Gene Transfer Therapy
Nathan’s Battle Foundation was established to aid in the development of therapies
for Late Infantile Batten Disease. Late infantile batten disease is a fatal, rare
degenerative neurological disease. This disease takes no mercy on its young victims.
Children typically have seizures, loss of motor control, as well as the ability to think and
reason coherently and end up bedridden requiring a feeding tube for nourishment with the
average life expectancy of ten years of age.
The beginning of Nathan’s Battle Foundation came about when Nathan, the son
of Phil and Tricia Milto, was diagnosed with Late Infantile Batten Disease. Nathan’s
parents identified a need to spearhead therapeutic research for this devastating disorder.
The Milto’s discovered that very little scientific research was being performed in this
area, thus the need for such a foundation. The Nathan’s Battle Foundation was
established in 1999 and formally received Non-For-Profit determination in May of 2000.
For the Milto’s this fight became increasingly more important as their younger
son PJ was also diagnosed with this fatal disease. Their futures as well as the future of
over 500 other children depend on this crucial research, research that is within reach if
given the financial backing.
There has been many steps taken to accomplish their mission. Joined with
Cornell University their mission is close at hand. Promising therapeutic approaches have
been developed. Included in these approaches is gene transfer therapy. This therapy
would be a long-term cure for Late Infantile Batten Disease. Nathan’s Battle Foundation
and Cornell University joined together in developing a five-stage process that would
ultimately complete a clinical trail for gene transfer therapy. Stage one, defining the
scope, plan and timeline, has been completed. In addition, stage two consisting of
creating specific plans and timelines has also been accomplished. However, the
remaining three stages required funding that has not been established at this time.
This funding will provide Nathan’s Battle Foundation with the ability to complete
the main objective of a clinical trail through the remaining three stages. The third stage
of this process is where there is vector production and development of a clinical plan.
Vector testing / validation and regulatory process will be completed in the fourth stage.
And, the remaining task of clinical trail will be the final stage. These stages are
demanding and crucial at the same time. Without funding for these stages of the gene
transfer therapy Nathan, PJ and many others will be left with no hope for the future and
no chances of a cure during their short lifetimes.
Nathan’s battle is a battle that can and must be won for the sake of Nathan, PJ and
the many other children who are innocent victims of this fatal disease.
Total Dollar Amount Needed: $2,100,000
Project Duration date: Stage Three 5/15/01 – 6/28/02
Stage Four 7/02/01 – 8/04/03
Stage Five 8/05/03
Nathan is a five-year-old who is loosing his function, and it is for him that
Nathan’s Battle Foundation was established. Nathan has gone from a child who was
active to a child who can no longer accomplish basic daily tasks. Since his diagnosis he
has lost his eyesight and his cognitive and communication skills have deteriorated. And,
he is not alone in his suffering, there are over 500 other children including his younger
brother PJ who have been diagnosed with the fatal Late Infantile Battens Disease.
Batten disease is one of a family of diseases called neuronal ceroid lipofuscinoses
(or NCL’s) that attack the metabolic properties of the nervous system. When the
metabolic systems are compromised, the cells of the body cannot properly recycle their
waste. Without that recycling process, the cells and the body breaks down. Over time,
affected children suffer mental impairment, seizures, and loss of sight and motor skills.
Batten disease is always fatal. Late Infantile Batten disease, also known as CLN2, affects
1 in 250,000 new births. When all the 40 similar diseases that can benefit from this
research are added up, the rate of incidents drops to less than 1 in 6,700.
However, these children diagnosed with CLN 2 have hope for their future with
your help. There is a potential therapy that may enable these children to live a long
fulfilling life. Gene Transfer Therapy is a promising approach to Late Infantile Battens
Disease. Gene therapy using the Adeno-associated virus (AAV) has been associated to
be effective at reducing lysosomal storage in many tissues including neurons of the
central nervous system in a murine model of a lysosomal storage disease. In addition, the
use of AAV as a gene transfer vector is based on over 15 years of basic research.
Nathan’s Battle Foundation has initiated and recruited key organizations,
institutions, and renowned research scientist as well as large and small companies in their
fight. Their united efforts have proven successful in initiating the process and beginning
the vital stages. However, without key funding their efforts will come to an abrupt halt.
