Sabine:
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. Gara Armin in 1994, Agenus is a clinical stage biopharmaceutical company that discovers, manufactures, and develops immunotherapies for the treatment of cancer. Agenus Bio recognizes the importance of personalized medicine and tailoring treatments to individual patients. Through their 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 the delivery of more precise and effective cancer treatments.
Today, I’m delighted to be joined by Dr. Jennifer Buell. She is an accomplished leader from Agenus Bio, and our conversation promises to be nothing short of extraordinary. Jen is the president and CEO of Mink Therapeutics and chairman of the executive council at Agenus. Her career spans over 25 years in the biopharmaceutical industry and is 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 to clinical development and commercialization.
Today, we will be delving into her experiences during her time as president and Chief Operating Officer to Jen’s bio, 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 has experienced exponential growth, expanding from a team of 50 to an impressive 500 individuals. Agenus boasts an exceptional pipeline with a staggering 17 molecules which went into the clinic within five years. However, such successes do not 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 is such a pleasure to have you here today and I’m really pleased to spend some time with you. So thank you very much for being here. And we’ve
Sabine:
We’ve had the opportunity to have many conversations. And as I think back, there was really one statement that stuck with me. And you describe agendas as being purposely different. And can you share with us today, where does that statement come from and why is agendas 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 a Agenus different and purposefully so? I’ll tell you first, it’s our talent. And this isn’t really just cliche. We’ve concentrated our talent into a deeply dense group. And this allows us not only to move more effectively, but much more efficiently as well. And when it comes to innovation, what we’ve really found is that it is truly the few over the many. People are the most critical asset that we have in our organization. And it’s through them that we’ve been able to actually realize a pipeline that appears to be unprecedented in immune oncology. And this component, deepening our talent density, has been a tenant 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 the biotech company of our size.
Control over the quality and the speed of our products and the lifecycle of our products, we have found, is best controlled in our own hands, in the hands of our own internal experts. And so internalizing capability from discovery technology to manufacturing technology to clinical research operations, which is very unique in a biotech, owning and holding your own clinical research operations internally. It not only allows us to lead from the front, but it also enables us full control of the speed and quality with which we move. That’s been really, really core to our strategy.
I’ll tell you a little bit more about that. In 2013, as you mentioned, we were a 50-person company with a single product, and that was a pioneering product, which was an individualized vaccine product in which we would take a patient’s tumor and create their treatment. And in doing so, we built on a capacity here, which includes taking a patient’s tumor from patients all around the world. We are domiciled here in Lexington, Massachusetts, and we would have tumors shipped to us post-surgery from Australia, New Zealand, Israel, Russia, everywhere, really. The tumors would arrive and we would create a patient’s treatment and have it back to them within about three weeks, which was completely disruptive in the industry.
Sabine:
Wow, that is very disruptive already. Yeah, amazing.
Jennifer Buell:
And I think that what we were able to learn from that is that we could actually take a patient’s tumor and immunize them against their cancer. And it was really powerful. We could see that the patient’s immune system could be educated, it could seek out, it could find the patient’s cancer, and it could start to destroy it. As we were continuing to develop that program, we had amassed quite a bit of learning. And that was essentially that in some patients we had curative responses. we saw that the tumor was stronger than the immune system. So we set out on a quest in order to be able to really address those immune escape mechanisms or those escape hatches where the tumor was really evading the immune system. And so in doing so, we started with discovery.
As opposed to getting access to molecules that were commercially available or already in the field, we wanted really to harbor those within our own pipeline. So we started with the Discovery Engine and we acquired an antibody platform. It was called 4antibody at the time and it had come out of Roche Diagnostics. And 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. So going from a single product, we now have a pipeline of over 22 molecules, and 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. And our most advanced asset is a product called Botan-Cilumab, which we created in our own hands, which actually 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, create a molecule that addressed the areas where tumors are escaping. And these are a host of highly prevalent tumors that are unresponsive to really anything that’s available to them. And Botan-Columab has been able to break through and in over 11 tumors really showcase that value. And that truly came from our own. internal engineering. And that was a 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 that were out there.
