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A Solicitation of the National Institutes of Health (NIH) and The Centers for Disease Control and Prevention (CDC) for Small Business Innovation Research (SBIR) Contract Proposals
NOTE: The Solicitations and topics listed on this site are copies from the various SBIR agency solicitations and are not necessarily the latest and most up-to-date. For this reason, you should use the agency link listed below which will take you directly to the appropriate agency server where you can read the official version of this solicitation and download the appropriate forms and rules.
The official link for this solicitation is: https://sam.gov/opp/aa72581c848947f0b61c15062e604862/view
Application Due Date:
Available Funding Topics
(Fast-Track and Direct to Phase 2 proposals will not be accepted. Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning.) Number of anticipated awards: 2 to 3 Budget (total costs, per award): Phase I: $325,000 for 9 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; Preclinical drug development is a time and cost-intensive process that involves synthesizing analogs as part of a medicinal chemistry drug discovery campaign. Typically, chemists in small and mid-sized laboratories are tasked with preparing multiple targets at the same time, relying on cumbersome batch synthesis methods in order to find key intermediates that can rapidly undergo the final transformations prior to biological testing. To reduce the steps to obtain the intermediate that will support structure-activity relationship (SAR) studies by medicinal chemists, the key pharmacophore or key structural component must be known where one can perform strategic chemical modification. The translational burden required in the process of synthesizing iterative rounds of analogs for biological screening activities can be alleviated by keeping to a minimum, the amount of work involved in tuning the synthesis of each new target. Often this can be achieved by identifying the shortest synthetic route, requiring the least number of isolation methods, while maintaining desired purity and yields for lead compounds. The key to accelerating molecules into the clinic is the ability to use automation to make the lead compound, and the early involvement of process chemists with medicinal chemists to identify the correct late-stage intermediate to produce the final drug target. Major advancements in the area of computer-aided drug discovery/design methods have proven to play a critical role in the development of therapeutically important small molecules in recent decades. Critical finished products such as pharmaceutical drugs rely on intermediate materials utilized to produce the bulk drug substance. Often vulnerable to supply chain disruptions, the availability of these important intermediates as starting materials, dictate production capabilities of critical pharmaceutical drug products in both local and national scenes, which in turn directly impact healthcare outcomes. This initiative seeks proposals from the small business community to support the development of compact tools and devices capable of manufacturing key chemical intermediates at the benchtop, for just-in-time delivery of such materials in quantities that optimally Page 76 impact the throughput of research operations. Using new or existing chemistries, in tandem with innovative solutions through engineering approaches, the purpose of this device is to speed up the preclinical drug development stage, by providing on-demand access to key intermediates that can be rapidly diversified to analogs or used to scale-up material for animal studies. Robust laboratory instruments that are amenable to automation and real-time data acquisition/monitoring will assist medicinal chemists in synthesizing critical intermediates. Like the development of peptide synthesizers in the mid-80’s, the paradigm shift envisioned in this project is an innovative platform capable of supporting a broad range of chemical transformations as opposed to a single transformation type (e.g. peptide synthesis), in a reliable manner suitable to automation. We seek to leverage trends in automation in synthetic chemistry to shift the way that common intermediates in medicinal chemistry are currently acquired in the laboratory. The innovative platform must incorporate creative solutions to address current limitations in reagent delivery systems, reagent formulations, and data interpretation through a versatile, reconfigurable system that utilizes step changes in the workflow based on the type of chemistries involved. This project also supports innovation for the acceleration of molecules into the drug development pipeline using these newly developed tools, in lieu of traditional synthetic chemistry efforts. This may potentially have implications in domestic supply chain availability of pharmaceutical intermediates, especially for those that are largely produced overseas. By shortening the design-synthesize-test cycle in drug discovery, this project aims to increase access to preclinical candidates and allow for more rapid exploration of chemical space surrounding a disease target.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Page 79 Summary Among men, prostate cancer is the second leading cause of cancer mortality in the US and fifth worldwide. The largest, randomized clinical trial of prostate-specific antigen (PSA) screening (ERSPC) reported a 20% reduction in prostate cancer mortality at 16 years among screened men compared to an unscreened control group and a 30% reduction in the cumulative risk of metastases after a median follow-up of 12 years. In 1994, the FDA approved PSA testing to aid in the detection of prostate cancer. In the first 20 years following this approval, prostate cancer mortality decreased by 50%. However, after the 2012 United States Preventive Services Task Force (USPSTF) recommended against prostate cancer screening, the prostate cancer mortality curve flattened, and the incidence of metastatic disease increased. In 2018, the USPSTF recommended that men aged 55-69 years engage in shared decision-making with healthcare providers to consider the benefits and harms of PSA screening in the context of family history, race, comorbid medical conditions, values, and preferences. The National Comprehensive Cancer Network, American Urology Association, and the American Cancer Society recommend that men discuss the pros and cons of PSA screening with their healthcare provider, starting at age 40 to 55 years. The prostate cancer mortality rate is high among African American men, who face disproportionately greater barriers to health care services, including cancer screening, compared to the general population. Decision analysis models suggest that PSA-based screening may provide greater benefit to African American men. Therefore, greater adoption of PSA screening in African American and other high-risk men has the potential to reduce the burden of cancer treatment by increasing the detection of disease amenable to curative therapy (when indicated) or surveillance (when appropriate). The development of an accurate, inexpensive home test for PSA is both an unmet need and an NCI priority in the context of President Biden’s Moonshot goal of reducing cancer mortality by half within 25 years. While the availability of home or point-of-care testing cannot overcome structural impediments to screening, the knowledge that one has an elevated PSA would remove a substantial barrier to screening by helping men prioritize this issue. This topic is aligned with the Cancer Moonshot Blue Ribbon Panel recommendation to expand the use of proven cancer prevention and early detection strategies (G).
