Accelerating Speed to Patient: A Conversation With Eli Lilly’s Sarah O’Keeffe

While Eli Lilly continues to ride an historic stretch of company growth and performance in the annals of Big Pharma, the now 150-year-old organization, which formally celebrated the milestone last month, is going all in on future bold bets in the world of drug development.

Not lost in the recent flurry of momentum and activity — marked also by the solid rollout of Lilly’s new GLP-1 receptor agonist pill, Foundayo; dramatic trial results from its anticipated triple-agonist weight loss candidate, retatrutide; and a string of notable biotech acquisitions, including assets in oncology and infectious disease prevention — are Lilly expansion pursuits internally.

In May, for instance, the company opened a new genetic medicine facility in Lebanon, Indiana, not far from its Indianapolis headquarters. The site is the first of three planned facilities on the Lebanon campus, which will also include a new active pharmaceutical ingredients site and the Lilly Medicine Foundry.

It is the latter component in particular that could become a prime stage-setter for future treatment successes. First unveiled in October 2024 as part of a $4.5 billion investment, the Foundry is slated to open in late 2027. According to Lilly, it will be the first facility of its kind to combine research and manufacturing in a single location.

The engine behind the Foundry is Lilly’s product research and development (PRD) arm, helmed by Sarah O’Keeffe, Ph.D., its group vice president. A trained chemist, O’Keeffe oversees the specialized division, which consists of 1,500 scientists and engineers and is responsible for translating promising discoveries into scalable medicines that can move reliably through clinical development and ultimately reach patients across the globe. An Ireland native and Lilly veteran who began her career as a postdoctoral scientist nearly 19 years ago, O’Keeffe became senior vice president of PRD in 2024 and has helped lead the organization’s push toward more integrated and digitally connected drug development systems, including the formation of the Foundry.

The center, O’Keeffe explained during a recent interview with Pharmaceutical Executive, is designed to collapse traditional barriers between discovery, development and manufacturing while creating a more flexible infrastructure to produce increasingly sophisticated medicines, including peptides, RNA-based therapies, biologics and advanced oncology platforms.

In the following exclusive Q&A, O’Keeffe goes inside the conception of the Foundry and its fundamental mission; what she believes are the evolving bottlenecks in modern drug development; and why “speed to patient” has become Lilly’s guiding principle. She also discusses the company’s strategy around manufacturing innovation and shares the leadership philosophy of a chemist who never stopped being curious, directing efforts today at the convergence of science and operations.

Pharmaceutical Executive: The Foundry initiative signals a shift toward rethinking how medicines are developed and manufactured. What was the strategic philosophy behind the center’s creation?

Sarah O’Keeffe: It’s probably been a few years in the making, and a lot of things converged for us. We have internal capability today to supply biologic-based medicines — your typical monoclonal antibodies. During COVID-19, that internal capability was critical and a game changer. As we went from working on discovering what we needed to actually manufacturing it and supplying it to patients — obviously exceptional circumstances — I think more broadly within, in [chemistry, manufacturing, and controls] and development, we recognized that internal capability can be leveraged and give us real flexibility. I think in enabling speed to patient is where we were maximizing that opportunity.

But we didn’t have the same capability internally for small molecules. We had a pilot plant that we used to supply drug substance to clinical trials, but we shut that down back in 2008 for strategic reasons. So we’d been very much relying on some great external partnerships to manufacture our drug substance for clinical supply.

The other piece that was emerging during that time was this evolution in what we refer to as modalities or different therapies. The classic platforms or medicines we used to make were either a small molecule, typically a pill, or a biologic like a monoclonal antibody, which ends up being a parenteral formulation, an injection, etc. But then discovery began unlocking new biology, and we were able to design different molecules that might have better precision. We looked at these and said, these don’t look like molecules we’re used to figuring out how to make at scale. And when we started to work on them, we realized no one has really figured out how to make these well — we need different equipment, different analytics, different chemistry.

So we had all these ideas, and then working with partners, it was a struggle. They have fixed infrastructure; they may not have the technical capability. And Lilly’s Chief Scientific and Product Officer Dan Skovronsky said, “We’re missing opportunities here, Sarah. You need your own facility.” That was refreshing — to get that support and understanding from the executive level. They agreed, and they said go do it. That’s the convergence: pipeline, infrastructure, innovation and the biology itself, all at once. I really feel like discovery is no longer the bottleneck. They’re identifying targets and designing molecules extremely fast. The bottleneck is how quickly we can develop a manufacturing process and scale it so we can supply it to patients.

PE: How do you see the Foundry changing the traditional handoff between R&D and manufacturing across Lilly’s pipeline?

O’Keeffe: The life cycle of a drug is very sequential: discovery scientists hand it to the development team, the development team hands it to manufacturing. There are sequences and handoffs, and understandably there are delays in that. That’s what we’re trying to solve.

In this era of digitization, it’s not about people meeting in a room doing transfers — “let me tell you about what we’ve learned about how to build this molecule.” We’re trying to digitize all of that. There will be no paper in this building; everything at the click of a button. And I think ultimately — it’s not glamorous — but the amount of time you can unlock between all those handoffs is significant.

Our focus is always very simple: speed innovation to patients. And time, as it’s measured in innovation, is measured in days for a patient. Every day we can take out of that journey is a day we can get a medicine to a patient, whether in a clinical trial or a commercial setting. That’s the mindset we’re operating in.

The Foundry will also have spaces where we can flex in, flex out, plug and play — future-proofing it for whatever new science or new design our discovery colleagues come up with.

PE: You mentioned discovery is no longer the bottleneck. What factors do you think have driven that evolution?

