DRAFT Solicitation ARPA 6.18 Amendment2.docx

[DRAFT] PROGRAM SOLICITATION

Sections 1, 3, 9

47QFCA24R0036

SBIR/STTR Phase I and II in support of:

ADVANCED RESEARCH PROJECTS AGENCY FOR HEALTH (ARPA-H)

This is a Small Business Innovation Research (SBIR)/Small Business Technology Transfer (STTR) Solicitation in accordance with SBIR/STTR Policy Directive (May 3, 2023).

Issued by:

U.S General Services Administration (GSA) Federal Acquisition Service (FAS) Assisted Acquisition Services (AAS) Innovation

(June X, 2024 )

Controlled by: Suzanne.kixmiller@gsa.gov

IMPORTANT

Please read the entire solicitation carefully prior to submitting questions and/or a proposal.

Only Procurement contracts will be awarded resulting from this solicitation; Grants will not be awarded.

ARPA-H Webinar: All potential offerors are encouraged to attend the ARPA-H Webinar for this solicitation. The webinar will highlight important aspects of the SBIR/STTR Program, ARPA-H’s mission, Topic Areas, and important elements of this solicitation. The Webinar is being held on TBD. Please see the webinar specific announcement for more details.

Deadline for Questions: Solicitation questions must be received by TBD . All questions shall be submitted via email to GSA-ARPA-H-SBIR@gsa.gov and in accordance with Section X of this Solicitation.

Deadline for Receipt: All written proposals shall be received by TBD. The offeror shall submit its written proposal via email to GSA-ARPA-H-SBIR@gsa.gov in accordance with Section X of this Solicitation. Hard copies/Paper proposals will not be accepted.

All potential offerors, new to the Small Business Administration’s SBIR/STTR program, are highly encouraged to read the SBIR/STTR Policy Directive issued by the Small Business Administration with special attention directed to the inclusion of a new proposal requirements found in Section X – Disclosure of Foreign Relationships. The SBIR/STTR Policy Directive can be found here: https://www.sbir.gov/sites/default/files/SBA%20SBIR_STTR_POLICY_DIRECTIVE_May2023.pdf

1 Program Description

1.1 Introduction

The U.S. General Services Administration (GSA), Federal Acquisition Service (FAS), Assisted Acquisition Service - Innovation (AAS) in direct support of The Advanced Research Projects Agency for Health (ARPA-H) invites small business concerns (SBCs) to submit innovative research proposals under this Small Business Innovation Research (SBIR)/Small Business Technology Transfer (STTR) Contract Solicitation. The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are highly competitive programs that encourage domestic small businesses to engage in Federal Research/Research and Development (R/R&D) with the potential for commercialization. Through a competitive awards-based program, SBIR and STTR enable small businesses to explore their technological potential and provide the incentive to profit from its commercialization. By including qualified small businesses in the nation's R&D arena, high-tech innovation is stimulated, and the United States gains entrepreneurial spirit as it meets its specific research and development needs. Firms with the capability to conduct research and development (R&D) in any of the health-related topic areas described in Section X, and to commercialize the results of that innovative R&D, are encouraged to participate.

This solicitation contains opportunities to submit a proposal under a variety of different Topics, which are summarized in Section X below. AAS in direct support of ARPA-H is under no obligation to fund any proposals or any specific number of proposals in a given topic. It may also elect to fund several or none of the proposed approaches to a given topic. All awards are subject to the availability of funds. The Government is not responsible for any monies expended by the offeror before award of any contract. Only Procurement contracts will be awarded resulting from this solicitation; Grants will not be awarded.

The mission of ARPA-H is to accelerate better health outcomes for everyone by supporting the development of high-impact solutions to society’s most challenging health problems. Awardees will develop groundbreaking new ways to tackle health-related challenges through high potential, high-impact biomedical and health research. With a scope spanning the molecular to the societal, ARPA-H seeks SBIR/STTR proposals that aim to rapidly achieve better health outcomes across patient populations, communities, disease, and health conditions, including in support of the Cancer Moonshot. Proposals are expected to use innovative approaches to enable revolutionary advances in science, technology, or systems. Specifically excluded are proposals that represent an evolutionary or incremental advance in the current state of the art. Additionally, proposals directed towards policy changes, traditional education and training, or center coordination and construction of physical infrastructure are outside the scope of the ARPA-H mission.

1.2 Program Background

The basic design of the ARPA-H SBIR/STTR program is in accordance with the Small Business Administration (SBA) SBIR/STTR Program Policy Directive dated May 3, 2023. This SBIR/STTR solicitation strives to encourage scientific and technical innovation in areas specifically identified by ARPA-H. The potential contributions of the proposed effort are relevant to health outcomes for all Americans. Specifically, ARPA-H’s mission is to benefit the health of all Americans by catalyzing health breakthroughs that cannot readily be accomplished through traditional research or commercial activity. The guidelines presented in this solicitation reflect the flexibility provided in the SBIR/STTR Policy Directive to encourage proposals based on scientific and technical approaches most likely to yield results important to ARPA-H and to the private sector.

