Prescient Therapeutics CEO interview

Prescient Therapeutics (ASX:PTX): We spoke with Steve Yatomi-Clarke, CEO of Prescient Therapeutics, about the exciting new world of CAR-T therapy for the treatment of cancer and how Prescient, thanks to some interesting technology developed at the University of Pennsylvania and at Oxford, has the Next Big Thing in this space.

 

Read our most recent article on PTX here

 

 

Transcription

 

Stuart: Hello. And welcome to Stocks Down Under. My name is Stuart Roberts and I’m one of the co-founders of our publication. And with me on the afternoon of Wednesday, the 20th of October 2021 is Steve Yatomi-Clarke who’s the CEO of Prescient Therapeutics (ASX:PTX). Steve, good afternoon.

Steve: Good day mate. How are you?

Stuart: How are you feeling? Melbourne is just about to come out of lockdown. So, you must be feeling pretty good.

Steve: It feels like being reborn all over again, mate, we’ve been chewing a whole lot of crap over the last 18 months. And I think we all really deserve it. Looking forward to it.

Stuart: Right. But professionally, this has probably been the highlight of your career, building Prescient Therapeutics. I took a look at the OmniCAR technology which you’ve been licensed from UPenn. You’ve got hold of a technology called OmniCAR. For the viewers who know about CAR-T therapies, I’m confident enough in saying this is the next big thing in the CAR-T field.

So, let’s just step through it. A few years ago, people were talking about CAR-T as being probably the biggest step forward in cancer therapy in a generation. Carl June at the University of Pennsylvania had invented a way to target the immune system to be able to block cancer to the point where kilograms of tumor were falling off of patients. The first of those therapies have gone live in recent days. You’ve had Kymriah from the Novartis. You’ve had Yescarta from Gilead, Abecma from BMS. They’re the first three therapies. You’re the next step along the pathway. So, talk to us about what makes your CAR-T different from the CAR-T that we’ve had up till now.

Steve: Think of it, and I don’t want to besmirch CAR-T because we’re so enthused about the whole platform, but really, it’s… Yes, it’s been the biggest revolution in cancer treatment, as you say, in a generation, which is to say ever.

Stuart: Right.

Steve: And the responses that we’ve seen have emboldened some very conservative clinicians to dare to think about the word cure, which is not used lightly, but it’s a step in that direction of weaponizing our own immune systems.

Stuart: Yeah. And it’s not cranks who were saying cure. This is serious, serious scientists who were looking at the data, right?

Steve: Yeah, absolutely. And that’s why people are persisting with what’s currently a very bespoken and clunky therapy because it bloody works. So, think of it like this. I’m old enough to remember what VHS tapes were and how they revolutionized the way we looked at movies. But prior to that, my family weren’t particularly well to do and we’d have to save a couple of times a year and go to the movies if we’re lucky. But all of a sudden, we’re able to, you know, watch movies at home and rewatch them and stop them and invite friends over and rewind it and fast forward. But who has VHS today? And CAR-T is today as wonderful as CAR-T is, those three examples you said, that is VHS.

Stuart: Right.

Steve: And it’s as clunky as it gets. Now, if you look at fast forward into the future, and not too far into the future of what it’s going to be, it is going to have the power of, the cancer-killing power of a T-cell which is your own immune system, but you’re gonna give it the control and the predictability and the flexibility to be controlled by the clinician once it’s infused and to be able to redirect it to where you want to target various types of cancers. And that’s what we’ve got. If you think of it, we’re taking those same immune cells, but like a Lego set, we’ve got a plug-and-play. And we can… By taking this plug-and-play approach, not only can we control the activity of the cells like a remote control, but we can direct it, we can switch them on, switch them off directly against cancer one, cancer two, cancer three. And this is the type of modularity that is really gonna take the entire field to the next level by solving the bottlenecks that are holding it back from treating other cancers.

Stuart: All right. So, let’s just review a bit of basic sites. CAR-T is Chimeric Antigen Receptor T-cells. So, one part of a CAR-T construct targets to the tumor. You pick a marker on the tumor cell. And traditionally, for those first three therapies, we were talking about its CD19. The other part was a T-cell signaling domain, to tell the T-cell, “Hey, there’s a bad… This stuff is bad.” He’d come and kill it. If I could summarize in layman’s language what’s happening here. But when we first started hearing about CAR-T, some folks were saying only CD19-based cancers, which is blood-based tumors would be treatable. Now, your big step forward is, as you say, the plug-and-play component. We take whatever targeting agent we want and then we can plug in the T-cell signaling domain. That’s relatively new to science. So, pick whatever cancer target you like, you can go after.

