Dear Colleague:
The Children’s Tumor Foundation Drug Discovery Initiative (DDI) funds and
facilitates early stage screening of candidate therapies for neurofibromatosis (NF).
DDI Awards provide seed funding of up to $25,000 (+ up to $2,500 indirect costs)
to support in vitro or in vivo studies targeted at testing candidate NF therapies for
efficacy in cells & animal models.
The next DDI Award deadline is June 30th, 2007. The current RFA and application
form are attached.
A principal goal of DDI Awards is rapid review & funding.
We hope to announce successful awardees from this round in August 2007!
In conjunction with DDI Awards, the DDI Toolbox is a publicly available resource of
tools to help in NF drug discovery - in vitro and in vivo NF screening models,
candidate drugs, etc. DDI provides a partnering & information exchange forum to
help drive progress in NF drug discovery. Learn more about the DDI Toolbox and
how to share your tools at www.ctf.org.
The DDI Awards Request for Applications (RFA) & Application Form are attached. I
look forward to reading your application.
Good Luck!
Kim Hunter-Schaedle, Ph.D.
Chief Scientific Officer, Children’s Tumor Foundation
Drug Discovery Initiative Award:
Request for Applications
The Children’s Tumor Foundation Drug Discovery Initiative (DDI) Award offers seed
funding of to support screening of candidate therapeutics for neurofibromatosis.
DDI Awards
DDI Award funding is offered at two levels:
Funding Amount Overheads/
In vitro $10,000
In vivo $25,000
Intended purpose
To facilitate the screening of candidate
therapeutics in appropriate primary cultures or
cell lines relevant to neurofibromatosis
To facilitate the in vivo screening of candidate
therapeutics that have already demonstrated
in vitro efficacy for neurofibromatosis
What is neurofibromatosis?
Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder affecting
1:3,000 births. 50% of cases are inherited, 50% are spontaneous. The Nf1 gene is on
Chromosome 17; its product, neurofibromin, is a 220kD protein and tumor suppressor that
targets the RAS pathway. NF1 can cause tumors of peripheral nerve origin to grow anywhere
in the nervous system; bone abnormalities; learning disabilities and blindness.
Neurofibromatosis Type 2 (NF2) is also an autosomal dominant genetic disorder affecting
1:25,000 births. 50% of cases are inherited, 50% are spontaneous. The NF2 gene is on
Chromosome 22 and produces merlin (or schwannomin), a 65kD cytoskeleton-associated
membrane protein of the ezrin, moesin, radixin (ERM) family. Merlin is believed to have
tumor suppressor functions but its role is less clearly understood than that of neurofibromin:
merlin appears to regulate apoptosis and cell-cell contact inhibition signaling. NF2 causes
tumors on the 8th cranial nerve, surgical removal of which frequently leads to deafness. The
disorder has a poor prognosis often with only 20 years survival after diagnosis.
Schwannomatosis is a recently recognized NF-like disease that causes multiple schwannomas
but without the vestibular tumors of NF2. Schwannomatosis is clinically and genetically
distinct from NF1 and NF2, although some individuals with multiple schwannomas eventually
fulfill NF2 diagnostic criteria. It causes multiple, very painful tumors to grow in the nervous
system. The gene is not known but it is believed to be on Chromosome 22; one candidate
gene, INI-1, was announced in February 2007. The patterns of Schwannomatosis inheritance
are not yet well understood.
The challenge and opportunity of identifying candidate therapeutics for NF
NF represents an orphan disorder market of 100,000 persons in the US and an estimated 1
million persons worldwide. NF1 - 90% of the NF market - diagnosis typically occurs in
childhood; tumors and other manifestations including bone abnormalities & learning
disabilities persist throughout life, making NF a lifelong chronic disorder with a potential need
for continued drug management. Though only 10% of the NF market, NF2 also represents a
community in desperate need of effective drug therapies for tumors where surgical
intervention frequently leads to deafness or paralysis, and which are usually fatal.
There is currently no effective drug treatment for NF. Chemotherapy agents such as
cisplatin and vinblastine are used in a variety of regimes to treat NF malignancies, but there
are as yet no effective targeted drugs. However, the molecular signaling pathways affected
by neurofibromin and merlin dysfunction – and therefore the candidate drug targets - are
common to other tumor disorders:
Cytokine receptors
SOS, Grb2
Merlin (NF2)
Neurofibromin (NF1)
MEK 1,2
ERK 1,2
……………………….Downstream Signaling Pathways………………………………..
