Treating Cancer using Targeted Radiotherapeutics with Jack Hoppin and John Babich of Ratio Therapeutics

Today we have Dr. Jack Hoppin CEO of Ratio Therapeutics and Dr. John Babich Chief Science Officer of Ratio Therapeutics. The team at Ratio Therapeutics is developing a suite of innovative technologies to develop best-in-class targeted radiotherapeutics for the treatment of cancers. They just recently opened a 19,000-square-foot headquarters and R&D facility in Boston to continue their exciting innovation.

We’ll dive into how Ratio started, their growth, and what you can learn from their journey from Lab to Launch.

Show notes:
https://ratiotx.com/ 

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Music by keldez

Transcript

Meg Sinclair: 0:17

Hi everyone, and welcome to From Lab to Launch by Qualio. I'm Meg, your host. Thanks for tuning in today. Before we jump in, we'd love it if you would rate the podcast and share it with any of your science nerd friends. We know you have some. If you'd like to be on the show, please fill out the application linked in the show notes. We're grateful for all the interests we've had lately. So today we have Dr. Jack Hoffman, c e o of Ratio Therapeutics, and Dr. John Babbit, chief Science Officer of Ratio Therapeutics. The team at Ther Ratio Therapeutics is developing a suite of innovative technologies to develop best in class targeted radiotherapeutics for the treatment of cancers. They recently just opened a 19,000 square foot headquarters, an r and d facility in Boston to continue their exciting innovation. We'll dive into how Ratio started, their growth, and what you can learn from their journey from lab to launch. All right, let's bring these gentlemen in. Welcome to From Lab to Launch. We're glad you're here.

Jack Hoppin: 1:22

Well, thanks for having us. Wonderful to be here.

Meg Sinclair: 1:24

Yeah. So Jack and John, to kick things off, we have a wide range of listeners on this show. Some chemistry nerds, others like myself, not so much. Can you help us better understand what Ratio Therapeutics does as if you were explaining it to your grandmother? Sure.

Jack Hoppin: 1:42

Go ahead John. I have to learn. Another language is funny, my grandmother, but, um, the simple, the simple, uh, the simple. Basis for Target to Radiotherapeutics. Right. So what we're, what we're doing is, um, is administering a radioactive drug that localizes in cancer and, and just like, um, typical radiation oncology is delivering energy into that cancer in a way that will kill the cancer. The difference really is that, um, typical radiation oncology uses machinery. And directs beams that you know, from multiple different angles so that you know, you could, you could basically hit the tumor in a crisscross pattern without hitting lots of other tissue at the same intensity. We have to administer a drug intravenously. And so our, um, our objective really is to design a drug in such a way that it will, the most of the radioactivity that gets administered to patient will localize in that tumor. We're in the cancer and stay there for a prolonged period of time so it can actually release its energy, deposit its energy into the tumor, affect the kill. So it's a, a field of nuclear medicine. This is the use of radioactive materials for diagnosis and therapy. Uh, we're particularly interested in the therapeutic applications. Uh, we have a series of, um, approaches to that that we are, we're working on right now. Atsu.

Meg Sinclair: 3:06

That sounds really cutting edge. Is there a particular cancer that, um, you're focused on or is this applied to kind of all cancers across the board?

