gene therapy principles
– Commitment and dedication to the successful treatment of NCL
patients
– Previous clinical trial experience
– Ability to produce or acquire, clinical grade AAV
– A center committed to host a site for the clinical trial
– Committed clinicians with experience in degenerative neurological
disorders

Clinical Trial Partnership Strategy
Organizational Structure
NCLRA
 NIH
 FDA
 Mark S. Sands
 Organizations
 Universities
 Therapeutic Investigators and Advisors

AAV Viability

Lysosomal Storage Diseases
– Enzyme Deficiency
– Cross Correction
Little or no toxicity with high expression
 MPS VII Results

AAV Viability
Lysosomal Storage Diseases
 Little or no toxicity with high expression
 MPS VII Results

Implementation Strategy
CLN1 and CLN2
 Other LSDs
 Metabolic Disorders

Lysosomal Storage Disorders
Projections Table
Industrialized
Nations’
Annual Birth
Rate*
31,742,916
*
**
***
LSD
Prevalence**
1 : 6,700
Annual New
Cases
4,843
Projected
Market***
$242,168,336
U.S. Bureau of the Census, International Data Base.
Frequency numbers are from Meikle, Hopwood,
Clague, Carey; Prevalence of Lysosomal Storage
Disorders JAMA, Jan 20, 1999, Vol 281, No. 3, 249254
Estimated AAV sales price of $50,000 per treatment.
Metabolic Disorder Prevalence
Disease
Familial hypercholesterolemia
Familial type III hyperlipoproteinemia
Lysosomal Storage Diseases
alpha1 Antitrypsin deficiency
Phenylketonuria (PKU)
Hemophilia (Factor VIII)
Hemophilia (Factor IX)
Ornithine Transcarbamolase (OTC)
Total Estimated Metabolic New
Cases per Year
*
**
* Frequency
1:1,000
1:5,000
** 1:6,700
1:7,000
1:10,000
1:10,000
1:70,000
1:80,000
Number
131,165
26,233
19,577
18,738
13,116
16,396
1,874
1,640
228,738
Frequency numbers are from Scriver, Beaudet, Sly, Valle eds; The Metabolic and Molecular
Bases of Inherited Disease, McGraw Hill, New York, NY, 1995, pg. 1-50.
Frequency numbers are from Meikle, Hopwood, Clague, Carey; Prevalence of Lysosomal
Storage Disorders, JAMA, Jan 20, 1999, Vol 281, No. 3, 249-254
Metabolic Disorder Projections
Industrialized
Nations’
Annual Birth
Rate
31,742,916
*
Metabolic
Disorders
Combined
Prevalence *
1 : 628
Annual New
Cases
51,747
Projected Market
$2,587,352,446
Frequency numbers are calculated by averaging the prior listed
metabolic prevalence frequencies.
NCL Prevalence


NCLs Prevalence numbers are 1 : 12,000 to 1 : 78,000
1 : 20800 average NCL prevalence
Industrialized
Nations’ Annual
Birth Rate
31,742,916
*
NCL
Prevalence*
1 : 20,800
Annual New
Cases
1,560
The prevalence number used is based on a calculated
average for all NCL forms derived from published
numbers from Rider JA, Rider DL. Batten disease:
past, present, and future. Am J Med Genet Suppl.
1988;5:21-26.
CLN1 and CLN2 Prevalence
Industrialized
Nations’
Annual Birth
Rate
NCL
Prevalence*
Annual
New
Cases
31,742,916
1 : 20,800
1,560
*
**
US NCL Ratio
(CLN1 and CLN2
vs CLN3)**
50%
CLN1 and
CLN2
Estimated
Annual New
Cases
780
The prevalence number used is based on a calculated average for all NCL forms derived
from published numbers from Rider JA, Rider DL. Batten disease: past, present, and
future. Am J Med Genet Suppl. 1988;5:21-26.
Approximate documented US cases is 600 total NCL cases. Of the 600, 100 CLN1, 200
CLN2, and 300 CLN3 cases are estimated. This ratio is applied above
CLN1/CLN2 Financial Plan



$31 Million Fifth Year Bottom Line
Break-even and Profit in Year 2
Total Estimated Start-up Cost are $1.5 Million
– Obtaining remaining pre-clinical data and protocol
development has an estimated cost of $200,000
» Protocol development ($60k)
» Finalizing necessary pre-clinical Data ($60k)
» Performing primate testing ($80k)
– Estimated Clinical Trial Funding is approximately $1.3
Million
Five Year Financial Forecast
Year 1
Number of patients treated
Year 2
Year 3
Year 4
Year 5
10
150
300
600
780
AAV Sales Price
$
-
$50,000
$50,000
$50,000
$50,000
Total Revenue
$
-
$7,500,000
$15,000,000
$30,000,000
$39,000,000
AAV production cost/treatment
Total AAV production cost
Toxicity testing
Center Fee
$100,000
25000
20000
15000
10000
$1,000,000
$3,750,000
$6,000,000
$9,000,000
$7,800,000
$5,000
$25,000
Hospital Fees
Hospital bed charges
$5,000
Operating room charges
$10,000
Surgeons fees
$50,000
Pre and Post clinical evaluations
MRI ($2500/test)
$50,000
ERG ($2000/test)
$40,000
EEG ($500/test)
$10,000
OT ($200/evaluation)
$4,000
PT ($200/evaluation)
$4,000
Speech ($200/evaluation)
$4,000
Filing patent applications
IND consultants
Licensing agreements
$10,000
$7,500
$7,500
Legal document preparation
$10,000
General expenses and overhead
$10,000
$10,000
$10,000
$10,000
$10,000
$1,252,000
$3,760,000
$6,010,000
$9,010,000
$7,810,000
$(1,252,000)
$3,740,000
$8,990,000
$20,990,000
$31,190,000
Total Expenses
Profit
Profit and Break-Even Chart
$48,500,000
$38,500,000
Revenue
Total Expenses
Profit
$28,500,000
$18,500,000
$8,500,000
($1,500,000)
Year 1
Year 2
Year 3
Year 4
Year 5
Why CLN1/CLN2?









Prevalence of LSDs (enzyme deficient disorder)
Prognosis of CLN1/CLN2 patients
NIH Involvement
FDA’s Orphan Drug Act – Fast Tracking IND
Consenting Patient Population
Leading Scientists
Promising Financial Returns
Establish Gene Therapy Info-structure / Model
Answer Unknown Questions by Validating Science
Next Steps

Establish Clinical Trial Sponsor Partnerships
–
–
–
–




Sponsorship
Trial Administration
Trial Sites
Clinicians and Surgeons
Obtain Clinical Grade Vector
Gather “Necessary” Pre-Clinical Data
Develop Trial Protocol and Points of
Consideration (IRB, RAC, FDA)
Finalize IND for Submission
Next Steps