Foundery: Max Krummel & Michel Streuli
Foundery: Max Krummel & Michel Streuli
“We are trying to drive discovery that matters.”
Science can be surprisingly artisanal—university labs are rarely the serious, industrial environments depicted on TV. Coffee-stained papers and journals pile precariously on desks, posters of ornate signaling pathways hang crooked on walls, and thriving philodendrons line windowsills. Discussions of real or imagined experiments, laughter, and gossip punch through a background hum of centrifuges, freezers, and fume hoods. It is creative and chaotic: “What is really exciting about science is that it allows you to imagine the ‘hidden world’ as it could be,” describes Max Krummel, Professor of Pathology at UCSF and co-founder of Foundery Innovations.
Academics are trained to generate novel ideas and test them—not to develop drugs: “As academics, we know a lot about what we study…but we are not trained to translate our work to humans,” says Krummel. Enter biotech and pharma—entities rarely described as “artisanal.” The emphasis there is to efficiently move towards clinical products that can help patients: “Doing science in an industry setting is different,” describes Michel Streuli, CEO of Foundery Innovations. “You have to see drug development firsthand to really learn it.” To be successful in biotech requires combining the unfettered creativity of academia with the practical skillsets of pharma veterans—according to Krummel, "we wanted to create an infrastructure where the benefits of academia and industry can swirl around each other.”
After discovering and patenting the first CTLA-4 inhibitor in Jim Allison’s lab (developed into Yervoy), Max Krummel embarked on a career as an academic. For decades, his lab has studied how immune cells interact with tumors, stromal cells, and other immune cells. Through his work, he became convinced that modulating macrophage function in the tumor micro-environment could combat cancer: “In 2015, our lab had found some interesting myeloid targets as an alternative way to hit tumors. I wanted to test the therapeutic hypothesis that this ‘myeloid tuning’ would benefit patients. So, I founded a company [Pionyr Therapeutics], got an incubator space, and started to pitch VCs.” During his pitch process he met Michel Streuli, a 20+ year pharma veteran. After running an academic lab at Dana Farber Cancer Institute for 10 years, Michel decided to jump to industry: “Fundamentally, I wanted to use what I had learned [in academia] to make drugs,” says Streuli. After helping develop Keytruda (at Organon, Schering Plough and Merck) and a three-year stint as head of immunology at Gilead, Streuli met Max while consulting for a VC: “I was taken by his ability to tell a story, and his energy. So that was an enormously positive first impression,” reflects Streuli.
Michel bought into Max’s vision and joined what became Pionyr Therapeutics—becoming the company’s CSO. Yet Pionyr’s subsequent success (and partial acquisition by Gilead in 2020), meant that it was time for Michel and Max to move on: “There was this point where everything was going to the clinic. There is an adage that ‘when R&D teams have success, they frequently write their own pink slip.’ R&D is not needed in the same way—there is a disassembling of the band,” explains Krummel. “After the Pionyr experience, we wanted to imagine drug development as it could be—a world where these successful ‘bands’ stay together.”
In 2021, Max and Michel formalized this vision to create Foundery—an immunology-focused venture studio that “puts discovery first.” PIs from any university or research institution can contact the Foundery with their early-stage ideas—after an initial meeting, the Foundery team will decide whether or not to pursue the project and run experiments in their own labs (adjacent to UCSF). When they accept a project into the portfolio, the PIs involved receive shares in the “Foundery partnership.” As their project hits milestones, they receive more shares in the partnership and in any NewCo formed: “Our ethos is that we want to do right by the academics because we value the mutual advantage of being partners,” explains Streuli. Foundery has inked a master licensing agreement with UCSF—one that streamlines legal processes and gives the university and founders a greater share: “[the agreement] really makes our interactions friction-free…and sets the whole partnership off on the right footing,” says Streuli.