1.3 Phased Program

1.3.1 SBIR/STTR Phased Program

The SBIR/STTR program consists of three separate phases as detailed below. Note: This solicitation is not accepting Phase III proposals. Please refer to the individual topics above as to which phase is being considered.

Phase I: Feasibility The objective of Phase I is to determine the scientific or technical feasibility and commercial merit of the proposed research or R&D efforts.

Phase II: Full R/R&D Effort The objective of Phase II is to further develop the research or R&D efforts initiated in Phase I. If your project has already demonstrated feasibility, you may prepare a Direct-to-Phase II proposal and begin your Federal SBIR/STTR award at Phase II.

Phase III: Commercialization stage without SBIR/STTR funds Phase III refers to work that derives from, extends, or completes an effort made under prior SBIR/STTR Funding Agreements, but is funded by sources other than the SBIR/STTR programs. Each of the following types of activity constitutes SBIR/STTR Phase III work:

(i) Commercial application of SBIR/STTR funded R/R&D that is financed by non-Federal sources of capital.

(ii) SBIR/STTR derived products or services intended for use by the Federal Government, funded by non- SBIR/STTR sources of Federal funding.

(iii) Continuation of SBIR/STTR work, funded by non-SBIR/STTR sources of Federal funding including R/R&D. For HHS SBIR/STTR projects, Phase III is primary financed by non-Federal sources of capital.

The competition for SBIR Phase I and Phase II awards satisfies the competition requirements of the Competition in Contracting Act. Therefore, an agency that wishes to fund an SBIR project beyond the Phase II and the project is derived from, extends, or logically concludes efforts performed under prior SBIR funding agreements may award a Phase III contract on a sole source basis.

1) Phase I Proposals As part of this solicitation, the Government may award a Phase I contract to an offeror that believes it has a concept that might provide a solution to one of the Topics listed in section X, but has not built a prototype and tested its technical feasibility. The purpose of the Phase I contract will be to determine the scientific or technical feasibility and commercial merit of the proposed research or R&D effort.

2) Direct to Phase II Proposals As part of this solicitation, the Government may award a Direct to Phase II contract to an offeror whose project has already demonstrated feasibility, but the offeror has not received a Phase I SBIR or STTR award. The offeror can apply for a Direct to Phase II award and bypass Phase I. Offerors applying for Direct to Phase II awards must have already built a technology prototype and tested its technical feasibility. The purpose of the Phase II R&D contract will be to test the functional viability of the prototype according to scientific methods and potential for commercial development. Refer to Section X List of Topics for notation of Topics allowing Direct to Phase II proposals.

3) Fast Track Proposals As part of this solicitation, the Government may award a Fast Track contract to an offeror whose Fast Track proposal may result in an initial award for a Phase I contract with a contractual option that the Government may exercise to continue the effort into Phase II without the need to re-solicit the topic. This mechanism allows for streamlined processes that have the potential to significantly minimize the funding gap between Phase I and Phase II. However, it shall be noted the Government is not obligated to fund the Phase II contractual option. The awardee may only start performing the Phase II effort unless and until the Government exercises that option.

If a Topic notes that Fast Track proposals will be accepted, a Phase I proposal and a Phase II proposal may be submitted simultaneously. As described in Section X “Proposal Instructions,” a Fast Track submission consists of one complete Phase I proposal and one complete Phase II proposal, separately paginated. The Phase I proposal and Phase II proposal will be separately evaluated as set forth in Section X “Technical Evaluation Criteria.”

2 CERTIFICATIONS [Placeholder]

It is important to read and follow the proposal preparation instructions carefully, which are outlined below. Pay special attention to the requirements concerning Human Subjects and use of Vertebrate Animals if your project will encompass either of item.

3.2 Proposal Instructions

A complete Phase I proposal consists of a Technical Proposal (Appendix A) and a Business Proposal (Appendix B).

A complete Phase II proposal consists of a Technical Proposal (Appendix C) and a Business Proposal (Appendix D). Each proposal will be submitted via the application template in the corresponding Appendix.

A complete Fast-Track proposal consists of both a complete Phase I proposal and a separate, complete Phase II proposal. To identify the submission as a Fast Track proposal, check the box marked “Yes,” next to the words “Fast Track Proposal” shown on the Phase I and Phase II applications. The Phase I proposal and the Phase II proposal in a Fast Track submission will be evaluated and scored individually. However, if a Phase I proposal is evaluated and found to be unacceptable, the corresponding Phase II Fast Track proposal will not be evaluated.

Please see below for additional proposal submission instructions.

3.3 Human Subjects and Clinical Trials Information Form and Attachments

Appendix A.1. is required for every proposal submission. If your proposal does not involve Human Subjects or Clinical Trials, you must still note this on the form and submit the form. If applicable, Appendix A.2. – Study Record must be attached to Appendix A.1.

