High-risk investments by ARPA-H aim to catalyze a new era in cancer research

The Advanced Research Projects Agency for Health is setting up a network of partners that would enable the federal government to fund and roll out new initiatives nationwide.

The recently announced ARPA-H Health Innovation Network would include hospitals, investors, and healthcare organizations—all entities that can contribute to developing and commercializing technologies that may improve patient outcomes. 

“Working with the federal government, loud and clear feedback from the community is very hard—it’s these very complex interactions with the government,” ARPA-H Director Renee Wegrzyn said to The Cancer Letter. “But we want to work with the little guys and the non-traditional partners that wouldn’t normally feel up to the task of working with the government because it is so cumbersome. And so, that’s what this network helps to relieve.”

The new network’s name—ARPANET-H—is derived from the Defense Advanced Research Projects Agency’s original ARPANET initiative that eventually became the internet.

ARPA-H’s latest big-project announcement is a key manifestation of the agency’s mandate to innovate outside the constraints of traditional research processes, agency officials say.

ARPANET-H relies on a hub-and-spoke  administrative structure where regional hubs connect to institutions, stakeholders, and communities across all 50 states.

As an independent federal research and development funding agency established within NIH, ARPA-H breaks the mold of biomedical innovation: it’s disease-agnostic. Also, the agency has no intramural research laboratories.

Instead of study sections and grant-based awards, ARPA-H’s “high-risk/ high-impact” model relies on federal contracting mechanisms, including cooperative agreements and a unique “other transaction authority” procurement instrument to fund expert-driven research.

“Federally funded science is just super linear,” Wegrzyn said. “We don’t want to take that traditional path, and we really want to have a contracting mechanism that helps us have those quick, iterative design tests, build cycles, during the course of any product development or program development.”

To that end, how would the agency use the ARPANET-H hub-and-spoke network?

Improving access to clinical trials could be a good start.

On Oct. 19, ARPA-H announced a clinical trials network—Advancing Clinical Trials Readiness (ACTR)—as the first health innovation initiative to be deployed through ARPANET-H. 

The ACTR network aims to enable 90% of all eligible Americans to participate in a clinical trial at locations within 30 minutes from their homes. 

For perspective, 41% of Americans reported not knowing anything about clinical trials, and fewer than half of the 9% of U.S. adults who had been invited to join a trial were actually enrolled, according to nationally representative data from the 2020 cycle of NCI’s Health Information National Trends Survey.

“That clinical trial network that we launched last week—it’s a draft right now, we’re looking for feedback—but it is going to be released and say, ‘Hey, we’re going to actually stand up this [ACTR] network, and they’ll help us recruit those players on the ground, so that when as we launch new initiatives from ARPA-H, we’re able to immediately work with those partners and not wait for a 5-, 6-, 7- month process to bring them on board,’” Wegrzyn said.

The ACTR network is one example of how the agency can utilize ARPANET-H to achieve broader impact sooner.

“We can use the ARPANET-H to identify those partners that want to participate, but then we’ll have that contracting mechanism to get them participating very quickly. And so, this way, that contracting matches the timeline of these programs.

“In the future, maybe we want to launch a pediatric cancer program a year from now, we can go ahead and launch that directly on ARPANET-H,” Wegrzyn said. “It just allows us to move really quickly.”

A conversation with Wegrzyn appears in this issue. 

NCI grantee institutions and NCI-designated cancer centers will have a role  to play in ARPANET-H, said Jill S. Barnholtz-Sloan, associate director of the Informatics and Data Science Program at the NCI Center for Biomedical Informatics and Information Technology.

“This new initiative will work with groups across the country, including but not limited to NCI-funded and NCI designated cancer centers, to innovate access to clinical trials,” Barnholtz-Sloan said to The Cancer Letter. “While the ACTR is not solely focused on cancer, it is sure to have impact in the cancer space.”