John Babich: 3:15

So, you know, every, every time we contemplate a cancer, we have to match the, um, the cancer type with a, a particular target that, that cancer might possess that, and, and, and then target being a particular protein that sits on the surface of the cancer so that we could get access to it. From the blood supply. And so we have to think those, those things are, those are not, you know, they don't just sort of fall out of trees, so to speak. And so we have to really think about that. Right now we have a program that's ongoing in prostate cancer with a particular target. Uh, and we have a program that's a li a bit more broadly focused. And that is to look at, um, really a component of a, of a, of a tumor. So if you think about, uh, the difference between a cancer and a tumor, a tumor is really a swelling. You know, the lump somebody would feel in the breast or the lump you would feel on, in a prostate digital exam or some lump that you would find that you think maybe this could be a cancer. Um, that lump is generically Latin referred to as a tumor. Um, but it may be a cancer may not be. So what what it turns out is that there are a lot of cancers that accumulate tissue, um, side by side with the cancer cells that are from the host. And so they. You know, it's giving out lots of signals. It wants to grow, it wants nutrients, it wants blood supply. And in the process of actually sending out signals, it'll recruit something called fiberglass. And these are the, these are the kind of, uh, cells that would make the scar form. If you have gotta cut yourself the healing part of the, of the, of, of the, of the, of your body, that actually gets recruited into sort of stitch or cut form a form a, a scab. And, and then basically, Renew that tissue. So you, you get the cancer cells recruiting. Um, these various, what are known as fibroblasts, because of the signaling, they get turned on. When they get turned on, they, they present a fibroblast associated protein, which is known as fibroblast activating protein, alpha or f. And this turns out to be something that's expressed on many, many types of cancers in the, in the combined. Um, environment that the cancer cells and the host cells make. So they call it the tumor stroma. This is a, a sort of mixture of cells from the host and the cancer itself. And so we're going after that. It's called f Uh, we have a diagnostic program with, uh, uh, one of a former collaborators, lampists on development of diagnostic, the image of a variety of cancer, and also image any type of disease that provokes a fibro fibrotic response. We also have the, uh, rights, uh, for the application in therapy. And this would have application along many different cancers from pancreatic to breast to colorectal to lung, and also say liver cancer. There's a variety of cancers we could apply that to, and that's what we're developing right now.

Meg Sinclair: 6:11

That's very exciting. I have known people personally affected by each of those three cancers you mentioned. So, um, amazing work that you guys were doing over there at Ratio Therapeutics. Kind of shifting gears a little bit, you've both founded companies in the past, but why did you start Ratio Together and how did you two get connected?

John Babich: 6:30

Sure. Um, well, yeah, we, we've known each other for a long time Yeah. But had never worked together. And, um, Jay, you may wanna tell you, you tell a story better than I do.

Jack Hoppin: 6:40

No, so not, not necessarily. It's like asking a

Meg Sinclair: 6:43

couple how they met. I love that. Yeah.

Jack Hoppin: 6:45

So, uh,

John Babich: 6:46

yeah, we met a long time ago, but in

Jack Hoppin: 6:48

2018, uh, at the time, uh, John was, uh, professor at Cornell while Cornell in Manhattan. And, uh, at the time I was overseeing a company I had founded. And Vro that, um, was really kind of the leaders in imaging, um, drugs and, and discovery and also as a, as an

John Babich: 7:09

endpoint

Jack Hoppin: 7:10

in clinical trials. And many people, this class of drug that John just nicely described is really an emerging, not a new concept. Uh, radioactive iodine was FDA approved in 1951, but it's, it's in the last decade that, um, it's really. Gotten a, a big movement. Um, Novartis and Bayer have joined the space and Novartis has recently gotten a big prostate cancer drug approved. And um, so we were seeing lots of drugs of this class and, and over the last, uh, five or seven years. And it's really to John's point about where the drug goes. How it accumulates and doesn't have the right ratio of residents time in the tumor as compared to any ex expiratory or off-target, uh, residents time. And John showed up with, uh, something he had invented and developed and, and really thought through. He's, he's been a pioneer in this space and studied a lot of drugs and, um, we, we, my corecon is really in the, the studying of the pharmacokinetics of these drugs and trying to model them and understand where they go and quantify. It's very quantitative. Sport as we always radio label at first and take a pet scan or a spec scan, we do, we do a scan. We actually can see where and, uh, when and where over time the drug is. And so John showed up with this concept and I immediately said that is the right idea. That is brilliant. Uh, it's really about tuning the pharmacokinetics of the drug. And John invented a class, uh, a platform where, The binding mode is targeting the cancer itself. Two, he mentioned two targets, PSMA and prostate and FAP in a pan. Cancer, uh, target.

