Description:
Fast- Track proposals will be accepted.
Direct-to-Phase II proposals will NOT be accepted.
Number of anticipated awards: 1 to 2
Budget (total costs, per award): Phase I: $350,000 for 12 months; Phase II: $2,000,000 for 2 years
It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets
exceeding the above amounts and project periods may not be funded.
Summary:
Americans are living longer than ever before. Life expectancy nearly doubled during the 20th century with a 10- fold increase in the
number of Americans age 65 or older. As life expectancy increases, diseases and conditions that are associated with older age have
become a major health burden. A major risk factor for the development and progression of some of the most prevalent late onset
declines in function and health, such as wound healing, osteoporosis, sarcopenia, joint soft tissue deterioration and others are thought
to be contributed by depletion or dysfunction of stem cells.
Stem cell rejuvenation via heterochronic parabiosis in mice has demonstrated blood stem cells and their factors from young mice
contribute to improved wound repair and motor function in old mice. It has also been demonstrated by the ability to generate “youthful”
induced pluripotent stem cells derived from aging tissues. In addition, the development of novel adult stem cell-based therapies is on
the rise and include the use of adult stem cells or biologics that facilitate healthy repair after orthopedic surgeries and in wound repair.
However, the majority of these studies have based their efficacy and mode of action using young animal models despite the need and
market pressure to treat older people. Thus, a better understanding of how aging stem cells or tissue environments respond to potential
treatments is needed. The goal of the SBIR contract topic is to support small businesses that are in the early to mid-developmental
stages testing adult stem cell or related biologics in aging animal or aging human tissue models to develop novel adult stem cell
treatments.
The impetus of this SBIR contract solicitation is to promote full use of the base of knowledge of stem cell biology for adult stem cellrelated target validation and drug discovery and development for treatment and prevention of age-related afflictions. 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 stem cell therapeutics that target the increasing aging population. Great advances have been made in the past decade
in our understanding of adult stem cells in health and in aging. Many molecular processes that have gone awry during cellular aging
have been identified, and new information on the difference between a young and aged stem cell continues to be added to this wealth
of knowledge. It is now incumbent that this knowledge be used to mount a new direction that targets the use of this knowledge to
facilitate tissue regeneration and rejuvenation of aged stem cells and to use stem cell technologies to target treatments that afflict the
aging population. While the empiric approaches of stem cell therapies are on the rise, this new paradigm demands a more reasoned and
knowledge-based approach. The search for molecules or agents with translational potential that will rejuvenate or subvert the
deleterious effect of aging on adult stem cells or the study of biologics and the pursuit of knowledge of the molecular mechanisms that
they target which facilitate the regeneration of aging tissues will be an important component of this SBIR contract solicitation. These
agents could be chemical or biological, manmade or naturally occurring, but well characterized or subject to characterization as
potential therapeutic agents for age-related afflictions. Areas of focus may include improved tools, methods, standards, or applied
science that support a better understanding and improved evaluation of in-depth product characterization, manufacturing, potency,
identity, quality, safety, in vivo function and integration, or effectiveness. The development and utilization of modern tools for target
validation and drug discovery, including combinatorial libraries and high throughput screening, would be appropriate. However, the
development of new assays and innovative technologies for monitoring stem cell maintenance and differentiation will not be sufficient;
their development in conjunction with molecular target identification and validation, and drug discovery and development will be
appropriate.
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Applicable research may also include developing biologics (e.g., growth factors, cytokines) and biomaterials (e.g., extracellular matrix,
scaffolds) that stimulate an older adult’s stem cell self-renewal, proliferation, differentiation, and/or function or otherwise directly act
upon adult stems cells to support innate host healing mechanisms, treat disease, and/or restore function. Funding could also be used
for the appropriate chemistry, manufacturing, and controls development to support the production of such products for aging clinical
trials using current good manufacturing practices (cGMP).
Project goals:
This contract will support research directed toward developing therapeutics with clearly established proof of mechanisms to facilitate
aging tissue regeneration at the molecular, cellular, tissue organism level. The goal is to provide evidence for a stem cell-based product
with defined direct and/or indirect alterations of cellular and/or molecular processes (senescence, inflammation, metabolism, DNA
repair, etc.) that contributes to its therapeutic use for the aging community. Projects will include in-depth aging stem cell
characterization (RNA-seq, proteomics, metabolomics, etc.) including responses in senescence and inflammation using cells, tissues,
or animals. Appropriate applications will span a diverse range of technical and methodological approaches in an effort to generate adult
stem-cell based therapies that can facilitate regeneration and repair for aging, mechanisms of their action, and how this knowledge may
be exploited for the identification and development of novel therapeutic targets. Emphasis will be given to projects that focus on
developing stem cell-based strategies and to define their molecular and/or cellular mechanisms that promote healthy stem cell aging or
treatment of age-related diseases.