These signaling pathways also represent some of the candidate therapeutic targets for the
treatment of NF1 and NF2, in which the tumor suppressor functions of neurofibromin and
merlin, respectively, are disabled.
The ‘downstream signaling pathways’ are progressively becoming a focus as effective, specific
therapeutics for NF1 and NF2, and those that might be effective in Schwannomatosis, are
For updated information on current NF clinical trials, visit www.ctf.org
DDI Award Applicant Eligibility
1. Applicant (principal investigator) should have an MD, Ph.D. or equivalent and head an
independent research laboratory with access to all resources needed for the proposed
2. As the program offers only seed funding, it is anticipated applicants already have
established, in their laboratory, or have direct access to, any additional resources
needed to complete the proposed research
3. Applications are welcomed from both the academic and private sectors. Partnerships
between the two are actively encouraged.
4. There are no citizenship requirements for this program. Applications are welcomed
from all qualified individuals worldwide.
How to Complete the DDI Award Application Form
The Application must come from the individual who will oversee the drug screening
experiments. Collaborators, e.g. those providing therapeutics, can be listed as subcontractors
and receive part of the funding, but the grant will be administered through the institution of
the principal investigator as defined above.
A. Application Checklist:
Please sign this page verifying you have submitted all required information and that to the best
of your knowledge this material is correct.
B. Applicant Information:
Ensure that your email address and the information entered for the Administrative and
Financial Official is current and correct.
C. Research Focus Checklist:
Indicate Disorder and Focus Area. Check off the appropriate boxes as indicated.
D. Assurances:
Animal usage approval documentation should be included for in vivo screens. If this is pending
please include anticipated date of approval.
E. Certification:
You MUST have the signatures of all of the officials listed. If one person has more than one
responsibility, then they must sign in all of the appropriate places
F. Scientific & Lay Abstracts:
Use ONLY the space provided. Provide a description of your work for those outside of the
medical community (patients, donors, etc.)
G. Budget Information:
Indicate whether you are seeking in vitro or in vivo funding levels.
H. Budget Justification:
Please describe how funds requested from CTF will be spent.
I. Cover Page for Research Plan:
The research plan is limited to THREE pages and should encapsulate the rationale for the
proposed screen, how it will be conducted and the anticipated timeframe for generating
Note: The anticipated expenditure period of the award is no more than 6 months. Progress
reports are due to the Foundation at 4 months and 8 months.
Please be sure to provide all of the information necessary for a complete review of the
application by CTF (e.g. gene identity, drug identity, etc.)
K. Biographical Sketch:
Biographical Sketches should be included for the Principal Investigator and all collaborators
including those who will provide the therapeutic for screening.
L. Continuation Page
Make copies of the attached template before making any changes.
Letters of commitment must be included from individuals who will be providing therapeutics
or other resources that are required for the screen.
Applications should be submitted as follows:
A CD with all submission materials, a signed original and FIVE copies of the application should
be submitted to:
Research Program Director
Children’s Tumor Foundation
95 Pine Street, 16th Floor
New York, NY 10005
Email: mwong@ctf.org
DDI Awards
*We must RECEIVED the complete application by June 29th 2007.
Review Process
Applications will be reviewed by a Foundation-appointed peer review panel who will consider:
- Drug & screening model selection rationale
- Preliminary data: If an in vivo screen is proposed, is there sufficient in vitro data or
other preliminary findings to support advancing to the animal model? For an in vitro
screen, is there sufficient data to support the use of this system to identify new
promising compounds?
- Feasability of proposed study
- Is applicant is qualified?
- Are all required resources available?
Based on an assessment of these merits, the DDI Review Panel will select and recommend
applications for funding. Recommendations will then be evaluated by the Foundation’s Board
of Directors (BOD), which will make the final determination on those applications that will be
funded. No funding decision will be final until approval by the BOD.
Applicant Notification
Applicants will be notified as soon as possible as to the outcome of the review. All applicants,
both funded and not funded, will be provided with feedback highlighting the key comments of
the reviewers.
DDI Award Activation and Payment
The following documents must be signed by the Awardee & by Institution officials before the
DDI Award can be activated:
- Award Activation Form: requesting information on applicant, institution and contact
officials for award disbursement
- Patent Policy: All awardees’ institutions will be required to sign Children’s Tumor
Foundation Patent Policy (see below) before award disbursement can be initiated.