John Babich: 8:55

And, and then another part of the molecule

Jack Hoppin: 8:58

at a much lower binding affinity. A worse binding affinity. It kind of hitchhikes albumin, which is a ubiquitous protein in your blood. You're, um, got about a coffee mug full of albumin flowing through at all times, and, and this extends the blood. The bioavailability of the drug and the blood, and then that really allows more of it to get into the tumor and often changes its clearance mechanism. And so right away I was, uh, e excited about by this and there was a, that was a, uh, a previous effort and that drug was sold to buyer in 2021, which simultaneously, um, spawned ratio. Dar quit his day job. I had. Uh, subsequently retired according to my LinkedIn page briefly. And, uh, we, we came back and, and started the company with a partnership with buyer, a partnership with Lampists that was already discussed, and, uh, raised some capital and built a team. And now we sit in this headquarters. We're 35 people. Very technical team, very interdis. There's a very interdisciplinary sport. You need chemistry, radio, chemistry, biology, this quantitative pharmacology. Um, you need physics, you need radiation, dosimetry. Um, you, you know, it's just a, a lot of PhDs of, of, and not that. PhDs, a lot of scientists of varying backgrounds here. Very technical squad and, and, um, we are, it's

John Babich: 10:18

going well. Right, and I'll just, I'll just say it, you know, one of the reasons I I reached out to Jack is I saw the, I saw that this would be, this technology would be amenable to actually. The application of modeling. So this is a, an a, a really tremendous skillset that Jack has and his team in at his previous company and that we've expanded on here as well to understand, can you actually model mathematically, model what's happening in a human, and then take that modeling information and then, you know, through trial and error, make the molecule match what you expect the model to do. And so this is kind of. We, we talk about math meeting medicine. This is kind of where this comes together. The idea that, you know, the, there is so much to do when it comes to quant quantitatively assessing where these molecules go because they have an impact on the therapeutic benefit and on the, on the side effect profile. And, and there's a lot of calculation on this, right? So not, it's not just pharmacology for pharmacology's sake, it's also pharmacokinetics and, and the delivery is important and the ratios between. How much gets delivered to the tumor versus other tissues is critical. So this is a, a real nice opportunity to use all this kind of expertise to sort of design drugs and understand drugs in a way that we, we maybe haven't understood them before. That's great. It

Meg Sinclair: 11:41

sounds like a great partnership, um, between yourselves, Jack and John. Speaking of partnerships, um, we've mentioned a few big names in the industry like Bear and Merck, um, and some others. How are you getting going about commercializing and executing on your go-to-market strategy with these big partners?

Jack Hoppin: 11:59

Yeah, I think, um, there is a, a really large appetite, uh, in this market, um, for novel.

John Babich: 12:09

Drugs. And

Jack Hoppin: 12:10

I, I think what's great about this field is the interdisciplinary nature. Um, there, I think there are many people who felt like, I have a failed drug. I'm gonna repurpose it, put radioactivity on it, and make a target radio therapeutic. Or there's people who say, I have a new isotope and I'm gonna find a binder and, and I'm gonna have a new drug. But it, it, it truly takes knowledge both in. Pharmacology in, in standard pharmaceutical sciences, which is obviously very challenging given the failure rates and in nuclear medicine. I think that's what we wanted to build here. And so it's great to have partnerships because you, you expand sort of your skillset and domain, uh, knowledge. You know, we're still a very small company of 35 folk and so, um, to, to have partnerships where, You can bring something to the table, but also, you know, with, with the might of some of these larger enterprises, um, not just from a dollar perspective, but also from a domain knowledge perspective. So I, I think we're very eager to partner with folks

John Babich: 13:14

and, and that's working out.

Meg Sinclair: 13:17

That's great to hear. Um, yeah. One of the things we like to discuss here, um, on our podcast is quality management. Since Quality O is a quality management software, um, can you tell us a little bit about the quality culture you're seeking at ratio? It seems like you're definitely. After product quality. Um, but what does that quality culture look like? And how do you balance quality, quality and product development?