Healthcare organizations and health-related entities can apply to join ARPANET-H and “become a spoke” to one of three network hubs, each managed by a consortium management firm:

• The Customer Experience hub, located in Dallas, focuses on research, developing health solutions, and improving equitable health outcomes. The ACTR will be coordinated through this hub, which is managed by Advanced Technology International.
• The Investor Catalyst hub, located in Cambridge, MA, focuses on building collaborations between researchers, entrepreneurs, and investors to provide business support and bring novel ideas to market at speed. VentureWell manages this hub.
• The Stakeholder and Operations hub, to be located in the Washington, D.C. area, will be “adjacent” to intergovernmental partners and stakeholders. More details, including the final site location, will be announced later in 2023.

“Last week, we officially launched our ARPANET-H Customer Experience hub in Dallas,” Wegrzyn said. “[On Oct. 26,] we officially launched our Investor Catalyst hub. I’m actually calling you from our new Cambridge site.

“What you see, a lot of our investment now is laying those foundations so that we can really have this flow of new programs into the future to ensure their success.”

ARPA-H investments in oncology

To date, ARPA-H has received $2.5 billion from Congress—$1 billion in the FY2022 appropriations and an additional $1.5 billion in the Consolidated Appropriations Act, 2023. 

After much deliberation in the House and Senate on ARPA-H’s placement within the Department of Health and Human Services, the PREVENT Pandemics Act established the agency within NIH as part of the FY23 Consolidated Appropriations Act. 

We want to work with the little guys and the non-traditional partners that wouldn’t normally feel up to the task of working with the government because it is so cumbersome.

Renee Wegrzyn

ARPA-H’s position within NIH notwithstanding, Wegrzyn reports directly to the HHS secretary and has the authority to set an independent agenda for the agency. As director, Wegrzyn has a term limit of four years and may be reappointed only for one consecutive four-year term.

Pending Monica Bertagnolli’s confirmation  to the NIH directorship by the full Senate, Wegrzyn and Bertagnolli are expected to work closely as peers—they’ve been in touch even before stepping into their roles in federal government (The Cancer Letter, Dec. 9, 2022).

The NCI and ARPA-H missions are complementary, officials say.

“Both agencies fund research and development projects; however, the NCI’s focus is on understanding the underpinnings of cancer and other diseases to develop new treatments, promote prevention and early detection, and provide resources and data to the public,” NCI’s Barnholtz-Sloan said.

“At the same time, ARPA-H has a broader health focus. ARPA-H’s emphasis on high-risk, high-reward technology development offers a great opportunity to catalyze cancer research and treatment breakthroughs to improve patient care.

“We hope to have multiple deliverables from collaborative efforts with ARPA-H that would lead to acceleration of discoveries and health innovations to advance cancer research and patient care,” Barnholtz-Sloan said.

In its first year, ARPA-H has invested hundreds of millions of dollars in cancer-related projects—funding decisions that are made according to the agency’s assessment of a meritorious idea or project, as opposed to budgetary allocations for disease-specific research.

“We don’t sit down and say, ‘X dollars is going to be for cancer,’” Wegrzyn said. “What we say is, ‘We are looking for these best innovations where we think ARPA-H investment will really give an asymmetrical advancement of the state-of-the-art.’”

In September, the White House announced 25 Cancer Moonshot initiatives, including $240 million in ARPA-H awards for an array of cancer-related projects, including the ACTR network (The Cancer Letter, Sept. 22, 2023). Other noteworthy initiatives include:

• Biomedical Data Fabric Toolbox, a federal interagency collaboration—including with NCI—designed to transform data accessibility across all medical domains and break down data siloes in research.
• APECx: Antigens Predicted for Broad Viral Efficacy through Computational Experimentation, an initiative led by ARPA-H Program Manager Andy Kilianski, who aims to transform vaccine antigen discovery, first by developing toolkits that successfully design broadly effective antigens, targeting entire viral families, and then demonstrating the toolkits’ accuracy by evaluating candidate vaccine antigens in clinical trials.
• PSI: Precision Surgical Interventions, an initiative led by ARPA-H Program Manager Ileana Hancu, who seeks to develop technologies that would improve cancer surgeons’ ability to visualize the edge of tumors as well as critical anatomy to improve patient outcomes. 

Organizational Attributes

Nucleus of the Organization

Facilitating the Future

Program Managers are the nucleus of the organization, and their energy and passion drive the mission.

ODs and DIRO “work for” the PMs to facilitate success.

