Nathan’s Battle

Grant Request Proposal

Introduction

The Nathan’s Battle Foundation was established in 1999 and formally received Non-For-Profit determination in May of 2000. Rare genetic diseases afflict hundreds of thousands of children across the world with little hope for therapy. One such disease, Late Infantile Batten disease, afflicted a little boy named Nathan Milto. 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.

Nathan’s parents, Phil and Tricia Milto, 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. After organizing current researchers and related scientist, the Milto’s uncovered a few viable therapeutic options for Late Infantile Batten disease. The foundation continues to drive the development for these therapies and has been extremely effective in accomplishing its goals. The Nathan’s Battle Foundation’s efforts will aid and advance the development of therapies for numerous rare diseases and has been a leader in propelling medical research for the thousands of afflicted children with rare diseases around the world.

Need/Problem/Issue Statement

Current project funding request are for developing a gene therapy for Late Infantile Batten disease with Institute of Genetic Medicine Weill Medical College of Cornell University. A formal feasibility study has been performed to professionally confirm the viability of such a therapy and it was the conclusion of Cornell University, that it is possible to initiate a clinical trial for the CNS of Late Infantile Batten disease. A detailed work plan has been developed for this project with tasks, milestones, and timeframes. The objective of this project is to develop gene therapy for the central nervous system for Late Infantile Batten disease. The intention of this therapy is to cure this disease. Once successful, over 40 other diseases will benefit this life saving therapy. The project is scheduled to be completed within thirty months and can be accelerated with additional resources applied.

Major milestones are:

Timeframe / Milestones /

Min. Estimated Cost

11/12/01

/

Drug development and testing procedures

/ $300,000
1/21/02 / Pre-clinical studies for distribution and expression / $500,000
5/15/02 / GMP vector process development / $300,000
6/28/02 / Clinical protocol development / $500,000
2/10/03 / Toxicology studies / Previously included
6/24/03 / FDA submission and approvals / Previously included
8/05/03 / Clinical trial initiation / $500,000

Minimum Estimated Total Costs:

/ $2,100,000

Definitive results will be produced from this project. Return from all funding contributions can be measured via accomplishments of project milestones and the ultimate objective of saving children lives.

Expected Impact of Project

The development of a gene therapy will directly benefit the over 500 hundred children that are afflicted with this gruesome disease through out the world. The potential of this project can have an impact on over 40 other rare diseases, which would include a population of over 50,000 fatally ill people. The principle of this project is to pioneer rare disease therapy development to create a platform for other rare diseases.

Budget

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.

Budgeted

Project Milestone ExpensesAmount

Vector and analytic development $300,000

Initial vector construction

Develop analytical methods

Pre-clinical Studies$500,000

Distribution Studies

Expression Studies

Toxicology studies

GMP clinical grade vector process development$300,000

GMP Process development

GMP characterization

GMP batch development

GMP clinical production and quality control

Clinical protocol development$500,000

Clinical protocol development

Assemble clinical team

IRB submission

RAC submission

FDA submission

Phase I Human Clinical Trial$500,000

Commence clinical protocol

Total estimated expenses $2,100,000

2001 Project Budget:

Percentage Amount

Milestonecompleted in ‘01Needed

Vector and analytic development / 100% of $300,000 / $300,000
Pre-clinical Studies / 80% of $500,000 / $400,000
GMP clinical grade vector process development / 25% of $300,000 / $75,000
Clinical protocol development / 25%of $500,000 / $125,000
Phase I Human Clinical Trial / 0% of $500,000 / $0
Total estimated expenses for 2001 / $900,000

2002 Project Budget:

Percentage Amount

Milestonecompleted in ‘02Needed

Vector and analytic development / 100% of $300,000 / $0
Pre-clinical Studies / 20% of $500,000 / $100,000
GMP clinical grade vector process development / 75% of $300,000 / $225,000
Clinical protocol development / 75%of $500,000 / $375,000
Phase I Human Clinical Trial / 0% of $500,000 / $0
Total estimated expenses for 2002 / $700,000

2003 Project Budget:

Percentage Amount

Milestonecompleted in ‘03Needed

Vector and analytic development / 100% of $300,000 / $0
Pre-clinical Studies / 100% of $500,000 / $0
GMP clinical grade vector process development / 100% of $300,000 / $0
Clinical protocol development / 100%of $500,000 / $0
Phase I Human Clinical Trial / 100% of $500,000 / $500,000
Total estimated expenses for 2003 / $500,000

Budget Explanation

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 as follows:

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
1999 Expenses
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 – Nathan’s Battle Under the Big Top / $95,000
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 Revenue / $143,800
2000 Expenses
Washington University CLN2 Gene Therapy Research – Dr. Sands’s Lab / $20,000
The Nathan’s Battle Under the Big Top / $2,583
The Nathan’s Battle Golf outing / $2,075.75
NCLRA’s Clinical Trial Initiative Conference – May 2000 / $3,000
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 Disease Research – CA. / $130,000
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 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 Disease Research – CA. / $60,000
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 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
Cash / $105,540.74
Other Assets / $0
Total Assets / $105,540.74
1999 Liabilities
Outstanding Debt / $0
Total 1999 Liabilities / $0
2000 Assets and Liabilities
2000 Assets / Amount
Cash / $96,681.99
Other Assets / $0
Total Assets / $96,681.99
2000 Liabilities
Outstanding Debt / $0
Total 2000 Liabilities / $0

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.

Evaluation Method

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.

Continuation or Sustainability Strategies

Once the project is completed and 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).

Appendices

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)