From Scientific Promise to Clinical Reality

Welcome back to the FLASH Effect podcast. My name is Justin Starbird and today I get to welcome co-founder of TibaRay, Dr. Peter Maxim. He's also a member of the board of directors. Peter, thank you so much for joining me today.

Well, thank you, Justin. Great to be here.

It's really exciting to have you on to hear your vision. You know, what led you to this today? Talk a little bit about your career and, you know, how you got started.

Yeah, yeah. So I'm Peter Maxim. I'm a medical physicist by training. And if you're wondering what medical physicists do, so my job is basically to deliver the radiation exactly where it should go and with the exact dose.

So we're implementing the safest delivery of radiation when we treat cancer patients with radiation. So I spent my entire career in academic medicine, first at Stanford and now at the University of California, Irvine, where I'm the vice chair of medical physics, so leading the physics group.

And so early on, while I was working with Bill Loo and my colleagues at SLAC and Stanford, we were struck by one real fundamental question: What happens if we were able to deliver the radiation fast enough? Many research laboratories have shown that, you know, there's some really interesting biology that comes out from that.

We were able to kill the tumor as effectively as we do with conventional radiation, but we're sparing the normal tissue for some unknown reason yet. So that led us to the question as well: can we actually do that in a clinical setting? So that's how we all got together and devised a method or a machine, designed a machine, you know, to be able to do that.

So as a medical physicist, my job will be to deliver the radiation really safely, accurately, just the way we want it to cure cancer.

It was a big surprise that the technology really existed and it really came out from Sami Tantawi's, one of our co-founders' lab, while he was working at SLAC National Accelerator Laboratory for different purposes. But some of the technology that has been developed for different purposes turned out to be very effective or very suitable for, you know, building a machine that can treat cancer patients with radiation.

So what initiated as originally a research collaboration between SLAC and Stanford really culminated in the formation of TibaRay with the mission to build such a machine that will be able to deliver the radiation in a flash or very, very fast, faster than a second.

Wow. When you guys were initially talking and thinking through how this would actually become a reality, at what point did you realize that it was going to go beyond Stanford and SLAC collaboration and spin out into a company?

Well, the idea, so let me go back to the idea first. So my colleague, Dr. Loo and I were tasked at Stanford, you know, to deal with what we call motion in the body or motion management in the body. Everything in the body moves. So if you want to deliver the radiation very precisely with submillimeter precision, you really have to deal with the motion.

So we've implemented many, many motion management strategies like coach the patients to, you know, hold their breath during treatment so to freeze that tumor motion, or to synchronize the radiation with the breathing cycle—so only turn on the radiation beam when a patient exhales, for example.

So we've done all these implementations and technologies, you know, to deal with the organ motion, which we believe is the remaining barrier for the most precise radiotherapy.

And so at some point we came up with the idea: what if we turn this around? What if we make radiation faster than physiologic motion, effectively freezing motion? And so that was the clinical need that first came out of that.

And then in 2014, a pivotal paper from the Curie Group in Paris, France came out that has shown that if you deliver the radiation fast enough in a sub-second time scale—so 400, 500 times faster than we currently do—there's this really wonderful, magical biology happening: you kill the tumor effectively, but you spare the normal tissue more efficiently than conventional radiation.

So that gave us the reason, that was the reason why we then sat down and brainstormed how can we make this a reality. And so TibaRay was born to develop this technology to be able to deliver the radiation in a sub-second time frame. So that was the original clinical need on that. With the right partnership at the right time, we found each other and then formed TibaRay with a mission to really build such a machine that is currently non-existent.

Yeah, it was really interesting hearing your perspective of this too, because we had Dr. Bill Loo, your colleague, on just before talking about and sharing similar sentiments, but from his perspective, it's really interesting to see how fortuitous that all this kind of happened while you were thinking about it and asking these big questions.

And that was, you know, now we're looking back, this is 12, 15 years ago, where the idea of, you know, some of the technology hadn't even been considered yet. And I'm thinking of like AI and how that is all built into stuff too. How has the advancement gone in the last 10 years or so to where this is an actual reality now?

Well, it was a rocky road for sure. You know, so this is a really big project, which is capital intensive. So, and when we first started as a research collaboration between SLAC and Stanford, you know, we basically wrote a lot of, we applied for a lot of federal funding to help us, you know, with proof of concept studies, with initial designs and all that.

But, you know, fabricating a machine, you know, to full scale with FDA clearance and standards that the FDA requires, you need a lot more funding to do that. So we realized early on that, you know, research funding was generous and great, and we were very successful obtaining federal funding, [but it] was not enough really to start a company and make this on an industrial scale with all the regulatory requirements.

So as scientists, we, you know, we were good at our fields, but we were not businessmen. So I think the company, once we were able to attract business developers and business people like Thinh, who's leading the company right now, really made a big impact in terms of, you know, developing a clear business plan, path forward, in addition to the science that we have to push forward.

So it's been a rocky road, and we're still looking for investment because, again, building such a big machine for such an ambitious project is beyond what the federal government in terms of funding can offer. So it's been definitely rocky, but we've made good strides. We have a good scientific team. We have a good engineering team. We have a good business development team. And so we are looking to really take this to the next step and really make this as a clinical product that can be deployed worldwide, essentially. And there's significant interest in this, of course.

Talk a little bit about what you've gotten for feedback from folks and some of the milestones that you've been able to hit so far.

Well, it was positive. It's definitely a paradigm-changing technology. So it's not an improvement on an old idea. We really went to the drawing board and completely challenged radiotherapy as we practiced for the last 50, 60, 70 years. So this technology has been really groundbreaking.

