Innovation Unleashed: Exploring the Intersection of Science and Creativity – An Unconventional Growth Strategy

Sabine Hutchison
Agenus Bio has a mission to harness the power of the immune system by making better immunotherapies, to increase the potential for cancer cures. Co-founded by Dr. Garo Armen in 1994, Agenus is a clinical-stage biopharmaceutical company that discovers, manufactures, and develops immunotherapies for the treatment of cancer. Agenus recognizes the importance of personalized medicine and tailoring treatments to individual patients — through innovative approaches such as personalized cancer vaccines, they strive to develop therapies that can effectively target specific tumor types and patient populations. This personalized-medicine focus holds tremendous promise for delivering more precise and effective cancer treatments.
Today, I'm delighted to be joined by Dr. Jennifer Buell. She's an accomplished leader from Agenus, and our conversation promises to be nothing short of extraordinary. Jen is president and CEO of MiNK Therapeutics, and chairman of the executive council at Agenus. Her career spans over 25 years in the biopharmaceutical industry, filled with exceptional achievements — while I'll be sharing many of her career highlights, you'll find her full bio in our session notes. Jen's expertise has led teams to successfully drive numerous discovery candidates from conception through clinical development and commercialization.
Today, we'll be delving into her experiences, including her time as president and chief operating officer of Agenus, where she still plays a key role in the leadership and mission of the company. Jen is a powerhouse in the biotech world, and every interaction I've had with her leaves me inspired by her visionary outlook and unwavering dedication. Today, Jen will be sharing her experiences from Agenus, which is no ordinary biotech company — over the past decade, it's experienced exponential growth, expanding from a team of 50 to an impressive 500 individuals. Agenus boasts an exceptional pipeline, with a staggering 17 molecules that went into the clinic within five years. However, such successes don't come without challenges, which Agenus has tackled with a masterful touch. Jen has described the Agenus approach as "purposely different," with the ability to disrupt in a highly regulated industry, which is truly commendable, and I can't wait to explore the innovative strategies that have propelled the company's outstanding achievements. So, without further ado, let's dive in and gain some insights from Jen's remarkable journey, and the unparalleled success of Agenus.
Jen, it's such a pleasure to have you here today, and I'm really pleased to spend some time with you — thank you very much for being here. We've had the opportunity to have many conversations, and as I think back, there was really one statement that stuck with me — you described Agenus as being "purposely different." Can you share with us today where that statement comes from, and why is Agenus purposely different? And how can a biotech actually be disruptive in our highly regulated industry?

Jennifer Buell
Sabine, I'm so glad to be here — I've been a fan of your podcast, and I'm really glad to be a part of it. Thanks for your question: how is Agenus different, and purposefully so? I'll tell you first, it's our talent — and this isn't just a cliché, we've concentrated our talent into a deeply dense group, which allows us not only to move more effectively, but much more efficiently as well. When it comes to innovation, what we've really found is that it's truly the few over the many — people are the most critical asset we have in our organization, and it's through them that we've been able to realize a pipeline that appears unprecedented in immuno-oncology. This component — deepening our talent density — has been a tenet of our growth strategy since 2013.
And next, of course, is our capability, and this is what I think truly sets us apart from what you might see with a biotech company of our size. Control over the quality and the speed of our products, and the lifecycle of our products, we've found is best controlled in our own hands, in the hands of our own internal experts. So internalizing capability — from discovery technology, to manufacturing technology, to clinical research operations, which is very unique for a biotech, owning and holding your own clinical research operations internally — not only allows us to lead from the front, it also enables us full control of the speed and quality with which we move. That's been really core to our strategy.
I'll tell you a little more about that. In 2013, as you mentioned, we were a 50-person company with a single product — a pioneering product, an individualized vaccine, in which we'd take a patient's tumor and create their treatment. In doing so, we built a capacity here that includes taking a patient's tumor from patients all around the world — we're domiciled here in Lexington, Massachusetts, and we'd have tumors shipped to us, post-surgery, from Australia, New Zealand, Israel, Russia, everywhere really. The tumors would arrive, and we'd create a patient's treatment and have it back to them within about three weeks, which was completely disruptive in the industry.