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Only Direct-to-Phase II and Fast-Track proposals will be accepted. Phase I proposals will NOT be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Cervical cancer is the fourth most common cancer in women. When pre-cancer or cancer is diagnosed early, cervical cancer is one of the most preventable or treatable forms of cancer. Cervical cancer has become a cancer that defines global health disparity populations based on inequities in the feasibility of delivering effective, but complex and costly screening programs based on cytology and colposcopic diagnosis in low-resource settings. Because of this, the World Health Organization (WHO) Cervical Cancer Elimination strategy calls for screening the majority of women with a high-performance HPV test twice in their lifetime. Realization of that goal using current commercial HPV tests is unlikely. To realize cervical cancer screening elimination goals in low-resource settings, it is essential that new tests can be performed and analyzed outside of traditional healthcare settings and are at a price point that is affordable to enable scalability. Fortunately, emerging test chemistries, including those based on isothermal amplification of HPV DNA, have shown significant promise for the design of highly accurate HPV diagnostics at a lower cost than existing tests. Recent developments in microfluidics, microfabrication, and hand-held computers further improve the prospects for adaptation of accurate, low-cost point-of-care versions of existing lab-based assays. The overarching goal of the work to be supported by this initiative is to bring new alternatives for HPV testing to the market that are, both in a form factor as well as price point, will enable self-testing programs to be established globally at point-ofcare or near point-of-care. This topic is aligned with the Cancer Moonshot Blue Ribbon Panel recommendation to expand the use of proven cancer prevention and early detection strategies (G)
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Technologies that can assess metastatic risk early and facilitate prompt interventions can significantly improve cancer outcomes because most cancer deaths are due to metastasis. Currently, very few markers are available for predicting metastatic risk. Disseminated tumor cells that enter circulation are pivotal in the metastatic cascade, and circulating tumor cells (CTCs) are being used as putative markers for monitoring tumor dynamics and treatment response. However, accumulating evidence suggests that tumor-derived cell clusters (TDCCs) may be a more important factor in metastasis and associated poor progression-free survival and overall survival. Clustering is an adaptive mechanism that enhances CTC survival and migration in the harsh conditions of the bloodstream, confers stemness, immune evasiveness, and increases their metastatic potential. TDCCs are reported to consist of either homotypic clusters composed of only cancer cells; or heterotypic clusters made of stromal cells or immune cells including fibroblasts (CAFs), macrophage-like cells (CAMLs), endothelial cells (TECs), tumor-macrophage hybrid cells (TMHCs), and neutrophils, along with tumor cells. Compared to single CTCs, TDCCs have been shown to have distinct molecular features, exhibit a higher proliferation rate, and 20 to 230-fold more metastatic potential than individual CTCs. Overall, these data suggest that composition and heterogeneity of TDCCs may be more informative for assessing metastatic risk or for predicting and following treatment response than assays based on single CTCs. The biology of formation, dissemination, and metastatic mechanisms associated with TDCCs are poorly understood because currently, very few technologies exist to study TDCCs. Studies that detect TDCCs or elucidate their biology merely adapt existing CTC-based technologies that are grossly inadequate for heterotypic clusters. There is an unmet need for technologies that combine cluster enrichment, enumeration, and downstream molecular analysis to better understand biology and the role of different cells in metastasis
Fast-Track proposals will NOT be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 4-6 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary This proposal is for the development of microbiome-based technologies for cancer research, diagnosis, and patient management (e.g., prognosis, treatment assignment, and efficacy monitoring). Although early and accurate diagnosis is key to successful treatment, effective methods for early detection do not exist for many cancers. Indeed, the available diagnostic tests are characterized by either high false positive rates due to low specificity resulting in unnecessary surgeries for diagnostic confirmation (e.g., CT scan for lung cancers) and/or high false negative rates due to low sensitivity (e.g., CA125 and trans-vaginal ultrasound for ovarian cancers). For example, the sole FDA-approved biomarker for pancreatic cancer, serum CA19-9, is mostly used for disease monitoring rather than screening due to inherent limits in specificity as its levels can be elevated in several other concomitant conditions. Other types of diagnostics using liquid biopsies can detect cell-freecirculating DNA (ctDNA) derived from tumors in late-stage cancers (stages III and IV), as traditional ctDNA-based analyses lack the sensitivity required to detect small tumors/early lesions. Furthermore, accurate technologies are also needed for cancer prognosis, treatment assignment, and efficacy monitoring. In addition to addressing the specificity/sensitivity issues of the currently available approaches, microbiome-based technologies would ideally be capable of using liquid biopsies that are safer, more cost-effective, and faster to obtain than solid biopsies for a wider adoption in clinics. Recently, the microbiome was added to the list of cancer hallmarks and multiple clinical and preclinical studies have revealed an association of specific microbiome signatures with individual cancers and with response to therapy (chemotherapy, immunotherapy, and radiotherapy). In addition, recent advances integrating the analysis of large datasets from nextgeneration DNA sequencing, and new methods of computational modeling using AI and machine learning, have shown the feasibility of using microbial biomarkers for early cancer detection, and personalized medicine. Thus, the development of microbial signatures from cancer patient samples, ideally from liquid biopsies, to be used alone or in combination with other biomarkers, offers an exciting opportunity to develop new and innovative tools for better cancer diagnosis, prognosis, and patient management. These technologies using microbial signatures as biomarkers for cancer detection and patient management will also enable researchers to better understand the fundamental underlying biology and molecular dynamics of microbe-tumor interactions as the causes and roles of microbial changes associated with cancer are not well understood.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary The NIH Office of Disease Prevention recently held a Pathways to Prevention workshop, which explored the evidence for nutritional interventions and cancer health outcomes. A report of the workshop by an independent panel recommended baseline screening for nutrition risk following cancer diagnosis and repeated through treatment. This recommendation is supported by evidence linking cancer-associated malnutrition to poorer outcomes, including decreased treatment completion, greater healthcare utilization, and overall worse survival. The poor outcomes are driven substantially by the depletion of skeletal muscle, such as in sarcopenia, and by the emerging abnormal body composition phenotype of low muscle mass and high adipose tissue or sarcopenic obesity. Nutritional screening is the first step in the identification and treatment of patients with or at risk for malnutrition, especially those patients with cancer types that have the highest prevalence of malnutrition including upper gastrointestinal, head and neck, hematological, gynecological, colorectal, and lung cancers. Several quick and simple-to-administer questionnaire-based screening tools validated in the oncology setting capture changes in appetite and unintentional weight loss; they are often short, easy to administer, and can be incorporated into the electronic health record (EHR). However, they fail to capture abnormal body composition, which is fundamental for the identification of hidden abnormalities, such as sarcopenia and myosteatosis. State-of-the-art approaches based on diagnostic imaging are available to quantify the depletion of skeletal muscle and abnormal body composition changes that occur in patients with cancer. For example, CT scans, which are accessible in most cancer populations for routine diagnosis and follow-up of treatment response, can be ‘re-purposed’ for assessing muscle and adipose tissue and is considered gold standard methodology. Biomedical image segmentation and automated segmentation of skeletal muscle and adipose tissue from CT scans provides a time-efficient, clinic-friendly, and accurate assessment of muscle and adipose tissues. Developing an automated nutrition screener that combines the questionnaire-based tools with diagnostic imaging would greatly improve the identification of cancer patients with or at risk for malnutrition and will aid in the optimal timing for nutritional intervention.
Fast-Track proposals will NOT be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Page 88 Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Oncology data science and analytics is a burgeoning area of artificial intelligence (AI) and machine learning (ML) technologies that have fueled interest across the industrial and academic sectors. During the past few years, several startups and large companies have focused on AI/ML technologies with the aim of reducing complexities in clinical workflow or increasing accuracy in detection, diagnosis, and treatment of cancer. While tremendous amounts of data are generated through clinical practice, significant gaps remain to leverage the data for device development and evaluation, including: 1) generation/acquisition of patient outcome data; 2) truthing of images by clinicians; 3) correlation of multi-modal imaging, comprehensive clinical, and genomic data in common repositories; 4) extraction of information from unstructured electronic health records (EHR) data; and 5) availability of clinically infrequent variants. This topic supports an unmet need for the development of large, well-curated, and statistically robust datasets that can be used for the evaluation of cancer medical devices subject to regulation by Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA). Datasets that may be used to develop new devices as a measure of device effectiveness or performance, and support regulatory decision-making may be eligible for CDRH’s Medical Device Development Tools (MDDT) program. A tool eligible for consideration by the MDDT Program is one that reduces the regulatory burden of industry and the FDA. CDRH’s mission is to protect and promote public health by assuring that patients and providers have timely and continued access to safe, effective, and high-quality medical devices. To qualify a dataset as an MDDT, CDRH evaluates the dataset and concurs with the available supporting evidence that the dataset produces scientifically plausible measurements and works as intended within the specified context of use. More information about the FDA’s MDDT Program can be found here. CDRH’s MDDT program collaboration with the NCI SBIR Development Center can help incentivize the small business community to develop and qualify innovative tools for oncology-related regulatory decision-making. These tools can be sold to industry or academia developing new device technologies that would benefit from using the MDDT in product development and evidence generation for a regulatory submission, thus stimulating and supporting translation of innovative devices to the clinic. Given these similar areas of interest, FDA CDRH and NCI SBIR have developed this joint contract topic to support innovation across our overlapping communities.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary An important development in the field of radiation oncology is demonstration that ultra-fast dose rate (also known as FLASH) radiation therapy has fewer side effects than regular radiation therapy at the same delivered dose. This finding is under intense investigation globally and a race is underway to understand and subsequently implement this methodology in the clinic. The current devices that measure radiation dose lack response times sufficient to adequately address ultra-fast dose rates of 40-120 Gy/second. This is especially problematic when the total prescribed dose may be only 8-20 Gy. Current medical practice dictates that radiation dose must be given within 20% of the prescription, or else be subject to a formal reportable medical event, as regulated by the United States Nuclear Regulatory Commission. To safely utilize FLASH treatment technique in the clinic, radiation detectors need to be developed that can reliably function at dose rate from 2-10 Gy/minute to 40-120 Gy/second. Additionally, the time structure and the fluence shape of the pulse must be verified to meet FLASH specifications. FLASH radiation delivery’s biological effect may be a function of a unique fine delivery structure that requires ultrafast dose measurement capacity to confirm that the proper, optimal time structure is being used (pulses versus continuous beam delivery).
