FLEXIBLE SYSTEM TO ADVANCE INNOVATIVE RESEARCH FOR CANCER DRUG DISCOVERY BY
SMALL BUSINESSES

Release Date:  August 20, 1998

RFA:  CA-98-022

P.T.

National Cancer Institute

Letter of Intent Receipt Dates:  October 20, 1998 and June 22, 1999
Application Receipt Dates:       November 17, 1998 and July 20, 1999

PURPOSE

Discovery and development of new cancer therapeutics, including both drugs and
vaccines, normally involve lengthy and costly projects.  The multiple
components of the overall process including discovery, efficacy testing,
development of lead agents, toxicology and pharmacology, Investigational New
Drug Application (IND) filing, and clinical evaluation, may require years and
several million dollars.  The small business community is an active
participant in the cancer therapy discovery effort.  The Small Business
Innovation Research (SBIR) and Small Business Technology Transfer (STTR)
programs have supported these efforts; however, the extent of such support has
been limited by the traditional stringent guidelines of the Phase I and Phase
II components.  Recently the NIH has announced that applicants may request a
larger budget and period of support if necessary for completion of the project
(See NIH Guide for Grants and Contracts, February 13, 1998
(http://grants.nih.gov/grants/guide/notice-files/not98-014.html).  This RFA
provides a flexible system within the SBIR and STTR programs to accommodate
the extensive needs and complex discovery and development process, at least
partially, from basic discovery through proof of principle demonstration in
clinical trials.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, Flexible System to Advance
Innovative Research for Cancer Drug Discovery by Small Businesses, is related
to the priority area of cancer.  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or Summary
Report:  Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone 202-
512-1800).

ELIGIBILITY REQUIREMENTS

Eligibility requirements are described in the OMNIBUS SOLICITATIONS.  Any
small business, independently owned and operated by United States citizens or
permanent resident aliens may apply.  It must be organized for-profit, cannot
be dominant in its field of expertise, and must have its principal place of
business in the United States.  Including any affiliates, the company can be
the employer of no more than 500 people.

MECHANISM OF SUPPORT

Support for the RFA is through the SBIR and STTR mechanisms, which are set-
aside programs.  This RFA is a one-time RFA, which may be reissued.

Applications can be submitted for support as Phase I STTR (R41) or Phase I
SBIR (R43) grants: Phase II STTR (R42) or Phase II SBIR (R44) grants; or under
the SBIR/STTR  FAST-TRACK option as described in the OMNIBUS SOLICITATIONS. 
Phase II applications in response to this RFA will only be accepted as
competing continuations of previously funded NIH Phase I SBIR/STTR awards. 
The Phase II proposal must be a logical extension of the Phase I research.

Information on the FAST-TRACK process and the OMNIBUS SOLICITATIONS are
available at: http://grants.nih.gov/grants/funding/sbir.htm

Except as otherwise stated in this RFA awards will be administered under PHS
grants policy as stated in the Public Health Service Grants Policy Statement,
DHHS Publication No. (OASH) 94-50,000 (Rev) April 1, 1994.

FUNDS AVAILABLE

It is expected that five awards will be made in FY99, and $1.8 million from
the SBIR and STTR set-asides will be designated for this purpose.  The number
of awards will be dependent upon receipt of a sufficient number and diversity
of applications with high scientific merit.

RESEARCH OBJECTIVES

Recent advances in all branches of medical sciences provide new insight into
the underlying mechanisms in malignancy and suggest new targets and approaches
for therapy.  For example, key growth regulatory pathways are being
delineated, genes mutated in cancer cells have been identified, array
technology for expression of thousands of genes as well as computer-assisted
evaluation of data are available, new technologies in chemistry allow facile
synthesis of millions of new chemicals, and high resolution structures of
important target proteins are becoming available.