PMs are responsible for the full program lifecycle, from new start proposal to transition.

Radical Change

Evolutionary proposers need not apply

ARPA-H investments should seek to address seemingly impossible barriers in demonstrating “proof of concept” for solutions to major challenges — not incremental advances.

Projects should be high-payoff, high- risk, with the most forward-looking science and technology.

Autonomy

Programs are PM directed

Workshops, consultations, seedlings are encouraged, but no advisory/guidance committees.

PMs should practice “full contact” management, with metrics/milestones for program, empowered to stop underperforming projects.

PMs manage multiple programs, including programs they inherit from departing PMs.

Term Limits

A “projects” agency, not a career

Terms limited to 3 years (renewable once for 6 total years) for PMs, ODs, and DDs, allowing inflow of new ideas.

Limits create urgency and focus on successful NSPs — aligned with office/agency.

Limits remove incentives for empires, organization-building, span of control, bureaucracy, etc.

Source ARPA-H.

ARPA-H’s investment model relies primarily on the agency’s team of program managers, who are  subject to a three-year term limit.

These managers are hired based on  scientific expertise as well as a track record of project execution and team-building to catalyze rapid innovation in the early stages of discovery and development.

For example, Hancu’s PSI program showcases ARPA-H’s preference for investing in projects that could produce technologies or health solutions that can be applied across the health ecosystem, Wegrzyn said.

“That’s her program, that was her job talk. She’s like, ‘This is what I’m passionate about. I think ARPA-H investment can help patients, and this is a problem worth solving, but I need ARPA-H resources to do it because nobody else is doing it. The private sector isn’t doing it in this way, and the federal government is not funding it in this way,’” Wegrzyn said. “And so, she convinced us that that was the case.”

ARPA-H’s first program, NITRO: Novel Innovations for Tissue Regeneration in Osteoarthritis, announced earlier this year, focuses on developing new ways of helping the human body repair its own joints (The Cancer Letter, June 16, 2023).

The agency also funds “revolutionary ideas” that aren’t currently covered by a program through its Open Broad Agency Announcement (BAA), which accepts abstract submissions on a rolling basis. 

Cancer-related projects that have received Open BAA awards include:

• $49.5 million for CODA: Mapping the Cancer and Organ Degradome Atlas to Unlock Synthetic Biomarkers for Multi-Cancer Early Detection, a platform that “uses cutting-edge synthetic biology and cell engineering technologies to catalog cellular profiles unique to diseased cancer cells and leverages them to build bioengineered sensors that can be deployed inside the body to hunt for malignant cells.” This contract is led by Gabe A. Kwong, director of the Laboratory for Synthetic Immunity and an associate professor at the Georgia Institute of Technology.
• Up to $19.9 million for SPIKEs: Programmable Scalable Therapeutics for Immune-directed Cancer-killing, a platform that “utilizes genetically programmable bacteria designed to sense tumor-associated metabolites as an exquisitely precise homing mechanism and then deliver therapeutic payloads that activate immune-directed killing of solid tumor cells without the need for the long and costly processes currently used.” This contract is led by Paul de Figueiredo, the NextGen Precision Health Endowed Professor of Molecular Microbiology & Immunology and principal investigator at the Christopher S. Bond Life Science Center at the University of Missouri.
• Up to $45 million for THOR: Targeted Hybrid Oncotherapeutic Regulation, a project that aims to create a compact device that would be “implanted in proximity of the tumor and will house specialized cells responsible for producing and delivering therapeutic molecules” that would trigger the immune system against tumors. This contract is led by Omid Veiseh, associate professor of bioengineering and CPRIT Scholar in Cancer Research at Rice University.
• Up to $24 million for CUREIT: Curing the Uncurable via RNA-Encoded Immunogene Tuning, a platform that would address immune dysregulation by “directly programming immune cell function to both enhance protective immune responses as well as modulate insufficient or ineffective immune profiles.” This contract is awarded to Emory University and led by Philip J. Santangelo, a professor at the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University.

“Right now, we have awarded, as of last week, $268 million that are projects that are related to cancer,” Wegrzyn said. “So, some of them are almost exclusively cancer. 