Why is putting money into Foundery Innovations a smart investment for LPs? Krummel explains that they “use an internal team to cheaply and quickly identify the most promising targets…we are going to do the things that are brand new. Investments will be in targets that no one's heard of yet, with science that we have validated in-house. These types of companies will be game-changing.” Immuno-oncology is a crowded space, and as developers of the first anti-CTLA4 and anti-PD1 antibodies, Krummel and Streuli know this all too well. To find novel biology, Foundery is giving PIs access to a “plug and play” discovery engine powered by Streuli and his team of drug developers: “young investigators have a risk-free opportunity to test out their bold ideas, without sacrificing their academic career,” says Krummel.
Unlike traditional venture investors or creators, the Foundery team will physically create reagents, run experiments and even help publish papers prior to company formation: “We place discovery ahead of expensive company creation…we won’t be forced into making one idea work. We believe that we are putting the cart behind the horse—where it should be,” concludes Krummel. When asked what success looks like for the Foundery in 10 years, Streuli replies: “Our mission is to become the ‘go-to’ partner for university researchers doing the most innovative work. In 5-10 years from now, if PIs are coming to us with exciting ideas, and we are fulfilling an important need, it will be a success.”
Initiatives like Foundery invite a re-imagining of the academic lab experience described in the first sentences of this piece:
After laughing with lab mates, running a gel and grabbing a cup of coffee, a grad student walks across the street to the Foundery labs. There she meets with a team of experienced drug hunters to discuss toxicology experiments, clinical biomarkers, competitive landscapes, and formation of a NewCo based on her thesis work. Coffee now finished, the grad student heads back across the street to lab—all in time to quickly eat lunch, water her philodendron and, of course, get back to running experiments.
Below is an interview with Dr. Max Krummel and Dr. Michel Streuli of Foundery Innovations from March, 2023:
1. What do you consider to be your first taste of science? Whom do you consider to be your greatest scientific mentors?
Max Krummel (MK): In college, I was a chemistry major. I joined a lab where I studied marine natural products. I was essentially looking for drugs made by sea creatures that could inhibit either bacterial growth or induce cytotoxicity in cancer cell lines.
I had a great mentor—I felt like the lab was a place where I could go where it would just be “my time.” I had access to all this equipment and a bunch of smart people. The idea there was really to explore, learn, and try to carry those findings downstream. Specifically, we isolated sea squirts, which make drugs to compete for life under the ocean. They cross compete by poisoning each other. You may be familiar with tunicamycin—which comes from tunicates like these sea squirts.
My college chemistry lab was a really good introduction to science, where I could just play. I have stories of almost blowing up the lab by trying funny reactions that I wasn't supposed to be doing—but it was just a really fun time. That [spirit of independent discovery] is essentially what I looked for in a PhD lab. My graduate mentor, Jim Allison, was quite hands-off and traveled a lot. I always had a defined project, but I could also go off on tangents and three weeks later present my results.
[Did you always try to apply your science to improving human health?]
MK: I think the interest in science that many people find is one of practical applicability—having a proximal goal can make science even more fun. I always wanted to have the sense that I could discover something really important.
For example, the idea that you might discover in a sea creature something that cures cancer is a big thought—if you take a bunch of sea squirts, grind them up, put them over a column, you could find a new drug. I found the idea of discovering something that other people think is important, and can help people, to be really cool.
[Michel, were you always destined to be a scientist from childhood? How did you come to it initially?]
Michel Streuli (MS): My father was a physician, so that influenced me towards science and medicine from an early age. I remember when my family moved to the States, one of the most formative experiences I had was building a washing machine in the third grade. In retrospect, I think that really instilled in me the desire to build things; as well as the importance of teamwork—because it was a group of us who did it.
Experiences like these instilled in me a lot of the foundations that I think you need to be a productive scientist. Later on, when I was a young graduate student, we had cloned interferons in the lab. I had specifically sequenced interferon-alpha-2b, which became INTRON ®. In those days we used the Maxim-Gilbert method and would then read the sequence from a gel.
After we had the sequence in hand, I remember my PI [Charles Weissmann] looking at me and saying: “you've just leapfrogged a Nobel laureate’s about 7 years’ worth of work.” He said that because [Christian] Anfinsen had been trying to get the direct protein sequence of interferons as well. We however, were using molecular biology techniques [cloning, DNA sequencing]. This was a profound experience because it taught me the importance of technology—what you can do with it, and how tech development is often the precursor to big scientific discovery. I think that experience in grad school was profound. It also explains why I really enjoy working with Max [Krummel]: he is someone who pushes the technological boundaries to make foundational new discoveries.