The application or translation of these new discoveries and innovations into
clinical benefit for the cancer patient is essential; however, the process is
lengthy and costly.  Following initial discovery, efficacy testing, and
optimization, lead compounds must undergo a series of rigorous evaluations
culminating with the clinical trial.  The actual procedures for these
evaluations vary somewhat with each agent to be tested, and, with innovative
approaches often required for new agents, an extensive  research effort may be
necessary for successful development and eventual commercialization. The
objective of this RFA is to support the research activities required to enable
small businesses to bring their research efforts for drug discovery and
development to clinical evaluation.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their sub-populations must be included  in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research.  This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 20, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

Investigators also may obtain copies of the policy from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN
RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are clear and compelling scientific and ethical reasons not
to include them.  This policy applies to all initial (Type 1) applications
submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit, by the receipt dates listed at the
beginning of this RFA, a letter of intent that includes a descriptive title of
the proposed research, the name, address, and telephone number of the
Principal Investigator, the identities of other key personnel and
participating institutions, and the number and title of the RFA in response to
which the application may be submitted.  Although a letter of intent is not
required, is not binding, and does not enter into the review of a subsequent
application, the information that it contains allows NCI staff to estimate the
potential review workload and avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. George S. Johnson, NCI, at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

This RFA must be read in conjunction with the OMNIBUS SOLICITATION OF THE
PUBLIC HEALTH SERVICE FOR SMALL BUSINESS INNOVATION RESEARCH GRANT (SBIR)
APPLICATIONS (PHS 98-2) and the OMNIBUS SOLICITATION OF THE NATIONAL
INSTITUTES OF HEALTH FOR SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT
APPLICATIONS (PHS 98-3).  All of the instructions within the omnibus
solicitation apply with the following exceptions:

-Special receipt dates
-Initial review convened by the NCI Division of Extramural Activities
-Additional review considerations.
-More flexible time and budget specifications

Applications received in response to this RFA are to be prepared as described
in the OMNIBUS SOLICITATIONS for the SBIR and STTR programs.  OMNIBUS
SOLICITATIONS are available electronically through the NIH, Office of
Extramural Research "Small Business Funding Opportunities" website: 
http://grants.nih.gov/grants/funding/sbir.htm.  Hard copies, subject to
availability, may be obtained from the PHS SBIR/STTR Solicitation Office,
phone (301) 206-9385; FAX (301) 206-9722; email a2y@cu.nih.gov.  Helpful
information in preparation of the application can be obtained:
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf

Applications in response to this RFA are to be submitted on the applicable
grant application forms as follows:

SBIR Phase I - PHS 6246-1 (1/98)
http://grants.nih.gov/grants/funding/sbir1/sbir.htm

STTR Phase I - PHS 6246-3 (1/98)
http://grants.nih.gov/grants/funding/sbirsttr1/index.htm

SBIR Phase II - PHS 6246-2 (1/98)
http://grants.nih.gov/grants/funding/sbir2/index.htm

STTR Phase II - PHS 6246-4 (1/98)
http://grants.nih.gov/grants/funding/sttr2/index.html

The application forms are also located in the back pages of the OMNIBUS
SOLICITATIONS.  Applications  will be accepted on November 17, 1998, and July
20, 1999.  The RFA title and number must be typed in line 2 on the face page
of the application form.

If an application is received after the application receipt dates, it will be
returned to the applicant without review.  The Center for Scientific Review
(CSR) will not accept any application in response to this RFA that is
essentially the same as one currently pending review, unless the applicant
withdraws the pending application.  This does not preclude the submission of
substantial revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

SBIR/STTR projects submitted in response to this RFA must contain a Phase I
feasibility segment that must be successful prior to a Phase II award. 
Applications can be submitted for Phase I or Phase II support, or as a
combined Phase I and II (FAST TRACK).  Phase II applications will only be
accepted as continuations of previously funded Phase I grants.  The Phase II
proposal must be a logical extension of the Phase I research but not
necessarily a Phase I supported in response to this RFA.

Projects may be presented for SBIR/STTR support at all stages of the drug
discovery and development process.  Projects will be evaluated on overall
innovation, strength of the drug discovery approach, and probability of
clinical success, with less emphasis on the nature of the specific stage
proposed in the application.  This aspect is especially important if
applications are focused on later stages of the drug discovery and evaluation
process, which are generally more routine and often considered less innovative
as stand alone projects.

PHASE I:  Demonstration of feasibility for the next step in the drug discovery
and development process.  It would be expected, but not required, that Phase I
would support relatively early discovery and evaluation projects.  Phase I
projects should focus on research required to advance to the next stage in the
development process and present a plan and time line outlining accomplishments
and milestones to be achieved at each stage.  Applicants should emphasize
innovative aspects of the agent or project as well as the potential for
clinical relevance.  Applications should include a plan for the complete
development of the agents and clearly state how the proposed Phase I fits into
this plan.  If the allowed 25 pages for Phase I projects i not sufficient,
applicants should contact the Scientific Review Administrator (SRA) after
receipt and assignment of the application to request approval for submission
of supplementary information for review.