“In the coming weeks and months, there will be additional announcements and those numbers will be made public when we make those awards, when those negotiations are complete,” Wegrzyn said.

“I hope your community has some magic wands they want to wave, because we would love to hear about those, and we have the program manager talent here to help make that a reality.” 

Program Lifecycle

From ideas to solutions in the real world

Design Programs

• ARPA-Hard and well-defined problems in health.
• Heilmeier Framework.
• High risk/High consequence.
• Stakeholder Insights.

Build a Performer Team

• Solicit Solutions from the community.
• Find the best non- traditional, industry, and academics to solve.
• Build new coalitions.

Execute and Measure

• Active program management against metrics;PM=CEO.
• Stakeholder engagement throughout to ensure transition.
• Pivot resources when needed.

Learn and Grow

• Capture and share insights.
• Technical honesty.
• Advance the state of the art; 10x+ improvement, no incremental change.

Commercialize and Transition

• Assist company formation or licencing.
• Provide mentorship, connections to customers, investors.
• De-risk investments.

Source ARPA-H.

Remarks to The Cancer Letter—on ARPA-H’s cancer portfolio and future directions for research—follow:

President Biden had the vision for a new agency to complement the world-leading research already conducted in the United States—but with a singular focus on delivering bold new progress to improve human health by advancing new ways to prevent, detect, and treat cancer and other diseases and conditions. 

He introduced ARPA-H as a way to advance the Biden Cancer Moonshot and as part of the President’s Unity Agenda, issues that we can all get behind and work on together to deliver for the American people. 

With bipartisan support from Congress, the Biden-Harris Administration has brought that vision to reality, with approximately $500 million committed this year on projects, for example, to deliver breakthroughs in more effective surgical approaches, new tools to spur the immune system to kill cancer cells, and vaccines that could prevent future pandemics.

ARPA-H has demonstrated its potential to contribute toward ending cancer as we know it and so much more.

NCI and ARPA-H are driven by the Cancer Moonshot Initiative’s goals and the goals of the National Cancer Plan to modernize medical research capabilities and accelerate discoveries that can improve health outcomes. 

Both agencies fund research and development projects; however, the NCI’s focus is on understanding the underpinnings of cancer and other diseases to develop new treatments, promote prevention and early detection, and provide resources and data to the public. 

At the same time, ARPA-H has a broader health focus. ARPA-H’s emphasis on high-risk, high-reward technology development offers a great opportunity to catalyze cancer research and treatment breakthroughs to improve patient care.

NCI and ARPA-H have launched a new program, ARPA-H Biomedical Data Fabric (BDF) Toolbox, to build a “fabric” of software tools that can thread together research and clinical data from labs and centers across the country to make biomedical data more accessible, easier to use, reduce effort for data integration, and enable new capabilities and models that can be applied across disease domains. 

Cancer data will be the first use case for the BDF Toolbox with a broader vision to use the data fabric toolbox to connect data sources across additional disease types. For more information, please visit ARPA-H BDF Toolbox.

ARPA-H is also co-funding small business research projects in collaboration with the NCI. The mission of NCI’s SBIR program synergizes with the ARPA-H mission as SBIR seeks to support highly innovative, early stage projects. ARPA-H has co-funded two SBIR contracts and two Bridge Award Phase IIB contracts. 

The contracts co-funded by ARPA-H were awarded to Quel Imaging to develop biomimetic optical phantoms to support the development and adoption of fluorescent probes for cancer margin detection, and Proteios Technology for an automated modular system for cell therapy manufacturing. 

ARPA-H also saw value in co-funding two NCI Bridge Award projects, the largest awards offered by the NCI SBIR program. The first of these was to Applikate Technologies, for clinical validation of their multiphoton microscopy based digital pathology platform, and the second to OncoNano Medicine for a clinical trial testing their pH-sensitive fluorescent imaging agent to improve tumor margin detection.    

A new ARPA-H initiative to improve clinical trials to drive better health outcomes was announced. This will be the first initiative within the recently announced ARPANET-H Health Innovation Network.  This new initiative will work with groups across the country, including but not limited to NCI-funded and NCI designated cancer centers, to innovate access to clinical trials. While the ACTR (Advancing Clinical Trial Readiness) is not solely focused on cancer, it is sure to have impact in the cancer space.  