Sabine Hutchison
Wow, that is very disruptive already. Amazing.

Jennifer Buell
And I think what we were able to learn from that is that we could actually take a patient's tumor and immunize them against their cancer — it was really powerful. We could see that the patient's immune system could be educated, could seek out and find the patient's cancer, and start to destroy it. As we continued to develop that program, we amassed quite a bit of learning — essentially, that in some patients we had curative responses, and in some the tumor was stronger than the immune system. So we set out on a quest to be able to really address those immune-escape mechanisms, or escape hatches, where the tumor was evading the immune system. And in doing so, we started with discovery.
Rather than getting access to molecules that were commercially available or already in the field, we wanted to harbor those within our own pipeline. So we started with the discovery engine, and acquired an antibody platform — it was called 4-Antibody at the time, and had come out of Roche Diagnostics. From there, we were able to create molecules that could address really any biologic target, and the success of this acquisition is really evident in our own pipeline — from a single product, we now have a pipeline of over 22 molecules, 17 of which went into the clinic within a five-year period. So from discovery to first-in-man trials and beyond, we were able to move 17 of those into patients, which was really an exciting feat for us. Our most advanced asset is a product called botensilimab, which we created in our own hands — it exemplifies the power of putting the discovery capability, or the discovery technology, in our experts' hands: we were able to take learnings from the field and create a molecule that addressed the areas where tumors are escaping. These are a host of highly prevalent tumors that are unresponsive to really anything currently available. Botensilimab has been able to break through, and in over 11 tumor types has really showcased that value — and that truly came from our own internal engineering. That was part of the underpinnings of how important it is to truly internalize capabilities, and put them with our own talent, to be able to address the unaddressed needs out there.
And it doesn't end there — because once you make the discovery, create the molecule, define the biologic properties, you need to manufacture it. That's actually where most biotech companies encounter encumbrances, issues with speed and quality. This is where we essentially said, we were just tired of waiting in line, waiting for a slot with a manufacturing partner, and then depending on that partner to scale our invention — which is fraught with risk, quality issues, and timeline issues. So that was the third piece we did: our solution was to internalize manufacturing, which we did — we made a very strategic acquisition of a Xoma manufacturing facility and their team, and we then had full control from discovery of the molecule, into the production of the molecule for the clinic. As we got further into development, we needed to commercialize that molecule, and again, we didn't want to depend on external parties to do so — so we just completed, a couple of months ago, the ribbon-cutting for our commercial-scale facility in Emeryville, California, which now gives us control from discovery, to manufacturing, to full commercial production. And in parallel, we acquired a clinical operations facility that also operates independently — so the capabilities of our clinical research organization support our own needs, but can also independently support the needs of even some of our largest competitors and partners.
So those capabilities allow us to say: from the point of discovery, to the first time we bring that product into a human, to all the data that's really critical to bring those products to patients broadly and commercially — we control that entire chain with a population of about 500 employees, which allows us to be incredibly agile, and to move quickly, bringing our innovations forward with great speed.

Sabine Hutchison
Yes, I think I can attest to that. I know, working with the Agenus team, that agility, speed, and decision-making is actually very high within the team, and that's an amazing accomplishment in a short period of time. So, to summarize: it's the people, it's the ability to manufacture in-house, and now the next step has been the commercialization side — really, truly bringing everything in-house. Quite a feat.

Jennifer Buell
That's right, thank you. I think that level of control allows you to determine your destiny — the speed with which you want to move, and the quality with which you can do so.

Sabine Hutchison
Yes, and you mentioned there — I think this is something so many biotechs deal with, this notion of being at the back of the line, or not being a platinum partner. We've seen this too in vendor-selection processes we've worked on — if you don't have a high volume of business, it can be difficult to get slots, specifically around manufacturing. So this kind of struggle, being at the back of the line — how soon did this start, or how quickly did you decide you needed to make this shift, to bring these activities and services in-house?

