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

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

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.”

conversation with Wegrzyn appears in this issue.

Diagram of ARPA-H’s health ecosystem, including public and private stakeholders.
Source: ARPA-H

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.

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 LetterDec. 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 LetterSept. 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.

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 LetterJune 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.


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

Jeff Allen
Jeff Allen, PhD
President, chief executive officer, 
Friends of Cancer Research

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.