O’Keeffe: You look back over the history of medicine, small molecules were the heroes. But I think there’s been so much we’ve learned about biology — human genome projects, for example — and so we’re actually now beginning to understand how to target different things in the body. It’s always been about how do you get the medicine to the right place, whether it’s the right cell, the right tissue, the right component of the cell.

[But] I think our understanding of biology is so much more. Now you think genetic medicines that work on the DNA, the RNA, the elements of the cell that tells it what to do. RNA medicines today can reprogram a process that isn’t working and can quickly replace or fix a missing function within a cell. It’s all about delivery. So we use these nanoparticles to try and package up the RNA medicine that can get into the cell and get to the right kind of component.

It’s a pretty elegant design, so then it becomes, “okay, these are great, but these are very complex new medicines.” And that’s my job and my team’s job — to figure out then how to make these reliably at scale. The reliable piece is important. If you’re stuck or we’re having to fix it time and time again, that introduces slowdowns, and it hurts our ability to be able to reliably supply medicine to the clinic.

Once we get to the point where we’re in phase 3, and there’s a level of confidence about this becoming a commercial product, we’ll hand it over to our manufacturing colleagues to get ready. But our ultimate job is to make sure we can supply the clinic, and then give manufacturing a process and a recipe that they can make the same way each and every time, and then they can scale wherever they need to go in the world to supply the medicine.

PE: What operational or technology innovations are most critical to closing the gap between early discovery and production?

O’Keeffe: Everything just seems to be getting more complex, and that ultimately requires a different level of science and technology to make these molecules. Take peptides. There have been Nobel Prize-winning methodologies for building long-chain peptides, but the challenge is that approach was appropriate for a certain scale. We want to make a lot of this peptide — the infrastructure required at that scale is enormous. So is there a different way? Our chemists and engineers and analytical scientists have developed different ways to build these peptides that are more efficient, greener, use less solvent and are more reliable.

The other piece is digital and [artificial intelligence]. We generate so much data in development. We make medicine for the clinic, but all the way along we’re collecting information on how best to run this molecule — impurities, quality, everything. All of that goes into a regulatory filing. And the experiments that fail in the lab are often the most informative — that went wrong for whatever reason, but we learned something about the product. How do you harness all that information and make it accessible?

What we’re building within the Foundry is a connected system where you can access that information and your digital infrastructure is telling you what you need to do. A chemist works out a process in the lab, and today that knowledge has to be transferred — to engineers, to automation teams, to the analytical lab. Those are all handoffs. We want a system where that knowledge flows, where analytical instruments sit directly at the manufacturing equipment and test in real time, no human getting a sample and walking it to a lab.

We want a self-driving system. It sounds like it should be straightforward, like surely someone has cracked this before now. But it is genuinely complex, and that’s where we can win — slicking up those interfaces. That’s where the time gets lost.

PE: You’ve had a unique career path, starting as a bench chemist before transitioning into leadership. What originally inspired your journey into pharma?

O’Keeffe: I grew up in Cork, Ireland. I was always passionate about science, but I didn’t initially know I wanted to be a chemist. During college, I had an experiment not go as planned. It was a recrystallization, and my yield was low; it was below the range listed in the notebook. I was able to diagnose it, but I was frustrated. The lab technician told me something that stuck with me: “It’s not about chasing the right number — you understood what happened.”

That is the nature of science, right? It’s leaning into the ambiguity, that discomfort of kind of not knowing — that’s the work. I think that kind of perspective probably lifted the veil for me. I like asking questions. I’m curious. And it’s not always about being fixated on that end outcome; that can be distracting. The nature of our role in science, whether you’re in discovery or development or even manufacturing, is you have to sit through that discomfort.

I eventually came to the U.S. for a postdoc, and from there I just kept saying yes to opportunities I probably wasn’t fully ready for. But I learned from each one. Yeah, there became new skills certainly within the management regime, but I love the science. I haven’t let go of the curiosity and the innovation agendas that I’m working with my teams on. I can understand them, I can advocate for them and I can invest in them.

So I’m enjoying it. I work with just the smartest people, so I feel very privileged. That is kind of my internal motivation.

PE: Does that scientific foundation, and those lessons during your earlier work, shape how you lead today?

O’Keeffe: Yes and no, because there are biases you can bring to the table too, and you’ve got to stay humble. In one of my early management roles, I actually led an engineering group as a chemist. That was by design — my supervisor’s design, not mine. His view was that these brilliant engineers didn’t need scientific leadership; they needed strategic leadership. Someone to help them focus on the right things, stay the course, persevere. And what I found was that my appreciation for the science helped me connect different groups. I could tell the chemist, “You should go talk to the engineer on this one,” and vice versa.

If you tweak the chemistry, that might upset the output, but the engineer might have a solution in the equipment design that counterbalances it. It’s a highly integrated process.

The other thing is first principles. Yes, these are new modalities, but they’re still grounded in fundamentals of chemistry and physics. They may look like different molecules, but from a first-principles approach, the science is there. I try to set that tone culturally as well — you’re not just a small-molecule chemist. You can be a peptide chemist and a nucleic acid chemist. You have to keep learning. The technology we figured out on small molecules, on continuous manufacturing, we took that capability and applied it to peptides. We didn’t know at the time how broadly it would be applied. But we built something good and it translated.

And when I’m able to advocate to executive leadership — I want to build this Foundry, it comes with an expensive price tag — I can articulate why it matters, what the return on investment will be, how it serves patients. I understand it, I believe it and I think that credibility of being a scientist in a leadership position helps.

Patients are waiting and the science is moving fast, but the problems are getting harder. I think that creates an obligation to keep learning faster and improving faster and pushing ourselves to raise the standard for what’s possible.