And it doesn’t end there, because once you make the discovery, you create the molecule, you define the biologic properties, you need to manufacture it. And that’s actually where most biotech companies encounter encumbrances or issues with speed and with quality. This is where we essentially say we just were tired of waiting in line, waiting for a slot in a manufacturing partner. And then we depend on that partner really to scale our invention. And that’s fraught with risks and quality and timelines. So that was the third piece that we did. Our solution was to internalize manufacturing, which we did. We made a very strategic acquisition of a Zoma 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. And then as we got further into development, we needed to commercialize that molecule. And again, we did not want to depend on external parties to do so. So we’ve just completed just a couple of months ago, the ribbon cutting for our commercial scale facility in Emeryville, California, which now gives us the control from discovery to manufacturing to then full commercial production of that. And in parallel, we acquired a clinical operations facility that also is independently operating. So the capabilities of our clinical research organization supports our own needs, but they also can independently operate and 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 that we’re bringing that product into the human, into all of the data that’s really critical to bring those products to patients broadly, commercially. We control that entire entity with just a population of about 500 employees, which allows us to be incredibly agile. and to move quickly, bring our innovations forward with great speed.
Sabine:
Yes, I think that I can attest to that. I know that working with the Agenus team, that agility and speed and decision making is actually a very, is very high within the team. And that is 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. So really, truly bringing everything in-house. Quite a feat.
Jennifer Buell:
That’s right. Thank you. Yeah, 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:
Yes, and you mentioned there, I think that this is something that so many biotechs deal with. It’s this notion of being at the back of the line or not being platinum partners. We’ve seen this also in vendor selection processes that we’ve worked with that if you don’t have a high volume of business, it can be difficult to get slots. Specifically, you mentioned around the manufacturing. And so this kind of struggle or being at the back of the line, How soon did this start or how quickly did you decide that you needed to make this shift to try to bring the activities and services in-house?
Jennifer Buell:
That’s a great question. And in 2013, as we were interrogating ways in which we can identify capabilities to start building molecules that could block the tumor’s ability to escape immune attack, our learnings from the vaccine technology, once we identified that discovery capability and started producing molecules, we were building our timelines. And there were very specific set of activities that need to be completed. And we were watching that as we were going to manufacturing partners externalizing our manufacturing of our antibodies, we realized that this was adding really many, many months to years on our development timelines. And that was untenable for us. When you think about it, and many of us have all experienced in our families or even in ourselves the experience with cancer, which is so devastating. And with that diagnosis, the urgency that patients feel is unprecedented. And I think that as we started to look at the impact of these capabilities and having to depend on external parties who did not have the sense of urgency that we had for our patients, then we decided that there was no other way to do this than to bring in the capability.
And I think that, so it seems, you know, now it seems very obvious to us. And at the time, of course, there were a number of considerations that we needed to really think through. And first was identifying a capability, a team that was really form fitted, that had the capacity, that had the capability, that had the production. that had a place, a home, in which we could create our molecules with a team that had done so reproducibly. And that’s where we were incredibly fortunate to be able to make a strategic acquisition of the manufacturing capability of Zoma. And Zoma’s team at the time was led by Al Datsun, who we were able to bring in, and he is the Chief Manufacturing Officer today still of Agenus. And what he and his team, at the time of 30, we retained 100% of those members of the team. And then we expanded that team.
We reinvested in the capability and expanded the capability. And then we revolutionized the capability by now building a commercial manufacturing and production facility. And we were able to do that because of the density of the talent that Al had, the vision that we shared together. and the interest that we had in bringing these molecules to patients really quickly. And I think that something that we don’t think too much about is once you make a decision to bring these technologies in and you identify the right technology and the right people and the right fit, and you do so, it’s difficult as a pre-revenue generating biotech company to actually think about financing it. And I think it’s beyond the scope of what many biotech CEOs can think through.
And because it seems in some capacity, really lofty and cumbersome and costly. However, our model, which I think was truly exciting and differentiated was to identify parties who actually truly shared our core values and the urgency of our mission. And in that sharing, they also knew that together, really, the sum of the parts could be truly invaluable to our patients. And so we were able to strategically make some of these acquisitions through the shared vision that coming together, we would be able to create value for all of our stakeholders and share in the upside. So through some very thoughtful. predominantly equity-based transactions, we were able to bring in these capabilities and we were able to do so in ways that have been so rewarding for our patients, for our employees, and for these partners that we brought on board. And the beneficiary of this, once you have these capabilities, we’ve been able to leverage these capabilities to actually finance our business.
Our discovery capability has given rise to about a billion dollars in up-fronts and milestones with partners. We’ve created molecules for Merck, we’ve created molecules for Insight, for GSK, for our partner in China, Beta Pharmaceuticals, for Gilead, and most recently for Bristol-Meyer Squibb. So that innovation has allowed us to move things forward really quickly and also take advantage of strategic collaborations that could help us accelerate access to patients for our innovations.