Payment of the DDI Award will be made in full at the time of activation. Pending signature &
receipt of the above documents the Foundation aims to disburse awards in full within 4 weeks
or less of award notification.
Patent Policy Relating to Foundation Funded Research
Prior to activation of Children’s Tumor Foundation funding awards, the awardee’s institution
must sign the Children’s Tumor Foundation Patent Policy. The Patent Policy is intended to
ensure that any inventions or patented technologies arising from research supported by the
Children’s Tumor Foundation are commercialized where possible. Children’s Tumor
Foundation anticipates recouping some revenues arising from commercialized technologies it
has supported, that is in proportion to the contribution made by the funding initially provided
by the Children’s Tumor Foundation.
Submitting your Tools to The Drug Discovery Initiative Toolbox
In receiving this award, it is anticipated that you will be willing to submit information on the
research tools being used in the award – mice, cell lines, etc. – to the DDI Toolbox. Listing
your tools in the Toolbox is simply ‘intent to share’; it is understood that actual sharing of
Tools will be subject to Material Transfer Agreements, etc. between your institution & the
recipient institution. Listing your tools in the Toolbox makes other researchers aware of tools
available for NF research, and could provide an opportunity for you to identify future
For information on submitting to the Toolbox, visit http://www.ctf.org or contact the
Public Notification of Awards Funded
Once the Award has been accepted, the Children’s Tumor Foundation will advertise online
and in other Foundation public documentation the Principal Investigators/Institutions and
title of applications that have received funding through DDI.
DDI Award Reporting
Progress Reports must be submitted to the Foundation at 4 and 8 months after the
commencement of DDI Award funding. A template for these reports will be provided by the
Foundation. Acknowledging that these reports will contain details of unpublished work, they
will not be made public by the Foundation. However high-level outcomes from these reports
(e.g. successful hit in vivo/in vitro; tumor type represented by assay; etc.) will be used in
summary reports on DDI.
Financial Reporting
A financial statement must be provided to Children’s Tumor Foundation itemizing
expenditures for the DDI Award at the completion of funding. This report is due within 60
days after the end of the anticipated 12-month period during which the DDI award will be
used. An Expenditure Report template will be provided by the Foundation. Financial reports
should be signed both by the awardee and by the responsible institutional financial officer.
Any unexpended and uncommitted funds in the possession of the awardee at the end of the
award period shall be returned to the Foundation within 60 days of the end of the award. In
addition to the above, interim accounting may be requested by the Children’s Tumor
Publications or Exhibits of an Awardee
The Foundation should be notified at the time of public disclosures by the awardee based on
their work supported by a Foundation (when a paper is published; a presentation (e.g. poster,
slide presentation) is made before a professional organization; etc). These must credit
support from Children’s Tumor Foundation.
The Foundation requests that the awardee submits to the Foundation an electronic (PDF or
Word) copy of the paper, abstract with slide presentation, or copy of the poster materials.
This material should be forwarded to the Foundation if possible once accepted for publication
or presentation, and certainly immediately following publication or presentation, together
with the name of the publication or the organization accepting it, and the time and place of
the meeting. This information shall be considered confidential by the Foundation until
publicly presented or published by the awardee.
The Foundation will coordinate with the awardee in promoting the presentation or publication
on the Children’s Tumor Foundation website (www.ctf.org) or in other Foundation
communications to its constituents (newsletters, Foundation presentations, etc.)
No awardee shall release for publication, other than through the usual professional or
scientific journals, the results of his work without notifying the Foundation of his/her
intention to do so and furnishing a copy of the material intended for release. All
announcements to any media of public information pertaining to an awardee and/or work to
be done or accomplished under a Children’s Tumor Foundation award must have the approval
of the awardee, the awardee's institution, and the Foundation.
Status of Personnel Compensated Under an Award
The awardee shall be considered to be an employee of the awardee's institution, and not of
the Foundation.
Award Status Change
Any fundamental change in the purpose for which an award was originally made must have
prior written consent of the Foundation.
Page: 1
Principal Investigator:
Application Checklist/PI Assurance (signatures required)
Applicant Information
Research Focus Checklist
Assurances (attach animal usage approval documentation)
Institutional Certification (signatures required)
Scientific & Lay Abstracts
Budget Information
Cover Page for Research Plan
Biographical Sketch (make copies as needed)
Other Support Form
Continuation Page (make copies as needed)
How did you learn about DDI?
