Bplan

Report
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
In d u stria lized
N a tio n s’
A n n u a l B irth
R a te*
3 1 ,7 4 2 ,9 1 6
*
**
***
LSD
P reva len ce* *
1 : 6 ,7 0 0
A n n u a l N ew
C a ses
4 ,8 4 3
P ro jected
M a rk et* * *
$ 2 4 2 ,1 6 8 ,3 3 6
U .S . B u reau o f th e C en su s, In tern atio n al D ata B ase.
F req u en cy n u m b ers are fro m M eikle, H o p w o o d ,
C la g u e, C a rey; P reva len ce o f L yso so m a l S to ra g e
D iso rd ers JA M A , Ja n 2 0 , 1 9 9 9 , V o l 2 8 1 , N o . 3 , 2 4 9 254
E stim ated A A V sales p rice o f $ 5 0 ,0 0 0 p er treatm en t.
Metabolic Disorder Prevalence
D isea se
F am ilial h y p erch o lestero lem ia
F am ilial ty p e III h y p erlip o p ro tein em ia
L y so so m al S to rag e D iseases
alp h a1 A n titry p sin d eficien cy
P h en y lk eto n u ria (P K U )
H em o p h ilia (F acto r V III)
H em o p h ilia (F acto r IX )
O rn ith in e T ran scarb am o lase (O T C )
T o ta l E stim a ted M eta b o lic N ew
C a ses p er Y ea r
*
**
* F req u en cy
1 :1 ,0 0 0
1 :5 ,0 0 0
* * 1 :6 ,7 0 0
1 :7 ,0 0 0
1 :1 0 ,0 0 0
1 :1 0 ,0 0 0
1 :7 0 ,0 0 0
1 :8 0 ,0 0 0
N u m b er
1 3 1 ,1 6 5
2 6 ,2 3 3
1 9 ,5 7 7
1 8 ,7 3 8
1 3 ,1 1 6
1 6 ,3 9 6
1 ,8 7 4
1 ,6 4 0
2 2 8 ,7 3 8
F req u en cy n u m b ers are fro m S criver, B ea u d et, S ly, V a lle ed s; T h e M eta b o lic a n d M o lecu la r
B a ses o f In h erited D isea se, M cG ra w H ill, N ew Y o rk, N Y , 1 9 9 5 , p g . 1 -5 0 .
F req u en cy n u m b ers are fro m M eikle, H o p w o o d , C la g u e, C a rey; P reva len ce o f L yso so m a l
S to ra g e D iso rd ers, JA M A , Ja n 2 0 , 1 9 9 9 , V o l 2 8 1 , N o . 3 , 2 4 9 -2 5 4
Metabolic Disorder Projections
In d u stria lized
N a tio n s’
A n n u a l B irth
R a te
3 1 ,7 4 2 ,9 1 6
*
M eta b o lic
D iso rd ers
C o m b in ed
P reva len ce *
1 : 628
A n n u a l N ew
C a ses
5 1 ,7 4 7
P ro jected M a rk et
$ 2 ,5 8 7 ,3 5 2 ,4 4 6
F req u en cy n u m b ers are calcu lated b y av erag in g th e p rio r listed
m etab o lic p rev alen ce freq u en c ies.
NCL Prevalence