ARPA-H’s mission is to fund contracts for high-risk, high-reward projects that pursue aggressive goals. Investigators can receive funding from both agencies if projects are independent of one another and do not overlap in scope. If interested in applying for funding from ARPA-H investigators should refer to the general ARPA-H BAA and/or contact on the of the ARPA-H project managers.  

 We hope to have multiple deliverables from collaborative efforts with ARPA-H that would lead to acceleration of discoveries and health innovations to advance cancer research and patient care. 

First, we hope to have a set of innovative data science “tools” and technologies that will help transform how data is organized, standardized, and used by everyone in the cancer research community, e.g. patients, clinicians, and researchers. 

Second, we hope to have a set of innovative technologies that allow us to probe the universe of cancer more deeply and broadly and that provide new approaches to the development of screening, diagnostics, and therapies.

We were pleased to see at its creation that ARPA-H included cancer as an important focus and that innovating the nation’s clinical trial system will be the first project for the newly formed ARPANET-H. Harnessing the collective wisdom of our community to design cutting edge research is vital to the progress that our patients need and deserve. 

The new agency has done a good job communicating with the public and stakeholders the many upcoming and new research programs, and hosting several proposers’ days to give more information about their research funding opportunities and application process. Consistent and increased funding will be necessary to ensure these programs can be completed and that the results reach the patients.

We are also interested in how the innovative ideas and resulting information will flow through the many hubs and spokes recently announced for ARPANET-H, and more importantly out to the broader health care community. There’s a lot to understand about the new health network, but we are excited to learn and join in the potential transformative changes that could result from this network. 

The Advancing Clinical Trial Readiness goals of ARPANET-H are timely, and ASCO has been working diligently in this area of making clinical trials more patient-centric and overcoming the many challenges including access and inclusion, interoperability, consent, complex study protocols and processes, coverage and financial burdens, and broadening eligibility criteria. 

I have been fortunate enough to have had several conversations with ARPA- H program managers. Although cancer is not the only area of interest, it’s clear that the program managers understand President Biden’s strong commitment to oncology. I am optimistic that this will be an area of significant emphasis. 

I think what is particularly exciting is the ability of ARPA-H to bring partners together across the healthcare ecosystem as well as from areas far removed from medicine. The internal clock ticking loudly in every program manager’s brain also brings a sense of tremendous urgency to rapidly solve cancer problems that is quite refreshing.

I love that ARPA-H has jumped in fully into the clinical trial space. Increasing the number of patients on clinical trials can accelerate innovative cancer care and tends to raise the overall quality of care in the community. ACS is also deeply committed to this space, but the multifactorial barriers to enrollment on clinical trials needs funding which eases enrollment every step of the way and provides access to decentralized clinical trials.

As you know, at the core of ACS is our commitment to cancer prevention, screening and early detection. Devising strategies to provide easy screening opportunities for folks discouraged from screening due to geography, work schedule, or lack of regular primary care services could dramatically increase the number of patients whose cancers are diagnosed at a curable stage. 

We know millions of patients live a significant distance from basic screening and innovative ways to ease that will take a multi-prong effort. In addition, tying this to research in multi-cancer early detection could be incredibly helpful for decreasing cancer mortality.

There is a significant innovation need and we know there is a gap that an agency like ARPA-H can fill, which is supplemental to the work of NCI and NIH. We will continue to support funding needs via appropriations in Congress.

ARPA-H is leveraging public-private partnerships as an effective way to rapidly advance potentially transformative technologies. This enables the incorporation of a diverse set of expertise tailored to each individual project and goal.

Even in its early days, ARPA-H leadership has identified key priorities that hold promise of remarkable shifts in cancer detection, treatment, and monitoring. Continued advancements in each of these areas are in lockstep with the President’s Cancer Moonshot.

The implementation of ARPANET-H is an opportunity to enhance connectivity at a local level with national scale. We’ve seen the unparalleled role that NCI cancer centers have brought to care in local communities and nationwide research simultaneously. 

The same could be true through ARPANET-H in areas such as community engagement, financial partnership, and technological advancement.