And that is truly a testament to the value of bringing in the capabilities from discovery to manufacturing, and then leveraging those to scale 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:
Wow, that is impressive. That is very impressive. And also, I think when you look at the time that it’s taken to do this, it’s quite impressive. If you look at what other larger organizations, the amount of time that they need to do exactly what you’ve just talked about in, I think, really a few years is incredible. And building on that, when in some of our previous conversations, we’ve talked about also the commercialization, because I think that that’s also another unusual trajectory and strategy that you have for Agenus moving forward as compared to other biotech companies, because many outsource the commercialization side of the business or that next phase. But you’re also looking at moving away from a traditional commercialization method. And could you expand on that a bit more?
Jennifer Buell:
I’d be happy to. I think that we are particularly in the US, but we’re also seeing trends internationally in which there’s the space between the product and the product development group, the regulators, the doctors, and the patients continues to grow. And they’re being really interrupted and severed and pushed apart by a number of other parties in the mix, which includes distribution centers and 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 that they can treat their patient really quickly. And we want to eliminate that. We want to move as quickly as possible from an approval into the hands of a doctor so that they can treat their patients. And a big part of that process will be through deep education.
So what Agenus has been, and you may have seen this, we’ve been 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 that these molecules are bringing to patients. And I think that that’s necessary. you know, the immunology of cancer is quite complex and education is going to be really a major part of allowing physicians to be comfortable and to understand the patients who may benefit the most and how to administer these treatments effectively. And I believe we can do that best in the hands of the individuals who have actually given rise to these products and who understand the way that these molecules work.
And part of this effort started by the onboarding of a world leader. Dr. Steven O’Day is a 30-year veteran from the clinic. He trained at Hopkins and Dana-Farber, and then he led the John Wayne Institute Cancer Center. And he brought curative therapies to patients, immune therapies to patients with metastatic melanoma. Now this was a fatal disease, and effectively there have been no treatments for this historically. And Stephen O’Dea gave the plenary session at ASCO that led to the approval of now what’s called Yervoy and Opdivo. These are two checkpoint modulating antibodies that have demonstrated curative potential for patients with metastatic melanoma. Now these are patients that have now exceeded five and almost 10 years and their disease has not returned. And that is just remarkable. We were able to bring Stephen onto our scientific advisory board. as we were building our pipeline and bringing it into the clinic. And he was taken by the assets that we had and what we had 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 who are doing the same, bridging what we’ve learned of delivering immune therapies that are effective to patients with melanoma, now to diseases that have never before responded. And these are What we’re seeing are long-term survival, exceeding 75% in patients with diseases that are highly prevalent and have never responded to therapies. MSS, colorectal cancer, for example, it’s a disease that has about a 2% response rate from available therapies and a benefit of about 1.7 months of life extension. And we’re seeing effectively a tenfold improvement over response rates and a dramatic nearly doubling of survival in those patients. And 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 much more effectively. And we’re looking to do so.
Now, certainly, there are areas where we may want to leverage. large pharma’s footprint in order to enable access in regions where we may not have a deep footprint. However, our initial priority is to find ways in which we can get these molecules into the hands of doctors in really unique ways. And the most important part of this is while we’re seeing that our molecules are working very well, in disease settings where patients have undergone surgery. or toxic chemotherapy and their disease is still persisting. And we are able to salvage them and eliminate their disease in a host of different cancer types. We also believe that with this technology, if we could get the product into patients while they’re, before they have to undergo the toxicity of certain types of chemotherapeutic agents or the difficulties of surgery. where we believe that that’s where our molecules may be best fit, where we can actually eliminate the disease as soon as it’s identified. And 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 and urgency and effectively responsibility to get these. to patients. And so taking control of that in our own hands is a big part of our imperative to be able to deliver on the responsibility that we feel so heavily.
Sabine:
Yeah. And you know, it’s, um, you’re, you’re so consistent every time I speak to you and I’ve had conversations with yourself and Gara in the past and, you know, your pipeline. I remember the first time we, um, we had a conversation and I did research on the company. I was blown away. And I think that was one of my first comments. He was like, this is, this is incredible. This, um, super impressive pipeline that you have. But also this. this drive of getting treatments to patients early. I think that is something that I’ve heard from you over and over again in every conversation. And if you think about, so this intersection, what you’ve talked about with discovery and getting treatments to patients, you also have thought about and will commercialize products yourself, but also work with other, potentially partner with other pharmaceutical companies. I’m curious to hear your strategy around how you decide which path you will take in asset.
