MOLECULAR TARGET DRUG DISCOVERY FOR CANCER: SMALL BUSINESS GRANTS

Release Date:  February 16, 2000

PA NUMBER:  PAR-00-061
 
National Cancer Institute

Letter of Intent Receipt Date:  June 6, 2000
Application Receipt Date:       July 18, 2000

PURPOSE

The National Cancer Institute (NCI) defines new, extraordinary research 
opportunities through stated goals in a "Bypass Budget".   Among the 
priorities of the 2001 Bypass Budget was to identify and use molecular 
targets for the discovery and clinical testing of new anticancer agents based 
on the molecular mechanisms that underlie neoplastic transformations, cancer 
growth and metastasis.  Accordingly, the Developmental Therapeutics Program, 
Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI), 
and the Chemoprevention Agent Development Research Group,  the Division of 
Cancer Prevention, NCI  invite Small Business Innovative Research Program 
(SBIR) and Small Business Technology Transfer Program (STTR) applications to 
exploit molecular targets for drug discovery.  New insights into our 
understanding of cancer cell biology provide a new opportunity for a 
fundamental re-ordering of approaches to cancer drug discovery.  Rather than 
depending on in vitro and in vivo screens for antiproliferative activity, 
investigators can now focus on new molecular targets and pathways essential 
for the development and maintenance of the cancer phenotype.  As a result, 
the NCI is reorganizing its drug development programs from early drug 
discovery phases to the conduct of clinical trials in order to bring forward 
new types of agents based on strong rationales.  The plan also involves 
changes in the clinical evaluation of new agents that will include 
appropriate measurements to verify target modulation. 

In addition to the present announcement, the NCI announces three related  
initiatives in molecular target drug discovery for cancer treatment and 
prevention:  Cooperative Agreement (U01) applications (see 
http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-00-002.html) which are 
suitable for more mature projects defined by preliminary data; 
Exploratory/Development Grant (R21) awards (see 
http://grants.nih.gov/grants/guide/pa-files/PAR-00-060.html) for pilot 
projects for which preliminary data are lacking that would make the project 
NCI awardees (see http://grants.nih.gov/grants/guide/pa-files/PAR-00-062.html), 
which can be used to extend the goals of active grants to include 
studies related to drug discovery.  See the Home Pages of either the 
Developmental Therapeutics Program (http://dtp.nci.nih.gov) or the 
Chemoprevention Agent Development Group (http://dcp.nci.nih.gov/cb) for 
further information or contact individuals listed under “INQUIRIES” of this 
PA.  Further information on research opportunities regarding molecular 
targets in drug discovery can be found in the NCI ByPass Budget, The Nation’s 
Investment in Cancer Research: A Budget Proposal for Fiscal Year 2001 at 
http://2001.cancer.gov.

The purpose of this Program Announcement (PA) is to reorganize the “front 
end” or gateway to drug discovery.  Investigators are being asked to identify 
a novel molecular target, to validate the target as a basis for cancer drug 
discovery, or to develop an assay for the target.  Given the fact that some 
investigators may already have considerable preliminary data on a signaling 
pathway, they nevertheless may not have focused on the point of greatest 
vulnerability in the pathway and therefore, perhaps the optimal point of drug 
attack.  This PA would support an investigator to validate a target or to 
develop an assay based on the target.  Applicants may address targets related 
to the treatment of established cancers, or the prevention of molecular 
changes which may cause cancer.  Investigators may use their own creativity 
in defining their approach.  For example, some may prefer to 1) use a 
genetic, structural biology or molecular biology approach to target 
identification/validation using information from genetic studies or studies 
of pathways, whereas others may prefer to 2) identify the function of a 
cellular target after first finding the target as a result of exploring 
binding patterns of natural products or other ligands to the novel target.  
The PA requires that the proposed target in each application be novel and not 
addressed by drugs already approved for clinical use.