Jennifer Buell
That's a great question. In 2013, as we were interrogating ways to identify capabilities to start building molecules that could block the tumor's ability to escape immune attack — building on our learnings from the vaccine technology — once we identified that discovery capability and started producing molecules, we were building our timelines, and there was a very specific set of activities that needed to be completed. As we were going to manufacturing partners, externalizing the manufacturing of our antibodies, we realized this was adding many months, even years, onto our development timelines, and that was untenable for us. When you think about it — and many of us have experienced cancer in our families, or ourselves, which is so devastating — with that diagnosis, the urgency patients feel is unprecedented. As we started to look at the impact of depending on external parties who didn't have the sense of urgency we had for our patients, we decided there was no other way to do this than to bring the capability in-house.
It seems very obvious to us now, but at the time there were a number of considerations we needed to think through. First was identifying a capability, a team that was really form-fitted — that had the capacity, the capability, the production, a home, in which we could create our molecules, with a team that had done so reproducibly. That's where we were incredibly fortunate to make a strategic acquisition of the manufacturing capability of Xoma. Xoma's team at the time was led by Al Dotson, who we were able to bring in, and he's the chief manufacturing officer of Agenus today still. At the time it was a team of about 30 — we retained 100% of those team members, and then we expanded that team.
We reinvested in the capability and expanded it, then revolutionized it by building a commercial manufacturing and production facility, which we were able to do because of the density of talent that Al had, the vision we shared together, and the shared interest in bringing these molecules to patients really quickly. Something we don't think too much about is that once you decide to bring these technologies in-house, and identify the right technology, the right people, and the right fit, it's difficult for a pre-revenue biotech to actually finance it — I think it's beyond the scope of what many biotech CEOs can think through, because it can seem lofty, cumbersome, and costly.
However, our model — which I think was truly exciting and differentiated — was to identify parties who genuinely shared our core values and the urgency of our mission. In that shared understanding, they also knew that together, the sum of the parts could be truly invaluable to our patients. So we were able to strategically make these acquisitions through that shared vision — that coming together, we could create value for all of our stakeholders and share in the upside. Through some very thoughtful, predominantly equity-based transactions, we were able to bring in these capabilities in ways that have been so rewarding for our patients, our employees, and the partners we brought on board. And the beneficiary of this, once you have these capabilities, is that we've been able to leverage them to actually finance our business.
Our discovery capability has given rise to about a billion dollars in upfronts and milestones with partners — we've created molecules for Merck, for Incyte, for GSK, for our partner in China, Betta Pharmaceuticals, for Gilead, and most recently for Bristol Myers Squibb. So that innovation has allowed us to move things forward really quickly, and also take advantage of strategic collaborations that could help accelerate access to patients for our innovations. That's truly a testament to the value of bringing in capabilities from discovery to manufacturing, and then leveraging those to scale in our own hands — and be able to move molecules to patients much more quickly, in our own hands as well as in the hands of partners.

Sabine Hutchison
Wow, that is impressive — that is very impressive. And also, I think when you look at the time it's taken to do this, that's quite impressive too — if you look at what other, larger organizations, the amount of time they need to do exactly what you've just described, doing it in, I think, really just a few years is incredible. Building on that — in some of our previous conversations we've talked about commercialization too, because I think that's also another unusual trajectory and strategy you have for Agenus moving forward, compared to other biotech companies — many outsource the commercialization side of the business, that next phase, but you're also looking at moving away from a traditional commercialization method. Could you expand on that a bit more?

