Purpose Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI), National Institute of Biomedical Imaging and Bioengineering (NIBIB), and National Institute on Drug Abuse (NIDA) intend to support early-career academic scientists interested in transitioning to entrepreneurship while also supporting the transfer of technology from academic laboratories into small businesses. For the purposes of this funding announcement, eligibility as an early career scientist is limited to applicants with 10 years, or less, of post-graduate experience. This NOFO proposes a new and unique Fast-Track only award structure comprised of a Phase I STTR that transitions to a Phase II SBIR. Only small businesses can apply for and receive SBIR or STTR awards. However, this RFA utilizes an STTR in phase I because the STTR program is intended for projects in which the awardee small business is working closely with a university and therefore allows more work to be completed at the university as well as allowing more flexibility in terms of PI employment. Awards made under this NOFO will begin as a Phase I STTR to allow the early career scientist PI, or candidate, complete proof of concept studies at the academic site and prepare the technology to move into the small business. Upon successful completion of the STTR phase I activities, awards that transition to Phase II will convert to an SBIR award, requiring the PI to move their place of employment to the small business and limiting university involvement. Mentoring is a key component of Small Business Transition Grant awards. Traditionally, mentoring has not been a factor in SBIR/STTR funding decisions, however, because mentoring is critical to facilitate the transition from junior academic scientist to entrepreneur, a mentoring plan is required in the application and included in the peer review scoring criteria for this NOFO. The ideal candidate for a Small Business Transition Grant award is a postdoctoral researcher who participated in technology discovery during their academic work and is now ready to move to a small business with the support of an experienced team to advise them. To be responsive to this NOFO, proposed projects MUST pertain to the mission space of one of the participating Institutes and propose the development of a technology that fits into the technology categories described below under additional Institute/Center Priorities. Furthermore, all proposals must include clear, quantitative milestones (i.e. a quantitative definition of success) for each aim. In some cases, additional milestones or timelines may be requested as part of the Just In Time process or post-award. For awards made under this NOFO, transition from phase I to phase II will only occur after demonstration that all of the following criteria have been met; the candidate continues to receive mentoring support by both technical and business development (BD) mentors, all necessary IP agreement(s) are updated to reflect the next award phase timeline, a demonstration that all phase I technical milestones have been achieved (more information under Section IV. Application Submission Information). Background and Rationale Academic laboratories are critical partners for U.S. small businesses that are supported by the NIH SBIR/STTR Programs. These academic laboratories fulfill many roles, including both as the technology originators and collaborators of U.S. small businesses. This NOFO was developed, with the participation of multiple NIH ICs, to support a changing landscape of entrepreneurship where universities are increasingly encouraging junior scientists to become entrepreneurs. Specific Areas of Research Interest from the participating NIH ICs of this NOFO are listed below. Applicants are strongly encouraged to contact the Scientific/Research Contacts from various NIH ICs listed in Section VII prior to submission to discuss IC program relevance. The National Cancer Institute (NCI) SBIR/STTR programs support the development, translation, and commercialization of novel therapeutics, devices, diagnostics, and processes that are aimed at reducing the burden of cancer. A retrospective economic impact analysis of NCI SBIR/STTR Phase II grants from 1998-2010 indicated there was a substantial rate of commercialization, with 247 products commercialized from 690 Phase II grants. Sales of products and services associated with these grants were reported at $9.1 billion. Based on the reported sales, economic modeling calculated that over 107,000 jobs were created and $26.2 billion of economic output was produced. The National Institute on Drug Abuse (NIDA) is the Federal Government’s lead agency for supporting scientific research on drug abuse and addiction. Over the last two decades, these research efforts, primarily conducted by academic institutions, have led to a substantial advance in the fundamental understanding of the neurobiological basis of substance use disorders (SUD). However, these insights and scientific breakthroughs have not been efficiently translated into scalable and effective solutions for SUD. For example, there are no pharmacotherapies approved to treat cannabis or stimulant use disorders, and the efficacy of available therapies for other SUDs such as opioid use disorder is limited. Through participation in this funding opportunity announcement, NIDA aims to empower the biomedical small business propagation