Ann Berry (2:49)

CME Group provides a wide range of global benchmark products based on interest rates, equity indexes, foreign exchange, exchange, cryptocurrencies, energy, agricultural products and metals.

John Crotteau (2:58)

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Ann Berry (3:04)

now my conversation with Ben Zeskind, Founder and Chief Executive Officer of Immuneering. Well, I'm delighted to welcome Ben Zeskind, Founder and Chief Executive Officer of Immuneering. And I have been dying to have this conversation, Ben, for ages because we've spoken before and I've often said to the team here, if we could find one person who can explain the science of cancer treatment in a way that both got real depth and is easy for everybody to understand, because investing is for everybody. But often the jargon is the barrier to getting into names like this. You are my top pick. So thank you, thank you, thank you for coming. And it's very exciting. You're in here. Can you just talk?

Ben Zeskind (3:41)

Thanks for having me. And no, it's an honor, Honor to be on your show. You have all the, all the best guests. We do.

Ann Berry (3:46)

We've had a great run of guests and thrilled to have you talk to us. Ben, explain in as layperson's time as you can, but don't compromise on the science. Your latest innovation in trying to work on the treatment of pancreatic cancer.

Ben Zeskind (4:02)

Sure. So essentially at Immuneering, we've figured out a better way to keep cancer patients alive longer. And it's really about counteracting the mechanisms that cancer uses to get around existing therapies. Because if you think about it, no one should be dying of cancer in 2026. Right? With everything that we understand, with all the research that's been done, the billions of dollars that have been poured into treatment, and yet there's still far too many people dying of cancer. I mean, there's 50,000 deaths a year in the US alone from pancreatic cancer. So why is that? And how do we change it? Right? And we are changing it. So essentially, we invented a new category of cancer medicines called deep sicklec inhibitors. And what we announced in January is a 64% overall survival at 12 months in a group of pancreatic cancer patients. 34 patients treated with our drug candidate, atebimetinib in Combination with chemotherapy.

Ann Berry (5:02)

And how does that 64% compare with other treatments out there right now?

Ben Zeskind (5:06)

Yeah, so the benchmark, the standard of care, GNP chemotherapy, it's 35% survival at 12 months. So essentially for patients who had received that standard of care treatment in the first line setting, it's called kind of the first treatment they get after their cancer has spread. Sadly, it's about a one in three chance of living past a year according to the kind of, the pivotal study, the big study that established that as a standard treatment. And again with ours, in our study that we announced in January, it's about a two thirds chance of getting past a year. So really exciting to see that this, this goal we've been working towards for a long time is really playing out in the, in the survival data.

Ann Berry (5:51)

There's also quality of life, right. So people talk about trying to extend life, but there's also how people suffer once when going through these treatments. Does your approach, do the deep cyclic inhibitors change that outcome as well?

Ben Zeskind (6:05)

Absolutely. And that's, that's one of the three goals. And it, you know, I think people have just, just sort of come to accept that cancer therapy is grueling. Right. It has tons of side effect. Generally it's toxic. People describe the tolerability as acceptable and it doesn't have to be that way. But to change that, up until we invented the deep cyclic inhibitors, there was just this trade off that people couldn't break. Sort of the better the treatment was, the more side effects. And if you tried to dial out the side effects, the treatment wouldn't work as well.

Ann Berry (6:43)

That's the preconception, Right.

Ben Zeskind (6:45)

It's like a seesaw. They're just, they're linked. And what we were able to invent with the technology behind deep sickling inhibition was to basically sort of break that link. So you can do both. You can have really good tolerability and you can be very effective in shrinking tumors. And so that wasn't something that people knew how to do before we had to invent the technology to do that because the side effects are on target. Side effects, Right. Basically the, you know, the signaling pathways that tell cancer to grow and divide rapidly are pathways that we have anyway. We have them for a reason in our healthy cells. So one of you know, so back to the question of why are people still dying of cancer? Cancer's not that smart, right. It's not some paranormal force. It doesn't operate by magic. It just has basically these three tricks that it uses that the existing generation of cancer Therapies haven't been good at getting around them. And one of those tricks is it's good at hiding among the healthy cells. So the current generation of cancer therapies, they hit the cancer, but they also hit a lot of the healthy cells that are around it. And that's why you get the side effects. And so that was one of the most important things that we had to invent with deep segment inhibitors was how do you selectively target the cancer cells and not the healthy cells when they're. They're all using the same signaling pathways. So that was one big part of it. And then the second thing was, you know, cancer evolves very rapidly, right? It's not that smart, but it's very flexible. So most cancer therapies work for a while, but then they stop working, right? The tumor evolves, it finds a way around it. So we really had to figure out a way, invent a way to reduce that, to mitigate that. It's called resistance. And then the third thing is that cancer really eats away at a patient's muscles. In a lot of cases, it reduces body mass. This is why, sadly, late stage cancer patients, you often see that emaciated appearance, and that contributes to death. It reduces survival. And so we had to figure out a way to counteract that as well. And the beauty of deep cyclic inhibitors like atabametinib is it's a triple threat. They have mechanisms that address each of those three things that really cancer has been using to get around existing drugs.