Jennifer Buell
I'd be happy to. I think, particularly in the US, but we're also seeing trends internationally, that the space between the product — the product-development group, the regulators, the doctors, and the patients — continues to grow. It's being interrupted and severed and pushed apart by a number of other parties in the mix, including distribution centers, PBMs, and a whole host of other parties who actually delay or impair our ability to get the product from where it needs to be to the doctor, so they can treat their patient quickly. We want to eliminate that — we want to move as quickly as possible from approval into the hands of a doctor, so they can treat their patients. A big part of that process is deep education.
So what Agenus has done — and you may have seen this — is be incredibly visible at a number of the highest-profile conferences and congresses, with nine plenary session presentations, to educate on the sophistication of these molecules and the benefit they're bringing to patients. I think that's necessary — the immunology of cancer is quite complex, and education is going to be a major part of allowing physicians to be comfortable, to understand which patients may benefit most, and how to administer these treatments effectively. And I believe we can do that best in the hands of the individuals who actually gave rise to these products, and who understand how these molecules work.
Part of this effort started with the onboarding of a world leader, Dr. Steven O'Day — a 30-year veteran of the clinic. He trained at Hopkins and Dana-Farber, then led the John Wayne Cancer Institute, and brought curative immune therapies to patients with metastatic melanoma — a disease that was historically fatal, with effectively no treatments. Steven O'Day gave the plenary session at ASCO that led to the approval of what's now called Yervoy and Opdivo — two checkpoint-modulating antibodies that have demonstrated curative potential for patients with metastatic melanoma. These are patients who've now exceeded five, almost ten years, and their disease hasn't returned — which is remarkable. We were able to bring Steven onto our scientific advisory board as we were building our pipeline and bringing it into the clinic, and he was taken by the assets we'd built and the potential for his patients at the time. He ultimately joined our company about two and a half years ago as our chief medical officer, and he's built a team of oncologists in disease-specific areas doing the same thing — bridging what we've learned from delivering effective immune therapies to melanoma patients, now to diseases that have never before responded. What we're seeing is long-term survival exceeding 75% in patients with diseases that are highly prevalent and have never responded to therapies. MSS colorectal cancer, for example, is a disease with about a 2% response rate to available therapies, and a benefit of about 1.7 months of life extension — and we're seeing effectively a tenfold improvement in response rates, and a dramatic, nearly doubling of survival in those patients. We most recently presented data at ESMO-GI. When we see that level of effect, we believe that through our own hands, we can bring this molecule to patients much more efficiently and effectively, and we're looking to do so.
Now, certainly, there are areas where we may want to leverage large pharma's footprint, to enable access in regions where we don't have a deep footprint. But our initial priority is to find ways to get these molecules into the hands of doctors in really unique ways. And the most important part of this — while we're seeing our molecules work very well in disease settings where patients have undergone surgery, or toxic chemotherapy, and their disease is still persisting, and we're able to salvage them and eliminate their disease across a host of different cancer types — we also believe that with this technology, if we could get the product into patients before they have to undergo the toxicity of certain chemotherapeutic agents, or the difficulties of surgery, that's where our molecules may be best fit — where we can actually eliminate the disease as soon as it's identified. We're starting to generate data in that disease setting as well. So all of these findings give us so much excitement around the potential of our pipeline. It also gives us a huge sense of ownership, urgency, and, effectively, responsibility to get these to patients. Taking control of that in our own hands is a big part of our imperative, to be able to deliver on the responsibility we feel so heavily.

Sabine Hutchison
Yeah. You're so consistent every time I speak to you — I've had conversations with both you and Garo in the past, and your pipeline — I remember the first time we had a conversation, I did research on the company and I was blown away, and I think that was one of my first comments: this is incredible, this super-impressive pipeline that you have. But also this drive of getting treatments to patients early — that's something I've heard from you over and over again, in every conversation. If you think about this intersection of what you've talked about — discovery, and getting treatments to patients — you've also thought about commercializing products yourselves, but also working with, potentially partnering with, other pharmaceutical companies. I'm curious to hear your strategy for how you decide which path to take with an asset.