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary 2D monolayer cultures fail to recapitulate the totality of the tumor microenvironments. More complex cancer in vitro models have been developed, but they still lack organ-level structures, fluid flows, and mechanobiological cues that cells experience in vivo. Therefore, physiologically and clinically relevant reproducible models that mimic tissue and tumor microenvironments are urgently needed to improve preclinical radiobiological research. Such model systems could impact several areas, such as the ability to predict efficacy and toxicities of drug-radiation combinations, to determine the relative biological effectiveness of proton therapy, etc. These models are also applicable in other areas of cancer research. Generally, they will reduce the cost of research by improving the preclinical research quality and potentially reducing animal use in research. Microfluidics (materials and techniques) have potential applications in radiobiology, and commonly used siliconebased compounds, such as polydimethylsiloxane (PDMS), have already been tested and found resistant to radiation-induced brittleness and aging and have demonstrated required stability and water equivalency. Lab-on-chip (LOC) microfluidic and “tissue mimetic” technologies have evolved into advanced Organ-on-Chips (OoC). OoC systems containing perfused hollow microchannels populated with living cells have the ability of multiplexed drug testing and may be applied to many radiobiological studies. OoC technologies are already at a higher technological level of maturity. Further development and validation of OoC guided by its intended context of use for translational radiobiological studies are necessary. This SBIR contract mechanism accelerates further development and integration of advanced OoCs into cancer treatment development and translational pipelines in radiobiology and drug radiation combination studies.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of Anticipated Awards: 3-5 Budget (total cost, per award): Phase I: up to $400,000 for 12 months Phase II: up to $2,000,000 for 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Page 95 Summary The purpose of this technology-agnostic contract solicitation is to bring highly sensitive cancer-specific imaging agents and technologies capable of detecting very small volume (1 mm3 ) tumors in humans to clinical utility. Current imaging technologies/techniques are in use for non-invasive cancer detection, but clinical methods are limited to detecting masses several millimeters to centimeters in size. To image small primary or metastatic tumor sites composed of 1 – 10 million cells, imaging sensitivity must be improved. This can be achieved without significant hardware advances by improving the contrast between diseased and healthy tissue captured in the image. Thus, there is a clinical need for techniques that improve image contrast between tumors and surrounding normal tissue. There are several methods that rely on the use of specialized agents that are activated when coupled to a tumor target. Such activatable agents dramatically increase the contrast between small tumor cell masses and surrounding tissue. Efforts to develop activated imaging agents and techniques have been ongoing for over a decade, and successful demonstration in cancer-bearing animals has been achieved. These developmental successes now need to be translated for clinical use. This SBIR solicitation thus supports translation of novel activatable agents and/or techniques for sensitive cancer detection in human subjects. Clinical translation and validation should be the primary goals of the proposed research. The bulk of the proposed research must focus on translating improvements in imaging sensitivity to a clinical environment with the goal of demonstrating that tumor cell aggregates on the order of 1 mm3 in volume can be detected in cancer patients. Research toward development and establishing biological safety of the agent or technique in preparation for clinical validation will be accepted under this solicitation in Phase I. Thus, this solicitation supports translation of developing technologies for small tumor detection in human subjects. It is not intended to support continued major development and testing of techniques or novel agents. Any technique or strategy that dramatically enhances contrast between very small cancer and normal tissue is acceptable for consideration, which can include software techniques (such as AI/ML) that have already been validated in cancer-bearing animal models prior to submission of the application.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary The cancer research field has become intensely focused on the generation of high-throughput datasets to better understand cancer and, ultimately, to inform the development of better treatment and prevention tools. NIH and NCI have supported numerous programs, including The Cancer Genome Atlas (TCGA), The Cancer Imaging Archive (TCIA), Therapeutically Applicable Research to Generate Effective Treatment (TARGET), Clinical Proteomic Tumor Atlas Consortium (CPTAC), and Human Tumor Atlas Network (HTAN) to generate a wealth of multi-modal data to be leveraged by the cancer research community. However, we are still limited in our ability to draw insights and meaningful interpretations from these datasets, which include multi-omics, imaging, and clinical data, by challenges in integration across disparate datasets. To address these challenges, NCI has created the Cancer Research Data Commons (CRDC) as part of the National Cancer Data Ecosystem recommended by the Cancer MoonshotSM Blue Ribbon Panel. The CRDC brings together data with cloud computing infrastructure to provide secure access to various data types across scientific domains which allows users to analyze, share, and store results by leveraging the storage and elastic compute of the cloud. This contract topic will support commercial sector participation to develop novel and impactful commercial analytic tools for the cancer research community that integrate CRDC multimodal data. The SBIR contract funding mechanism will offer the opportunity for small businesses to contribute solutions to address unmet challenges of big data analysis that are not currently provided by existing tools in the CRDC through the development of tools and resources that integrate into the rapidly evolving CRDC. Through this contract topic, NCI seeks to enable engagement of the CRDC community by offering enhanced data analysis capabilities, visualization tools, and data access and sharing platforms to enhance users' ability to make data-driven discoveries.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Slow and incomplete accrual of diverse participants to cancer prevention and treatment clinical trials continues to hamper the rate of drug development and medical progress. A study in 2014 reported that 1 in 4 cancer clinical trials were terminated early with 1 in 10 being terminated for poor accrual. A recent study found worsening underrepresentation of patients from racial and ethnic minority groups in Phase 1 cancer clinical trials between 2000 and 2018. There are no easy solutions to solving accrual challenges. Retention of subjects enrolled in trials can also be a challenge, especially in long-term or demanding trials. Recruitment, retention, and adherence obstacles are magnified in cancer prevention trials due to eligible participants being at varying levels of cancer risk, generally asymptomatic and active, lacking the motivation of a patient with a cancer diagnosis, and finding non-standard-of-care procedures more objectionable. Many NCI networks provide program and protocol-specific recruitment manuals, tools, and educational resources. However, more innovative, generalizable tools that increase accrual of diverse participant populations and are based on empirical evidence are mostly lacking. This solicitation has the potential to enhance clinical trials recruitment, retention, and adherence through the development of tools that could be used across the cancer continuum. The goal of these tools is to enhance communication Page 99 between study staff and participants, build long-term trusted relationships, improve the study participation experience, and reduce the burden of clinical trials to both staff and participants. This topic is aligned with the Cancer Moonshot Blue Ribbon Panel recommendation to establish a network for direct patient engagement (A).