In addition, Nathan’s Battle Foundation has developed a working relationship
with the Institute of Genetic Medicine Weill Medical College of Cornell University
which can provided clinical trails for this therapy. They have already completed the
groundwork and now they need funding to gather the pre-trial data and to initiate the
clinical trails. Their work already accomplished will serve as a base. Here the scope has
been defined, timelines have been determined and plans have been developed. Cornell
University has allowed Nathan’s Battle Foundation to pay $100,000 per month because
of the tremendous promise the project has. Gene therapy has been proven to be effective
in treating similar disorders by getting a functioning gene back into the central nervous
system to produce the missing enzyme and curing the disease.
Results of gene transfer therapy have far-reaching potential. Once proven
successful, there are hundreds of children that will be given a renewed chance at life.
And, the information learned from these trails will provide a basis for other gene
therapies for the future. Thus providing vital information for over 40 other rare diseases.
Therefore, this clinical trail could have an impact in over 50,000 people’s lives. This
project can advance medical science by being one of the first gene therapy projects into
the central nervous system. It is the cutting edge in medical science and has great
potential for shaping the future of medicine.
As a result of this award the five-stage process developed by Cornell University
will be completed. Since the first two stages are completed the funding will assist in
completing the remaining three stages which are included in the following objectives:
Objective #1. Completion of proposed stage three. This stage will consist of
vector and analytic development as well as pre-clinical studies for distribution and
expression. And, the production of GMP grade vectors and the completion of a
Objective #2. Completion of proposed stage four. This stage will consist of
testing and validating the clinical grade vectors, obtaining IRB, IBC, and RAC
approvals, writing an IND application, obtaining FDA approval and initiating
Objective #3. Completion of proposed stage five. This stage will consist of the
initiation and completion of clinical trails.
Objective #4. Generate a model for other gene therapy clinical trails.
Proposed Method/ Procedure
Clinical trails are time consuming and financially expensive. In addition they
require the knowledge of experts and the scientific know how to develop appropriate
trials that maintain within guidelines. Nathan’s Battle has established a working
relationship to obtain these needs of the clinical trail. Cornell University has established
what they would be able to accomplish to assist in this clinical trail. They have explained
out the various procedures that are necessary and the methods in which these procedures
will be implemented. The stages remaining to be completed and the procedures in which
they will be carried out are broken down into tasks below and noted by their purpose,
time frame and cost.
Purpose/ step needed Time frame Costs
Vector and analytic development 5/ 01 – 11/01 $300,000
Pre-clinical studies for distribution 5/01 – 1/02 $500,000
GMP vector process development 5/01 – 5/02 $300,000
Clinical protocol development 7/01 – 6/02 $500,000
Toxicology studies 8/02 – 2/03 Previously
FDA submission 6/03 – 8/03 Previously
Clinical Trials initiation 8/03 – unknown $500,000
Estimated total costs: $2,100,000
It is important to note that in regards to the FDA submission of this process the
investigational new drug submission for AAV gene therapy for CLN 1 and CLN 2 is
being designated as a compassionate use drug. This designation under the Orphan Drug
Act will allow for fast tracking priority review expediting the process. Also, under the
Orphan Drug Act, the FDA is willing to work with this trial on the necessary
requirements. Targeting the NCL disorders is a low risk, high reward situation.
Once the project is completed the first phases of a clinical trial are completed, we
will have proven the efficacy of the drug for a biotech company to manufacture.
Negotiations with a biotech company (Genzyme) have been established to commercialize
the drug to make it available to the community (see the attached Non-For-Profit Therapy
Development Model Diagram).
The gene therapy project can be easily evaluated by reviewing the progress
against the tasks and time frames defined in the work plan. Following the work plan
timeline closely will be a major emphasis. We are fighting time with this disease so the
project will be measured regularly to facilitate the timely success.