Since the SBIR and STTR mechanisms require the research to result in a 
commercial product (see "Mechanism of Support"), it would seem that projects 
such as assay development or combinatorial chemistry library generation to 
assist target validation might be more suitable than, for example, target 
identification.

Applications submitted to the NIH will be reviewed by the NCI according to 
the criteria established for this PA as described below under REVIEW 
CONSIDERATIONS.

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 PA, Molecular 
Target Drug Discovery for Cancer, is related to priority areas of human 
cancer treatment and prevention.  Potential applicants may obtain a copy of 
"Healthy People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000 .
 
ELIGIBILITY REQUIREMENTS 
 
Eligibility requirements are described in the SBIR STTR OMNIBUS SOLICITATION: 
http://grants.nih.gov/grants/funding/sbir.htm.  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.  For both Phase I and Phase II, the research 
or R&D must be performed in its entirety in the United States.  Including any 
affiliates, the company can be the employer of no more than 500 people.

Racial/ethnic minority individuals, women, and persons with disabilities are 
encouraged to apply as principal investigators.   
 
MECHANISM OF SUPPORT 
 
Support for the PA is through the SBIR and STTR mechanisms, which are 
set-aside programs.  This is a one-time PA, which may be reissued.  Unless 
otherwise noted, all NIH grants policies apply.

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 (PHS 2000-2).  Phase II applications in response to this PA 
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: 
RESEARCH OBJECTIVES
 
Background
							
The past 20 years have seen an explosion in the understanding of how cancer 
cells work.  Specific molecules have been identified which cause the 
initiation and progressive growth of tumors.  From this work, a fundamental 
re-ordering of the approach to drug discovery and development for the 
treatment and prevention of cancer has emerged.  There is the opportunity to 
move away from screening agents by their effects on tumor cell growth, in 
vivo or in vitro, and targets that have been thoroughly exploited.  While it 
remains true that these methods might continue to be the basis for the 
development of clinically useful agents, these agents may not be the best 
lead compounds that effect a particular pathway of biologic importance 
specific for cancer establishment or progression.  Drugs discovered by these 
early methods have historically demonstrated clear limitations in clinical 
efficacy.  The hope is that drugs targeting new, specific molecular lesions 
in cancer cells will provide more effective therapy or prevention approaches, 
alone or in combination with other agents.  The focus of attention in this 
new approach to cancer drug discovery is a compound’s effect against a novel 
molecular target, or a target operating in a defined biochemical pathway, 
with the intent of causing a gain or loss in function to reverse, stop, or 
delay cancer progression.  The cancer cell selectivity of lead compounds 
should be enhanced by screens based on a novel target or a critical pathway 
that represents a true Achilles heel.

The evaluation of drugs in the clinic which have emerged from these types of 
approaches is beginning.  Examples would include the farnesyl transferase 
inhibitors (FTIs), protein kinase (PK) antagonists of various sorts, matrix 
metalloprotease inhibitors, and growth factor receptor or other effector 
antagonists (endothelin, tamoxifen, TRAIL, etc.).  It is striking that in 
this process the pharmaceutical industry has clearly seized a defining role 
in expeditiously advancing potentially useful compounds to a clinical test.  
However, in each of the instances cited, the pioneering studies on the 
targets to which these drugs are directed occurred largely (if not 
exclusively) in the academic sector.

Objectives and Scope

The goal of this PA is the discovery and/or validation of molecular targets 
for cancer prevention or treatment intervention which can be developed into 
drug discovery assays.  Identification of a potential target might present 
varying degrees of difficulty, but validation (an indication of a target’s 
predictive capacity to aid in the selection of clinical drugs) is apt to be 
uniformly more problematic.  Leads for many existing clinical drugs were not 
discovered through the use of  macro-molecular targets but rather through in 
vivo or in vitro anti-proliferative assays.  Accordingly, the cornerstone of 
this effort is the validation of targets of demonstrated importance.  
Projects are acceptable at all stages of development, mature projects as well 
as novel insights at an early investigational stage.  Approaches and projects 
appropriate for this PA should be in one, or all, of three general areas as 
follows:

First, investigative activities establishing a molecule as a potential cancer 
drug discovery target can have as its focus any aspect of early dysplasia or 
cancer cell biology that may reveal a vulnerability in the cancer cell.  
These might include cell cycle checkpoints, DNA repair, cell stress, or cell 
death pathways; cassettes of altered transcription factor activity; or 
activation of pathways allowing cell growth in hypoxic or hypo-vascularized 
conditions.  Oncogenic viral targets also would be appropriate.  In fact, any 
difference between a cancer and normal cell could potentially be exploitable 
as a therapeutic maneuver.  Modern science has afforded numerous 
opportunities to demonstrate the likely value of this approach.  These 
include: (1) engineered animals of various sorts (transgene-expressing, 
knock-out, etc.); (2) “smart” assays designed to give information, not only 
about phenotypic alteration, such as growth arrest or cell death, but also 
about the effect on particular molecular targets of pathways known or 
suspected to have biological relevance to cancer; (3) array technology, where 
the action of a candidate drug lead against its target can be placed rapidly 
in the context of expected action against other cellular and indeed organ-
specific molecules; and (4) cancer gene discovery programs, such as the 
Cancer Genome Anatomy Project (CGAP) (http://www.ncbi.nlm.nih.gov/CGAP/), 
which has identified numerous mutational sites in cancer cells, some of which 
are possibly unique to specific types of cancer.  Accordingly, a requirement 
is to establish that a molecular target likely affects important aspects of 
cancer cell function.

Second, the validation of new molecular targets, with the intent of 
discovering new agents for the treatment or prevention of cancer, is an 
important and necessary activity.  At present, science appears to offer too 
many targets.  Therefore, projects should focus on determining which of these 
numerous potential defects are sites of critical vulnerability which could be 
exploited for intervention.  Ideally one would expect to demonstrate that 
manipulation of the target function would cause a phenotypic change in the 
cancer cell.  Clearly if a prime target is fully validated, such that the 
target can be used to totally exploit a unique difference between a healthy 
and a cancerous cell, control of cancer would then only await the discovery 
of a drug molecule through a systematic screening and/or drug design program; 
in real laboratory experience, validation occurs in stages or degrees.  
Demonstration of some phenotypic or functional change that is desirable, such 
as elimination or reversal of dysplasia, tumor shrinkage or change in a 
validated surrogate marker, would provide evidence of the importance of a 
target.  Approaches to target validation might involve the use of antisense 
or engineered animals, such as transgene-expressing or gene knock-outs.  
Small, bioactive molecules, obtained either from natural products libraries 
or from chemical libraries, may be used as ligands to select and validate 
proteins from arrays.  If an investigator chooses to utilize crude extracts 
of natural products, as from the NCI Active Repository, expertise must be 
available for chemical fractionation of the extracts.  Thus, validation can 
be conceptualized as a series of milestones.   A proposal to reach validation 
milestones could be responsive to this PA.  There are many good rationales 
for selecting targets, but validation requires considerable imagination and 
skill on the part of the investigator.  Therefore, also responsive to this PA 
would be an insightful and clever validation of a target suggested by others 
as a possible intervention point.  While it is true that the ultimate 
validation can only come from a successful clinical trial, having information 
on the importance of the target prior to the trial should provide important 
feedback in case therapies are ineffective.

Applicants proposing to access the Natural Products Repository of the NCI 
must obtain and execute the Natural Products Repository Material Transfer 
Agreement in advance of submitting a grant application.  Similarly, 
applicants proposing to access the synthetic repository of the NCI must 
obtain and execute the synthetic Material Transfer Agreement.  These 
agreements are available at http://dtp.nci.nih.gov  (On the panel, left side, 
click on "Organization", select "Natural Products Branch", select "Natural 
Products Repository", then scroll down to and select "Material Transfer 
Agreement").  For information concerning the NCI synthetic or natural product 
repositories go to the Developmental Therapeutics web site, 
http://dtp.nci.nih.gov  (On the panel, left side, click on "Samples and 
Services").  