Number of anticipated awards: 1 to 2 Budget (total costs, per award): Phase I: $500,000 for 12 months; Phase II: $2,500,000 for 2 years Fast- Track proposals will be accepted. Direct-to-Phase II proposals will be accepted for companies that have already demonstrated feasibility and rigorously achieved the deliverables as described for Phase I. 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: Characterizing the exposome requires collection of both environmental and biological samples. However, under resourced populations, who often carry the highest burden of age-related diseases, are often precluded from participating in epidemiologic studies due to difficulties in collecting these environmental and/or biological samples. By lowering the barriers to these data collection efforts, NIA will be better able to study the etiology of complex diseases such as Alzheimer’s and related dementias in more representative populations. The development of technologies that will enable remote or self-sampling will enable greater participation of under resourced populations in research. However, there are several unmet needs for remote sampling tools that enable self- or caregiver-collected specimens that will allow longitudinal population-based studies to link environmental exposures to molecular changes associated with adverse aging and development of Alzheimer’s and related dementias over a period of time. Short term changes (weeks/months) are useful for following disease progression, while longer term changes (years/decades) are useful for developing predictive biomarkers and understanding the etiology of disease. Furthermore, there is a need for portable air sampling devices that capture both physical and bioaerosols in liquid media to maintain their viability, as well as a need for need for technologies that are user friendly and enable sample capture at the point of exposure (e.g., homes, workplaces, public spaces) with the samples shipped back to a central lab facility for high content biological and chemical analysis. The ability to combine remote/point-of-exposure collection devices with technology that samples human specimens will provide a powerful lens into a person's exposure and their physiological response to those exposures. For large population-based cohort studies, environmental and physiological samples can be collected prospectively and analyzed at a later point once it is known which study participants will experience outcomes later in life (e.g., onset of dementia, etc.).
Fast Track Proposals will be accepted. Direct-to-Phase II will not be accepted. Number of anticipated awards: 1-3 Budget (total costs): Phase I: $ 300,000 for up to 1 year. Phase II: $ 2 million for up to 3 years. Background Passive immunization by antibody administration has been used to prevent and/or treat several infectious diseases, including RSV, hepatitis A and B, rabies, and COVID-19. The Antibody Mediated Prevention (AMP) trials established proof-of-concept that delivery of a broadly neutralizing antibody (bNAb), VRC01, can protect against acquisition of bNAbsensitive HIV-1 strains. VRC01 has an excellent safety profile, does not depend on daily adherence for efficacy, and lacks the side effects that can deter pre-exposure prophylaxis (PrEP) use. NIAID and its partners are building on the success of the AMP trials by engineering next-generation bNAb candidates to enhance potency, increase tissue levels, extend half-life, and contend with the ever-evolving global diversity of HIV-1. Effective antibody-based HIV prevention will require a more potent combination of bNAbs with greater neutralization breadth than VRC01 and must target multiple sites of vulnerability on the HIV Envelope (Env) glycoprotein. Developing bNAb cocktails presents additional challenges: complex pharmacokinetics, larger injection volumes, multi-product formulations, and complicated manufacturing. Currently, HIV-1 bNAb administration requires frequent injections. In the AMP trials, recipient acceptability of intravenous (IV) administration was high. However, high cost and logistical burdens slowed the early uptake of monoclonal antibodies for prevention and treatment of SARS-CoV-2, suggesting that IV administration can be challenging outside the context of a clinical trial. Subcutaneous (SC) administration has low recipient acceptability due to local reactogenicity. Improvements in bNAb delivery would benefit the field as NIAID and its partners develop the next generation of bNAbs for HIV-1 prevention or other indications. Examples of devices and materials include, but are not limited to, dermal patches, controlled-release hydrogels, nanoparticle carriers, vaginal rings, implantable devices, and nucleic acid delivery. New or improved delivery devices and materials have the potential to increase end-user acceptability, increase adherence, reduce administration-associated cost and time, and improve efficacy by maintaining sustained antibody titers.
Phase I and Fast Track proposals will be accepted Direct-to-Phase II proposals will not be accepted Number of anticipated awards: 2-3 Budget (total costs): Phase I: $ 300,000 for up to 2 years Phase II: $ 1 million for up to 3 years. Page 105 Background Globally, an estimated 58 million people have chronic hepatitis C virus (HCV) infection, with about 1.5 million new cases occurring per year. Among people living with human immunodeficiency virus (HIV), morbidity and mortality are increasingly driven by coinfections. For such individuals, the odds of acquiring HCV are six times higher than for their HIV-negative counterparts. In the United States, an estimated 15 to 30% of persons living with HIV have HCV coinfection, but these rates vary significantly based on the individual's risk factor for acquiring HIV. WHO-recommended direct-acting antiviral (DAA) drug combination therapy can cure up to 95% of persons with hepatitis C infection, and treatment duration is usually 8-12 weeks (in the absence of cirrhosis). However, access to HCV diagnosis and treatment, although improving worldwide, remains limited, especially in low-income and lower-middle-income countries. Compliance is also of concern in treatment success, particularly in people co-infected with HIV-HCV who are required to adhere to co-administration of multiple drugs. These challenges may potentially be overcome by the use of long-acting (LA) treatments for HCV to allow intermittent dosing intervals, and, ideally, a one-dose alternative to cure the HCV infection. It is anticipated that LA treatments will be more expensive than standard drug regimens due to increased costs in manufacture, storage, and delivery. However, such LA products, now being highly acceptable by patients and providers, offer notable advantages as (1) they would allow a much-simplified test and treat strategies, (2) reduce the health care infrastructure needs for HCV medicines thereby enabling treatments to be deployed even in very remote settings, and (3) significantly mitigate concern about drug resistance development due to non-compliance. Thus, in the long term, the LA drug products could potentially help to eradicate Hepatitis C.
Phase I and Fast Track proposals will be accepted Direct-to-Phase II proposals will not be accepted Number of anticipated awards: 4-5 Budget (total costs): Phase I: $ 300,000 for up to 2 years Phase II: $ 1 million for up to 3 years Background An estimated 1.1 million people in the US are living with HIV, and one in seven are unaware of their infection. As a result, they are not accessing the care and treatment they need to stay healthy and reduce the likelihood of transmitting the virus to their partners. A US Government initiative, Ending the HIV Epidemic (https://www.hiv.gov/federal-response/ending-thehiv-epidemic/overview), and the National HIV/AIDS Strategy (https://www.hiv.gov/federal-response/national-hiv-aidsstrategy/national-hiv-aids-strategy-2022-2025#) seeks to reduce the number of new HIV infections in the United States by 90 percent by 2030. Part of this goal includes widespread HIV testing to reduce undiagnosed HIV infection and connect people to HIV medical care as soon as possible, which will improve the health of people living with HIV and prevent transmission. The small business innovation program is uniquely suited to reduce HIV incidence in the US because funds can only be spent domestically and not abroad
Phase I or Fast Track proposals will be accepted. Direct-to-Phase II proposals will not be accepted. Number of anticipated awards: 2-3 Budget (total costs): Phase I: $ 300,000 for up to 1 year Phase II: $ 2 million for up to 3 years Background Viral infections due to hepatitis B virus (HBV) and hepatitis C virus (HCV) are major global public health burdens, and account for more than 3.0 million new cases and over 1.1 million deaths each year (WHO 2020). Despite the existence of a safe and effective vaccine for HBV, and effective antiviral medications for HCV cure, diagnosis and linkage to care are poor in both developing and high-income countries. Consequently, 80-90% of all people living with HBV and HCV remain undiagnosed and untreated each year, leading to increased morbidity and death due to cirrhosis and hepatocellular carcinoma (HCC). In the United States alone, it is estimated that only 15% of all people living with HBV are aware of their status, and of these, only 4.5% are treated. These global gaps highlight the critical need for novel, innovative, and improved strategies to target hard-to-reach populations and facilitate earlier detection, diagnosis, and linkage to care and treatment for people living with HBV and HCV. Experiences and lessons learned from implementation of HIV self-testing strategies, and the COVID-19 pandemic, have demonstrated the importance of self-testing as an approach to increase access to and uptake of testing among key populations, including many first-time testers. HIV and viral hepatitis infections share common modes of transmission and social and structural barriers to accessing care and services among key populations, including men who have sex with men (MSM), injection drug users (IDUs), and commercial sex workers. Of the estimated 38 million people living with HIV (PLWH), 2.7 and 2.3 million people are estimated to be coinfected with HBV and HCV, with a global prevalence of 7.4 and 6.2 percent, respectively (WHO 2020). Coinfection with HIV significantly impacts the pathogenesis of HBV and HCV and is associated with reduced spontaneous clearance of HCV and HBsAg, higher rates of chronicity and occult HBV, higher HCV viral loads, rapid disease Page 108 progression, and increased risk of morbidity and mortality due to cirrhosis and HCC. Integrated strategies for screening and diagnosis of HIV and viral hepatitis infections are therefore critical to an effective global health response. Technological innovations, including the development of multiplexed patient administered (e.g., self-collection, selftesting) tests, have the potential to overcome barriers to healthcare access and stigma, increase access to testing, facilitate early diagnosis and treatment initiation, reduce transmission, and improve linkage to care and health outcomes for currently undiagnosed and hard-to-reach populations who have either never been tested or have limited access to clinical care.