Ann Berry (9:03)

Can you just go back in history a bit and walk us through the story of how you and your team invented this? When did it happen, how did it happen? And then what we'll come back to, and the reason I'm asking is the following. Biotech is one of those sectors that a lot of investors struggle to get their minds around. It's deep in jargon. It's hard to understand the very long life cycle and the time to bringing a product to commercial markets. So talk to us a little bit about what that journey looked like. And then where along that journey you decided actually going public is maybe a good idea.

Ben Zeskind (9:35)

Yeah, absolutely. So the company's 18 years old. I started it after doing a PhD at MIT, as well as some business school. And really we wanted from the beginning to figure out how to keep cancer patients alive longer and really keep them alive longer and longer and longer, till eventually they live so long that they outlive their disease. Kind of the way HIV has been transformed in our lifetimes from something that was frequently fatal in the 80s and early 90s to something that now is chronic and manageable and people live with it. So that was our goal from the beginning. But I think being sort of an MIT engineer at heart, we took a very different approach than most oncology companies. So most oncology companies, the way they start out trying to create cancer medicines is they grow cancer cells in a petri dish and they screen different molecules and they just try to kill the cancer as potently as possible. Kill the cancer in the dish. It's very, it's tunnel vision. It's just right now in the moment, how can we shrink the tumor as quickly as possible? Right in the moment? We took a really, at the time, we didn't, I think, realize quite how opposite it was. We took the opposite approach. We said, let's study the small group of patients who actually do really well on existing cancer therapies. Because most cancer therapies, there's a few patients that do exceedingly well that have very long survival. And at the time, the immunotherapies, the checkpoint inhibitors were just sort of coming online and there was this group of 10, 20% of patients that would just live for a really long time. And we said, let's study them. Let's really, you know, take all our, all our MIT expertise, informatics and really figure out what's going on in those long survivors. And then how can we use that to make that happen in more people, to make, make ultimately everyone live longer and longer. And so that, that was our goal. It was really kind of a kind of reverse engineering survival versus just trying to kill the tumor. Right now.

Ann Berry (11:39)

I had to look up. There's a book, and I can't remember but the name. I will find it and I will post it and send it to you. But there's a book that talks about pattern spotting. And there were engineers who looked at fighter plan, I think it was during World War II. And they were trying to figure out how those weren't shot down by looking at where the bullet holes had hit and trying to figure out how the pilots made it back anyway, until someone said, no, no, no, you should be looking at where the bullets didn't hit to try and figure out how they made it back. And I'm just reminded of you speaking about how just inverting the way you look at something can lead to real creativity.

Ben Zeskind (12:10)

Exactly. Yeah. I think that's a, that's a great, great analogy. And I mean, you know, it really led us to focus on a very different set of priorities. Right. The patients that were living longer, generally they have better tolerability. Right? So that's the thing about these harsh side effects that you see with kind of the current generation of cancer therapies, not only do they make patients lives miserable, but they also, they shorten the amount of time that patients live. And there's hard numbers to back that up. So when you look at there's something called a patient's performance status, which is sort of a way of capturing are they able to get out of bed, are they able to work, are they able to take care of themselves? And when a patient declines on that scale, they actually have a 48% increase in their risk of death. So there's hard numbers linking that to survival. And I think we've all seen it. When someone can't get out of bed anymore, they can't go about their activities, they kind of can start to spiral. So counteracting those harsh side effects, figuring out a way, as I said, inventing a way to break that relationship between the tumor shrinking and the survival that was so important, not only to make it a better experience for patients to enhance the quality of life, but also as sort of one of these three mechanisms that all together help patients survive longer, help them live longer. So that was really one of the key things that we came up with and again, resistance, figuring out how to prevent the tumor from getting around the treatment and how to preserve body mass. So all of those were our priorities from the beginning. And it was just a really different set of priorities for most companies. And I think that's what led us over time to develop really such a different kind of therapy, this really new category of deep cyclic inhibitors.