· APPENDIX A.1 — HUMAN SUBJECTS AND CLINICAL TRIALS INFORMATION FORM

Instructions to complete this form can be found at: https://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixH.1.pdf

· APPENDIX A.2. — STUDY RECORD, ATTACHMENT TO HUMAN SUBJECTS AND CLINICAL TRIALS INFORMATION FORM

For SBIR or STTR Phase I and II Technical Proposals, the Human Subjects and Clinical Trials Information form and its attachments (Appendix A.1., and, if applicable, Appendix A.2.) are excluded from Appendix A and are to be submitted as a separate document from the Technical Proposal. Ensure proposal submission specifically identifies the Human Subjects and Clinical Trials Information Form and its attachments, separate from the Technical Proposal.

3.4 Business Proposal

The award will result in a Firm-Fixed Price (FFP) contract type. The offeror shall fully support all proposed costs/prices. The offeror’s proposal is presumed to represent the offeror’s best efforts in response to the solicitation. Any inconsistency, whether real or apparent, between promised performance and cost/price, shall be explained in the proposal. The Business Proposal includes the Pricing Proposal and Summary of Related Activities, as well as the following:

1. SBIR Application VCOC Certification, if applicable. See SECTION X – PROPOSAL FUNDAMENTALS to determine if this applies to your organization. If applicable, please complete this form in Appendix B - Business Proposal.

2. Proof of Registration in the SBA Company Registry is required at proposal submission. Refer to SECTION X – PROPOSAL FUNDAMENTALS for directions. All applicants to the SBIR and STTR programs are required to register at the SBA Company Registry prior to proposal submission and attach proof of registration to the Business Proposal.

3. The offeror shall provide a statement that it has been registered in ASSIST and that all information in ASSIST is up to date (assist.gsa.gov/assist-web/registration/contractor/search).

3.4.1 Content of the Business Proposal (Item Two)

Complete the Pricing Item in the format shown in the Pricing Proposal. Some items in the Pricing Proposal may not apply to the proposed project. If that is the case, there is no need to provide information on each and every item. What matters is that enough information be provided to allow us to understand how you plan to use the requested funds if a contract is awarded.

· List all key personnel by name as well as by number of hours dedicated to the project as direct labor.

· While special tooling and test equipment and material cost may be included under Phase I, the inclusion of equipment and material will be carefully reviewed relative to need and appropriateness for the work proposed. The purchase of special tooling and test equipment must, in the opinion of the AAS Contracting Officer, be advantageous to the Government and should be related directly to the specific topic. These may include such items as innovative instrumentation or automatic test equipment. Title to property furnished by the Government or acquired with Government funds will be vested with the HHS Component; unless it is determined that transfer of title to the contractor would be more cost effective than recovery of the equipment by the HHS Component.

· Cost for travel funds must be justified and related to the needs of the project. Describe reason for travel, location of travel, number of travelers, and number of nights of lodging in the Description fields in Appendix C.

· Cost sharing is permitted for proposals under this solicitation; however, cost sharing is not required, nor will it be an evaluation factor in the consideration of a Phase I proposal.

· All subcontractor costs and consultant costs must be detailed at the same level as prime contractor costs in regard to labor, travel, equipment, etc. Provide detailed substantiation of subcontractor costs in your cost proposal. Enter this information in the Explanatory Material section of the on-line cost proposal form.

· Policy on Threshold for Negotiation of General and Administrative (G&A)/Indirect Costs (IDC) Rates for SBIR proposals – SBIR offerors who propose a G&A/IDC rate of 40 percent of total direct costs or less will not be required to negotiate Final Indirect Rates with the NIH Division of Financial Advisory Services (DFAS), or other cognizant auditing agency. However, awarding AAS Contracting Officers may require offerors to document how they calculated their IDC rate(s) in order to determine that these costs are fair and reasonable. Furthermore, the Division of Financial Advisory Services (DFAS) will retain the authority to require well-documented proposals for G&A/IDC rates on an ad hoc basis. If the SBC has a currently effective negotiated indirect cost rate(s) with a Federal agency, such rate(s) shall be used when calculating proposed G&A/IDC costs for a proposal. (However, the rate(s) must be adjusted for IR&D expenses, which are not allowable under HHS awards.)

SBCs are reminded that only actual G&A/IDC costs may be charged to projects. If awarded at a rate of 40 percent or less of total direct costs, the rate used to charge actual G&A/ID costs to projects cannot exceed the awarded rate unless the SBC negotiates an indirect cost rate(s) with DFAS.

· Offerors submitting proposals may include the amount of up to $6,500 per year for a Phase I and up to $50,000 per Phase II project (across all years) for technical assistance as discussed and outlined in Section X State Assistance and Technical Assistance of SECTION X – PROPOSAL FUNDAMENTALS of the solicitation. Include a detailed description of the technical or business assistance that your vendor/s will provide, including the name of the vendor/s and the expected benefits and results of the technical or business assistance provided. A letter of support from the vendor describing their qualifications and services to be provided is recommended.

· Prior, Current, or Pending Support of Similar Proposals or Awards.

If a proposal submitted in response to this solicitation is for essentially equivalent work (as defined in this solicitation) as another proposal that was funded, is now being funded, or is pending with a federal agency, you must make the appropriate certification in Appendix A, as well as provide the following information in Appendix C:

1) Name and address of the Federal Agency(s) or HHS Component, to which a proposal was submitted, will be submitted, or from which an award is expected or has been received.

