MOLECULAR TARGETS FOR CANCER DRUG DISCOVERY: SBIR/STTR RELEASE DATE: November 7, 2002 PA NUMBER: PA-03-021 EXPIRATION DATE: April 2, 2003, unless reissued. National Cancer Institute (NCI) (http://www.nci.nih.gov/) APPLICATION RECEIPT DATE: April 1, 2003 This Program Announcement (PA) replaces PAR-00-061, which was published in the NIH Guide on February 18, 2000. THIS PA CONTAINS THE FOLLOWING INFORMATION o Purpose of the PA o Research Objectives o Mechanisms of Support o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Submitting an Application o Peer Review Process o Review Criteria o Award Criteria o Required Federal Citations PURPOSE OF THIS PA The purpose of this Program Announcement (PA) is to promote full use of the base of knowledge of cancer biology for cancer-related target validation and drug discovery and development for treatment and prevention. Similar to the Exploratory Grant (R21) initiative (https://grants.nih.gov/grants/guide/pa-files/PA-03-020.html), this initiative is intended to encourage and support young, upstart biotechnology companies and also more established firms to direct their efforts into new ventures in cancer therapeutics. That great advances have been made in the past decade in our understanding of the cell in health and disease is unquestioned. Many genes that have mutated and many molecular processes that have gone awry in a cancer cell have been identified, and new information on the difference between a normal and a cancer cells continues to be added to this wealth of knowledge. It is now incumbent that this knowledge be used to mount a renewed attack on cancer - for its prevention and its treatment. While the empiric approach may have yielded its dividends, the new paradigm demands a more reasoned and knowledge-based approach. The search for molecules or agents with translational potential that will redirect the behavior of the target and subvert its deleterious effect will be an important component of this PA. These agents could be chemical or biological, man made or naturally occurring, but well characterized or subject to characterization as potential therapeutic agents. The development and utilization of modern tools for target validation and drug discovery, including combinatorial libraries and high throughput screening, would be appropriate. More information on this program can be found at http://dtp.nci.nih.gov and at http://dcp.nci.nih.gov. For a better appreciation of the contextual frame work of this initiative, see the NCI document -- The Nation's Investment in Cancer Research: Plans and Priorities for Cancer Research -- at http://plan.cancer.gov This Program Announcement (PA) must be read in conjunction with the current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, CENTERS FOR DISEASE CONTROL AND PREVENTION, AND FOOD AND DRUG ADMINISTRATION FORSMALL BUSINESS INNOVATION RESEARCH (SBIR) and SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT APPLICATIONS (see https://grants.nih.gov/grants/funding/sbir.htm). RESEARCH OBJECTIVES Background The past decade has witnessed an unprecedented accumulation of knowledge of the genetic make up and biological function of the cell. In parallel there have been technological advancements allowing ever more detailed inquiry into its structure and function. The deciphering of the human genome sequence with its boost to functional genomics and proteomics is a harbinger of things to come. Much is now known about the molecules and molecular processes that sustain the life of the cell. The structural and functional differences between a normal and a cancer cell are being defined with increasing precision. A detailed understanding of such cellular processes as signal transduction from within or without, cell cycle regulation, apoptosis, migration and metastasis are revealing new points of potential vulnerability in a cancer cell. The events that occur in the initiation and in the maintenance of cancer, including metastasis are being delineated with increasing confidence. Thus, the stage is set for exciting new approaches for the discovery and development of drugs for cancer prevention and treatment. Objectives The objective of this initiative is to support initial preclinical studies towards developing novel drugs for cancer treatment and prevention. The focus will be on new molecular targets and new agents that modulate them. The exploration of new targets will include their characterization, and establishment of their relevance to cancer. Novel ways of looking at and exploiting previously known targets also would be appropriate, but mere extension or reconfirmation of what is already known will not be. These targets may be relevant to any type of cancer, including pediatric cancers. The targets may encompass any cellular process, from cell cycle and apoptosis to angiogenesis and metastasis, and also the components of the immune system. However, this process must be that which is clearly altered in cancer cells and is well defined in molecular terms for monitoring and manipulation. The development of new assays and innovative technologies for monitoring in itself will not be sufficient; their development in conjunction with molecular target identification and validation, and drug discovery and development will be appropriate. For the NCI resources available to qualified investigators in support of research, such as the compound libraries and the natural product repository, see http://dtp.nci.nih.gov. The SBIR/STTR mechanism requires that the research be directed toward commercialization of a product or a service. MECHANISMS OF SUPPORT Support for this PA is through the SBIR and STTR mechanisms that are set-aside programs. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. This PA is a one-time announcement that may be reissued. Except as otherwise stated in this PA, awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement, March 2001, available at: https://grants.nih.gov/grants/policy/nihgps_2001/ 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 the SBIR/STTR FAST-TRACK option as described in the OMNIBUS SOLICITATION. 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 application must be a logical extension of the Phase I research. The Phase I research need not have been supported by the original issue – PAR-00-61. Information on the FAST-TRACK process and the OMNIBUS SOLICITATION are available at: https://grants.nih.gov/grants/funding/sbirsttr1/index.pdf. ELIGIBLE INSTITUTIONS Eligibility requirements are described in the OMNIBUS SOLICITATION. Small business concerns are eligible to submit applications. A small business concern is one that, on the date of award for both Phase I and Phase II agreements, meets ALL of the following criteria: o is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor; o is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture (as defined in this section) there can be no more than 49 percent participation by foreign business entities in the joint venture; o is at least 51 percent owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States; has, including its affiliates, not more than 500 employees, and meets the other regulatory requirements found in 13 CFR Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Control can be exercised through common ownership, common management, and contractual relationships. The term "affiliates" is defined in greater detail in 13 CFR 121.3-2(a). The term "number of employees" is defined in 13 CFR 121.3-2(t). Business concerns include, but are not limited to, any individual (sole proprietorship), partnership, corporation, joint venture, association, or cooperative. Further information may be obtained by contacting the Small Business Administration Size District Office at http://www.sba.gov/size/. For both Phase I and Phase II, the R&D must be performed in its entirety in the United States. INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. On an SBIR, the principal investigator must have his/her primary employment with the small business at the time of award and for the duration of the project. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/research and financial or grants management issues: o Direct your questions about scientific issues in cancer treatment to: Suresh K. Arya, Ph.D. Development Therapeutics Program Division of Cancer Treatment and Diagnosis National Cancer Institute 6130 Executive Boulevard, EPN 8153 Bethesda, MD 20892-7456 (For express/courier service: Rockville, MD 20852) Tel: 301-496-8783 Fax: 301-402-5200 Email: aryas@exchange.nih.gov Direct your questions about scientific issues in cancer prevention to: Winfred F. Malone, Ph.D. Chemoprevention Agents Development Research Group Division of Cancer Prevention National Cancer Institute 6130 Executive Boulevard, EPN 200A Bethesda, MD 20892-7322 (For express/courier service: Rockville, MD 20852) Tel: 301-594-0460 Fax: 301-402-0553 Email: malonew@mail.nih.gov o Direct your questions about financial or grants management matters to: Eileen M. Natoli Grants Administration Branch National Cancer Institute 6120 Executive Blvd. – EPS 243 Bethesda, MD 20892 Telephone: (301) 496-8791 Email: natolie@gab.nci.nih.gov SUBMITTING AN APPLICATION The PHS 398 research grant application (rev. 5/2001) must be used. Instructions and forms are available at https://grants.nih.gov/grants/funding/phs398/phs398.html. Refer to Chapter VI for specific instructions for SBIR and STTR applications. Applications will be accepted on the dates listed on the first page of this PA. This version of PHS 398 is available in an interactive, searchable PDF and HTML format. The NIH will return applications that are not submitted on the 5/2001 version. For further assistance contact GrantsInfo, Telephone: (301) 710-0267, Email: mailto:GrantsInfo@nih.gov. The SBIR/STTR OMNIBUS SOLICITATION is available electronically through the NIH, Office of Extramural Research Small Business Funding Opportunities web site: https://grants.nih.gov/grants/funding/sbirsttr1/index.pdf. The solicitation contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. Applicants are required to use the PHS398 forms for all SBIR and STTR submissions. Helpful information for preparation of the application can be obtained at: https://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf. THE TITLE AND NUMBER OF THIS PA MUST BE TYPED ON LINE 2 OF THE FACE PAGE OF THE APPLICATION. All instructions within the solicitation apply. FAST TRACK: The NIH Fast-Track mechanism expedites the decision and award of SBIR and STTR Phase II funding for scientifically meritorious applications that have a high potential for commercialization. Fast Track incorporates a submission and review process, in which complete Phase I and Phase II grant applications are submitted simultaneously and reviewed together. The FAST-TRACK must have a section labeled Milestones at the end of the Phase I Research Plan. This section must include well-defined quantifiable milestones for completion of Phase I, a discussion of the suitability of the proposed milestones for assessing the success in Phase I, and a discussion of the implications of successful completion of these milestones on the proposed Phase II. Failure to provide such information 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 an appropriate scientific review group convened by the NIH. In addition, the Phase II portion of a Fast Track application must include a concise Product Development Plan (limited to ten pages). Label this section clearly and include it in Section J of the Phase II Research Plan. More detailed instructions on the preparation of a Fast Track application are described in the PHS 398 at https://grants.nih.gov/grants/funding/sbirsttr1/index.pdf#page=21. APPLICATION RECEIPT DATE: Applications submitted in response to this program announcement will be accepted by the receipt date listed at the beginning of this program announcement. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package 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) APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE CENTER FOR SCIENTIFIC REVIEW WILL NO LONGER BE ACCEPTED. This policy does not apply to courier deliveries (i.e. FEDEX, UPS, DHL, etc.) (https://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-012.html) APPLICATION PROCESSING: Applications must be received by or mailed on or before the receipt date(s) listed at the top of the first page of this PA. The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique. PEER REVIEW PROCESS Applications submitted for this PA will be assigned on the basis of established PHS referral guidelines. An appropriate scientific review group convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit. Applications that are complete and adhere to the guidelines of this PA will be evaluated for scientific and technical merit and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of this PA by an appropriate peer review group convened by the Center for Scientific Review, in accordance with the peer review criteria listed below. As part of the initial merit review, all applications will: o Receive a written critique o 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 and assigned a priority score o Those which receive a priority score will undergo a second-level review by an appropriate advisory council or board. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of your application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals: o Significance o Approach o Innovation o Investigator o Environment The scientific review group will address and consider each of these criteria in assigning your application's overall score, weighting them as appropriate for each application. Your application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, you may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. SIGNIFICANCE. Does the 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/alternative 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 sub-contractors (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? Is there a detailed validation plan? 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 9.j in the Instructions for the SBIR/STTR applications? To what extent was the applicant able to obtain letters of interest, additional funding commitment and/or resources from private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization? The initial review group will evaluate the specific goals for both the R43 and R44 phase. A single priority score will be assigned to each application. The initial review group has the option of recommending support for a shorter duration than that requested and basing the final merit rating on the recommended portion of the application. For FAST TRACK applications, this may result in a recommendation that only the R43 phase be supported. ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your application will also be reviewed with respect to the following: PROTECTIONS: 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. INCLUSION: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria included in the section on Federal Citations, below). BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. AWARD CRITERIA Applications submitted in response to a PA will compete for available funds with all other recommended SBIR and STTR applications. Portions of the SBIR and STTR allotments will not be designated for this initiative. The following will be considered in making funding decisions: o Scientific merit of the proposed project as determined by peer review o Availability of funds o Relevance to program priorities 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, grant Program staff'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. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Dates: March 3, 2003 Application Receipt Dates: April 1, 2003 Council Review Dates: September 9, 2003 Earliest Anticipated Award Date: September 30, 2003 REQUIRED FEDERAL CITATIONS REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS. NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at https://grants.nih.gov/grants/guide/notice- files/NOT-OD-00-039.html. A continuing education program in the protection of human participants in research in now available online at: http://cme.nci.nih.gov/ HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at https://grants.nih.gov/grants/stem_cells.htm and at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Guidance for investigators and institutional review boards regarding research involving human embryonic stem cells, germ cells, and stem cell-derived test articles can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-044.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide the official NIH identifier(s)) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: 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 the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research, and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 described at https://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.. The PHS strongly encourages all grant recipients to provide a smoke- free workplace and discourage the 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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