Fast-Track proposals will be accepted. Direct-to-phase II proposals will be accepted. Number of anticipated awards: 1-3 Budget (total costs): Phase I: $300,000/year for up to 2 years Phase II: $1,000,000/year with appropriate justification by the applicant for up to 3 years Mission: IID and BIOD COR: Kentner Singleton Background The goal of this program is to support the pre-clinical development of vaccine adjuvants for use in vaccines to prevent or treat human disease caused by infectious pathogens or immune-mediated diseases (e.g., allergic diseases, autoimmune diseases). Vaccine adjuvants are agents that stimulate and direct the immune system, which are used to enhance or modulate immune responses to a target antigen. The quality, magnitude, tissue distribution, isotype and subclass, and duration of antibody responses elicited by a vaccine can be influenced by the choice of adjuvant. Adjuvants also can drive antigen specific CD8 T cell responses, which are important for eliciting protection against some target pathogens. Adjuvants are used to specifically improve vaccine efficacy in at-risk populations such as neonates, young children, pregnant women, the immunocompromised, and the elderly as these populations have unique immune system characteristics and needs. Adjuvants can broaden vaccine accessibility worldwide by reducing the effective antigen dose or booster requirements, thereby extending the number of doses available or simplifying immunization schedules. Within the context of immunemediated diseases (e.g., allergy, autoimmunity), adjuvants could drive immune deviation (e.g., Th2 to Th1 immune response) or induce immune unresponsiveness/tolerance in an antigen-specific manner (e.g., Treg induction). In the field of allergic diseases, adjuvants could help reduce the dose, frequency, and duration of allergen administration in the context of allergen immunotherapy and reduce adverse allergic reactions thus leading to higher acceptance and effectiveness. New, improved, and widely accessible adjuvants are needed to support vaccine development. Because different pathogens or immune-mediated diseases require different immune responses for protection or treatment, each vaccine will require an appropriate adjuvant. Some adjuvants have increased or decreased vaccine efficacy in different populations; for example, a vaccine for use in the elderly may require a different adjuvant than one for a pediatric population. Different routes of administration (intranasal vs. intramuscular) or antigens can have different formulation needs, which some adjuvants are able to accommodate, while others cannot. Finally, intellectual property (IP) can re.strict use of an established vaccine adjuvant, where having additional options, including functional mimics of late-stage adjuvants or adjuvants in licensed vaccines, would offer more flexibility to vaccine developers, for the net benefit of the public
Fast-Track proposals will be accepted Direct-to-phase II proposals will be accepted Number of anticipated awards: 3-5 Mission: IID or BioD or both: both COR: Joy Liu Budget (total costs): Phase I: $300,000/year for up to 2 years Phase II: $1,500,000 with appropriate justification by the applicant for up to 3 years Background This program addresses the limited availability of reagents (e.g., antibodies, immune receptor ligands) for the identification and discrimination of immune cells and the characterization of immune responses in non-mammalian models and/or in specific underrepresented mammalian models. Non-mammalian models of interest include amphibians, arthropods, fish (e.g., jawless fish, sharks, zebrafish), marine echinoids, and nematodes; and under-represented mammalian models of interest include bats, cats, cotton rats, dogs, ferrets, guinea pigs, hamsters, marmosets, minks, pigs (including minipigs), rabbits, and sheep. Many non-mammalian models are easily tractable model systems to study basic, conserved immune defense pathways and mechanisms. For example, the characterization of the Drosophila Toll signaling pathway facilitated the discovery of mammalian Toll-Like Receptors (TLR), which significantly accelerated progress in the field of innate immunity. Nonmammalian models can be much more easily adapted to high-throughput screening formats than mammalian organisms. Caenorhabditis elegans has been used for whole-organism, high-throughput screening assays to identify developmental and immune response genes, as well as for drug screening. Many non-mammalian species are natural hosts for human Page 112 pathogens and share many conserved innate immune pathways with humans, such as the NF-kB pathway in mosquitoes, the intermediate hosts for Plasmodia parasites. However, studies to better understand immune regulation within nonmammalian models have been constrained by the limited availability of antibodies and other immune-based reagents. Certain mammalian species display specific features of human immunity that make them highly valuable models but are similarly underutilized due to the limitations noted above. For example, sheep are useful for understanding the role of the immune system in pregnancy and in xenotransplantation studies. However, the lack of high-quality immunologic reagents for sheep immune markers continues to slow advances in these areas. Minks are highly susceptible to SARS-CoV-2 infection with the potential for zoonotic pathogen transmission. However, there are almost no reagents available for immunological studies in this species. Similarly, bats are the natural reservoir and vectors for several major zoonotic diseases that cause severe human diseases, but the lack of reagents has impeded studies of how bats’ adaptive or innate immune responses control these pathogens without the manifestation of disease. Advances have been made recently in the development of reagents for a number of these under-represented mammalian and non-mammalian models, and relevant immune reagents may already be commercially available. Therefore, offerors are urged to focus on potential targets for which no antibodies are available, or for which commercially available reagents do not perform well in specific assays, produce inadequately strong signals, or have undesirable off-target effects. Proposals that focus on targets for which sub-optimal reagents already exist must include the corresponding commercially available reagent(s) as a comparator
Fast-Track proposals will be accepted Direct-to-phase II proposals will be accepted Number of anticipated awards: 1-3 Mission: BioD COR: Wolfgang Leitner Budget (total costs): Phase I: $300,000/year for up to 2 years Phase II: $1,000,000/year with appropriate justification by the applicant for up to 3 years Background The goal of this program is to support 1) the screening for new vaccine adjuvant candidates against infectious diseases or for tolerogenic adjuvants for the treatment of autoimmune or allergic diseases, or 2) the down-selection of adjuvants to support the subsequent development of novel adjuvanted vaccines. For the purpose of this SBIR, the definition of vaccine adjuvants follows that of the U.S. Food and Drug Administration (FDA): “Agents added to, or used in conjunction with, vaccine antigens to augment or potentiate and possibly target the specific immune response to the antigen.” Tolerogenic adjuvants are defined as compounds that promote immunoregulatory or immunosuppressive signals to induce nonresponsiveness to self-antigens in autoimmune diseases or transplantation, or environmental antigens in allergic diseases. Currently, only a few adjuvants other than aluminum salts (“Alum”) have been licensed in the United States (U.S.) as components of vaccines against infectious diseases. In addition, adjuvants may facilitate the development of Page 114 immunotherapeutics for immune-mediated diseases (e.g., allergic rhinitis, asthma, food allergy, autoimmunity, transplant rejection). The field of tolerogenic adjuvants is still in its infancy and