For applications involving natural products, the applicant must provide a 
formal statement signed by an authorized representative of the applicant 
institution which assures that an equitable portion of royalties or profits 
arising from drugs discovered, if any, will benefit indigenous peoples, 
research collaborators, research institutions or governmental entities as 
appropriate, in the country of origin of the natural product sample from 
which the drug was derived.  Plans for the procurement of proper collection 
and export permits must be provided.  The signed document must be submitted 
prior to award to Dr. Gordon Cragg at the Developmental Therapeutics Program 
web site, http://dtp.nci.nih.gov  (On the panel, left side, click on 
"Organization", select "Natural Products Branch" then click on "Organization/ 
Staff Directory").

Third, the target system should be amenable to conversion into a screen for 
effectors of the target’s function (at minimum on a laboratory scale), or the 
molecular structure determined through biophysical techniques as a prelude to 
drug discovery studies .  These aspects are critical components which would 
form the thrust of any molecularly focused drug discovery effort.  The 
practical nature of drug discovery research is of high importance.  While the 
desirability of this approach might seem obvious, the tools for accomplishing 
this task are only now becoming routinely available.  These include sequence 
information defining the primary structure of relevant target proteins or 
other macromolecules; expression vectors for their large scale production; 
biophysical (e.g. X-ray and NMR) and computational techniques to allow the 
determination of three-dimensional structure; advances in screening 
technology to allow ever increasing speed and efficiency in assessing large 
numbers of candidate structures; and combinatorial chemistry to generate 
large numbers of candidate drug structures.

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 subpopulations 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 28, 
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, 
Volume 23, Number 11, March 18, 1994, available on the web at the following 
URL address: http://grants.nih.gov/grants/guide/notice-files/not94-100.html.
 
Investigators may also obtain copies of the policy from the program staff 
mentioned in the GCOB web site, 
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.

As part of the scientific and technical merit evaluation of the research 
plan, reviewers will be instructed to address the adequacy of plans for 
including children as appropriate for the scientific goals of the research, 
or justification for exclusion.

LETTER OF INTENT
 
Prospective applicants are asked to submit, by June 6, 2000, a letter of 
intent that includes a descriptive title of the proposed research, name, 
address, and telephone number of the Principal Investigator, identities of 
other key personnel and participating institutions, and number and title of 
the PA 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 subsequent applications, the information allows NCI staff to 
estimate the potential review workload and to avoid conflict of interest in 
the review. 
 
The Letter of Intent is to be sent to a program representative at the address 
listed under INQUIRIES by the letter of intent receipt date listed in the 
heading of this PA.
 
APPLICATION PROCEDURES

This PA must be read in conjunction with the OMNIBUS SOLICITATION OF THE 
PUBLIC HEALTH SERVICE FOR SMALL BUSINESS INNOVATION RESEARCH GRANT (SBIR) 
APPLICATIONS (PHS 2000-2) and for SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) 
GRANT APPLICATIONS (PHS 2000-2).  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.

Applications received in response to this PA are to be prepared as described 
in the OMNIBUS SOLICITATION (PHS 2000-2) for the SBIR and STTR programs.  
OMNIBUS SOLICITATION is 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.

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view Internet sites.  Reviewers are cautioned that their anonymity may be 
compromised when they directly access an Internet site (see  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-004.html).

Applications in response to this PA 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/sbirsttr1/index.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 
SOLICITATION.  Applications  will be accepted up to July 18, 2000.  The PA 
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 PA 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.

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 PA.