Steve: Yeah. It’s like a universal adapter.

Stuart: Right.

Steve: That’s right. So, we’re agnostic on the type of cancer and the type of antigens on that cancer. But still, Prescient Therapeutics is also agnostic on the type of cell. Now, this could be an autologous cell, someone’s own cells. It could be an off-the-shelf cell. It could be a T-cell. It could be an NK cell. I’m really agnostic on that. It’s too early to call the winners. And we’re agnostic on that. We’ve got as many horses in the race as you’d like. Our magic is in the modularity. And I will leave the people who are the zealots who were championing one cell over another cell good on and we’ll play with both of them. One target versus another target, we’ll play with both of them. So, we’re agnostic on that. Our magic is in the modularity, and the modularity means control and efficacy.

Stuart: Right? Now, obviously, this technology has good provenance. You got it from the University of Pennsylvania, which as we were saying before, that was where CAR-T was effectively born under the aegis of Professor Carl June. You’ve been there and talked to a couple of geniuses by the name of Andrew Sarkis and Daniel Powell, who came up with this technology. But it’s an international effort. The actual point standing between the two parts of the construct came from Oxford University. Talk to us about how these elements of the technology have come together.

Steve: Yeah, yeah. So, Oxford designed the bits of Velcro that stick these together. To draw the analogy for listeners, think about it. We’ve licensed the sports car from Penn, but the engine was built at Oxford.

Stuart: Right.

Steve: Think about that. So, Oxford had developed this molecular Velcro, if you like, and they were using it for agricultural applications and they’ve got a vaccine spin out where they’re using this in clinical trials right now for vaccines, including, I believe, a COVID-19 vaccine. And what Penn did is say, “You know what? This type of binding is fantastic because it’s specific, it’s fast, and it’s covalent, which means these don’t… Unlike, as you’ve noticed in biology, things pop on and off and it’s…

Stuart: That’s right.

Steve: …association. You don’t want these coming off. So, they want it stuck on and they said, “We can use this to create a modular system.” So, that’s the application that they brought forward. So, yeah. It was, I guess, the combined brainpower of Oxford. And Penn is not a bad place to be.

Stuart: Right. And I did have a good chuckle. The folks at Oxford called their part, SpyCatcher.

Steve: That’s right. That’s right. Maybe it’s the British influence, the James Bond influence, right? SpyTag and SpyCatcher.

Stuart: All right. So, we’ve got technology developed both sides of the Atlantic and it suddenly goes into a knockabout Ozzie company chaired by a fellow with various write and exit here in your case in Melbourne. So, it’s become a truly international effort, and traded on ASX. Now, the proof of the pudding will be clinical work. I’ve looked at the preclinicals in the best animal models and you’ve been able to blast apart every cancer cell in the body of some of those animal models, basically.

Steve: That’s right. Yeah. The rubber hits the road for most of these in drug development and clinical trials. But when you’ve got a platform that can do things that are world-first in some cases, then you’re turning a lot of heads in preclinical models, and that’s what we’re doing. So, we’re basically proving up and we released some data last week that, you know, not only we’re killing all types of cancer, but we’re able to control the activity, we’re able to arm them and re-arm them and redirect cells. So, it’s proving to be, in short, a very obedient system. Science can be a little bit tricky to prove up what people are hoping to. But in this case, we have never seen not only is it proving very obedient and easy to work with, but these are working first time in our hands and quite complex experiments. And some of these are world firsts.

Stuart: Yeah. To that point. You look at the very original papers that came out, I’m guessing about 2014, I think it was, on the first generation of CAR-T. It’s the case study of the patient who should have died because of the cytokine storm from the amount of the immune system activity that had been generated against the cancer. He had to be hospitalized, survived, and where the heck did the cancer go? Well, that was the effect of CAR-T. Now, that then led to some concern, you have to be very selective on patients because only a certain…some patients would die from the therapy, not from the cancer.

Steve: That’s right.

Stuart: Whereas with you, Prescient Therapeutics can modulate the therapy because the plug-and-play gives you control over that. Right?