Jennifer Buell:
Very important part of our day-to-day considerations. And I think that to lean back into what you just mentioned, our sense of responsibility and our sense of urgency, those are our principles and our tenets from which we make these decisions. And there are a couple of things that we think about. One would be reach. How could we get to patients as quickly as practical? And in some cases, there are partners who may have access to molecules that we do not have in our own pipeline that could help patients to bridge the gap.
So their molecules may be effective to a certain extent, and we’ve built something to expand that benefit. And those molecules may work really well synergistically, or they may be really quite complementary to each other. And we think a lot about that. Would that approach, being able to have access within a pipeline? would it help to accelerate our innovations to patients? And that’s something that we think quite a bit about. We also think about how far can they get the products? We don’t currently have a footprint in China, for example. So we thought very carefully about how can we help a region where there are so many patients and so many patients in need? And that drove a strategy to pursue a partner who actually has not only a significant infrastructure throughout China, but also has deep partnerships in hospitals and with regulators so that they could move programs very quickly through their own pipeline. That was one of the imperatives for us to establish a partnership, a regional partnership, with better pharmaceuticals. And in other cases, we’ve generated molecules in which we believe that partners who may be positioned to get the molecule, such as our very novel TIDGET bispecific molecule that we most recently partnered with Bristol-Meier Squibb. That molecule had just limitless potential from what we can generate in our preclinical models. And when we spoke with Bristol about the molecule, they had effectively not only the hunger and the drive, but they also had a platform for which they could very rapidly bring the molecule forward in. a disease state that they had deep experience in. They have not yet disclosed this, but they may relatively soon.
What we were able to do very quickly with this partnership is we were able to bring the molecule, develop it, bring it into the clinic very, very quickly. And then we were able to leverage Bristol’s footprint to bring the molecule in certain disease-specific areas where they can do so with exceptional speed. And that was an enormously important part of the decision-making process with Bristol. And that allowed us not only to continue to finance our pipeline, which included an upfront of about $250 million, over $200 million from Bristol for the preclinical asset, but then 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 still retained access to the innovation while we were able to scale it to patients much more broadly. So it really is focusing on those tenants of getting the molecule to patients very quickly. We think about who can do so with great speed and efficiency and effectiveness while we’re continuing to be able to do so and retain some access so that we can expand. what we believe to be the potential across other combinations within our own pipeline.
Sabine:
Incredible. So thank you for sharing that. Jen, I think I could go on for hours with you. Lots of questions and lots of lovely conversations to have. So, this has been insightful and I so appreciate your openness and sharing some of these stories and paths you’ve taken with an agenus. It’s really when I look at the industry, I love the biotech industry, and it’s teaming with such innovation. I believe that 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 your ideas. I’m sure that they will continue to contribute to further innovation in the industry. As unfortunately, we have to wrap it up today, I do have a question for you, one final question. If you could summarize three points on how smaller mid-sized biotechs can actually move the needle, and really in exceptional ways, you know, what are differences that they can make and what would those three points be that you would suggest?
Jennifer Buell:
I would first start with the people, and I would deeply evaluate your talent team and increase the talent density to enable rapid innovation. I think delivering high science with great, through great individuals, I will say, it will eliminate delays in decision making. It will allow for super targeting in unique areas of unmet need and perfecting molecules that aren’t performing and expanding benefit for patients. critically important. The people are the highest priority in any organization, and you’ll see that just by bringing in the best talent, everything else becomes immensely easier, much easier, and also incredibly exciting.
Agility, being able to move fast, see further without any one or 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, allow us to deliver innovations really quickly and without really encumbering the stakeholders, which are our patients, et cetera. So, we could deliver a lot of innovation with very controlled costs and speed. And I think that that’s incredibly important. So, the talent, the 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 get to your ultimate goal of delivering medicines for patients quickly is such an important component of success, particularly of success in biotech and biotech innovation. I think that those are really three important areas and in the context of being quite creative and finding partners who share your vision. That’s a… critical for success as well.
Sabine:
Yeah, absolutely. And it’s interesting your first point is talent. And I think talent does attract other talent, doesn’t it? Because having phenomenal team members, they’re attracted to come to an organization. And I think that that’s so important not to underestimate how crucial that is when you bring in individuals into your team. Thank you again so much.
Jennifer Buell:
Sabina, thank you. It’s been such a pleasure. It’s really been such a pleasure talking with you as always.
Sabine:
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.
Tune into the podcast right here: https://www.seuss.plus/blog/episode-2-innovation-unleashed-exploring-the-intersection-of-science-and-creativity-an-unconventional-growth-strategy/