Projects may be presented for SBIR/STTR support at all stages of the target 
identification and validation process.  Projects will be evaluated on overall 
innovation, strength of the approach, and probability of clinical utility, 
with less emphasis on the nature of the specific stage proposed in the 
application. 

PHASE I:  Feasibility in the target validation process or assay development 
should be demonstrated.  Normally, the Phase I award period is one year with 
an assistance of $100,000 in total costs.  However, award levels are 
guidelines and not ceilings.  Applicants may request longer periods of time 
and/or higher budgets with convincing justification.  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 project as well 
as the potential for clinical relevance.  If the allowed 25 pages for Phase I 
projects is 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.

PHASE II:  Normally Phase II awards can be for up to two years and up to 
$750,000 in total costs per year for SBIR projects and $500,000 for STTR 
projects.  As with Phase I, requests for larger budgets and/or longer time 
periods may be considered, if justification is given.

FAST TRACK: Applications may be submitted for combined Phase I and Phase II, 
FAST TRACK consideration as described in the OMNIBUS SOLICITATION.  However, 
due to the complex nature of the target identification and validation 
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 milestones 
that should be achieved prior to Phase II funding.  Failure to provide 
measurable milestones 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 PA, if applicable.

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

The small business concern must 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 SOLICITATION.

The OMNIBUS SOLICITATION indicates the normal levels of support and period of 
time for SBIR and STTR Phase I and Phase II awards.  It is strongly 
recommended that applicants contact NCI staff at an early stage of 
application development to convey critical information, such as potentially 
large budgets requests or to discuss programmatic responsiveness of the 
proposed project.  Applications requesting a budget not to exceed $100,000 
total costs (direct costs, indirect costs and fixed fee) per year should use 
the Modular Grant format as presented in the OMNIBUS SOLICITATION.  Other 
applicants should provide a detailed budget.

SBIR Phase I applications requesting in excess of $100,000 total costs 
(direct costs, indirect costs and fixed fee) per year will use "Budget for 
Phase I Direct Costs" (form page 3 of PHS 6246-1), and justify this request 
using "Budget Justification" (form page 4 of PHS 6246-1).

STTR Phase I applications requesting up to $100,000 total costs (direct 
costs, indirect costs and fixed fee) will request budgets using "Budget 
Justification" (form page 5 of PHS 6246-3) ONLY.  Present the total amount 
requested for direct costs on line &a of the Face Page of PHS 6246-3.  The 
applicant small business organization is not to submit "Budget of Applicant 
Organization for Phase I - Direct Costs Only" (form page 3 of PHS 6246-3); it 
is to be used as a "worksheet" only.  However, the single, "partnering 
research institution must complete "Budget of Research Institution for Phase 
I" (form page 4) in an abbreviated manner by: (1) Entering the amount of its 
participation in the project under "Total Costs," and (2) Signing and dating 
the "Certificate of Research Institution Participation" portion of the form.

STTR Phase I applications requesting in excess of $100,000 total costs 
(direct costs, indirect costs and fixed fee) will use "Budget of Applicant 
Organization for Phase I - Direct Costs Only" (form page 4 of PHS 6246-3) and 
justify this request using "Budget Justification" (form page 5)."

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 three 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)

To expedite the review process, at the time of submission, send two 
additional copies of the application to:

Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239
Bethesda, MD  20892-8239
Rockville, MD  20852 (for express/courier service)

Applications must be received by the receipt date listed at the top of the 
first page of this PA announcement.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and for 
adherence to the guidelines by NCI.  Incomplete applications will be returned 
to the applicant without further consideration.
 