2) Date of proposal submission or date of award.

3) Title of proposal.

4) Name and title of principal investigator for each proposal submitted or award received.

5) Title, number, and date of solicitation(s) under which the proposal was submitted, will be submitted, or under which award is expected or has been received.

6) If award was received, state contract number.

7) Specify the applicable topics for each SBIR/STTR proposal submitted or award received.

4. Method of Selection and Evaluation [Placeholder]

5. Considerations [Placeholder]

6. Submissions of Proposal [Placeholder]

7. Scientific and Technical Information [Placeholder]

8. Submission Forms [Placeholder]

9. SBIR/STTR Research Topics

This solicitation invites proposals in the following areas. The detailed project descriptions can be found on the following pages. Each topic description contains “exams” meant to signal metrics and expectations for each topic area, and to assist offerors in developing a proposal for the topic area.

· ARPA-H 01 Ambulatory Edema Monitor

· ARPA-H 02 Predictive Language Models for Cognitive Disability Adaptive Communication Tools

· ARPA-H 03 Cell and Gene Therapy Process Analytical Technology and Quality Control Testing

· ARPA-H 04 Wearable Cell sorting and Gene Delivery Systems

· ARPA-H 05 Precision Brain Targeting: non-invasive delivery at the right place and time

· ARPA-H 06 NutriTech: Revolutionizing Personalized Food as Medicine

· ARPA-H 07 Clinic-ready Imaging Devices and Protocols for Visualizing the Inner Ear with High Accuracy

· ARPA-H 08 Advanced Continuously Wearable Blood Pressure Monitoring Technologies ARPA-H 01: Ambulatory Edema Monitor Only Direct to Phase II proposals will be accepted. This topic is open to SBIR or STTR.

Number of anticipated awards: 2-3 Budget (total costs, per award): Direct to Phase II: up to $3,500,000.00 for 1 to 3 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 will not be funded.

Background/Introduction:

The human heart pumps five liters of blood daily throughout the body, delivering oxygen and nutrients to cells and tissues. Approximately 90% returns through our veins and back to the heart, while 10% leaks out into our tissues via small blood capillaries into a space between our cells known as the interstitial space. It is here in interstitial space that our lymphatic system comes into play. The leaked fluid must be collected by the lymphatic system, a one-way system of vessels starting with terminal lymphatics and progressing through to larger lymphatic vessels to lymph nodes where protein-rich fluid is filtered to remove waste and pathogens. The remaining lymph moves up and into the thoracic duct, emptying back into the venous circulation.

The key here is that the lymphatic system is the ONLY body system that removes fluid from our tissues. If our lymphatic system is not working properly, then fluid will accumulate, causing edema — a swelling that occurs when too much fluid is trapped in the body's tissues and is unable to drain back into circulation.

Edema can affect any part of the body. Any insult to our lymphatic system, be it a medication, pregnancy (mechanical or hormonal), or a disease such as congestive heart failure (CHF), kidney disease, venous insufficiency, or cirrhosis of the liver, can cause edema.

There is no current means of quantitatively monitoring edema. Despite all our technical marvels, the only tool providers use to measure and monitor edema is literally a tape measure and/or pressing a finger into the skin of a patient’s extremity looking for “pitting”.

Early detection of edema will improve rapid diagnosis and early treatment of CHF and other edematous states like kidney disease, venous insufficiency, liver failure and lymphedema.

The topic is for wearable technology and on-skin interfaces (i.e., stocking, patch) to monitor peripheral edema enabling continuous assessment of the fluid status of patients with congestive heart failure or other fluid overload conditions (e.g., lymphedema).

The Small Business Program (SBP) mechanism will support the development of a prototype that can serve as an initial milestone for what is envisioned as a larger ARPA-H program non-invasive lymphatic diagnostics. A wearable system that enables a patient in an outpatient, with a strong focus on at-home, setting to monitor peripheral edema with minimal effort and with no expertise necessary.

Purpose & Goals:

Purpose and unmet need: The purpose of this overall topic area is to fill a huge and neglected gap in the field of lymphatic medicine – that of the inability to detect subclinical edema and, importantly, to do this in a scalable and equitable way.

The goal: Develop a wearable tool that can be used at home or in an outpatient setting even in rural areas around the country to detect early subclinical edema.

Why is this important? Early diagnosis = preventable complications. If patients, for example, in rural locations, could be identified early with edema, they could be triaged to appropriate facilities to address the edema before it causes serious health consequences and the condition is irreversible.

Why this is doable? Wearable sensors are not a new concept and several prototypes for other health conditions are currently successfully used (example: (1) ring sensor that monitors heart rate and oxygen in the blood , (2) a smart wristband for real-time perspiration analysis, (3) And SwellFit – a prototype of a wearable edema monitor.

References:

1. Asada, H. Harry, Phillip Shaltis, Andrew Reisner, Sokwoo Rhee, and Reginald C. Hutchinson. "Mobile monitoring with wearable photoplethysmographic biosensors." IEEE engineering in medicine and biology magazine 22, no. 3 (2003): 28-40.