CTF website
CTF NewsBlast
CTF Staff _____________________
CTF booth at convention
Other (describe) _____________________
Are you willing to submit information the tools described in this application to the DDI Toolbox with the
intent of making them available to share with other investigators?
To the best of my knowledge all information submitted in this application is accurate and complete. I
accept responsibility for the scientific and technical conduct of the research program and agrees to all
terms and conditions of the award.
Page: 2
Application Type (check one):
Applicant’s Name (Last, First)
Degree(s) & Field of Specialization
Title of Project:
Institution Name (if applicable):
Telephone & Fax#:
Name & Title of Administrative Official:
Telephone & Fax#:
Name & Title of Financial Official:
Telephone & Fax#:
Checks Payable to (name of institution as it should
appear on checks):
Mail checks to (name of responsible individual):
Mail Checks to (complete address):
in vitro screen
in vivo screen
Page: 3
Check ONE box for Disorder and all applicable boxes for Focus Area:
NF1 & NF2
All of the above
Focus within NF?
Plexiform Neurofibroma
Neurocutaneous Fibroma
Optic Glioma
Acoustic Neuroma
CNS Tumors – other
PNS Tumors – other
Bone Defects
Pain Mechanisms/Management
Cardiovascular Defects
Blood Disorders
Other ____________________
Does the program involve animal experimentation?
If yes:
Are copies of the institution’s animal care and use committee approval included with the
If no:
Give date of anticipated approval:
We the undersigned certify the information submitted is accurate and complete to the best
of our knowledge and accept the terms and conditions of CTF, in effect, if this application
is funded.
Signatures: Applicant
Administrative Official:
Financial Officer:
Page: 4
SCIENTIFIC ABSTRACT: (Keep to half a page)
LAY ABSTRACT: (Keep to half a page)
Page: 5
G: Budget Requested
DDI Awards will be disbursed in ONE payment.
In addition to the maximum award amounts, an additional 10% MAXIMUM may be requested to be used for
fringe/indirect costs.
Award Type
Award Amount
TOTAL funds
that can be
In vitro screens
In vivo screens
Please check one:
H: Budget Justification
Please provide a breakout of how requested funds will be utilized and provide a description. If
needed, please use a CONTINUATION PAGE.
Animal Costs (breeding,
maintenance & housing)
Drug Costs (purchase or synthesis)
Consumables & Lab Supplies
Miscellaneous (describe)
Overall fringe/indirect costs
Cover Page for Research Plan
The research plan should not exceed THREE pages. It can include narrative, figures, tables,
etc. The narrative section of the research plan should be typewritten, single-spaced, and in
typeface no smaller than 12-pt Arial font.
Completed information should be included to permit independent review without referring to other
a. Outline of proposed screen.
This should include a description of the proposed experiments with rationale and (for in vivo screens
and where available for in vitro screens) preliminary data.
b. Anticipated timeframe to completion of research plan.
In developing this timeline keep in mind that CTF requests a progress report at 4 months and 8
months after funding commences.
CTF is aware that it is impossible to predict outcomes on all projects, and therefore expects
applicants to employ an “estimated best-case scenario” when preparing a timeline.
c. Summary description of all resources available to the PI and collaborators.
Include all that will be used in this study (e.g. animal models; imaging facilities, etc).
d. Follow up plans.
Plans, if any at this time, for follow-up if the research yields positive data suggesting potentially
promising NF therapeutic.
Include as attachments:
- List of literature cited
- Appropriate institutional review board and/or animal care and use committee approval forms
Letters of commitment from individuals who will be providing therapeutics or other resources
required for the screen.
- Abstract pages and award amounts from all other grant-based sources of support (current or
pending) held/applied for by the Principal Investigator.
Biographical Sketch
Provide the following information for the applicant and each contributing
collaborator. Follow this format for each person. DO NOT EXCEED 2 PAGES for
each person
Position Title
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional
education, such as nursing, and include post-doctoral training)
Institution &
Field of Study
A. Positions and Honors. List in chronological order previous positions, concluding
with your present position. List any honors. Include present membership on
any public or private advisory committee.
B. Selected peer-reviewed publications (in chronological order). List the title and
complete reference to all publications during the past three years and to
representative earlier publications pertinent to the application. Do NOT
include publications submitted or in preparation. (Do not exceed this page plus
one continuation page. Consecutively number continuation pages for this
Continuation Page
Please reproduce as many pages as needed. These pages should be numbered throughout the
entire application