Ann Berry (13:59)

Let's take a break and when we come back, more of my conversation with Ben Zeskind. John, can you turn the phrase semiconductor suppliers growing revenue over 20% year over year into an investable index for me

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right now, off the top of my head, no.

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Ann Berry (15:36)

And now back to my conversation with Ben Zeskind, founder and chief executive officer of immuneering. So that's 18 years ago, and you've sort of shortcut the story. You know, that's a long amount, a big amount of time spent investing in that innovation and working through that. When did you decide to commercialize this? When did you decide to sort of turn this into a company that you were committed to scaling? And then when did you decide that going public was the right way to do it?

Ben Zeskind (16:01)

Yeah, yeah. So there were really two main chapters. You know, the first 10 or so years we were working with existing pharma companies, studying their medicines again to understand what was happening in those long survivors. And they paid us to do that because the answers were really valuable to them. So that was kind of what we were doing for the first 10 years. And then about eight years ago, we said, all right, we've learned a lot. Now we can really go after creating our own pipeline of wholly owned drug programs. So it's sort of. But those 10 years, it sort of took us 10 years to invent the technology, the informatics, the computational technology to figure out how to do this, how to break the relationship between side effects and activity. And so it took us 10 years to invent that technology. And then using that informatics technology, it took us another eight years to the present to really invent the specific type of new category of drugs, the Deep Siglec inhibitors. So it was really two stages. First inventing the informatics technology to figure out how to solve the problem and then inventing the actual drug candidates that solve the problem. So it was those two stages in terms of going public along the way. I mean we, you know, for the first 10 years we were funded by revenue, which was great. You know, we at about 10 years in we raised a series A as we started to take our own drug candidates into chemistry and into animal studies. That gets expensive. So we raised private money from a great group of family offices and high net worth individuals actually led by Peter Feinberg, who's on our board to this day, a wonderful member of our board. And from there we were able to raise kind of a crossover series B. And then the time was right to go public because really by going public we were able to raise the resources that we needed to take this into humans and to really demonstrate in humans that we can do this, that we can shrink tumors in a durable way while also minimizing side effects. And no one had really shown that before. So going public was really the way that we were able to really have the resources to take this into the clinic and really demonstrate what, you know, what we've shown today.

Ann Berry (18:26)

Let's talk about what's happened since going public. I remember the day that you IPO'd. It's a very exciting day. And your, you know, your share price was set and it sort of peaked at one point you're in the high 20 bucks immuneering and today trading at under $6. And this is not unusual for biotech. You see this a lot, you see huge volatility partly because these are smaller capitalizations and partly again because just the knowledge and the expertise that investors feel they need to have to really come to a long term view. It feels like a sector that's to break into. So when you look at this, I'm just taking a step back, right? You've got this great data, you're doing something really differentiated. If a pancreatic cancer, notoriously one of the toughest to crack. Yeah, but your share price isn't doing what you would intuit it would be doing. So what, what are folks missing, right? What's the market not getting here?

Ben Zeskind (19:15)

Yeah, I think it's an incredible opportunity. Incredible opportunity for.

Ann Berry (19:19)

But, but what, what's in the conversations you have with investors or you go to conferences. Are people asking the right questions? Are they going off on tangents like what's just not landing?

Ben Zeskind (19:29)

I think it's starting to land more and more over time. Right. And I think what you have to appreciate is that what we're doing is highly unconventional. Right? What we're doing is challenging the status quo, because the status quo since the 1970s, when Richard Nixon declared war on cancer, which is the wrong analogy, I think. I think that was the wrong thing. I think that caused the wrong mindset for, you know, for 50 years after

Ann Berry (19:57)

that, that pain and suffering is the

Nordstrom Rack Advertiser (19:59)

way to get through it, and that

Ben Zeskind (20:00)

a tumor is something you have to kill like it's an invading Army. So for 50 years, blame Nixon. Right? For 50 years, since the war on cancer was declared, everyone, you know, all these companies have had this. And investors, frankly, in a lot of cases, have had this tunnel vision where it's just kill the tumor now. Right. And so the way drugs are developed, the priority is how fast can you shrink the tumor right now, Right. With really not a lot of regard to the durability to how long that lasts. And that's why you have a whole generation of cancer therapies today, even some that are still in development, that markets get excited about, where they shrink the tumors really fast for a couple of months, and then the tumor finds a way around it, and it comes roaring back, worse than before. And meanwhile, they have all these side effects, you know, rashes in the vast majority of patients, diarrhea, nausea, vomiting. And this is the saddest quote. But it's so ingrained in the culture of how drugs are developed that the very metrics that people use to evaluate drugs in early clinical trials, there's something called overall response rate, which is basically what's the most the drug shrank at any point in time, Right?