2. Max, what led you to graduate school, and a switch from chemistry to immunology? What was it like working with Jim Allison, and pioneering the concept of checkpoint blockade?
MK: When I started my PhD, I was given a relatively small slice of the pie. For me, the excitement of joining Jim's lab was that there was this protein [CTLA4], which was interesting and weird. But at the time, it could have turned out to be a relatively unimportant molecule. There's always some element of luck to what you're working on.
We started with the premise that to understand immunology, one had to understand the molecules on the surface of the T cell—at the time, they were the next frontier. Today, of course we are into this area where we have the ability to look at multicellular dynamics and how everything works in a high throughput and aggregate way. But back then, it was pretty simple--there were like six known molecules on the surface of T cells. There was this visceral sense, because of the AIDS crisis, that if you lose T cells you are in bad shape. So, we knew these cells were important, but it was not clear what disease we were going to impact.
Coming at this from the standpoint of a fundamental question: I think the most exciting part of that experience was the point where I had a reagent [CTLA4 antibody] and could start to push on the biology. It took me years to do that because CTLA4 is internalized very quickly on T cells. So initially establishing reagents against it was hard. Then when we had antibodies, I spent two months characterizing them—unstructured experiments where we said: “let's inject that into a mouse and see what happens. Let's co-inject with superantigens or immunization protocols.” But once we had a protocol [for using anti-CTLA4], it was easy to do the crucial tumor experiment. Though, even after we published that paper, for years, people were not convinced that you could take the immune system and have it specifically kill cancer cells. About 5% to 10% of Keytruda patients end up getting things like diabetes and Addison's, so there was a real question there about specificity. Nevertheless at some point, when you get on a roll with the project, there is a low barrier to doing the next crazy experiment. And if that works, then you just keep going.
[What led you to Allison lab coming from a chemistry background?]
MK: The AIDS epidemic made everyone realize the profound importance of the immune system, and T cells in particular. Jim was working on the receptors on the T cell surface, and I thought: “yeah, that's the right question to ask right now. What are these receptors doing?” CLTA4 had just been cloned, and it had sequence homology to this mother molecule CD28. So that molecule and project was really interesting in Jim's lab; there were just a number of things that basically aligned to convince me that this is the right kind of project in an interesting area. Then again, it turned out to be way harder to ask the fundamentals and establish reagents. But once I got over that hump, progress was fast. When I mentor students, one of the big things that I remind them is: there is no “quid pro quo” in science; you can work for 100 hours and get nothing. And then you can work for one hour and get 100 times your output.
3. Michel, you were a Professor at Harvard/DFCI for 10 years. What initially led you to transition to industry? Briefly, what were some of the lessons learned here in drug development that are harder to come by in an academic setting?
MS: A confluence of factors led me to industry. I had been a postdoc at the Dana Farber, and then I was professor there for 10 years. At the time, the Farber was changing, and the head of my division had retired. There were also some personal factors. But fundamentally, I also wanted to use what I had learned to make drugs. During my graduate studies, I saw that you could do science to make a drug that changes people's lives [interferon-Alpha-2b, INTRON ®]. This is a narrative you hear quite a bit, about why people choose to go into industry.
[What were the lessons learned, specific to working in industry?]
MS: Part of the learnings relate to understanding the drug development process; you can learn about this only theoretically in universities. I think you have to do it, and see it firsthand to really learn [drug discovery]. Being at a large company, you do come to appreciate the specific skill sets needed to make a drug: toxicology, regulatory, clinical biomarkers and others. There is also an appreciation that doing science in an industry setting is different. Part of that is that there are a lot more resources—so you can do things that are statistically meaningful and have all the skill sets you need to generate and analyze that data. Another important difference is that industry is a team sport. In academia, science is still a little more of an individual endeavor: to be successful as a postdoc, and then as a faculty, you have to get grants, senior author papers, etc. So, academia has a different reward system and dynamic than industry.