in SUD fields and efficient technology transfer from academic labs. The Small Business program at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) is used to achieve the mission of the institute by supporting innovative technologies through various stages of commercial research and development. The NIBIB welcomes SBIR and STTR applications from small businesses proposing ideas relevant to its scientific program areas. Please contact program staff if you have questions about which institutes(s) would be the best fit for your technology. NHGRI supports resources, approaches, and technologies that accelerate genomic research focused on the structure and biology of genomes; the genomics of disease; the implementation and effectiveness of genomic medicine; computational genomics and data science; the impact of genomic technology, advances, and implementation on health disparities and health equity; and ethical, legal, and social issues related to genomic advances. Within these areas, approaches that are comprehensive across the genome or are generalizable across variants, tissues, diseases, or functions may be in scope for NHGRI. NHGRI recognizes the importance of diversity in the genomic workforce, without which the promise of genomics cannot be fully achieved. Institute/Center Priorities National Cancer Institute (NCI) NCI encourages proposals that fall into several technology areas, including; (1) Cancer Therapeutics and Preventative Agents; (2) Cancer Imaging Technologies, Interventional Devices, and In Vivo Diagnostics; (3) In Vitro and Ex Vivo Cancer Diagnostics and Prognostics; or (4) Technologies for Cancer Prevention and Control, Supportive Care, and Survivorship. National Institute of Biomedical Imaging and Bioengineering (NIBIB) NIBIB funding of clinical trials will be in accordance with NOT-EB-21-005 "NIBIB Guidance for Support of Clinical Trial Applications." Briefly, NIBIB will only support mission-focused (see NIBIB's program areas) early-stage clinical trial applications, i.e., feasibility, Phase I, first-in-human, safety, or other small clinical trials, that inform early stage technology development. NIBIB will not support applications proposing pivotal, Phase II, III, IV, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern. Also, mechanistic trials are not supported unless the primary focus of the project is on technology development. National Institute on Drug Abuse (NIDA) NIDA encourages proposals that fall into the following categories: Pharmacotherapeutic approaches for prevention and/or treatment; 2) Therapeutic and Diagnostic Devices, including Imaging Technologies, or (3) In Vitro and Ex Vivo Diagnostics. National Human Genome Research Institute (NHGRI) NHGRI encourages proposals that fall into the following research areas: 1) Genomic Technology and Methods Development; 2) Bioinformatics, Computational Genomics, and Data Science; 3) Population Genomics and Genomic Medicine; 4) Ethical, Legal, and Social Implications of Genomics; and 5) Genomics Training and Education. Research Objectives and Requirements Objectives of this NOFO This NOFO has two simultaneous objectives; (1) to support the transition of early-career scientists from academia to entrepreneurship, and (2) to support the advancement of technologies out of academic research laboratories into small U.S. businesses. Key Requirements for this NOFO A. Requirement for strong mentors Mentoring is a key component of this NOFO, and review of the mentors and mentoring plan is included in the scored peer review criteria. While candidates must have independent oversight over the project, each proposal must identify at least two mentors, one mentor who will advise the candidate on technology development, and one mentor who will advise the candidate on business development. More specifically, the purpose of the technical mentor is to help the candidate devise the best technical path forward by providing feedback on the appropriate assays and models to reach each developmental milestone. The purpose of the business development mentor is to help the candidate maintain a milestone-driven R&D plan and advise the candidate on which R&D milestones are appropriate for commercial development. Each mentor must provide a letter of support that outlines their commitment to the development of the technology and to the candidate. The identified mentors must meet the following criteria: Technical mentor: The technical mentor should be the head of the academic laboratory from where the technology originated or be recognized as a key opinion leader in the same field as the technology being developed. This person may also be a co-founder, owner, or a C-level executive in the small business. Business Development (BD) Mentor: The BD mentor could be an experienced BD executive, an experienced entrepreneur, an employee of a university’s technology transfer/innovation office, or an entrepreneur-in-residence (EIR). The BD mentor must have experience in an appropriate biotech sector relevant to the technology under development and should have experience as an executive in an industry setting or experience mentoring startups. Ideally, a BD mentor would have a track record of mentoring emerging entrepreneurs. Other mentors: Applicants can include, but are not required to include, additional mentors or mentoring teams that will help them identify appropriate milestones