2. Gao, Wei, Sam Emaminejad, Hnin Yin Yin Nyein, Samyuktha Challa, Kevin Chen, Austin Peck, Hossain M. Fahad et al. "Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis." Nature 529, no. 7587 (2016): 509-514.

3. Kim, Sunyoung, Yasha Iravantchi, and Krzysztof Gajos. SwellFit: developing a wearable sensor for monitoring peripheral edema. Proceedings of the 52nd Hawaii International Conference on System Sciences | 2019.

List Technical Deliverables and Success Metrics below:

The deliverable will be a prototype of a flexible wearable sensor which is: (1) comfortable and tolerable to wear, (2) mechanically feasible for human use, (3) wireless power and ability to transfer data to a personal device, and (4) capable of measuring fluid accumulation. Solutions should clearly address the three technical areas (TAs) listed below:

TA 1. Hardware sensing platform – several metrics to consider include bioimpedance, temperature changes, pressure sensing, accelerometer/gyroscope (movement patterns), infrared imaging, electrodermal activity, ultrasonography, heart rate variability (as swelling increases), machine learning algorithms.

TA 2. Mobile application (for data visualization) –(i.e., smartphones, tablets, laptop computers, smart watches, e-readers) TA 3. Web server with database for processing and storing data Initial exam:

1. Provide a detailed document outlining the specifications for the wearable sensor’s design and functionality.

2. Provide a computer aided design (CAD), schematic and a functional prototype of the edema detection wearable sensor.

3. Document detailing the data collection process, including ethical considerations.

Midterm exams

1. Beta testing for comfort and wearability with patient ambassadors demonstrates 85% satisfaction.

2. Provide a statistical analysis and validation report.

3. No edema detected in a normal control patient > 99% accuracy

4. Subclinical edema detection minimal result >75% accuracy Final exams

1. Optimized design of wearable sensor with >85% user satisfaction

2. Subclinical edema detection minimal result/ideal results ->85% accuracy/> 95% accuracy

- Ex. Detection threshold for patient with history of congestive heart failure over 24-hour period of time (allowing for timely intervention):

3. Provide a plan for continuous improvement and updates to the device

4. Upon submission provide a Target Product Profile (TPP) for your solution with measurable minimal and ideal results.

ARPA-H 02 Predictive Language Models for Cognitive Disability Adaptive Communication Tools Only Fast-Track proposals will be accepted. This topic is open to SBIR or STTR.

Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $600,000.00 for 6 months to 2 years. Phase II: up to $3,500,000.00 for 1 to 3 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 Will not be funded.

Background/Introduction:

Speech or language impairment impacts millions in the US, including those associated with Autism Spectrum Disorder and cognitive disabilities. Up to 1 in 36 children and 1 in 34 adults in the US have been diagnosed with an Autism Spectrum Disorder, with a total of ~5.5 million affected. Cognitive disabilities, including Down’s Syndrome, account for up to a million more. Many of these people will require lifelong care and support.

Recent research has shown that alternative and augmentative communication tools (AAC) dramatically improve the quality of life of people with cognitive and intellectual disabilities. Early introduction of AACs in education mainly shows dramatic outcomes with improved language acquisition, social cognition, and prospects for lifelong autonomy and independence.

Yet, AAC tools are in their infancy. Far from Stephen Hawking’s custom-built communication device, the tools currently available in the community are, at best, primitive due to limitations on-screen interaction and interface complexity. They are often limited to pragmatic requests and incapable of helping their users communicate their emotions, be expressive with their language, or grow with the user’s growing command of language. Large Language Models provide an opportunity to give AAC users such an expressive tool.

As more families from ethnic minority groups seek special education and autism services, the need for a multilingual tool also increases. In the past, families were recommended to pursue a monolingual approach to language learning in special education. However, recent studies show that a bilingual learning approach does not impede language acquisition and results in a significantly lower burden to families whose primary language is not English. As large language models are capable of multilingual operation and translation, a desired outcome would be a multimodal AAC tool that enables multilingual language learning and adaptive communication capabilities.

The overarching mission of this topic, in both content and program design, is to advance inclusion and autonomy for individuals with autism and neurocognitive disabilities.

Purpose & Goals:

The goal of this topic is to stimulate the development of intelligent, learning and adaptive AAC tools that will enable users with speech or language impairment to communicate expressively in education, social, and workplace environments. These tools should be aimed to foster language acquisition in the zone of proximal development, with the ultimate goal of communication-driven autonomy for the individual users.

As a ”stretch goal” for the topic, we suggest developing a brand-new, full-duplex Cognitive AAC tool. Utilizing cameras, microphones, and AR/mixed reality devices, this tool would use AI to interpret what the user is seeing and hearing, offer prompts, and suggest responses, thus closing the comprehension/response loop. Such a tool has never been developed before.

Current AAC tools are severely limited, with a conceptual vocabulary of 200-300 words and no ability to express complex thoughts or emotions. In comparison, a typically developing 5-year-old has a command of ~2000 words, growing to 25,000-50,000 by high school. This limitation is due to the users’ limited command of language and the user interface constraints for severe cognitive disabilities. Multiple reports suggest that AAC tools lose relevance as users acquire language and may hold them back in their development through their inherent limitations.