no adjuvanted vaccines have been licensed yet in the U.S. In contrast to drugs that are primarily used for treatment, tolerogenic or immunomodulatory adjuvants may regulate immune responses to specific antigens through a variety of mechanisms, including induction of regulatory T cells or alterations in the profile of the pathogenic lymphocyte response (e.g., Th1 to Th2 or vice versa). For tolerogenic and immune modifying adjuvants, the antigens may originate from environmental (allergy) or endogenous (autoimmunity) sources and may not need to be supplied exogenously together with the adjuvant. When pursuing this approach, the proposal must describe a compelling mechanism by which the adjuvant would modulate an antigen-specific response and include studies demonstrating altered or suppressed responses against the allergen or autoantigen. Advances in understanding of innate immune mechanisms continue to lead to new putative targets for vaccine adjuvants and for immunotherapy. Simultaneously, progress is being made in the identification of in vitro correlates of clinical adjuvanticity, which allows the design of in vitro screening assays to discover novel adjuvant candidates in a systematic manner. The gaps that need to be addressed by new adjuvants include improvements to existing vaccines (e.g., the acellular pertussis vaccine, influenza, etc), and development of vaccines for: emerging and re-emerging threats (e.g., Coronaviruses, Enteroviruses, MRSE); special populations that respond poorly to existing vaccines (e.g., elderly, newborns/infants, immunosuppressed patients); or treatment/prevention of immune-mediated diseases (e.g., allergic rhinitis, asthma, food allergy, autoimmunity, transplant rejection). For example, the combination of putative tolerogenic adjuvants with allergen immunotherapy should aim at accelerating tolerance induction, increasing the magnitude of tolerance and decreasing treatment duration. For transplantation, donor-derived major and minor histocompatibility molecules that are not matched between donor and recipient may be formulated with novel tolerogenic adjuvants and used to induce transplant tolerance in the recipient. In addition to the need for novel adjuvants, there is a need to identify the most suitable adjuvant for a novel vaccine candidate. Adjuvants are frequently selected purely based on availability, rather than as a result of systematic side-by-side comparisons of candidates to determine which adjuvant-antigen combination induces the most desirable response. This solicitation supports studies to down-select a lead adjuvant-antigen combination to generate the data for a subsequent vaccine development effort.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 2-3 Budget (total costs): Phase I: $300,000 for up to one year; Phase II: $1,500,000 for up to 3 years Background There is an urgent need for new therapeutics products for treating pulmonary diseases caused by mycobacteria. These include tuberculosis (TB), caused by Mycobacterium tuberculosis, and pulmonary infections caused by non-tuberculous mycobacterium (NTM) species such as Mycobacterium abscessus or Mycobacterium avium. In recent years, there has been an increase in the number of registered clinical studies focused on the therapeutic use of bacteriophage (i.e. “phage”) and there have been several published clinical studies using laboratory phage reagents compassionately and with sometimes beneficial individual results. However, currently there are no mycobacteria-directed, therapeutic phage products in commercial development. Additional research and development are needed to advance new phage therapies to clinical trial testing.
Fast-Track proposals will be accepted. Direct-to-Phase II proposals will NOT be accepted. Number of anticipated awards: 2-3 Budget (total costs): Phase I: $300,000 for up to one year; Phase II: $1,500,000 for up to 3 years. Background Diagnostics in current use for malaria and specific NTDs (visceral leishmaniasis, lymphatic filariasis, onchocerciasis, schistosomiasis) do not meet the sensitivity and/or specificity thresholds required to achieve elimination goals. As diseases Page 117 approach elimination, decreased prevalence and intensity of infection require highly sensitive and specific diagnostics to ensure that all true cases are detected and treated, to avoid false negatives, and to manage the larger volume of samples that must be tested to confirm interruption of transmission. NTDs that are targeted by mass drug administration (MDA), such as lymphatic filariasis, onchocerciasis and schistosomiasis, require the use of diagnostics that are increasingly sensitive and specific when progressing from monitoring, to MDA-stopping, to post-elimination surveillance. For P. falciparum malaria, rapid diagnostic tests (RDTs) in current use lack sensitivity to detect the asymptomatic reservoir, which contributes to onward transmission. Additionally, some P. falciparum isolates have deleted the targets (histidine-rich protein genes pfhrp2/3) of the most sensitive RDTs, therefore escaping detection all together. Assays to detect non-falciparum malaria species also lack needed sensitivity. Disease elimination goals are further threatened by an insufficient pipeline of novel, validated diagnostic biomarkers.
(Direct to Phase II proposals will not be accepted) (Fast-Track proposals will be accepted) Number of anticipated awards: 1-2 Budget (total costs): Phase I: $300,000 for up to 1 year; Phase II: $1,500,000 for up to 3 years Page 118 Background Over 60 million people in the U.S. have genital herpes which is caused by infection with herpes simplex virus type 1 or 2 (HSV-1, HSV-2). The WHO’s 2021 global progress report indicates that more than 500 million people are infected with HSV globally. Currently, genital herpes can be diagnosed based on clinical manifestations of the disease combined with very accurate nucleic acid tests to detect the virus in lesions or on mucosal surfaces. However, many patients with genital herpes are asymptomatic and do not shed virus and therefore a serological test is used to confirm HSV infection. Most available serologic tests, based on the enzyme-linked immunosorbent assay, are efficient but have very high false positive rates with positive predictive values (PPV) of about 50% or lower. Serologic tests for HSV infection using the Western blot have been shown to have high PPV and can readily distinguish HSV-1 and HSV-2. However, the Western blot is not suitable for wide-scale use in clinical settings.
Fast-Track proposals will be accepted Direct-to-Phase II proposals will be accepted Number of anticipated awards: 2-3 Budget (total costs): Phase I: $300,000 for up to one year; Phase II: $1,500,000 for up to 3 years Background Injectable benzathine penicillin (BPG) is currently the only CDC-recommended first line therapy for treatment of infection with Treponema pallidum (syphilis) in all populations, including pregnant persons and infants. There are several barriers that limit use of BPG: • BPG is not available orally. • Only a limited number of facilities in a single country currently manufacture the raw active pharmaceutical ingredient which means the supply chain can easily be disrupted and shortages of BPG are common in the US and globally. Page 119 • BPG may sometimes not be administered at lower-level facilities or by non-physician medical staff out of fear of anaphylactic reactions that might require referral to a tertiary care center. Alternative therapies to BPG that address some of these barriers are urgently needed, as acquired and congenital syphilis rates are increasing rapidly. WHO estimates over six million persons per year are infected with syphilis, and many more are treated presumptively for syphilis. Clinicians and health systems are eager for BPG alternatives. Recent advances in the ability to culture T. pallidum mean that identification of alternatives to BPG is now more feasible than has been possible in the past.