The current total estimated budget for the LINCL gene therapy project is $2.1
million dollars. The project costs are derived from the project work plan prepared by the
Institute of Genetic Medicine Weill Medical College of Cornell University (see appendix
for copy of work plan). The work plan specifies tasks and milestones associated with the
project. These tasks will require professional resources and associated supplies to
develop the drug. These funds will be used to accomplish major project milestone,
including the first phase of a life saving clinical trial on humans. The major project
milestones involve: the manufacturing of the drug, remaining necessary pre-clinical
testing, clinical protocol development, regulatory approval process, and human
administration in the first phase of the clinical trial. The costs associated with each
milestone are inclusive of scientific materials, laboratory specimens, equipment,
professional services, and indirect cost. Cornell University charges a reduced rate for
indirect charges for Non-For-Profit organizations of 25%.
The Nathan’s Battle Foundation will contribute all personnel time at no charge to
the project. Copies of the project budget from the first two stages of the LINCL project
are included in the appendix.
Project Milestone Expenses Amount
Vector and analytic development $300,000
Initial vector construction
Develop analytical methods
Pre-clinical Studies $500,000
GMP clinical grade vector process development $300,000
GMP Process development
GMP batch development
GMP clinical production and quality control
Clinical protocol development $500,000
Clinical protocol development
Assemble clinical team
Phase I Human Clinical Trial $500,000
Commence clinical protocol
Total estimated expenses $2,100,000
2001 Project Budget:
Milestone completed in ‘01 Needed
Vector and analytic 100% of $300,000 $300,000
Pre-clinical Studies 80% of $500,000 $400,000
GMP clinical grade 25% of $300,000 $75,000
Clinical protocol 25%of $500,000 $125,000
Phase I Human Clinical 0% of $500,000 $0
Total estimated $900,000
expenses for 2001
2002 Project Budget: Percentage
Milestone completed in ‘02 Needed
Vector and analytic 100% of $300,000 $0
Pre-clinical Studies 20% of $500,000 $100,000
GMP clinical grade 75% of $300,000 $225,000
Clinical protocol 75%of $500,000 $375,000
Phase I Human Clinical 0% of $500,000 $0
Total estimated $700,000
expenses for 2002
2003 Project Budget:
Milestone completed in ‘03 Needed
Vector and analytic 100% of $300,000 $0
Pre-clinical Studies 100% of $500,000 $0
GMP clinical grade 100% of $300,000 $0
Clinical protocol 100%of $500,000 $0
Phase I Human Clinical 100% of $500,000 $500,000
Total estimated $500,000
expenses for 2003
The project costs are associated with the milestones defined in the work plan.
These expenses are supported from actual cost of salaries, supplies, laboratory specimens,
equipment, and production materials. These cost are in-line with the CLN2 AAV Gene
Therapy Business Plan, which was developed in March of 2000. This business plan was
reviewed by a number of major biotech companies, such as Genzyme, Avigen, Targeted
Genetics, and Cell Genesys. The consensus from these companies was that the expenses
would be low for their organizations to perform this work, but an independent Non-For-
Profit foundation could accomplish the necessary tasks near the defined costs. A large
company has more overhead and bureaucracy to involve in a project of this nature. The
business plan was presented at a conference at the NIH in May of 2000 to these major
biotech companies (Clinical Trial Initiative Conference Summary is available upon
request). The required funding of $2 million is justified from the necessary supplies,
resources, personnel, and testing.
See appendix for AAV Gene Therapy Business Plan
Nathan’s Battle Financial Information
Financial Statement Information
The Nathan’s Battle Foundation was formally incorporated on 3/27/00 and
received the formal letter of 501(c)(3) determination in May of 2000. The Foundation
does not currently have a formal financial statement prepared from our CPA firm, but one
is currently being prepared to comply with the Non-For-Profit filing dates.
In summary given the currently planned fund raising events, the Nathan’s Battle
Foundation needs to raise over $652,000 to support the therapy development projects for
the 2001 fiscal year. For the fiscal year 2002 given the forecasted event revenue, the
foundation needs to raise an additional $605,500 to fund therapy development projects.
This funding is necessary to continue the development of therapies for LINCL.
Receiving all of the necessary funding in Q3 of 2001 is imperative and for 2002 by Q2.