[Max on the industry vs academia divide]
MK: What is really exciting about science is that it allows you to imagine the “hidden world” as it could be. There's a way we currently describe the world, and then there's the way that it could be. There is this traditional divide that Michel has just described [between academia and industry] The people that go into industry become “borgs” to use the Star Trek analogy—increased efficiency can come with a loss of control and ego. In academia, we have a pretty good personal drive [ego] but there is less teamwork and efficiency. We want to create an infrastructure where the benefits of both academia and industry can swirl around each other.
At Foundery, we are trying to drive discovery that matters. We want the academic research scientist to get the collaborative value of working in industry; at the same time the experts in drug development [from industry], can have agency in making major discoveries again. That is the big vision. The other point is that PIs know a lot about what we study in the lab. But we don't actually know a lot about what needs to happen to translate our work. [Translation] is a value element that Michel knows really well, I know less well, and my colleagues who haven't engaged with industry before may not know at all. Where do you need to go to develop a drug? What are the some of the standard best practices that you can put into place for immunotherapies? In August, the Foundery labs will be right across [from UCSF]. We can literally walk across the street and facilitate some of these interactions.
4. How did you two first meet and what type of work did you two initially do together? When considering a partner (in science or business) what are the types of things that you look for?
MK: I made and patented the first CTLA4 antibody. Initially, pharma and VCs were not interested. There was one exception to that rule, which is this company called Medarex, which ended up making the first CTLA4 human antibody, along with the first cLAG3 and others. Around this time (early 2000s), Michel joined Organon and helped develop Keytruda—so there was a parallel career development. Flash forward to 2015, our lab [at UCSF] had found some really interesting myeloid targets for an alternative way to hit certain kinds of tumors. I wanted to test the therapeutic hypothesis that this would benefit patients. So, I founded a small company [became Pionyr], got an incubator space, and started to pitch VCs. Michel had just left a position as head of Immunology at Gilead and was working for a venture capital firm—as a side gig. He listened to the pitch and was excited about it, and soon came on board as the CSO. We then got to know and respect each other. We appreciated the parallel tracks we had taken in academia and drug development [Yervoy and Keytruda development]. At Pionyr, there was this point where everything was going to the clinic. There is an adage that: “when an R&D team has success, they frequently write their own pink slip.” Small companies often focus on taking successful development candidates to the clinic and don’t need R&D in the same way anymore—there is a disassembling of the band, when the band has been successful. After the Pionyr experience, we wanted to imagine drug development as it could be—a world where these successful “bands” stay together. At Foundery, we want to bring the best people in, and plug that into to discovery on multiple fronts on a perpetual basis.
Cancer is not just about T-cells—there are all of these “me too” therapies and we both bear some responsibility for that [by developing the first CTLA4 and PD1 therapies]. Some of the best trigger points are not going to be T-cell checkpoint inhibitors—we have exhausted this “me too” science and need to think laterally. There is a ton of space to move in immunotherapy, distinct from T-cells. Michel and I are both very aligned on this idea, and we are pursuing this creative thinking at Foundery.
[What are the most important things you look for in a scientific partner?]
MS: Max touched on it a little bit—I think it's mutual respect along with complimentary skill sets and backgrounds. You need the whole to be much better than the sum of its parts. You also have to enjoy working with someone, I think that human element is so fundamental. I remember Max was pitching [Pionyr] to a VC firm that I was advising. I was just taken by his ability to tell the story and his energy. So that that was an enormously positive first impression. Those impressions turned out to be really important for me, because that has defined our relationship over the last seven or so years.
5. What was the need you saw in the scientific and biotech communities that led to the conception of Foundery Innovations?
MK: After CTLA4 and Pionyr, I had two other things that I thought I might pursue into translation. But I realized that there is this huge inefficiency. There is a huge amount of investment upfront, especially in the first two years—you are going to work an extra 40 hours a week, and will have to figure out licensing, which can cost $100,000 in legal fees. There is learning the whole pitching process—getting good at telling a story that people will buy into. There is also this huge inequity—older, more famous people will raise capital more easily because they get credence that they possibly deserve, or possibly don't deserve.