Applications that are complete will be evaluated for scientific and technical 
merit by an appropriate peer review group convened by the Division of 
Extramural Activities of the NCI in accordance with the review criteria 
stated below.  As part of the initial merit review, a process will be used by 
the initial review group in which 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

The goals of NIH-sponsored research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
Within this framework, the specific goals of this PA are the discovery and/or 
validation of new molecular targets with the potential for developing assays 
for the discovery of new agents to treat or prevent cancer.  At minimum, a 
target should be identified (de novo, or from the literature) and/or a 
validation plan outlined, and a conception of how the validated target can be 
developed into a drug assay.  Meritorious projects will include imaginative 
intervention points and/or insightful validation approaches, which overall 
will reveal an exploitable site of critical vulnerability.  In considering 
the scientific and technical merit of each application, the following 
criteria will be used as described in the OMNIBUS SOLICITATION (PHS 2000-2):

Significance.   Does this study address an important problem?  Does the 
proposed project have commercial potential to lead to a marketable product or 
process?  What may be the anticipated commercial and societal benefits of the 
proposed activity?  If the aims of the application are achieved, how will 
scientific knowledge be advanced?  Does the proposal lead to enabling 
technologies (instrumentation, software, etc.) for further discoveries?  Will 
the technology have a competitive advantage over existing/alternate 
technologies that can meet the market needs?

Approach.  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Is the proposed plan a sound approach for establishing technical 
and commercial feasibility?  Does the applicant acknowledge potential problem 
areas and consider alternative strategies?  Are the milestones and evaluation 
procedures appropriate?

Innovation.  Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies?  Are the aims original and 
innovative?

Investigator.  Is the Principal Investigator capable of coordinating and 
managing the proposed SBIR/STTR?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers, 
including consultants and subawardees (if any)?

Environment.  Is there sufficient access to resources (equipment, facilities, 
etc.)? Does the scientific and technological environment in which the work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific environment 
or employ useful collaborative arrangements?

For Phase II applications:   In addition to the above criteria, to what 
degree was progress toward the Phase I objectives met and feasibility 
demonstrated in providing a solid foundation for the proposed Phase II 
activity?

For Phase I/Phase II Fast Track applications, the following additional 
criteria will be applied:  Does the Phase I specify clear, measurable goals 
(milestones) that should be achieved prior to initiating Phase II?  Did the 
applicant submit a concise Product Development Plan that adequately addresses 
the four areas described in Section VI. G. of the SBIR/STTR solicitation?
To what extent was the applicant able to obtain letters of interest, 
additional funding commitments and/or resources from private sector or non-
SBIR/STTR funding sources that would enhance the likelihood for 
commercialization?

For all SBIR/STTR applications, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:  The 
adequacy of plans to include both genders, minorities, and their subgroups as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated.  The adequacy 
of the proposed protection for humans, animals or the environment, to the 
extent they may be adversely affected by the project proposed in the 
application.  The appropriateness of the proposed budget and duration in 
relation to the proposed research.

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.

INQUIRIES
 
Inquiries concerning this PA are encouraged.  The opportunity to clarify  any 
issues or questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic issues in cancer treatment and 
inquiries regarding access to the Natural Products Repository to the 
appropriate individuals given in the GCOB web site:   http://dtp.nci.nih.gov/ 
(On the panel, left side, click on "Funding", then scroll down to "Staff")

Direct inquiries regarding programmatic issues in cancer prevention to the 
DCP web site: http://dcp.nci.nih.gov/cb

Direct inquiries regarding review issues to:

Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8062, MSC 8239
Bethesda, MD  20892-8239
Rockville, MD  20852 (for express/courier service)
Telephone (301) 496-3428
Fax: (301) 402-0275
Email: tf12w@nih.gov
	
Direct inquiries regarding fiscal matters to: 
 
Ms.  Kathleen Shino
Grants Administration Branch 
National Cancer Institute 
Executive Plaza South 243 				
Bethesda, MD  20892-7150
Telephone:  (301) 496-8635 
Fax: (301) 496-8601
Email: shinok@gab.nci.nih.gov

AUTHORITY AND REGULATIONS
  
This program is described in the Catalog of Federal Domestic Assistance No. 
93.395, Cancer Treatment Research.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act, as amended, (42 USC 
241 and 284) and administered under NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 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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