John Babich: 13:40

I'm gonna, I'm gonna

Jack Hoppin: 13:40

let John answer this cuz he, uh, he is truly a, a foremost expert in, in putting, we both have a lot of experience putting radioactive drugs in people, but I will jokingly say like, there's actually no stress, no pressure putting radioactive new radioactive drugs into people, right? There's no quality. No, sorry, go ahead John. Yeah. So the bar

John Babich: 13:56

is, so I, I think, I think we take quality, um, Well, we take it very seriously. Not, not to imply others don't, but the, the, the issue with quality really starts at the very, very beginning of everything we do right? So, uh, and this is another, another, um, significant, I would say attribute of ratio and that we're trying to make sure that we dial in the quality from, go from, from the first time we make a molecule to when we track the molecule to how we. Um, curate data about a molecule, and I'm, I'm talking about chemistry obviously at the very beginning, but also on, uh, let's say, uh, protein-based assays, cell-based assays, preliminary evaluation in in animals, ultimately preliminary evaluation in humans, you know, making sure that quality is built into data generation. Data and data archiving, and then data, you know, at, at the point where you actually have to look at data. How do you curate the data and, and how do you present the data? So I, you know, I think quality in this organization comes at the at at go. And so there's also, you know, the, the QA functions of, you know, C M C and the QA associated with clinical trials. I mean, that. That to me is a given. But it's, it's, it's almost like, you know, when you, when you start to do that, you have to have quality. It's not, it's, you couldn't do it without it technically. Right. It would be, you would be going against GMP and, and, and, uh, all, all the, all the required obligations one would have from a regulatory perspective. So I think Q Quality Assurance really starts much earlier for us in our. In our tracking of information, a, about the molecules that we generate and how we, and how we move that information in order to make decisions, in order to move drugs forward. So I think it's, for us, it's uh, I think it's almost part of our DNA now that the, the quality of how we acquire information, how we store it and how we evaluate it is, is kind of been, um, I'm trying to think of another analogy, but is it, it really is baked into our systems. And then of course, then I would say typical, uh, in, in a way of quality assurance relative to, you know, clinical trial, you know, the, you know, site selection, vendor selection, um, you know, the quality assurance packages that go along with C M C. One of the things about this space, which is kind of different than maybe many other spaces, that whenever you're going to do a therapy, you actually have to make the drug. And so it's un unlike some. Uh, drugs that could be made in large quantity and then stored in a tablet form, or even in a solution form, and put in a fridge or put on a shelf, um, because it's radioactive. It's like making ice cream in the summertime, right? It's, it's, you make it and it's disappearing as soon as you finish making it. And so you have to actually make the drug over and over and over again. So say for a clinical trial, Of 30 patients, you might have to make the drug 30 times for 30 patients. You might wind up with a batch per patient only because of the way scheduling occurs. So there's a lot of quality assurance that's built into the manufacturing, and it has to be, you know, at, at a level that is, um, you know, uh, I would say, uh, repetitive is, is the best way I can say it. And then of course there's always the, the quality assurance that gets implemented in the readout and the regulatory filing. So I, it's, it's, It really is in our DNA here and it's in a big part of how we, how we make decisions is based on the quality that we put into those decisions. Yeah, I will,

Jack Hoppin: 17:32

I will just add, and John nicely stated it, and on to John's point of the ice cream, in addition to being ice cream, it's really, um, A micro, micro, micro dose of ice cream. So

John Babich: 17:46

the mass doses we

Jack Hoppin: 17:47

deal with, you know, when we, it's, we, we use for imaging, we use tens of micrograms and for, um, for therapy. It's low, hundreds of micrograms. And if you just think about a 200 milligram Advil and, and taking a, a thousandth of that, um, just the, just, it's just a really, sometimes things don't work and, and, uh, and this, this is one of those strange fields where sometimes people do a run and it, they don't get what they want. So there a lot of effort has to be, go, go into making sure. That you're able to deliver drug on that day, unlike having to John point a stockpile or a viz or what, whatever the No. So I, I guess, you know, the gene therapy folks on the phone, on the call would, uh, would, would maybe say ours is tougher. And I tt I don't think we'll disagree with that. Yeah, no. That, that is the point. That that's another thing. But it, it, it just, it, you know, it, it just, it just presents with challenges and, and there are failures. I love