Research projects responsive to this FOA are expected to involve aging models which may include human and nonhuman aging cells
and tissues and may include human or nonhuman adult stem cells. Research projects involving human or animal induced pluripotent
stem (iPS) cells may be supported, as long as the cells used to generate the iPS cells were not of fetal or embryonic origin. Offerors
must outline in their proposal the product, the molecular or cellular mechanism of action, and detailed characterization of the
biologic and/or adult stem cells involved in the therapy-based approach as well as the unmet needs required to treat the aging
population with stem cell-based strategies.
Inclusion: The emphasis to study the role of stem cell-based therapies in the aging population will help fulfill the commitment NIH
solidified in 2020 for inclusion across the lifespan by expanding the importance and relevance of this research in an aging body.
Special Note: This initiative also supports the 21st Century Act for the Regenerative Medicine Initiative to facilitating getting these
therapies into the clinic. These awards started four years ago with no further allotted support from the original allotment of $20
Million.
Activities not responsive to announcement:
The following will not be supported under this FOA and will not proceed to review:
• Research that does not utilize aging cells, tissues, or animal models
• Any research using embryonic or fetal stem cells. Such projects are non-responsive.
Phase I Activities and Expected Deliverables:
• Product testing of adult stem cells and related biologics in the aging body
• Product testing may include autologous adult stem cell transplants in animal species, exosomes, metabolites, non-translating
RNAs, blood components including but not limited to exosomes and non=translating RNA
• Physiological, molecular and cell characterization of the mechanism of action for adult stem cell-based treatment for repair or
regeneration of aging tissues. Included are changes in stem cell or hose tissue replication, maintenance, differentiation, senescence
and inflammatory responses
• Preclinical studies that contribute to conducting clinical trials that address specific clinical indications
• Development of methods, standards and cGMP for adult stem cell-based RM products for using in aging
• Phenotypic assay development, including stem cell technology platforms for stem cell “Aging-in-a-dish" applications and the
evaluation of toxicity
• Identification and validation of specific biological markers or biosignatures for aged adult stem cells including stem cell
characterization and deep fingerprinting
• Demonstrate in a small-scare, proof-of-concept study with in vivo animal studies or ex vivo human cells or tissue assays the
feasibility of the product as potential treatment for age-related affliction. Feasibility assays including proper controls should provide
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insight into whether the product can either accelerate or enhance standardized treatment pricated or provide treatment where there are
no currently effective treatment options. This study should be designed to assess the sensitivity and specificity of the molecular
mechanisms involved in the repair or regeneration of aging tissue
• Deliver to NIA the Standard Operating Procedures of the system for treating the aging dysfunction
• Develop a regulatory strategy/plan and timeline for seeking approval from FDA to market the stem-cell based product
Phase II Activities and Expected Deliverables:
• Refinement or modification of tools, methods, standards, or applied science that support a better understanding and improved
evaluation of in-depth product characterization, manufacturing, potency, identity, quality, safety, in vivo function and integration, or
effectiveness for treating the aging population
• Emphasis will be given to projects that address critical issues needed for product development relevant for regulatory submissions
• Demonstrates readiness of regenerative medicine products with well- characterized quality attributes for advancement into clinical
trials under an IND/IDE application to treat aging patients
• Addresses critical issues relevant to clinical research and regulatory submissions, including those related to improved evaluation of
product quality for aging
• Helps to significantly advance the field of regenerative medicine for the aging population by addressing well-recognized
challenges in clinical development to treat the aging population, including the development and evaluation of safe and effective RM
products
• Perform a large-scale usability study with at least 100 in vivo animal studies or 500 ex vivo human cells or tissue assays.
• Perform a large-scale validation study in in vivo animal studies or ex vivo human cells or tissue assays. The study should be
designed to show a statistically significant improvement in the performance of the treatment
• Optimally, by the end of Phase II the offeror will be able to both demonstrate commercial partnering/investment interest and
submission of a regulatory application to FDA