The proposed AAC tool must be able to:

• Run on commodity hardware (smartphone or tablet) without requiring custom sensors

• Employ an intelligent predictive model to enhance the users’ ability to communicate pragmatic needs, thoughts, and emotions to help users fully use expressive language capabilities.

• The tool should “meet the users where they are” in terms of vocabulary size and complexity and assist them with language acquisition and growth of conceptual vocabulary.

• The tool should be able to learn and accept user input through continuous online or offline retraining.

The tool should be capable of bilingual or multilingual operation, enabling improved communication with educators, family members, and caregivers whose first language is not English.

The tool should encapsulate typical interactions in the Special Education setting and enable the users to learn and communicate in varied settings and scenarios (e.g., taking a bus, grocery shopping, managing money, asking for help and accommodations, applying for a job, etc.). The tool should allow the introduction of concepts and vocabulary on an as-needed basis, with a focus on growth.

AAC tools specific to one setting or scenario (e.g., education, or simple pragmatics) will NOT be responsive to this solicitation.

Teams responding to this topic should include a special education specialist or a disability advocate and one or more persons with diagnosed autism or a cognitive disability associated with speech or language impairment as part of the core team. This requirement is intended not only to provide valuable first-person feedback during the development process but also to advance this program’s mission of inclusion and autonomy for individuals with autism and neuro-cognitive disabilities through employment in work that benefits the community.

List Technical Deliverables and Success Metrics below:

Initial Exam:

1) User-centered design for novel AAC’s. Must include people with disabilities, education specialists and disability advocates.

2)Initial prototype of the AAC model, shown to adapt to the locus of development.

3) Pilot test showing that the AAC system performs in at least two settings, with at least 10 participants.

4)Vocabulary > 2000 words.

5) Quantitative metrics for pilot:

a. Pre-and post-trial data via Vineland-3, FCP-R or equivalent metrics.

b. Discrete trial classroom metrics of classroom performance, language acquisition and use, social pragmatics, and rates of problematic behaviors during duration of the pilot test.

c. User, teacher and family feedback questionnaire.

Mid-term Exam:

1) Demonstration in at least four settings.

2) Demonstration of the ability to adapt with the users’ language acquisition.

3) Vocabulary > 10,000 words; ability to use LLM/machine translation for bilingual operation.

4) Ability to work with non-pragmatic topics, communicate emotional states and provide means of expressive language use.

5) Quantitative metrics of system usage in multiple defined settings as well as outside defined settings.

6) Initial public beta deployment of the AAC.

7) At least 500 active users.

Final Exam:

1) AAC tool fully deployed and available to everyone.

2) Full predictive capabilities allowing users to utilize the AAC tool in a variety of settings, including potential for unlimited expressive usage utilizing the LLM capabilities.

3) Vocabulary > 25,000 words/concepts; multilingual operations.

4) Demonstrated ability to respond to user feedback with model changes.

5) Deployment to both children and adults with cognitive disabilities.

6) At least 1000 active users and healthy growth rate.

7) Commercialization Plan ARPA-H 03: Cell and Gene Therapy Process Analytical Technology (PAT) and Quality Control (QC) Testing Phase I or Direct to Phase II proposals will only be accepted. This topic is open to SBIR only.

Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $600,000.00 for 6 months to 2 years. Direct to Phase II: up to $3,500,000.00 for 1 to 3 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.

Background/Introduction:

High manufacturing costs, drug shortages, expired/unstable intermediates or products, and regional treatment silos limit the ability to provide quality and economical health care for all. The one-product, one-facility design contributes to high patient costs, slow development times, and regional access limitations. Decentralized manufacturing is an advanced manufacturing concept that seeks to replace centralized facilities with multiple “like-for-like” distributed manufacturing (DM) facilities deployed regionally or near patient care (POC). Proof-of-concept DM/POC strategies are emerging in real-time for several modalities, including, but not necessarily limited to, autologous cell therapies (i.e., CAR-T) and oligonucleotide-based therapies (i.e., mRNA vaccines and personalized cancer treatments). The DM/POC paradigm has yet to be demonstrated in sufficient technical, quality, and operational readiness to minimize risk to drug manufacturers for broad implementation.

Decentralized manufacturing systems producing “small batch” drug products on demand will require additional innovation regarding process analytical and/or quality control testing to release drug products rapidly without further risk to safety or efficacy. Scalable solutions are needed to enable advanced in-line or at-line process analytical technologies informing on critical process parameters and/or rapid, automated product quality testing.

Successful development of process analytical technology and/or rapid, automated, walk-up lot release testing equipment would enable a quick tech-to-market win as these same technologies would be valuable to the centralized manufacturing paradigm of today. More importantly, these are enabling technologies that will integrate into a holistic solution for the decentralized manufacturing paradigms of the future.

Technical solutions will likely impact a broad array of cell and gene therapies, vaccines, and other biologics modalities, enabling faster release of high-quality products for cancer, infectious disease, and other indications.

Purpose & Goals:

Goal Area 1: Advanced in-line or at-line process analytical technologies informing on critical process parameters.