In the first two years, CTLA4 and myeloid tuning [Pionyr] were widely discounted by investors. The idea that you must take a two-year risk on something, particularly when you're in your 30s and 40s is difficult. For example, with CLTA4 I did not do that [start a company]. Michel and I were thinking about how to solve these inefficiencies, and we arrived at the Foundery—a lab that already has everything you need. We [Foundery] have also negotiated unique agreements with the university, where we give more equity to the academics (university + founders) than a VC normally would. But, in exchange for that, we can use private capital to quickly and efficiently run experiments and get proof of concept.
From the investor standpoint, it's five to 10 times cheaper as an endeavor than to set up a new company and then run the same experiments later. We can use an internal core team to quickly identify the most promising targets and science—if we fail, we swiftly move on to another project. This will be easier for academics, young PI's especially, to translate their work. Ultimately, it will also lead to investments in first-in-class products. We are going to do the things that are brand new, not just TIGIT or another checkpoint molecule, which is really where IO has gone recently. For the same investments, you will get targets that no one's heard of yet. These are the types of companies that will be game-changing.
[Foundery was started officially in 2021. When did talks get serious about starting this endeavor? How long has the Foundery been in the making?]
MS: After the partial acquisition of Pionyr by Gilead [June 2020], we knew that the company focus was going to change—this is a healthy part of a company's progression from preclinical to clinical stage. Max and I started saying it would be great to do something new, where we could really focus on the earlier stages of drug development and have more reach into university researchers. One of the things that I think is so important is that a lot of innovation happens fairly early in a scientist’s career. It is currently very hard to translate that innovation if you are in your late 20s, 30s, or even 40s—until you've established yourself. But early on, when there's so much innovation percolating, it’s an ideal time to collaborate [with Foundery]. What has been really rewarding to me is that as we reach out to faculty at UCSF, and other places—a lot of people have great ideas, but they are not thinking about how their science is relevant to treatment. In my mind, this clearly underscores the need for a different model, where young investigators have a “plug and play” opportunity to test out their ideas, without sacrificing their academic career. We put their concept through some paces, make sure it is reasonable, and that it warrants the time and effort needed to turn it into an early drug development program.
6. Are there any other incubators, creation funds, academic institutions that you looked to for inspiration? What were the elements from other incubators or creation studies that work or don’t work?
MS: We started Pionyr at the MBC biolabs in San Francisco, which is an incubator space. It’s a different model than Foundery—[at MBC] companies come in with their ideas and some funding, and the incubator offers cost-effective, shared services. But we saw how powerful it is to have a centralized entity to maximize the efficient utilization of resources. The incubator experience was a nice example to show that if you have the right people, the right resources, and the right mindset, you can do a lot more than by doing it alone.
The Foundery is currently open to anyone from any institution. We have a master licensing agreement with UCSF, which really makes the interaction friction-free. We think that [agreement] is a huge bonus because it sets the whole partnership off on the right footing. We've extended this master agreement now to another university and will look to establish it with multiple others. But we're very open to working with anyone who comes with an idea from any university. If the project gets through our internal vetting process, we will welcome anyone into the Foundery.
MK: Since we launched Foundery in 2021, a couple of other big VC firms have named things “studios” that basically look a lot like incubators to us. A good anchor point with what we are trying to emulate is a movie studio. Movie studios have economies of scope; in theory, they can take any script and turn it into a blockbuster because they have the requisite people, connections, cameras, lighting, and sets to make a movie. Studios also don't fire everybody when they finish making a movie. They take all that expertise and equipment and they utilize it to make another movie. Ultimately, we are creating something called a “studio” that is both an investment entity and a lab that has the R&D expertise and equipment that PIs can plug into. This is a place that has everything PIs need for their “script,” to make a great immunotherapy.
7. Foundery provides lab space, capital and talent/expertise to help develop ideas into licensable assets or promising NewCos. What are the points of differentiation between Foundery and creation firms or traditional venture studios/incubators?
MK: I think what those other entities do is that they first meet or form companies, and then try to “prove” them. We [Foundery] are not making the company until we make a discovery in our labs. We place discovery ahead of company creation, which we believe will have inherently better economics. We won’t be forced into making one asset or idea work. We believe that we are putting the cart behind the horse—where it should be.