Meg Sinclair: 18:52

that when the margin of error is so small quality in your dna, n a really helps from go. It's,

John Babich: 18:57

yeah. That's great. Yeah. And I, and I think, you know, to Jack's point, you, you know, we have to go through a quality control every time we release a batch. So that's, that has to be live and on the fly, right? It's not like you can wait and it, people are on the phone, people are sending emails, people are, you know, releasing, you know, um, you know, it, it, it remotely, right? Once, once the whole data comes in, we can evaluate things. So it's. It's, I wouldn't say it's touch and go, but it's, uh, certainly, uh, high pressure on the day of the manufacturer.

Meg Sinclair: 19:27

Certainly sounds like it. Speaking of high pressure, maybe, um, you recently had raised, um, four 40 million a few years ago. Congrats, by the way. How did you approach funding as often as the number one business problem for founders in this life sciences industry?

Jack Hoppin: 19:44

We had a, a very good. Um, founding in the sense we had a couple strategic partnerships at the gate and were able to just raise some, raise some seed capital and then, um, kind of based on previous experiences had, uh, business contacts that were enthusiastic about our partnership, the team we, we built and, and continue to build. And so we were able to raise capital through, um, really more. Angel High Network family offices and um, and existing

John Babich: 20:19

kind of partnerships we had.

Jack Hoppin: 20:21

Um, that didn't mean it wasn't incredibly stressful, it just means that it was, uh, um, it, it was different. I, you know, that that's the approach we took. Um, and, uh, and right, and, and in our series B we are exploring. More institutional, more, more classic venture capital, institutional, um, money. But there, there's a lot of partnerships out there, so we, it'll probably be some hybrid. Great.

Meg Sinclair: 20:50

Well, switching gears, um, back to yourselves. If you could go back to the start of your career and give yourself one piece of advice, um, kind of knowing how you've gotten to where you are now, what would it be?

John Babich: 21:04

Um, I dunno what we got here. Yeah. If I didn't get here, I'd give myself different advice. Um,

Meg Sinclair: 21:14

what advice would you give yourself to get here? Easier maybe?

Jack Hoppin: 21:18

Oh,

John Babich: 21:18

easier that then I, I would have a, I would've a hard time thinking it was, there was an easy way to get here. I would say

Jack Hoppin: 21:26

the, the joke I, uh, I tell people when they're, cause we having. And previously I started a few companies and ran one for a decade. Um, that did very well. Um, the joke I say to people if they're starting a company is like, when they say, what would you do differently? I say, probably not do that. Um, it's, it's really hard and a lot of work, but then again, there's no real, um, there's no credit without risk of blame and there's no success without risk of failure. So I, I guess, uh,

