Transcript Bplan
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