Steve: That’s right. Well, these are living cells. So you inject them. And one cell becomes two, two becomes four, four becomes eight, and so on, but the doctor has no control over that. And these are the same sorts of inflammatory reactions that were killing people early in the COVID-19 pandemic, to a rise of inflammatory response. Your body doesn’t know what to do with all of this gunk being blasted from the tumor and it gets overwhelmed and some really sick patients die. And that’s why CAR-T to this point with current generation is only being used in very sick patients for whom you can justify the risk-reward equation, knowing that the therapy itself has occasionally killed people and has caused neurological toxicities and all sorts of things. So, to even receive current generation CAR-T, patients have to be in an intensive care unit. But what we’re doing here is that if you were on any other medication and you’ve got an adverse event, or you’re at risk, so, the doctor would give you increasing amounts of the medicine until it was safe. And if it wasn’t safe, they would stop giving it or give you a lesser dose. And that’s what you can do with ours. So now it’s different. And by making it safe, Stuart, we can make this amazing therapy available to a whole bunch of patients for whom doctors cannot currently justify the risk-reward equation, which is most patients.

Stuart: Right. Okay. So, in terms of the clinical journey for this wonderful therapy we’ve created, what’s in the works at this stage?

Steve: So, we are matching pretty quickly towards clinical studies, which we certainly hope to have within two years. We’ll be looking to… So, we’ve got three programs, one for a blood cancer called AML, one for solid tumors, over-expressing something that I know you know well called HER2. And another one, an aggressive type of brain cancer called JBM. So, we’re running all three of these with purpose. We’ll be spitting out news over the coming months as… There will be signposts along the way to an initiation of a clinical trial, which we hope to initiate here in Australia, but, you know, probably under a U.S. IND as well. So, a U.S. driver’s license so we can take this wherever we need.

Stuart: Right. Now, the HER2 interests me in particular because, obviously, well, the whole solid tumor thing, the ability to be able to show, in this case, the HER2-positive breast cancer that a CAR-T construct can go beyond the traditional blood cancer setting in which they’ve been tried out before. That’s particularly important, right?

Steve: I think so. Some of the low-hanging fruit has been picked with current generation CAR-Ts, but it’s not made a dent yet in solid tumors. And that’s due to several reasons, one is trying to find the right target on the surface of cancers. And solid tumor cancers normally have lots of different proteins that you can target, meaning that picking just one which current CAR-Ts can do one, maybe two, it’s just not enough because it knocks out some clones, and the others keep growing, and the cancer rebounds. You’ve wasted a half million dollar therapy. And the other ones is, how do you get them to the solid tumors and how do you get them to hang around for long enough to work? Now these current generation CAR-Ts, it’s a single infusion. It’s half a million dollar therapy for a single infusion. And that’s easy enough in the blood but as you know, it’s not gonna move the needle on a solid tumor. But some people have… Some academic studies have shown that if you do five, six, seven different manufacturing runs of CAR-T, it starts to make a real dent in the disease and you get clinical benefit, but that’s gonna take… That’s 22 days and half a million dollars for each one of those seven manufacturing runs.

Stuart: Yeah. Australia might be able to afford that. But a lot of other jurisdictions can’t really accommodate that sort of expenditure.

Steve: It’s unfeasible. What we’ve got here is the ability, though, with the single-cell product to keep pulsing it with the dose of the binders. So, for the listeners giving it like any… You do the hard work with the cell. You give that once and then you keep giving the binder, say, once a month, and you keep stimulating them the way cells are supposed to be, you know, metronomically stimulated and you get them to last a lot longer. When they last a lot longer, they can do their job and get rid of a big solid tumor mess. And that’s been the big difference, the big…one of the main barriers holding back CAR-T therapy working in solid tumors like breast cancer, ovarian, gastric, and so on.

Stuart: Right. Now, that’s OmniCAR. And obviously, we’re expecting massive future payoffs for OmniCAR. Your foundation asset, which you inherited when you first became CEO of Prescient, was a repurposed drug that could go after a particular element of the signaling cascade called AKT. Now, that was in multiple studies at the time when you were only a $3 million market cap company. How are we going with that original program?