John Babich: 22:00

I don't know. Maybe eat better less. Yeah. Uh, you know, that's probably more sleep. Yeah. Sleep better sleep. A little more health. Yeah. I, I think, you know, and I, I think the other, so I've been involved in previous company, which is public, and I think one of the things that's really, um, critical is to understand your investor base. I think that's really, you know, I, and I wouldn't say we, I would say I've had now three experiences and, and you know, that that is probably one of the most important things to understand is who's investing. Why are they investing? What are their expectations? Uh, communication's key. I'm not saying we're not doing that. I'm just saying that, that, you know, to me that seems to be a crucial part for, um, particularly companies in this space where revenue is not right around the corner. Right? So you have to understand the, the sort of timeframe of your investor, you know, what their expectations are, and then, and then, you know, make sure there's lots of communication. Um, because bad things, bad things happen, right? This is, if it was easy, there'd be everybody there be a drug company on every corner, right? So, uh, but, and, and the rewards would probably be a lot less, but you know, if, when you ha do have success, so I, I think it's to understand that component of the business cuz it's a big part of the business. It's not, it's not in insignificant. Then I think also to make sure communication is, is, um, foremost upfront with, with your investor base. Yeah, I think that's great advice. Well, a good lawyer. Yeah. Yeah. A good IP lawyer. I think the other thing is get getting a good, I uh, IP attorney, you know, intellectual property attorney is critical. You know, again, when you're going into a business like this, you know, you really need to have a technological position. Um, and, and you may, you have to make sure you're, you're protected on that. So, I mean, these, these aren't things we haven't done. They have, they're things we have done, but I, I think they're cru crucial to. Getting established on the right footing and then, and then making sure you're going in the right direction. Cause you know, things, things happen as we know.

Jack Hoppin: 24:03

Yeah,

Meg Sinclair: 24:04

I think that's great advice for any investors, um, or, uh, innovators looking to join the space. Our last question that we like to wrap one up here is with the fun one. Um, for each of you, if we ran into at a bookstore like Barnes and Noble, in which section would we find you in?

Jack Hoppin: 24:24

Um, I can say for better or worse, I would like to read, uh, like history of science books. History of science. Yeah. I'm happy to read any

John Babich: 24:35

history book. Um,

Jack Hoppin: 24:37

but I typically would be reading some

John Babich: 24:39

sort of history of a science, math, or physics typically, but

Jack Hoppin: 24:45

that's

John Babich: 24:45

usually what I read. Interesting. I would not be in that island necessarily, but I would, I would be,

Jack Hoppin: 24:51

history of math is definitely not its own island. I, uh, island. It's not its own island.

John Babich: 24:57

No. I would probably be in the non-fiction section. Yeah. And I, I just, you know, not that I don't have math books, but you know, I, I think, uh, it's, it takes me a while to get into non, to get into fiction and it just, it just doesn't take me as long to get into non-fiction. So I tend to follow those books up more so, but, I like to, I like to understand, you know, other people's journeys and these sort sort of situations. And also, you know, the psychology, the, so the psychology behind decision making is really fascinating to me. Right. You know, some of Malcolm Gladwell's books, you know, blink, you know, the, the Taki's books and Canahan, I mean, it, it is just so many ways to understand how you think and how you react to information, how the world reacts to information. It's always. Humbling to, to have people study that and to see how kind of goofy we are at the end of the day. And when we think we're so, you know, driven by detail and then we, a bird goes by and we make a change in decision, you're like, okay, that, that wasn't very solid decision to make. So maybe I shouldn't pay attention to birds so much. But you know, there, there's a lot more to, and, and this goes, I'll, I'll, I'll bring the quality into it, right? It's like, how do you actually figure out. The best way to make a decision. How's the, how's the data, what is the data really telling you? And that you're not fooled by it, or you're not fooled by your own biases, right? So that to me is, is kind of where I define my head in a book.

Meg Sinclair: 26:23

Well, I hope you have lots of summer reading ahead. Um, thank you so much for joining us on LA from Lab to Launch here. Um, I learned so much about Ratio Therapeutics and what you guys are up to. I will be following along. Where can our listeners go to follow along and connect with you?

John Babich: 26:40

Well, certainly our website. Yeah. And, and,

Jack Hoppin: 26:43

you know, um, thanks to the great group at Russo Partners, our LinkedIn page is, is really active. Um, I admit I'm not a, I don't have a big social media presence personally, but the, you know, we're

John Babich: 26:57

certainly on social media, um, and LinkedIn. Yeah.

Meg Sinclair: 27:03

Right. Well, we'll add your website and LinkedIn in our show notes. Thank you so much for joining us today, Jack and John. Thank

Jack Hoppin: 27:09

awesome

John Babich: 27:09

meeting you, mag. Nice to meet you. Good luck. Likewise. Thank you. Cheer.