For this RFA, projects normally would be supported in Phase I for up to 2
years with a budget of up to $300,000, total costs, per year.  Larger budgets
could be considered if required for conduct of the research and appropriately
justified in the application.  The second year of support will be contingent
upon NCI programmatic evaluation to ensure that investigators are
accomplishing milestones and time lines presented in the original application.

PHASE II:  Continuing support for development of preclinical activities and
for establishment of proof of principle in clinical trials.  Support can be
requested for preclinical developmental activities including pharmacology,
formulation and toxicology.  Innovative aspects of the research necessary to
complete the projects such as development of new in vivo evaluation models
that may require "surrogate endpoints" should be clearly described.  Support
for clinical trial evaluation up to the point of establishing proof of
principle can be requested to commence following completion of the pre-
clinical activities and approval of the IND by the FDA.  A brief plan for the
clinical trial should be submitted with the application; however, a detailed
clinical plan, including a budget, must be submitted and approved by NCI
extramural staff prior to allocation of funds for this purpose.  If a clinical
evaluation is the direct object of the proposal, complete information should
be provide within the application or as an attached Appendix.

It is not possible for the SBIR/STTR program to provide full funding for the
complete development process.  Thus, a co-funding partner or other sources of
support should be identified prior to Phase II award.  The funds and/or
resources to be dedicated to activities directly related to the SBIR/STTR
project by the partner/company, including details of the commitment
contingencies, must be clearly specified in the application.  Appropriate
documentation of the commitment must be provided.

NCI contract-based resources through the Developmental Therapeutics Program
(DTP), independent of the SBIR/STTR award, may be used to meet the co-funding
requirement, but proper assurances from DTP/NCI must be provided prior to
review.  Conversion to a Cooperative Agreement (U44) may be advantageous if
the NCI is to be an active partner in the development.  A Cooperative Research
and Development Agreement (CRADA) could also be considered to support some
aspects of the development process; however, the CRADA should clearly state
that the SBIR supported activities would be considered the responsibility of
the small business and outside the terms of the CRADA.  A CRADA Letter of
Intent, if available, should be provided prior to review.  If use of NCI
contract resources, conversion to a cooperative agreement, or a CRADA are
planned, the applicant should contact Dr. George S. Johnson at the address
listed in INQUIRIES prior to submission of the application.

Collaboration with NCI to conduct the clinical trial would be appropriate if
agreed upon by the small business, the NCI, and all other involved
participants and proper documentation is provided.

Phase II awards can be for up to four years and $400,000, total costs, per
year.  As with Phase I, requests for larger budgets may be considered, and
support for years two to four is dependent upon NCI Programmatic review of
progress and achievement of proposed milestones and evaluation of additional
information not required in the original application.

FAST TRACK: Applications may be submitted for combined Phase I and Phase II,
FAST TRACK consideration as described in the OMNIBUS SOLICITATIONS.  However,
due to the complex nature of the drug development process, it is recommended
that only well defined and more advanced projects be proposed for support
through this mechanism.

Phase I, FAST TRACK applications must specify clear, measurable goals that
should be achieved prior to Phase II funding.  Failure to provide measurable
goals in the Phase I application and/or sufficient detail in the Phase II
application may be sufficient reason for the peer review committee to exclude
the Phase II from consideration.  If so, the applicant may apply later for
Phase II support.  Such applications will be reviewed by a standing Study
Section of CSR or by a special review group convened in response to a re-
issuance of this RFA, if applicable.

Special provisions described in this RFA pertaining to Phase I and Phase II
also apply to FAST TRACK applications.

An additional requirement of the FAST TRACK mechanism is the commitment for
funds and/or resources for commercialization of the product to ensure a rapid
transition to the market.  These funds are in addition to the funds required
for research support in Phase II described above. A Commitment Appendix to the
Phase II application must be included which specifies the amount of funds
and/or nature of resources that will be dedicated to the SBIR/STTR project and
must describe those activities.  If such commitment is from an  investor or
partner organization, a copy of the agreement or a letter describing the
details of the agreement must be provided.  The small business concern must
also submit a concise Product Development Plan (limited to five pages) as an
Appendix to the Phase II application addressing the four areas described in
the instructions for FAST TRACK applications in the OMNIBUS SOLICITATIONS.