MS: I think another important differentiator is that we're really focused on building partnerships. Max is our prototype--he’s an academic at a university, but we have this really strong collaboration with his lab. We see the mutual benefit of keeping that partnership in place for as long as it makes sense. I think this is a little different than in most companies or venture creation shops—there are a lot of things that you can do at a university lab that are difficult in a company, and vice versa. Having this close collaboration and putting discovery first, allows us to get the best of both worlds.
Jate Sam (CBO): Some other shops claim to have scientists that do experiments alongside the founders, but I think it's in more of a consulting capacity. They're not actually doing the physical work, in the way Michel and his team actually execute on experiments. I think this is another point of differentiation. We also go a little earlier than many traditional VCs—we are ideally looking for stories that are pre-publication. Given our relationships with institutions like UCSF, we can get to the science a little earlier. We are also focusing on oncology and autoimmunity for the time being, which aligns with the team's expertise. I think there is potential to expand indications going forward, however.
[What will the financial agreement be between the Foundery and academic founders?]
MK: It will definitely be a case-by-case basis. We are giving more to the “university share” than is traditional—this share goes to the founders as well. The academic founders are also part of the “Foundery partnership,” in addition to owning part of their NewCo.
MS: Our model is to take things from inception through what we call “pharma-ready” development candidates, and then spin out companies to follow the more standard trajectory. During the formation of the NewCo, the founders and academics who came with the project will also receive company shares or equity. One of the things that we're paying close attention to is making sure the people who work with us are treated fairly and that they profit. As Max has been saying, there is also a portfolio effect. When someone joins the Foundery, they join the “Foundery partnership.” They get a piece of the entire pie or an interest in the entire portfolio. If their individual projects do well, their equity position increases, which extends to when we eventually do a spin-out. Part of our ethos is that we want to do right by the PIs because we value the mutual advantage of being partners.
8. Let’s walk through two imaginary case studies:
Scenario 1: I am a post-doc in a lab at UCSF and have discovered a novel highly specific cell-surface target on colon cancer that could be therapeutically exploited. We just are getting ready to publish our work and have some promising preclinical responses in mice. I plan to apply to faculty positions next year. When and how should my PI and I engage with Foundery? What does a typical process and then success story look like?
MS: We start by having a meeting where we invite the postdoc, PI and other key personnel. We run them through a deck where we explain our process of what we're capable of doing, and how we vet targets. Then, of course, we want to learn as much as we can about their program. We are sensitive about confidentiality. If you're at UCSF, there is no issue because the “master agreement” we have put in place already specifies that anything we learn is confidential.
After the initial meeting, we start working with the PI to figure out how this program would fit into our portfolio. We want to ensure that we are competitive with what's out there—from a therapeutic, IP, and clinical perspective. We ask internally: how would we develop it, how would it fit into our pipeline? Then we start discussing what reagents are needed for specific experiments. For example, if you have a cool surface protein for colon cancer—we want to know what reagents are available in the public domain, and could we do an early experiment? Typically, we will take a reagent that is commercially available, clean it up, and QC it, so that we are comfortable. Alternatively, we may decide that this is worth the investment, and we will make our own monoclonal antibody or fusion protein. Ultimately, we will assemble the reagents to perform the “killer” experiment that can rule in the target. If we are unable to do so, we are very open to working with the PI to try to better understand the biology, which could help us make a decision about future resource allocation. In our model, if we don't continue with a program, we will give the preclinical reagents that we make to the PI.
After we run preliminary experiments and decide that there is a path forward, we seek input from the university as well. We have a joint steering committee with UCSF that will help oversee the programs in the Foundery. It is all nicely laid out [by the master agreement with UCSF] how if we decide to mutually “pull the trigger” [with the PIs & university on board] the program becomes a formal part of the Foundery. As a postdoc [in the above scenario] you are trusting us that we can develop your work faster and better than a lot of other VC shops or companies.