Jennifer Buell
A very important part of our day-to-day considerations. I think, leaning back into what you just mentioned — our sense of responsibility and our sense of urgency — those are the principles and tenets from which we make these decisions. There are a couple of things we think about. One is reach: how could we get to patients as quickly as practical? In some cases there are partners who may have access to molecules we don't have in our own pipeline, that could help patients bridge the gap.
Their molecules may be effective to a certain extent, and we've built something to expand that benefit — those molecules may work really well synergistically, or be complementary. We think a lot about whether that approach, having access within a pipeline, would help accelerate our innovations to patients. We also think about how far they can get the products — we don't currently have a footprint in China, for example, so we thought very carefully about how to help a region with so many patients in need. That drove the strategy to pursue a partner with significant infrastructure throughout China, as well as deep partnerships with hospitals and regulators, so they could move programs quickly through their own pipeline. That was one of the imperatives for establishing a regional partnership with Betta Pharmaceuticals.
In other cases, we've generated molecules where we believe partners may be better positioned to get the molecule forward — such as our very novel TIGIT bispecific molecule, which we most recently partnered on with Bristol Myers Squibb. That molecule had just limitless potential from what we could generate in our preclinical models, and when we spoke with Bristol about it, they had not only the hunger and the drive, but also a platform for which they could very rapidly bring the molecule forward, in a disease state where they had deep experience. They haven't yet disclosed this, but they may relatively soon.
What we were able to do very quickly with this partnership is bring the molecule forward, develop it, and get it into the clinic very quickly. And then we were able to leverage Bristol's footprint to bring the molecule into certain disease-specific areas where they could do so with exceptional speed — that was an enormously important part of the decision-making process with Bristol. That allowed us not only to continue financing our pipeline, which included an upfront of over $200 million from Bristol for the preclinical asset, but also set us up for a series of success milestones throughout the development of the program. And we were still able to retain access to the molecule for combinations in other parts of our pipeline — so we retained access to the innovation while scaling it to patients much more broadly. It really is about focusing on those tenets of getting the molecule to patients very quickly — thinking about who can do so with great speed, efficiency, and effectiveness, while retaining some access so we can expand the potential across other combinations within our own pipeline.

Sabine Hutchison
Incredible — thank you for sharing that, Jen. I think I could go on for hours with you, so many questions, so many lovely conversations to have. This has been insightful, and I so appreciate your openness in sharing some of these stories and the path you've taken with Agenus. When I look at the industry — I love the biotech industry, it's teeming with such innovation — I believe sharing these types of stories is so essential to help foster even more progress and ingenuity in the industry. Thank you for being willing to share your experiences and ideas — I'm sure they'll continue to contribute to further innovation in the industry. As, unfortunately, we have to wrap it up today, I do have one final question for you: if you could summarize three points on how smaller, mid-sized biotechs can actually move the needle, in really exceptional ways — what are the differences they can make, and what would those three points be that you'd suggest?

Jennifer Buell
I would first start with the people — I would deeply evaluate your talent and increase the talent density to enable rapid innovation. Delivering high science through great individuals will eliminate delays in decision-making, allow for super-targeting in unique areas of unmet need, and perfecting molecules that aren't performing, and expanding benefit for patients — critically important. People are the highest priority in any organization, and you'll see that just by bringing in the best talent, everything else becomes much easier, and also incredibly exciting.
Agility — being able to move fast, see further, without any blocks obscuring your view — allows you to accelerate development timelines, respond to emerging opportunities, and pivot when needed. We've really been purposefully small and efficient, to control costs and allow us to deliver innovations really quickly without encumbering our stakeholders, our patients, et cetera. So we could deliver a lot of innovation with very controlled costs and speed, and I think that's incredibly important. So, talent, agility, and strategic collaborations are really important — we've spoken quite a bit about this during this discussion.
Thinking about how others in the field may be able to help you get to the finish line, and to your ultimate goal of delivering medicines for patients quickly, is such an important component of success — particularly success in biotech innovation. I think those are three really important areas, in the context of being quite creative and finding partners who share your vision — that's critical for success as well.

Sabine Hutchison
Yeah, absolutely. And it's interesting, your first point is talent — I think talent does attract other talent, doesn't it? Having phenomenal team members, they're attracted to come to an organization, and I think that's so important not to underestimate, how crucial that is when you bring individuals into your team.
Thank you again so much.

Jennifer Buell
Sabine, thank you — it's been such a pleasure. It's really been such a pleasure talking with you, as always.

Sabine Hutchison
Yes, thanks, Jen. And maybe we'll see each other again on another edition of the podcast — I'm sure there are lots more questions to come.

Jennifer Buell
I'm counting on it. Thank you again, and thanks for the work that you're doing — it's incredible.