Ann Berry (21:13)

To your point. It's the very blunt instrument.

Ben Zeskind (21:15)

It's the moment, right? It's the moment in time. So. So the whole field has been set up. If you think of the old fable the tortoise and the hare, the whole field has been set up to root for the hare, the rabbit, who's going sprinting out at the beginning. And the way deep cycling inhibitors shrink tumors, it's slower, but it's more durable, and the patients feel much better.

Ann Berry (21:37)

Can I challenge you on something you said, Ben, which is back to the differentiation you have today?

Ben Zeskind (21:43)

Yes.

Ann Berry (21:44)

And I totally hear you on the fact that the way you've approached it's different. And the way in which you're talking about. It's very different.

Ben Zeskind (21:49)

Y.

Ann Berry (21:49)

Yes. But it did take you 10 years with the information that was available at the time. At the beginning.

Ben Zeskind (21:54)

Yes.

Ann Berry (21:55)

Then another eight years to sort of take this amazing theory invented and bring it to where you are today.

Ben Zeskind (22:00)

That's right.

Ann Berry (22:00)

Do you wake up and do you stay awake at night worrying about the following, that there could be a competitor who's either starting today or newer with the benefit of AI that can truncate the innovation cycle and catch up with you, and that what took you 10 years because the technology wasn't there yet could now take someone three.

Ben Zeskind (22:20)

No. You know, I think that that does not keep me up.

Ann Berry (22:23)

It doesn't? Why not?

Ben Zeskind (22:24)

Because AI has an incredible number of uses and it's extremely valuable. I think figuring out the science of actually discovering drugs is an area where AI is not well suited.

Ann Berry (22:39)

But it was used for vaccines during COVID I mean, that's become the classic example for how it was used. It was applied to sort of speed up and to fill the gaps just through iteration. Even if the why wasn't understood.

Ben Zeskind (22:50)

Right. To iterate on an existing approach.

Ann Berry (22:54)

Right, right.

Ben Zeskind (22:55)

It's good at that. But. But to innovate, to really, you know, do an experiment. You know, I do that. Look, I, you know, we all experiment with AI. Ask AI to invent a new form of clean energy. Right. I did that. You know, it came up with the most convoluted, impractical curved surface with bacteria in it. And AI is great at summarizing information and even synthesizing, but it's not great at innovating. And so the things that we had to do to really come up with this, the analyzing the data from the patients, the developing the informatics, and we use computation again, informatics. The algorithms were an essential part of how we figured this out. But look, artificial intelligence has been around. I took freshman year at mit, took a class on artificial intelligence. So it's been out there for a long time and it's doing really interesting things, but that's not our concern. And look, we have the great ip, we have composition of matter patent on our drug candidate tabimetinib was just granted over the summer. So I think that's. There's that kind of. And we're just really far ahead in terms of what we understand. We have a whole pipeline of preclinical programs. So, no, I think for me it's more about making sure we're telling the story and having people understand that even though the drug candidates that Today, maybe the market might be most excited about, or at least kind of the majority of the herd that have a lot of side effects. It doesn't have to be that way.

Ann Berry (24:36)

And I want to talk about what else is coming in your pipeline, because we talked about pancreatic cancer, but there are other applications here. And then ultimately I want to come to when, when you're through it all and through trials, who's going to pay for this ultimately? But let's just start about what you've got going on next in the rest of this year. Ben?

Ben Zeskind (24:52)

Yeah, so it's really exciting. We're taking atebetinib into a phase three study in first line pancreatic cancer.

Ann Berry (25:00)

What does that mean?

Ben Zeskind (25:01)

Again, these are the patients who are newly diagnosed with pancreatic cancer that has spread. A phase three trial is a large study. It's randomized. So patients come in and they get assigned either to the treatment or the control arm. And it's the kind of study that if and when it has a great outcome, you can use that to get the drug registered, get it approved and onto the market. So it's really, in a way, kind of the last major step in the clinical trial process.

Ann Berry (25:28)

And why is that happening for you? That's happening.

Ben Zeskind (25:30)

So we've guided to dosing the first patient in that phase three mid year.

Ann Berry (25:34)

Mid year. Okay.

Ben Zeskind (25:35)

Which is super exciting. I mean, this is something we've been working towards for a long time. There's a lot of excitement out there among the pancreatic cancer community because it represents again, the data we showed in January to show 64% survival at 12 months in pancreatic cancer with so few side effects. I mean, we only had two categories of side effects that were seen at the, the grade three level in more than 10% of patients. So just really well tolerated. And then 84% of the patients who, for whom we had data at 3, 3 months either either gained weight or were weight stable. So all of these things and just the stories coming out of our phase 2, the patients are having really remarkable quality of life.