MK: There are a couple of additional points to introduce. When Foundery decides to initially pull the trigger—we have done some background research--what is the archetype of the immune system you are trying to hit? What patient population are you trying to reach, and what does the density of that look like? We are already thinking about the company and its path, in addition to the biology. If we, and the academics, decide to move forward—the PI and postdoc will get shares in the “Foundery partnership.” They are now officially part of the Foundery, and have a team of senior scientists and technicians across the street performing the activities Michel described [making reagents, running experiments, etc.]. As this project moves towards NewCo creation, as you hit milestones, and conduct research, there is an inflection point where the PIs can get more shares in the Foundery upon hitting a project-related milestone. Once the NewCo is formed, the postdoc can come in as one of the major scientists, if they so choose. They can decide if industry is a career trajectory they want to pursue, or not. By this point, there's really been no risk to them [postdoc]—they have had reagents made and experiments run for them, which they can publish and start an academic lab. In our model, publishing is a stated goal—to honor the PIs and help the NewCo by building confidence and excitement in the programs.
Scenario 2: I am a graduate student in a lab at UCSF and have developed a cutting-edge AI-enabled platform to accurately predict tumor neoantigens displayed on HLA and targetable by TCR or cell therapy. We have identified several promising neoantigens and have done some in vitro validation, though we are not yet close to publishing our work, and have no IP. I [grad student] want to go into industry after graduation. What does working with Foundery look like?
MS: It is funny you should bring this example forward because one of our programs does actually allow us to make new fusion proteins to explore antigen-specific targeting. In this scenario, we would be delighted to work with you to see if we could generate a dataset that would build conviction that your neoantigen is targetable. We are happy to collaborate early on to look at the possibilities—we could eventually formalize that relationship or do a couple of experiments beforehand to build conviction. Our model is flexible. We want to find ways to work with people, especially if there is synergy with an existing program [as there may be in this scenario].
9. What excites you most about this initiative? Where do you see the studio in 10 years?
MK: First is this idea that you can break down the ivory tower or wall between academia and industry a bit—purely the concept that you don't have to consider yourself “dirty” if you want to commercialize your work as an academic. Ten years from now, if we've encouraged many more PIs to do that [work with groups like Foundery] it will be a big win.
Ultimately, I think a lot of diseases are going to be cured by a series of drugs that are given in a specific sequence. This is based on some work we've done recently, looking at how natural healing takes place at the level of the immune system. In a pharma setting, where you're looking at a single asset, you have to win with that drug. Less common is the explicit approach of combining multiple drugs at different time points to help patients longitudinally. I described this as like you're on a lily pond of disease, and you want to jump from one lily pad to the next, and then finally to shore. The idea of curing disease in this way, requires that you have the long-term vision and discipline to say: “I’m going to help PIs figure out each of these steps or jumps.”
We are not always going to get lucky where a single molecule, like CTLA4, which has a massive effect on disease. We might best treat disease by a series of progressive dials, which, when combined, make a huge difference. I hope that eventually, Foundery will have the ability to combine many of these treatment modalities—because we don’t form companies until we are ready. From my own personal standpoint, I think we will cure disease by taking it from “state 1” to “state 2” to “state 3” and so on. Being able to understand those pieces and put them together in sequence requires a longer-range vision. Companies that do this will be one of the big outputs of [Foundery] Fund I.
MS: Part of our mission is to become the “go to” partner for PIs doing the most innovative work. In 5-10 years from now, if PIs are coming to us with exciting ideas, and we are fulfilling an important need, it will be a success.
Immunology is very complex, and we still have a lot to learn. What I'm hoping is that our drugs and our tool reagents are part of that journey of understanding immunology in more depth. One of the other aspects that Max has been focusing on is understanding how different immune cell interact and which interactions cause dysfunction. How do you reverse that dysfunction? In 10 years from now, we want to have built a toolkit, either pre-clinically or clinically, that allows us to zero in on immunologically based diseases and inform treatment. I think this would speak to how the innovation we are pursuing now translates to human health.
10. How can PhDs/MDs who want to help advance Foundery Innovations’ mission get involved? Hiring/other announcements?
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- Website: www.founderyinnovations.com
- LinkedIn: www.linkedin.com/company/foundery-innovations-inc
- Twitter: @FounderyInc