Strengthening Early-Stage AMR Innovation: A Conversation with Dr. Erin Duffy, Chief of Research & Development at CARB-X

As the global threat of antimicrobial resistance (AMR) intensifies, CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) plays a pivotal role in tackling this crisis by focusing exclusively on the earliest stages of product development. Founded to reinvigorate a stalled pipeline, CARB-X’s mission is to advance groundbreaking products that can prevent, diagnose, and treat bacterial infections, addressing AMR from its roots. We spoke with Dr. Erin Duffy, Chief of Research & Development at CARB-X, about the organization’s frontline role in combating AMR, its strategic priorities, and the challenges and opportunities ahead.

Welcome, Erin! Congratulations on the recent $21M support from the Italian government. CARB-X plays a unique role in the AMR landscape, focusing specifically on early-stage development. Could you tell us about how CARB-X came to focus on this area and what inspired its mission?

Erin Duffy: Thank you! We are deeply grateful to the Italian government for their generous support. We also want to acknowledge our other funders over the years, including our largest funder – the US government through BARDA – as well as the UK government, the German government, the Canadian government, the Wellcome Trust, the Bill & Melinda Gates Foundation, and the Novo Nordisk Foundation.

CARB-X’s role is different from other organizations in the field. While we focus on early-stage development, groups like BARDA and the AMR Action Fund operate further downstream in advanced development. CARB-X was established in mid-2016 when the early-stage antibiotic pipeline had essentially stalled. We were founded with a clear mission: to drive drug discovery and early development, taking therapeutics from hit-to-lead through first-in-human safety demonstrations, after which organizations like BARDA and the AMR Action Fund can advance these candidates through pivotal studies and toward approval. Our mandate also includes preventatives, like vaccines, and rapid diagnostics—essentially, all the tools needed to prevent, test, and treat bacterial infections.

How does CARB-X decide which projects to support? What criteria are most important in this selection?

Erin Duffy: That’s a great question, and our approach has evolved as we’ve grown. Projects enter our portfolio through active funding calls. In the early days, these calls were very broad, with the idea, “If you have something relevant to AMR, please apply.”

Over time, and following strategic portfolio reviews in 2020 and late 2023, we’ve shifted to a more thematic approach. For example, in the 2022-2023 cycle, we focused on specific areas. In therapeutics, we targeted small molecules for infections mainly caused by gram-positive bacteria like MRSA, with a particular interest in oral therapeutics. We also looked for vaccines targeting neonatal sepsis from top bacterial pathogens and had a cross-pillar call for therapeutics, vaccines, and diagnostics related to gonorrhea.

Each call involves several stages: applicants submit a non-confidential expression of interest, which we review for alignment with the call’s focus. Next is a comprehensive proposal reviewed by a panel of external experts with relevant expertise. The final stage is a presentation to an advisory board, addressing any remaining questions. When selecting projects, we focus on three main areas: the underlying science or technology, the proposed work plan, and the team. Each is critical to our decision-making process.

I’m curious about the challenges that CARB-X-funded projects often face. Could you share some insights into these hurdles?

Erin Duffy: We fund projects in stages that correspond to key development phases, like hit-to-lead, lead optimization, preclinical, and first-in-human. Each stage has specific milestones, allowing for “failing fast” if necessary, while building a robust package that justifies moving forward. This stage-gated approach lets us assess each project individually.

However, we’ve observed common hurdles. One approach could be to address these individually, but we’ve found it more effective to take a proactive approach. For example, if we notice a widespread issue, like nephrotoxicity in certain antibiotic classes, we might design and fund studies ourselves. We may issue an RFP or work with a partner, then share the results, data, and tools with our portfolio teams and the broader ecosystem. Our goal is simple: if we can clear a path for one, we aim to clear it for all.

What unique challenges does translational work in AMR present?

Erin Duffy: The challenges vary across different pillars. In therapeutics, for example, bacterial infections are unique because the target is exogenous—it exists outside human cells. Unlike a drug that simply needs to reach a target organ, like the heart to lower blood pressure, an antibiotic must reach the infection site and penetrate not just the organ—such as the bladder in a urinary tract infection—but also the bacterial cell. This means crossing multiple membranes and avoiding efflux pumps that would expel the drug. So, while a new antibiotic might look promising in the lab, it must get in, stay in, and act effectively within the bacterial cell, all while being safe for the patient.