Fast Track Proposals will be accepted. Direct-to-Phase II will be accepted. Number of anticipated awards: 1-3 Budget (total costs): Phase I: $ 300,000 for up to 1 year. Phase II: $ 1.5 million for up to 3 years. Page 120 Background The ability of innovative data science approaches to accelerate research on infectious and immune-mediated diseases highly depends on the availability of high-quality, machine-actionable data compliant with the FAIR (Findable, Accessible, Interoperable, and Reusable) guiding principles. A central tenet of the FAIR principles is rich, standardized, and interoperable metadata in machine-actionable format. FAIR compliant metadata can accelerate discovery of new knowledge through automated, machine-assisted methods, such as automated reasoning, machine-learning, and artificial intelligence. Different types of metadata are used by the community, including descriptive, structural, administrative, reference, and other metadata. The term metadata is also used by some to denote patient phenotypic information related to clinical specimens. In some cases, the distinction between metadata and data can be unclear as both data and metadata represent knowledge and information about entities and relationships. This contract topic focuses on descriptive and administrative metadata that enable the discovery of data for secondary use, including information about the creators, data provenance, access and use permissions, data content and methods used to collect the data, etc. Creating FAIR-compliant metadata is time-consuming and requires specialized skills. As a result, metadata is often incomplete, of limited quality, and rarely machine actionable. There is an urgent need for (semi-)automated approaches and technologies that help researchers and data curators with creating new and augmenting existing metadata. Automated approaches should create, and augment metadata based on widely used and well documented ontologies and standard vocabularies, to enable computer algorithms to interpret the metadata. More efficient approaches for creating and augmenting metadata will also help researchers to comply with the growing demand for FAIR data sharing as recommended by new data sharing policies by publishers and funding agencies, such as the new NIH Data Management and Sharing Policy.
Fast Track Proposals will be accepted. Direct-to-Phase II will be accepted. Number of anticipated awards: 1-3 Budget (total costs): Phase I: $ 300,000 for up to 1 year. Phase II: $ 1.5 million for up to 3 years. Background Scientific research produces more data and knowledge than ever before and it is becoming increasingly challenging for researchers to digest and analyze the data to derive new knowledge and insights. Increasingly, researchers will depend on computer algorithms to assist them with data analysis and with the discovery of new information and knowledge. For example, during the COVID-19 pandemic, the discrepancy between the speed of data generation and the ability to digest and analyze the data was acutely illustrated with almost 25 thousand new papers published in the first half of 20201 . The public health response against emerging pandemic threats and the treatment and control of existing infectious- and immune-mediated diseases requires the continuous analysis of newly emerging data, information, and knowledge; a task that is increasingly complicated by the large volume of data that is being generated. Knowledge graphs (KG’s) have emerged as a prominent technology for data representation and integration and are widely used in the industry. KG’s represent information about entities and relationships between entities in a semantically rich way that enables efficient data retrieval and analysis by computational algorithms, such as automated reasoners and AI, and have shown great promise for data management and knowledge discovery. A familiar use case for KG’s in the scientific domain is for the analysis of collaborations between authors based on published papers, for the exploration of pathways in molecular biology, and for drug repurposing. A major bottleneck for leveraging KG’s for biomedical research and discovery is the difficulty to represent data and knowledge into a KG-compatible format. Many biomedical data are stored in formats that are not compatible with KG’s, such as spreadsheets and databases, and cannot be used by automated reasoners and other computer-assisted knowledge discovery methods, unless these data are represented in a KG format. Given the complexity of accurately representing semantic information on scientific data and related methods, automated methods and software will be essential to scale up the amount of data on infectious- and immune-mediated diseases available in KG’s for accelerating scientific discovery
Budget and number of awards: Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted Number of anticipated awards: 1 Phase I, 1 Phase II Budget (total costs per award): Phase I: $350,000 for 12 months; Phase II: $3,000,000 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 Hyperpolarized carbon 13 (13C) MRI is a rapid, noninvasive, and pathway-specific investigation of dynamic metabolic and physiologic processes. This emerging molecular imaging enables real-time in vivo investigations of metabolism in a variety of diseases, including cancer (13C-ketogutarate, 13C-pyruvate), cardiovascular disease (15N-metronidazole), lung fibrosis (15Nisoniazide), inflammation (13C-NAcetyl cysteine), and diseases of the liver and kidney. Current hyperpolarized imaging with dissolution DNP and superconducting MRI scanners is very powerful, but experiments are burdensome, slow, and expensive. The SABRE (Signal Amplification by Reversible Exchange) approach allows transfer of the 100% pure singlet spin order of parahydrogen (para-H2) into a target molecule with impressive levels of polarization, short signal build-up times, low cost, and scalability making SABRE promising modalities for studying metabolism in vivo using MR techniques. This method requires the design, implementation and fabrication of a dedicated clinical instrument.
(Fast-Track and Direct to Phase 2 proposals will not be accepted) Number of anticipated awards: 1-3 Budget (total costs): Phase I: $300,000 for up to 1 year; Phase II: $2,000,000 for up to 2 years. Background According to the Centers for Disease Control and Prevention (CDC), HIV remains a significant public health challenge both in the United States and globally. In the United States, an estimated 1.2 million people are currently living with HIV and globally over 38 million people are affected by HIV. Antiretroviral therapy (ART) has transformed the management of HIV infection, significantly improving patient outcomes and altering the trajectory of people living with HIV. ART involves the use of combinations of antiretroviral drugs that target different stages of the HIV life cycle, suppressing viral replication and restoring immune function. The goal of ART is to achieve and maintain viral suppression, defined as a decrease in HIV RNA levels to undetectable levels in the blood. Viral suppression not only benefits the individual by preserving immune function and reducing the risk of opportunistic infections but also has public health implications by reducing the risk of HIV transmission. However, the effectiveness of ART is highly dependent on consistent medication adherence and monitoring of viral load. One of the needs for people with HIV to maintain sustained viral suppression and reduce HIV incidence in the US are point-of-care assays that can measure viral load and adherence to ART.
(Fast-Track and Direct to Phase 2 proposals will not be accepted) Number of anticipated awards: 1-3 Budget (total costs): Phase I: $300,000 for up to 1 year; Phase II: $2,000,000 for up to 2 years. Background Central Nervous System complications associated with HIV continues to persist in people with HIV (PWH) despite effective Page 128 Antiretroviral therapy (ART). Although excellent virologic control in the periphery and brain has been achieved, CNS disease (NeuroHIV) including neurologic, neurocognitive, and mental health problems are observed. Considerable gaps exist in our understanding of pathogenesis of CNS disease associated with HIV. Basic research in the NeuroHIV field has primarily focused on modeling neuronal damage in the context of active viral replication or the impact of HIV proteins such as Tat/gp120, with endpoints such as encephalitis and neuronal death. However, the CNS disease outcomes observed in the pre-ART era, such as atrophy and encephalitis, are not apparent in the current era. Other mechanisms, such as neuroimmune dysfunction, legacy effects of long-term ART medications and chronic inflammation, in the context of co-morbidities, may play a role in the observed HIVassociated CNS disease outcomes. Other potential unexplored mechanisms and pathways may drive the development of CNS disease, such as subtle neuro-metabolic changes, alterations in neuronal circuitry, or altered signal transmission. There is a need for novel model systems that will help better understand the Immune-Central Nervous System (CNS) interactions in the context of HIV.
Phase I SBIR proposals will be accepted. Fast-Track proposals will not be accepted. Phase I clinical trials will not be accepted. Number of anticipated awards: 1 Budget (total costs): Phase I up to $243,500 for up to 6 months; Phase II of up to $1,927,828 and a Phase II duration of up to 2 years. PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Background Point of care diagnostic assays in outbreak or response settings are crucial for rapid detection of infection and determining appropriate next steps (isolation, contact tracing, treatment, etc.). Additionally, it’s critical to develop new diagnostics to meet evolving public health needs as testing availability can be impacted by competition for limited reagents/consumables during an outbreak. The development of a unique field-deployable diagnostic assay using non-overlapping reagents will address both preparedness concerns to improve response in the event of a Variola virus (VARV- the causative agent of smallpox) bioterror event, as well as monkeypox virus (MPXV) which continues to be an expanding global health threat. The SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) test will need to incorporate Page 130 multi-pathogen panels and be adjusted to various levels of specificity based on oligonucleotide sequences. These technologies have been documented to work with a variety of pathogens. Approaches for assay design could be two targets, one specific for MPXV and another for non-MPXV pathogens.