Potential measurements include but are not necessarily limited to:

· Cell – soft sensors enabling attribute-relevant chemometric models, cell density, cell viability, cell biophysical properties, -omics data, vector concentration, phenotypic markers, or other relevant biomarkers.

· Oligonucleotide - Critical reagent monitoring (i.e., enzymes, nucleotide triphosphates, capping reagent, plasmid DNA, process intermediates (i.e., RNA, dsRNA, etc.), or soft sensors enabling attribute-relevant chemometric models.

Current process analytical technology (i.e., pH, dissolved oxygen, temperature) will not be considered.

Goal Area 2: Rapid, automated, walk-up-enabled product quality testing.

Ideal lot release assays in a distributed manufacturing paradigm would require minimal hands-on sample processing. The instrument user interface would be intuitive, utilize pre-developed methods, and not require expert knowledge of the underlying principles of the measurement (walk-up enabled). Analytical methods should be completed in no less than 24 hours from sample acquisition to results. The software enabled with clear pass/fail metrics according to pre-programmed, product-specific lot release criteria is required.

Proposed systems may target product quality attributes, purity, or sterility testing. Proposed systems may be novel or significantly improve existing measurements via automation, integration, small footprint, or ease of operation. Representative measurements may include, but are not necessarily limited to:

o Cell therapies – cell viability, transgene expression, endotoxin, microorganism, mycoplasma, replication-competent virus, and other product quality attributes.

o Oligonucleotide-based therapies – identity, size and polydispersity, encapsulation efficiency, gene delivery vehicle composition, oligonucleotide integrity, endotoxin, sterility, and potency.

List Technical Deliverables and Success Metrics below:

Deliverables depend highly on the technology type identified, analyte, and complexity of the matrix (dependent on the process step to be utilized). The offeror will be required to propose analytical metric targets (i.e., LOD, LOQ, repeatability, reproducibility, sample needs, and time to data). The offeror shall also propose prototype samples to be used, including forced degradation samples and/or intentionally altered samples to demonstrate feasibility. Minimal metrics are listed below, noting the TRL at project initiation may heighten stage-gated metrics.

Initial Exam:

1) Proof of concept deliverables will include differential analysis of known positive and control samples. A high degree of assurance that the proposed analytical target is being monitored and a quantitative response is observable. Data acquisition and processing software must be developed.

Mid-term Exam:

1)Additional analytical performance metrics must be demonstrated to indicate sensitivity, dynamic range, and selectivity appropriate for the intended use case. Qualification shall be performed to demonstrate suitability for intended use.

Final Exam:

1) Integration of hardware and software components meets desired deliverables (i.e., automation, integration, walk-up status, etc.). Validation shall be performed to demonstrate utility for intended use.

ARPA-H 04: Wearable Cell sorting and Gene Delivery Systems Phase I or Direct to Phase II proposals will only be accepted. This topic is open to SBIR only.

Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $600,000.00 for 6 months to 2 years. Direct to Phase II: up to $3,500,000.00 for 1 to 3 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 will not be funded.

Background/Introduction:

The cost, manufacturing challenges, and logistics of centralized manufacturing of autologous cell therapies such as chimeric antigen T-cell receptor therapy (CAR-T) have spurred interest in alternative solutions for gene delivery. One approach has been the development of closed, automated, single use manufacturing systems that, in theory, can be moved closer to the point of care. The technical and operations readiness of these systems shows great promise. However, additional advancements in digital architecture, quality control, and logistics are still necessary. An additional alternative route being pursued is in vivo cell therapy, which shares the common operating principle of gene therapy, targeting genetic modification to a specific cell type in vivo. Several advances are being made in this space, however, the need to target specific tissues for gene delivery and the potential for unwanted incorporation continues to be technical hurdles An alternative approach is the in-situ delivery of genetic material with minimal ex vivo manipulation of cells. In this paradigm, the gene delivery system must be mechanically introduced to the desired cells or tissue that have been sufficiently isolated to enable targeted gene delivery. Such an approach may eliminate the need for time-consuming offline manufacturing and enable administration of the gene delivery in a hospital setting. Such a strategy would revolutionize the delivery of certain genetic medicines and enable more widespread uptake of life-altering medicines.

Purpose & Goals:

The purpose of this topic is to develop an entirely new format for cell and gene therapy delivery that maximizes the attributes of both ex vivo and in vivo cell therapy technologies. This SBIR would attempt to spur innovators that find the middle ground between fully ex vivo and in vivo by leveraging materials/device science AND biology to target cells more efficiently. Potential embodiments could include but are not necessarily limited to, engrafted scaffolds with functionalized gene delivery systems, mechanical delivery of a therapeutic expressing gene delivery system (topical, patch, electroporation), or miniaturized cell sorting and isolation devices that simultaneously perform CAR-T transformation, activation, and reintroduction. Devices of this nature would surpass the unmet needs of ex vivo cell therapy (long wait time and complex manufacturing logistics) as well as unmet needs of in vivo cell therapy (inadequate tissue targeting leading to potential unwanted off-target effects). Literature examples of this type of technology are sparse, with few academic examples of initial proof of concept. This field is ripe for small business spin-off companies to accelerate innovation into a new realm of cell therapy manufacturing. The lack of historical experience and regulatory pathway for such delivery platforms make them less likely for large companies to undertake and thus is a perfect ground for ARPA-H to catalyze further development.