For vaccines, the goal is to prevent infections entirely. Preventing bacterial infections through vaccination is ideal, but beyond pneumococcal and Hib vaccines, there are few bacterial vaccines due to gaps in basic science. We often lack correlates of protection, essential for identifying and optimizing antigens. Translating promising animal model findings to the clinic is also challenging, so there’s a lot of learning as we go.

In diagnostics, the complexity lies not only in distinguishing bacterial from viral infections but also in identifying the bacterial species and its antibiotic susceptibility. These are critical factors diagnostic developers must address.

Regarding diagnostics, what objectives and technologies are your priority?

Erin Duffy: It’s an evolving area. The “Holy Grail” is a rapid diagnostic for bloodstream infections to prevent sepsis, ideally working directly from whole blood. Right now, this is typically done after culturing bacteria, which can take 24 to 48 hours—far too long for septic patients. Speeding up this process is essential. We now have groups working on techniques that can get results in four to eight hours from whole blood using enrichment methods, which is a significant improvement but still not fast enough.

The need for rapid diagnostics varies by use case. For reference labs, much work is surveillance-based or is a reflex test, which is informative but not immediately useful for treatment. For test-and-treat scenarios, results need to be ready within a doctor’s visit. There’s a growing range of technologies across healthcare settings—from lab equipment to at-home tests. Many developers are now exploring how to adapt platforms to other sample types. I believe we’ll see tremendous benefits as these technologies advance.

What excites you most about CARB-X’s potential and the future of AMR research?

Erin Duffy: This is both the most exciting and humbling job I’ve had. Coming from a background in therapeutics, I now work across all three pillars—therapeutics, preventatives, and diagnostics. The innovation in AMR is remarkable. People often assume the most cutting-edge science happens in other therapeutic areas, but that’s simply not true. In AMR, we see everything from traditional approaches with new classes and targets to non-traditional therapeutics.

For example, we supported an antivirulence program from GSK, taking it through a First-in-Human; today, GSK is advancing it in a Phase 1b trial. The molecule targets FimH, a receptor on the bladder epithelium, to prevent E. coli and Klebsiella pneumoniae from adhering to the bladder wall, effectively preventing urinary tract infections. We’re also working on biofilm-targeting agents, novel vaccine technologies, and diagnostics.

I often say, “Innovation is alive.” Whether it thrives depends on our ability to fund it and bring these developments to patients. Since our first grants in 2017, we’ve seen 18 programs reach human safety trials, and four diagnostic programs are either on the market or in late-stage trials. The key is not just supporting the science but advancing it to create products that can truly impact lives.

How can we raise awareness and promote proactive measures against AMR to prevent it from becoming an even greater public health threat?

Erin Duffy: You have an amazing platform that reaches beyond the infectious disease community, and that’s essential for raising awareness. Broader awareness of AMR is crucial. For instance, developers working on advanced immuno-oncology agents need to understand that immunocompromised patients rely on effective antibiotics. The same applies to dialysis patients and many others across healthcare. All these groups depend on effective antibiotics and a robust pipeline.

A colleague once referred to antibiotics as the “fire extinguishers of medicine.” I think of this analogy often: we have a fire extinguisher under the sink, but when was the last time we checked it? This mindset—assuming antibiotics will always be there—is what we need to change. Ensuring their availability is essential.

If you could share one message with other stakeholders in the AMR field, what would it be?

Erin Duffy: To our colleagues in AMR, I’d say, keep going. Keep innovating, and keep spreading awareness. CARB-X focuses on “push” incentives, providing grants to help innovators move projects forward. But we also need to advocate for “pull” mechanisms—ensuring these innovations reach the market and are valued appropriately for a sustainable ecosystem. And for our broader community, let’s remember that antibiotics are life-saving drugs. They work, they work fast, and they enable people to get back to living fully. Recognize and value what they are in your life.