NCLs Prevalence numbers are 1 : 12,000 to 1 : 78,000
1 : 20800 average NCL prevalence
In d u stria lized
N a tio n s’ A n n u a l
B irth R a te
3 1 ,7 4 2 ,9 1 6
*
NCL
P reva len ce*
1 : 2 0 ,8 0 0
A n n u a l N ew
C a ses
1 ,5 6 0
T h e p rev alen ce n u m b er u sed is b ased o n a calcu lated
av erag e fo r all N C L fo rm s d eriv ed fro m p u b lish ed
n u m b ers fro m R id er JA , R id er D L . B a tten d isea s e:
p a st, p resen t, a n d fu tu re. A m J M ed G en et S u p p l.
1 9 8 8 ;5 :2 1 -2 6 .
CLN1 and CLN2 Prevalence
In d u stria lized
N a tio n s’
A n n u a l B irth
R a te
NCL
P reva len ce*
Annual
N ew
C a ses
3 1 ,7 4 2 ,9 1 6
1 : 2 0 ,8 0 0
1 ,5 6 0
*
**
U S N C L R a tio
(C L N 1 a n d C L N 2
vs C L N 3 )* *
50%
CLN 1 and
CLN2
E stim a ted
A n n u a l N ew
C a ses
780
T h e p rev alen ce n u m b er u sed is b ased o n a calcu lated av erag e fo r all N C L fo rm s d eriv ed
fro m p u b lish ed n u m b ers fro m R id er JA , R id er D L . B a tten d isea se: p a st, p resen t, a n d
fu tu re. A m J M ed G en et S u p p l. 1 9 8 8 ;5 :2 1 -2 6 .
A p p ro xim a te d o cu m en ted U S ca ses is 6 0 0 to ta l N C L ca ses. O f th e 6 0 0 , 1 0 0 C L N 1 , 2 0 0
C L N 2 , a n d 3 0 0 C L N 3 ca ses a re estim a ted . T h is ra tio is a p p lied a b o ve
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
Y ea r 1
N u m b er o f p a tien ts trea ted
Y ea r 2
Y ea r 3
Y ea r 4
Y ea r 5
10
150
300
600
780
A A V S a les P rice
$
-
$ 5 0 ,0 0 0
$ 5 0 ,0 0 0
$ 5 0 ,0 0 0
$ 5 0 ,0 0 0
T o ta l R ev en u e
$
-
$ 7 ,5 0 0 ,0 0 0
$ 1 5 ,0 0 0 ,0 0 0
$ 3 0 ,0 0 0 ,0 0 0
$ 3 9 ,0 0 0 ,0 0 0
A A V p ro d u ctio n co st/trea tm en t
T o ta l A A V p ro d u ctio n co st
T o x icity testin g
C en ter F ee
$ 1 0 0 ,0 0 0
25000
20000
15000
10000
$ 1 ,0 0 0 ,0 0 0
$ 3 ,7 5 0 ,0 0 0
$ 6 ,0 0 0 ,0 0 0
$ 9 ,0 0 0 ,0 0 0
$ 7 ,8 0 0 ,0 0 0
$ 5 ,0 0 0
$ 2 5 ,0 0 0
H o sp ita l F ees
H o sp ital b ed ch arg e s
$ 5 ,0 0 0
O p eratin g ro o m ch arg es
$ 1 0 ,0 0 0
S u rg eo n s fees
$ 5 0 ,0 0 0
P re a n d P o st clin ica l ev a lu a tio n s
M R I ($ 2 5 0 0 /test)
$ 5 0 ,0 0 0
E R G ($ 2 0 0 0 /test)
$ 4 0 ,0 0 0
E E G ($ 5 0 0 /test)
$ 1 0 ,0 0 0
O T ($ 2 0 0 /ev alu atio n )
$ 4 ,0 0 0
P T ($ 2 0 0 /ev alu atio n )
$ 4 ,0 0 0
S p eech ($ 2 0 0 /ev alu atio n )
$ 4 ,0 0 0
F ilin g p a ten t a p p lica tio n s
IN D co n su lta n ts
L icen sin g a g reem en ts
$ 1 0 ,0 0 0
$ 7 ,5 0 0
$ 7 ,5 0 0
L eg a l d o cu m en t p rep a ra tio n
$ 1 0 ,0 0 0
G en era l ex p en ses a n d o v erh ea d
$ 1 0 ,0 0 0
$ 1 0 ,0 0 0
$ 1 0 ,0 0 0
$ 1 0 ,0 0 0
$ 1 0 ,0 0 0
$ 1 ,2 5 2 ,0 0 0
$ 3 ,7 6 0 ,0 0 0
$ 6 ,0 1 0 ,0 0 0
$ 9 ,0 1 0 ,0 0 0
$ 7 ,8 1 0 ,0 0 0
$ (1 ,2 5 2 ,0 0 0 )
$ 3 ,7 4 0 ,0 0 0
$ 8 ,9 9 0 ,0 0 0
$ 2 0 ,9 9 0 ,0 0 0
$ 3 1 ,1 9 0 ,0 0 0
T o ta l E x p en ses
P ro fit
Profit and Break-Even Chart
$ 4 8 ,5 0 0 ,0 0 0
$ 3 8 ,5 0 0 ,0 0 0
R e ve n u e
$ 2 8 ,5 0 0 ,0 0 0
To ta l Ex pe n s e s
P ro fi t
$ 1 8 ,5 0 0 ,0 0 0
$ 8 ,5 0 0 ,0 0 0
($ 1 ,5 0 0 ,0 0 0 )
Ye ar 1
Ye ar 2
Ye ar 3
Ye ar 4
Ye ar 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

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