List Technical Deliverables and Success Metrics below:

Deliverables will be highly dependent on the technology type identified, gene delivery system, and target cell line. The offeror shall also propose prototype samples to be used. Minimal metrics are listed below, noting the degree of TRL at project initiation may heighten stage-gated metrics.

Initial Exam:

1)Proof of concept deliverables will include fabrication of the desired device to specifications.

Mid-term Exam:

1)Demonstrated ability to isolate the cells of interest to >70% from a complex mixture (i.e., whole blood or serum). The ability to incorporate the desired genetic medicine into the cell line will be evaluated using offline methods (PCR, NGS, flow cytometry, etc.).

Final Exam (Phase II only) 1)Demonstration of the ability to perform cell isolation and gene incorporation in an animal model or mimetic organoid system. Therapeutic effect will not be a requirement, however gene incorporation must be demonstrated with offline methods.

ARPA-H 05: Precision Brain Targeting: non-invasive delivery at the right place and time Phase I, Direct to Phase II, or Fast-track proposals will only be accepted. This topic is open to SBIR or STTR.

Number of anticipated awards: 2-3 Budget (total costs, per award): Phase I: up to $600,000.00 for 6 months to 2 years. Direct to Phase II: up to $3,500,000.00 for 1 to 3 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.

Background/Introduction:

In recent years, recognition has grown for the potential of noninvasive methods to precisely target the brain for diagnostic, monitoring, and therapeutic purposes. Traditional invasive procedures (e.g., those that require direct injection into the peripheral or central nervous system) carry inherent risks and limitations, prompting a surge in research efforts towards safer and more precise alternatives. This topic aims to catalyze innovation in neuroscience by fostering the development of novel non-peripheral or central nervous system (P/CNS) invasive techniques that can deliver diagnostics, monitoring devices, and therapeutic interventions to the brain with unprecedented precision and timing.

The health problem at hand is the need for effective treatments for brain disorders, ranging from neurodegenerative diseases to psychiatric disorders. These conditions pose significant challenges to public health, impacting millions of individuals worldwide. Current treatment options often involve invasive surgeries, direct injection into the P/CNS, or systemic drug administration, which can be imprecise, inefficient, imperfectly timed and associated with undesirable side effects. Diagnostic tools are largely limited to self-report/subjective tools and costly imaging techniques for many of the most common neurological and psychiatric disorders, which prevents earlier and accurate diagnosis needed for more effective treatment.

Purpose & Goals:

The overarching purpose of this topic area is to spur the development of innovative non-P/CNS invasive approaches (i.e., those that do not require injection into the P/CNS) for precise and timely brain targeting to treat brain-specific diseases such as glioblastoma, neurological, or psychiatric disorders. Currently, there are no available technologies that can be administered outside the P/CNS capable of targeting the brain, while providing a platform to modulate and turn off therapeutic delivery. By leveraging the unique capabilities of small businesses, we aim to address the unmet need for safer and more effective in vivo diagnostics, monitoring, and treatments for neurological and psychiatric disorders. Small businesses possess agility, creativity, and a strong entrepreneurial spirit, making them well-suited to tackle complex challenges in health care innovation.

Specific requirements supported under this topic area may include the development of novel non-C/PNS administered brain-targeting technologies, such as advanced imaging techniques, nanotechnology-based delivery systems, novel small molecule, and viral-based innovations. Non-invasive technologies should include delivery options outside the central AND peripheral nervous systems, as well as cerebrospinal fluid (CSF). Proposals focused on integrating these technologies with data analytics, artificial intelligence, or personalized medicine approaches are encouraged. Offerors should articulate a proof of concept of how the delivery will precisely reach a brain region and cell type of interest and express the delivered agent for a nominal amount of time that correlates with a diagnosis or therapeutic effect. Further the proposer should determine how the proposed agent will be able to be turned off. The offerors should target an inflection point for their delivery by the end of funding (for example: IND or IDE approval, first in-human demonstration, etc.)

Notably, proposals solely focused on incremental improvements to existing technologies (such as focused ultrasound) or those lacking clear potential for transformative impact will not be considered responsive under this topic area. We seek bold, high-risk, high-reward projects that have the potential to revolutionize the field of brain-targeted therapeutics. Interdisciplinary research teams with expertise across neuroscience and vascular biology are encouraged.

List Technical Deliverables and Success Metrics below:

Initial Exam:

· Outline the data collection and analysis plan in a report that includes ethical considerations (including how technology will be accessible to different populations).

Midterm Exam:

1) Demonstration of proof of concept for brain-targeting technology with a report outlining proof of concept.

2) Validation of delivery method reaching specific brain regions or cell types with accurate timing (time of delivery and/or duration of time, ability to up/downregulate therapy, and an “on/off switch”) to deliver the appropriate result with a report showing data and results.