and/or development strategy. The application must describe how each mentor will contribute to the success of the candidate and the success of the technology. B. Eligibility The purpose of the Small Business Transition Grant is to support early-career scientists who are transitioning from an academic research setting to a small business. Therefore, eligibility is limited to early-career scientists. For more information on who qualifies as an early career scientist, see eligibility in section III below. C. Scientific/Technical Scope Applications will be considered if they are within the mission of one of the participating Organizations/Institutes as described above under "Additional Institute/Center Priorities." Additional Institute/Center Requirements National Cancer Institute (NCI), National Human Genome Research Institute (NHGRI), and National Institute on Drug Abuse (NIDA) Each grant awarded through NCI or NHGRI or NIDA will be required to complete I-Corps at NIH (https://sbir.cancer.gov/programseducation/icorps). I-Corps at NIH is an entrepreneurial training program in which participants are required to interview at least 100 stakeholders to better identify market needs and therefore product-specific commercialization opportunities. Completion of I-Corps at NIH is required during the Phase I performance period and projects that do not fulfill the I-Corps at NIH requirement will not transition to phase II. In some circumstances when the project team has already completed a non-NIH I-Corps program prior to award, the project teams may be given an exemption from the I-Corps at NIH training requirement. An exemption request must be submitted in writing to the awardee's assigned NIH Program Officer. I-Corps at NIH exemptions will only be considered for awardees and will not be considered prior to application submission. Exemptions from I-Corps at NIH are case by case and are not guaranteed even if the project team has previously completed an I-Corps program. National Institute of Biomedical Imaging and Bioengineering (NIBIB) Each grant awarded through NIBIB will be required to completed one of the two C3i programs at NIH (https://www.nibib.nih.gov/research-program/c3i-program). The NIH C3i program is designed to provide medical device innovators with the specialized business frameworks and essential tools for successful translation of biomedical technologies from the lab (concept) to the market (clinic). There are two versions of this program, the educational C3i (eC3i) program is a 10-week virtual program, which the C3i Validation/Execution program is a 24-week in-depth commercialization course. Both programs require 10 hours of work each week divided by the team members. In some circumstances when the project team has already completed a non-NIH entrepreneur training program prior to award, the project teams may be given an exemption from the NIH C3i program requirement. An exemption request must be submitted in writing to the NIBIB small business office (NIBIB-SBIR@mail.nih.gov). Exemptions will only be considered for awardees and will not be considered prior to application submission. Exemptions from NIH C3i program are case by case and are not guaranteed even if the project team has previously completed an entrepreneur training program. Evaluation of Transitioning from Phase I to Phase II The transition from phase I to phase II will only occur after the following criteria are met and documentation approved by a transition committee coordinated by the funding IC; (1) a phase I final progress report that includes a description of the phase I success criteria and a demonstration that the success criteria were met, as well as a description of key learnings experiences of the Candidate (see description below); (2) an updated commercialization plan that identifies changes from the original commercialization plan including changes based on learnings from I-Corps at NIH or C3i program as well as other entrepreneurial activities and events; (3) an updated IP agreement and an updated letter of support from the university that describes the current status of the IP, e.g. license option extension or executed license, etc., the metrics that the university used to evaluate the IP and verification that the university continues to support the small businesses efforts to develop and commercialize the technology; (4) updated letters of support from the technology mentor and BD mentor that describe the professional growth of the Candidate during the phase I project period, and a description of the mentoring relationship in phase II based on the needs of the Candidate; (5) full participation and completion of I-Corps at NIH or C3i program, unless exempted in writing from their program officer; (6) Verification that all SBIR eligibility requirements are met as all awards must transition to SBIR in phase II (see below for SBIR eligibility criteria). Because of the dual focus on mentoring and product development, it is expected that the phase I portion of several applications may propose fairly high-risk activities. While high-risk activities are allowed in phase I, transition to phase II is dependent upon demonstrating adequate technical success in phase I, projects that fail to meet their success criteria or do not demonstrate adequate technical progress in phase I as determined by the transition committee, will not transition to phase II.