Ann Berry (26:14)

So if all goes well in phase three, let's assume it does or hope it does. That's going to be our strategy. When would we see these drugs coming out of this come to more widely available? When would that happen?

Ben Zeskind (26:27)

Yeah, so, you know, we've got it to a top line readout, kind of mid-2028, you know, and then there's a certain number of months of preparation to submit a regulatory application and then the regulatory agencies review it for A certain number of months, and then, you know, all going well, the drug gets approved, and then who pays for it is on the market.

Ann Berry (26:46)

Who pays for it? And just talk to us about that, because I think that's the other mystery to investors. Right. You can invest in a fantastic biotech company, but then ultimate. It's, you know, is it the insurance companies who are going to pay for this? Is it going to be patients having to do this out of pocket for some period of time? Where does that revenue stream ultimately come from?

Ben Zeskind (27:03)

Yeah, I mean, I think typically once drugs are approved and they become standard of care, you know, then generally the payers, the insurance companies pay for it. And, you know, I think really the, you know, what matters is the impact that you have for patients, the value that you're generating for patients. And. And based on the data we're seeing in phase two, tabimatinib could really generate an extraordinary amount of value for patients, helping them live substantially longer and also feel so much better. Patients in our study feel a lot better.

Ann Berry (27:39)

And just to finish the thought, then, Ben, are there cancers that you're gonna come up. We won't call it your war on cancer, but are there other varieties of cancer that you can see your innovation being applicable to treating?

Ben Zeskind (27:50)

Absolutely. So the signaling pathway that a tabimetinib targets drives about half of all cancers. So pancreatic cancer is just the beginning.

Ann Berry (28:00)

Okay.

Ben Zeskind (28:01)

And we have a phase two study that we're planning in lung cancer. And this is together with Regeneron, you know, great biotech company, and we're combining our drug candidate, atavimetinib, with one of their medicines, an anti PD one called libtio in lung cancer. And we're really excited about that. Cause preclinically, in animal studies, that combination is very, very effective against animal models of pancreatic cancer. So we're really excited for that study. We've guided to dosing the first patient in that study in the second half of this year. So that's coming fast. And then there's just a whole variety of other combinations that we're planning to pursue. With etabimetinib, one of the most cancer drugs are ultimately used in combination with other cancer drugs, because when you combine two, it's sort of harder for the tumor to get around it. One of those tricks that the tumor has, when you combine drugs, it's harder to get around it. And most drugs, what limits their ability to combine is the tolerability when one drug has a lot of side effects and another drug has a lot of side effects. You put them together. It's too many side effects for the patients. So the fact that a tevimetinib is so well tolerated has such good tolerability, so few harsh side effects, not only does it help the patients live longer, not only does it help them feel better, but it also enables us to combine it more readily with a lot of other things. And this is the future of cancer therapy. I mean, to not have to deal with all these harsh side effects. That's what patients deserve, that's what we're trying to bring forward. And I think anyone who believes in that future should be really excited about our company and want to be a part of it.

Ann Berry (29:40)

Well, Ben, you're immun. You had your earnings out pretty recently. Came out on March 6th. I took a look at your all of it to look at your presentation. But it does say that you ended 2025 with just under $220 million in cash and equivalents. Enough Runway, according to your press release, to last into 2029. So just having gone through that timeline with you, just sort of one person's view over here, just a reminder to investors, these are long term investments to make. So there's a lot of short term volatility, but this is one sector where it's a, it's a long, a longer stretch to hold these things and commensurate with the kind of innovation we're talking about. Well, huge thanks to Ben Zeskin for joining us. And if, like me, you are inspired by that story, you'll see that it is worth digging into stories like this. Whether you end up deciding it's the right stock for you to invest in or not. The point of this is we want to find those stories, those parts of the market that deserve a little bit more attention. That's it for today's Brew Markets Daily.

John Crotteau (30:35)

Brew Markets Daily is hosted by Anne Barry and produced by John Crotteau, Tarkab Delatif, Avani Laroya and Emily Miliron. Our technical director is Uchena Waugh. Brittany Detaco is our audio Engineer. Booking by A.B. silver. And the president of Morning Brew Inc. Is Devin Emery. If you have any feedback or a company you'd like us to COVID leave a comment or send an email to brewmarketshoworningbrew.com have a great weekend.

Ann Berry (30:56)

We'll see you back here on Monday, same time, same place.

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