Potential applicants are encouraged to contact program staff for guidance and
to read the advice and information on the web sites.  However, responsibility
for planning, direction, and execution of the proposed research will be solely
that of the applicant.

The completed original application and one legible copies must be sent or
delivered to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

One additional copies of the application must also be sent to:

Ms. Toby Friedberg
Referral Officer
National Cancer Institute
6130 Executive Boulevard, Room 636a
Bethesda, MD  20892-7405
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-3428
FAX:  (301) 402-0275

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by the CSR for completeness and by
the NCI for responsiveness.  Applications not adhering to application
instructions described above and those applications that are incomplete or
non-responsive will be returned to the applicant without review.

Applications will be reviewed for scientific and technical merit and the
documented ability of the investigators to meet the RESEARCH OBJECTIVES of
this RFA by an initial review group convened by the NCI Division of Extramural
Activities, in accordance with the standard NIH peer review procedures.  As
part of the initial merit review, all applications will receive a written
critique and undergo a process in which only those applications deemed to have
the highest scientific merit, generally the top half of the applications under
review, will be discussed, assigned a priority score, and receive a second
level review by the National Cancer Advisory Board.

Review Criteria

Review criteria are essentially as described in the OMNIBUS SOLICITATIONS with
the additional considerations specified for this RFA.

1.  The soundness and technical merit of the proposed approach.

2.  The qualifications of the proposed principal investigator, supporting
staff, and consultants.

3.  The scientific, technical, or technological innovation of the proposed
research.

4.  The potential of the proposed research for commercial application.

5.  The appropriateness of the budget requested.

6.  The adequacy and suitability of the facilities and research environment.

7.  Where appropriate, the adequacy of assurances detailing the proposed means
for (a) safeguarding human or animal subjects and/or (b) protecting against or
minimizing any adverse effect on the environment.

8.  Innovative aspects of the overall drug discovery and development plan.

9.  Potential clinical relevance of the research and agent proposed.

The Phase I application should specify clear, measurable goals (milestones)
that should be achieved prior to initiating Phase II.  Failure to provide
clear, measurable goals may be sufficient reason for the initial review group
to judge the application non-competitive.

The initial review group will also examine the adequacy of plans to include
both genders and minorities and their subgroups as appropriate for the
scientific goals of the research, plans for the recruitment and retention of
subjects; the adequacy of plans for including children as appropriate for the
scientific goals of the research, or justification for exclusion; the
provisions for the protection of human and animal subjects and the safety of
the research environment.

AWARD CRITERIA

Funding decisions for Phase I or Phase II applications will be based on
quality of the proposed project as determined by peer review,  program
priority, potential for clinical success, and availability of funds..

FAST TRACK, Phase II applications may be funded following submission of the
Phase I progress report and other documents necessary for continuation.  Phase
II applications will be selected for funding based on the initial priority
score, NCI's assessment of the Phase I progress and determination that Phase I
goals were achieved, the project's potential for commercial success, and the
availability of funds.

Schedule

Letter of Intent Receipt Date:          Oct 20, 1998      Jun 22, 1999
Application Receipt Date:               Nov 17,1998       Jul 20, 1999
National Cancer Advisory Board Review:  Jan 1999          Oct 1999
Anticipated Award Date:                 Mar/Apr 1999      Jan 2000

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

George S. Johnson, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, Room 841
Bethesda, MD  20892-7456
Telephone:  (301) 496-8783
FAX: (301) 402-5200
Email: gj16m@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Kathleen Shino
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext. 248
FAX:  (301) 496-8601
Email:  shinok@gab.nci.nih.gov

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636 - MSC 7407
Bethesda, MD  20892
Rockville, MD  20852-7407 (for express/courier service)
Telephone:  (301) 496 -3428
FAX:  (301) 402-0275
Email:  tf12w@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.395.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC
241 and 285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74 and part 92.  This program is not
subject to the intergovernmental review requirements of Executive Order 12372
or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.  In
addition, Public Law 103-227, the Pro- Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.


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