The earlier in the year is important to the viability of the project, without timely funding
the project will stop. Total additional funding needed for the next two years of 2001 and
2002, given planned and forecasted events, is $1,257,500. The 2003’s forecasted
required funding amount needed for the clinical trial initiation stage of the project is
expected to be $500,000. Estimated total funding needed is $1,757,000. The project
could be accelerated if we were able to secure the total $1,757,000 up front. Having the
funding now would enable us to perform more project tasks in parallel because of the
additional resources available to perform the work sooner. The critical path of the project
is less than 18 months to the clinic but with restricted funding resources the project will
take up to 30 months.. If we can secure the total funding in 2001 the project could be
shortened and kids could receive therapy more quickly. The revenues and expenses are
1999 Revenues and Expenses
1999 Revenue Amount
The Nathan’s Battle Benefit Dinner $91,263.75
The Nathan’s Battle Golf outing $16,969
Misc. Donations $4,528.51
Interest Paid $1,111.19
Total Revenue $113,872.49
The Nathan’s Battle Benefit Dinner $2,083
The Nathan’s Battle Golf outing $3,475.75
NCLRA Research Conference $2,713
Total 1999 Expenses $8,271.75
2000 Revenues and Expenses
2000 Revenue Amount
Ringling Brothers and Barnum Bailey Circus $95,000
– Nathan’s Battle Under the Big Top
The Nathan’s Battle Golf outing $10,500
Jeff and Teri Stoops sale of car donated $16,500
Grants and Awards – Ruth Lilly $5,000
Misc. Donations $15,000
Interest Paid $1,800
Total 2000 Revenue $143,800
Washington University CLN2 Gene Therapy $20,000
Research – Dr. Sands’s Lab
The Nathan’s Battle Under the Big Top $2,583
The Nathan’s Battle Golf outing $2,075.75
NCLRA’s Clinical Trial Initiative $3,000
Conference – May 2000
Cornell Feasibility Study $125,000
Total 2000 Expenses $152,658.75
2001 Revenues and Expenses Forecast
2001 Forecasted Revenues Amount
The Natalie Fund for Childhood Brain $130,000
Disease Research – CA.
The Bobbie Shone Trust – England* $20,000
The Nathan’s Battle Golf outings* $60,500
Grants and Awards* $5,000
Misc. Donations $45,000
Run Walk Event $22,000
Benefit Concert $23,000
Dinner Benefit at the Ritz* $50,000
Interest Paid $4,500
Philanthropic or Future Grant Support* (?)
Total 2001 Revenue $360,000 + (?)
2001 Forecasted Expenses
Cornell Clinical Trial Project $900,000
Dinner Benefit at the Ritz expenses* $3,000
The Nathan’s Battle Golf outings* $4,000
Misc. event expenses $5,000
High Through Put CLN2 Drug Screening* $100,000
Total 2001 Expenses $1,012,000
* These line items are forecasted revenues or expenses that have not
actually been received or incurred.
The 2001 amount needed to raise including currently planned forecasted events is $652,000
($1,012,000 - $360,000 = $652,000).
2002 Revenues and Expenses Forecast
2002 Forecasted Revenues Amount
The Natalie Fund for Childhood Brain $60,000
Disease Research – CA.
The Nathan’s Battle Golf outings $50,000
Grants and Awards $5,000
Misc. Donations $30,000
Interest Paid $4,500
Philanthropic or Future Grant Support (?)
Total 2002 Revenue $149,500 + (?)
2002 Forecasted Expenses
Cornell Clinical Trial Project $700,000
Misc. event expenses $5,000
High Through Put CLN2 Drug Screening $50,000
Total 2002 Expenses $755,000
The 2002 amount needed to raise including currently planned forecasted events is $605,500
(755,000 - $149,500 = $605,500).
Total additional funding needed for the next two years of 2001 and 2002,
given planned and forecasted events, is $1,257,500. The 2003’s forecasted
required funding needed for the clinical trial initiation stage of the project is
expected to be near $500,000. Estimated total funding needed is $1,700,000.
Balance Sheet Information
1999 Assets and Liabilities
1999 Assets Amount
Other Assets $0
Total Assets $105,540.74
Outstanding Debt $0
Total 1999 Liabilities $0
2000 Assets and Liabilities
2000 Assets Amount
Other Assets $0
Total Assets $96,681.99
Outstanding Debt $0
Total 2000 Liabilities $0
Impact of Grant
These children deserve a right to live a full life and have a fighting chance. But,
that right will not come without a cure for a disease that takes everything from them. A
disease that takes their abilities, their newfound skills and eventually their hope and
spirit. They need your help. They need these trials to continue.