Steve: Yeah. We’ve narrowed that down. That was in three clinical studies and we’ve narrowed that down to one to make sure that we’re in best use of funds at the end of the day in trying to bring those studies to Australia ultimately. But we’ve got a study going in AML. It’s a blood cancer. It’s under the leadership of Jeff Lancet who is a pioneer in this… He’s a bit of a key opinion leader in this space. And that’s had three complete queues so far complete responses also, a study so far in counting in a disease where people typically die within sort of 49 months. So, that’s very encouraging. And that’s ongoing. I think COVID’s held that up a little bit, unfortunately. We’ve not been immune from the effects of that. So, that slowed recruitment. We were hoping to have that finished by the end of the year. I’m still hoping that’s possible, but we’ll wait and see. Yeah. So, that’s where that is, but there’s utility in some other cancers as well where that can go that we’re looking for, you know, academic-led collaborations. So, we’re doing it off-balance sheet.

Stuart: All right. It’s October 2021. Imagine we’re having this conversation in October 2022. What do you hope Prescient will have achieved by that time?

Steve: We’ve not even spoken about one of the other foundational assets, PTX 100, which is showing good utility, and another type of blood cancer called T-cell lymphoma, proof of T-cell lymphoma. We’re chasing a really encouraging efficacy signal. Bottom line is, patients typically you’d expect them at best, a third of them might have a three-month duration of response. And we’ve had a couple so far, one with 12 months and one with probably now up to 20 months and counting. So, we’re chasing that sweet spot and that’ll be in clinical studies, an expansion cohort, a phase two equivalent, if you will, very shortly. And that’ll be reading out next year. So, I’d like to be talking about those results around this time next year. OmniCAR will be within touching distance of a study with three studies this time next year and we’ll have answers on PTX 200. There’s also two programs in stealth mode at the Peter McKellen Cancer Center and still was in cell therapy and they will well and truly be out of stealth mode by then. We’re in stealth mode because of patent reasons and competitive reasons. But that data is… Let’s just say we’re looking forward to talking about that data very shortly. So, this time next year, it’s gonna be a massive year for us, no doubt about that. Lots of [crosstalk 00:17:25.554]

Stuart: It’s good. One question might bother some viewers. Manufacturing of OmniCAR. How hard or easy is it to create these…to actually manufacture these constructs under GMP?

Steve: It’s tricky to make as any other cell therapy products. So, yeah. They do take… It’s currently a bespoke therapy. Again, we’re agnostic on the cell type, but our first iteration will use the patient’s own cells. And we’re using pretty much the same process that Novartis has used and BMS is used and Gilead are using. So, Australia is quite blessed to have places like cell therapies and there’s a couple of others in Australia that are licensed to make these and have the capabilities.

Stuart: And there’s a lot of expertise around cellular manufacturing. So, yeah, that’s straightforward. Yeah.

Steve: I would argue that ours might even be easier to make because we’re not making the entire construct. We’re making with a bit of velcro sticking out of it.

Stuart: Right.

Steve: So, we’re making… The big bit attaches to the cancer we add afterwards just like you would a drug. So, I wouldn’t expect that to be especially problematic.

Stuart: All right. And in terms of what keeps you awake at night, apart from the fact that you’ve got collaborators all around the world, and therefore every timezone that you’ve got to be awake for, what keeps you awake in a sense of worrying about stuff that could go wrong?

Steve: You know what? Two years ago, it would have been a very, very different answer. Now, it used to be… Again, a month ago would have been, “Will this work in our hands?” And now it’s not only working in our hands, it’s working spectacularly well in our hands and it’s working first time in our hands. So, that’s no longer keeping me up. It’s really… The things keeping me up now are the timelines. We’ve got a very, very aggressive timeline and keeping the whips cracking to get that done. We’ve got some good in-house expertise now. And I’m strapping in for the ride. Everyone’s running pretty fast at this internally and externally. So, timelines are the main things that keep me up at night. Technology redundancy does not because we’re so far ahead of the curve that… And we’re, again, target and so agnostic that we’ve got all of those redundancies built in where that’s very de-risked. And from the PTX 100 point of view would be, “Well, is that going to work or not?” But it’s going to be… That’s going to be, you know, 18 months before that’s got an opportunity to disappoint us. Yeah, I sleep a lot better than I used to, mate. That’s for sure.

Stuart: Well, Steve, it’s been wonderful watching this company build out, as it was $3 million market cap when you took charge, it’s $155 million market cap now. And you’re not only making a serious difference to the Prescient shareholders who’ve backed you on the journey, there’s a heck of a lot of patients who are likely to benefit from this in the future. So, on behalf of all those patients, thank you very much.

Steve: Thank you very much. And thanks for the attention and the wonderful questions and look forward to staying in touch.

Stuart: All right. Keep up the good work. See you.

Steve: Thanks, mate.