Phase I SBIR proposals will be accepted. Fast-Track proposals will not be accepted. Phase I clinical trials will not be accepted. Number of anticipated awards: 2 Budget (total costs): Phase I: up to $243,500 for up to 6 months; Phase II of up to $1,972,828 and a Phase II duration of up to 2 years. PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Background An estimated 13 billion pharmacy visits occur per year, which is more than 10 times the annual number of patient contacts with all other primary care providers combined. Public health partnerships with pharmacies can provide new access points for sexually transmitted infections (STIs) and HIV services. More than ever, we saw this need during the COVID-19 pandemic when many public health clinics had to reduce hours or suspend services. In recent years, pharmacy practices have embraced more patient-centered care approaches and trained providers to deliver counseling, point-of-care (POC) or rapid tests, administer injectables, vaccines/immunizations, and offer clinical referrals for a variety of health conditions. Opportunities exist for public health departments to strengthen partnerships with these accessible and trusted health professionals. Pharmacists are taking on a more significant role in delivering sexual health services in conjunction with health departments. For example, local health departments have been funded to partner with local pharmacies to offer expanded STD/HIV services (including PrEP) in their communities. Both entities have expressed a need to have software capabilities that would allow health departments and partnering pharmacies (and potentially patients) to all see testing and treatment info for a particular individual as close to real time as possible. However, there is no interoperable electronic system that enables the pharmacy and health department to securely transmit data and innovation is needed to ensure collaborative care communication, case and disease management, and reporting (among other things) between health departments and pharmacy practices. As part of the Pharmacist eCare Plan Initiative, approximately 20 pharmacy management with embedded clinical documentation systems exist. These software solutions are innovative tools that enable collaborative care communication, case and disease management, treatment, and can support workflows, billing, automation, and compliance. Similar software with real-time detection capabilities has been developed to help monitor prescription drugs for to detect opioid substance misuse and detect outbreaks. Software solutions exist, but enhancements are needed to ensure successful collaboration between the two entities. The software would need to allow for a pharmacist or any provider to be able to document treatment and close the loop. The following are some potential scenarios where this type of collaborative communication would be beneficial: • Pharmacist should be able to send STI test results to the health department (pharmacist ordered under a collaborative practice agreement (CPA) or standing order) – this would be a scenario where rapid STI POC tests were available at the pharmacy. • Pharmacist and health department are both able to see patient test results from self-collection kit (where the health department is working with 3rd party lab vendor) Pharmacist providing oral or injectable treatment can document that treatment was administered. This could be extended to include expedited partner therapy [EPT] patients, too
Phase I SBIR proposals will be accepted. Fast-track proposals will not be accepted. Phase I clinical trials will not be accepted. Number of anticipated awards: 1 Budget (total costs): Phase I up to $243,500 for up to 6 months; Phase II of up to $1,972,828 and a Phase II duration of up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Page 133 Background Electronic health record (EHR) technologies are increasingly promoted as innovative platforms to streamline preventive health programs and improve compliance with clinical guidelines. EHR alerts have been created to streamline hepatitis C virus (HCV) and HIV screening processes in primary care settings and to develop predictive models that identify patients at a high risk of HIV acquisition who may benefit from pre-exposure prophylaxis (PrEP). There is a lack of such functionality to identify patients with HIV not in care-to our knowledge; few medical centers have any “homegrown” electronic medical record algorithms in place to identify persons lost to HIV care. This SBIR project seeks to utilize EHR data that are typically available in EHR systems to develop a “core” algorithm that can be used in multiple healthcare systems to identify patients newly and previously diagnosed with HIV and categorize their linkage to care, antiretroviral (ART) prescriptions, retention in care, and viral suppression status. Interoperability of different EHR systems with regards to this functionality will also be explored to improve generalizability and functionality throughout the country. Persons living with HIV may not be engaged in HIV care but may continue to access the health care system in other settings such as other primary care or specialty clinics, emergency rooms, urgent care, and inpatient admissions. Such access can provide opportunities to reengage them to HIV care. The data derived from the algorithm could be displayed on an EHR dashboard which would be accessible in any clinical setting affiliated with a healthcare system. Healthcare providers could utilize the information displayed to immediately identify a patient as not-in-care, and initiate care coordination and re-engagement efforts. Alternatively, a health care system could query its EHR data at regular intervals to identify patients who may have fallen out of care.
Phase I SBIR proposals will be accepted. Fast-track proposals will not be accepted. Phase I clinical trials will not be accepted. Number of anticipated awards: 1 Budget (total costs): Phase I up to $243,500 for up to 6 months; Phase II of up to $1,972,828 and a Phase II duration of up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Background Hepatitis C virus (HCV) infection is a major global health problem and chronic HCV infection is a leading cause of cirrhosis and liver cancer. HCV infects an estimated 2.4 million people in the U.S. and 58 million people, globally. Effective and well-tolerated direct acting antiviral (DAA) drugs are available for the treatment of HCV infections and the World Health Organization (WHO) has established elimination goals of 90% reductions in the number of new HCV cases and 65% reductions in deaths associated with HCV infection by the year 2030. Achievement of these goals will require expanding access to HCV testing as only 20% of current infections have been globally diagnosed. Current HCV infections are diagnosed by the detection of either circulating HCV RNA or HCV core antigen in a person’s blood. HCV diagnostic testing methods often have high costs, slow turnaround times, and need to be performed in a laboratory, which lead to access problems and the potential to lose patients to health care provider follow up after a positive diagnosis. Ideally, HCV diagnosis would occur at the point of care while the patient waits, allowing for immediate linkage to care and treatment in people with HCV infections. Currently there are no point-of-care tests for the detection of HCV RNA available in the US. The development of a simple and inexpensive device that can perform nucleic acid extraction and detection workflows with minimal user intervention would allow for the diagnosis of HCV infection at the point of care, and greatly expand access to HCV diagnostic testing.
Phase I SBIR proposals will be accepted. Fast-track proposals will not be accepted. Phase I clinical trials will not be accepted. Number of anticipated awards: 1 Budget (total costs): Phase I up to $243,500 for up to 6 months; Phase II of up to $1,972,828 and a Phase II duration of up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Background Acute infections of measles, mumps, rubella, and varicella continue to place an undue burden on public health systems despite the availability of vaccines for all four pathogens. Over 100,000 deaths are still attributed to measles infection globally each year, and rubella Page 136 infection continues to cause over 100,000 children to be born with congenital rubella syndrome annually – mostly in developing countries. Sporadic mumps and varicella outbreaks – ranging from tens to thousands of cases – continue to occur in the United States. Strong surveillance systems are necessary for detecting sporadic cases of disease, preventing disease outbreaks, and maintaining disease elimination status. An essential component of surveillance is laboratory testing to rapidly confirm the presence of a specific pathogen and to help guide the public health response.
Phase I SBIR proposals will be accepted. Fast-track proposals will not be accepted. Phase I clinical trials will not be accepted. Number of anticipated awards: 1 Budget (total costs): Phase I up to $243,500 for up to 6 months; Phase II of up to $1,972,828 and a Phase II duration of up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Background Acute infections of measles and rubella continue to place an undue burden on public health systems, especially in countries with nascent vaccine programs or logistical challenges for achieving high levels of vaccination coverage or disease surveillance. Over 100,000 deaths are still attributed to measles infection globally each year, and rubella infection continues to cause over 100,000 children to be born with congenital rubella syndrome annually. Sporadic importations of measles and rubella continue to occur in the United States, with measles importations occasionally seeding large-scale outbreaks among susceptible communities. Strong surveillance systems are necessary for detecting sporadic cases of disease, preventing disease outbreaks, and maintaining disease elimination status. An essential component of surveillance is rapid confirmation of a specific pathogen to help guide the public health response.