Completion of clinical trials will provide scientists and the community with vital
information to assist in many rare diseases. The results, in particular, are anticipated to
prove as a cure for Late Infantile Batten Disease (CLN2). This successful completion of
clinical trials will save the lives of over 500 children directly. In addition, it will improve
the quality of life not only for the children who unfortunately have been diagnoses with
Batten’s disease. It will also serve as a mechanism for improving the quality of life for
all those who are intimately involved with that child.
In addition, the completion of gene transfer therapy is anticipating having positive
results for over 40 other rare diseases, which affect hundreds of thousands of people.
And, their lives could become more promising and fulfilling through these clinical trails.
The results of these clinical trials have far reaching impact. Gene transfer therapy can
serve to cure this disease, can improve the chance of cures for other diseases and will
improve the quality of scientific information that is available. The information gained
from this research and clinical trials will provide key information and knowledge that can
be utilized in future research and clinical trials for various other rare diseases.
Gene transfer therapy clinical trials must be completed to save the lives of these
children. If these trials are not perused then these children will die. And, those
intimately involved with these children will run the risk of loosing all hope and spirit.
These children have no other alternative at this time and time is of a crucial factor.
Perhaps other options will come about in the years to come. Unfortunately, these
children do not have years to come and everyday must be utilized to its fullest.
Nathan’s Battle Foundation can serve in the best position to institute these clinical
trials because they have established several crucial relationships to ensure the trials are
completed on a timely and efficiently way. They have already established the needed
relationship with Cornell University who will be able to initiate the trials. They have
been working in conjointly with The National Ceroid Lipofuscinoses Research Alliance
(NCLRA). And, they have coordinated relationship with leading scientists.
As an organization that is true to their mission, Nathan’s Battle Foundation has
the reputation and dedication to ensure these trials are completed. Nathan’s Battle
Foundation has strived to coordinate efforts with all key stakeholders. In addition, they
are open via publications and web site about all issues they are involved in. They
communicate effectively what is occurring with the clinical trials, what is needed and
why it is needed.
If these clinical trials are not completed the financial costs will result in the
healthcare that is needed to sustain these children’s final days. The human costs will be
the true price that will be paid. For, the financial impact is minimal. But, for these 500
plus children their lives are o the line and everyday, every minute truly is where the costs
are shown. If the clinical trials are delayed many of these children will face the same
result, death. Others will begin declining in their abilities. As a delay where to exist, the
longer the delay, and the more deaths this disease will cause.
Staff and Facilities
The Institute of Genetic Medicine Weill Medical College of Cornell University
will perform the Gene Therapy project for Late Infantile Batten Disease. The Weill
Medical College has a state of the art facility that was newly renovated in 1999 to make it
a world-class facility. This facility is one of the only laboratories that have the capability
of manufacturing clinical grade AAV GMP vector.
The Institute of Genetic Medicine at the Weill Medical College of Cornell
University is lead by Dr. Ronald Crystal. Dr. Ronal Crystal is a world renown leader in
the gene therapy field. Dr. Crytsal has taken potential therapies to the FDA and has
experience executing and performing clinical trials. Dr. Crystal’s leadership of this
project ensures the success of this extremely promising project. The excitement in the
scientific community regarding this project will foster the necessary collaborations to
provide the nations best experts to give guidance and direction.
The project will be managed by a partnership between the Cornell Institute of
Genetic Medicine and Nathan’s Battle Foundation. This partnership ensures the success
of the trial based on the main focus of each party involved. The Nathan’s Battle
Foundation will ensure that the project will be focused and progresses to accomplish
milestones on an aggressive schedule. The NBF will utilize its managerial skills and
developed relationships to aid in propelling the project to the clinic.
AAV Gene Therapy Business Plan
Cornell Project Feasibility Study Proposal for stages 1 and 2
Cornell Feasibility Study cover letter
Cornell Project Work Plan
Non-For-Profit Therapy Development Model Diagram
Feasibility Study of Gene Therapy of Late Infantile Neuronal Ceroid
Lipofuscinosis (available upon request 56 pages)
Clinical Trial Initiative Conference Summary (available upon request 51 pages)