And again, it's a paradigm-shifting technology that has not existed. It still doesn't exist. So the feedback for that, especially with the light of the biological data that came out early on, which is now sufficiently strong, suggesting that there is really a benefit of delivering the radiation fast enough and causing fewer side effects in a patient while killing the tumor more effectively, was well-received.

And it's generated quite an excitement in our field in radiation oncology. And so that culminated in many labs now studying the effect of FLASH radiation in preclinical models, like small animals and mice and rats and so on.

The feedback is that it is real, and the excitement is that this could potentially reach the patient at some point for a broader application for treating cancer, so not just niche applications that have been done in the past. So the feedback was overwhelmingly positive, and it's encouraging. In addition, the clinical data supports that this path that we're going on is really a very successful path that might redefine our understanding of how radiobiology really works. So the feedback was overwhelmingly positive.

That's awesome. And that's what I've seen, too, and heard as well. And I think that makes it something that truly has a path forward. And I think one of the things the audience would benefit from is, when you're evaluating a technology like this that is truly changing how people are treated with cancer, what are some of the most important pieces of evidence that matter in this in order for it to keep moving forward? What are the things that are most important for us at home, you know, watching as you continue to push this forward?

Well, so there are two things that we are addressing here. And one is more a practical issue that, you know, Bill and I tried to solve throughout our career. Radiation historically takes longer to deliver than the timescale of physiologic motion. For example, your breathing or your bladder filling. Everything in the body moves. Everything is in constant motion with different timescales, of course. Your heart beats faster than you breathe. But everything in the body moves.

So if you want to talk about precision medicine, and particularly in radiation oncology, that means you have to be able to hit the tumor with submillimeter precision. And our challenge, like any sniper, for example, does, we're always shooting on a moving target. And that predicates really on the fact that the delivery of radiation historically takes longer than the time scale of physiologic motion. Therefore, you have to deal with the motion.

So with this technology, we're eliminating the remaining barrier for the most precise treatment. And this is a practical issue. We're delivering the radiation faster than physiologic motion can happen. We can deliver the radiation between two heartbeats. So that's a practical solution in which we overcome the remaining barrier that we're always shooting on a moving target. If we're delivering the radiation faster, we effectively freeze that organ motion, and we can achieve that submillimeter precision that we're aiming for.

Secondly, the biological evidence that came out from preclinical studies, mainly in small animals and cats and dogs and some canine trials that are ongoing, have shown now in multiple laboratories—so it's reproducibly done in multiple laboratories across multiple continents now in several tumor tissues and normal tissues like in cats, mice, and rats—that this FLASH effect is real. So that means if you deliver the radiation in a sub-second time scale, you spare the normal tissue compared to conventional radiation that we're currently using in our clinic, but maintain the same tumor kill.

Now, if this translates to human therapy, when we have very, very few preliminary data that shows that, yeah, that is as good and better than what we currently do now. But if the FLASH effect translates into human therapy, and we see the same exact or maybe similar effects that we've shown in preclinical studies, then a transition to delivering the radiation very fast will be mandatory. And we are positioned well for this transition as a company.

No doubt about that, to be the first to be able to put this out there in a way that's meaningful. I mean, I feel like some of the challenges seem obvious, but what are some of the roadblocks that you still see in the way, in the near term and then long term?

Well, there are some roadblocks that are technological that may not be obvious to an investor, but, you know, measuring—given that this is a paradigm-shifting delivery system and we're delivering the radiation fast—all our dose measurement instrumentation that we've used now in the clinic on a daily basis are not suitable anymore for, you know, measuring dose exactly if you deliver it in this ultra-fast fashion. So it is something that's new.

Hold on, let me ask you a question. Sorry to interrupt. But in the current setting, if the dosages, if you use the existing dosages, it would be too much radiation because there's spillover? Or how do you—

No, it's mainly the effect of that the current dose measurement devices that we're using to measure currently the dose are not fast enough. They can't keep up with the accuracy that's needed, you know, if you deliver the radiation very fast. So there's a whole complete new technology [that] needs to be developed for dose measurements on these timescales. That's currently non-existent. There's many, many third-party vendors that are working in this space to create such instrumentations. But that is something, a major technological barrier that we have to overcome to measure the dose really accurately in the same fashion that we're doing it right now with conventional radiation.

The other part is, you know, there is this new linear accelerator engineering, which is really sort of one of the key components that TibaRay is developing. You know, the technology to deliver these fast doses will require new hardware, which we're developing. So those are hurdles that need to be overcome. We're very close, if not there already. But then there is the power requirement to power these accelerators, you know, to deliver doses very, very fast.

So there are some technological challenges that are pushing the forefront of innovation in a way to make this a reality. So this is something that, you know, it's not obvious, you know, to an investor immediately, but those are technological challenges that we'll have to face.

And then once we have overcome this, you know, we have to ensure that those same dose accuracies that we are accustomed to, that we're hitting the target in the same spot that we're intending to, and that has to be reproduced and independently verified. So those are all steps that will be required to overcome before this goes clinically live. So there are a few technological challenges that we need to overcome, and we will.

And I think, you know, I'm glad you shared a little bit about, you know, what stands in the way, because investors want to know what they're getting into. On the other side, there are some significant milestones that TibaRay is on the cusp of as well, in terms of how quickly you're actually meeting those challenges and solving for them. Not to mention the interest from the scientific community we mentioned before, and the investor community that's come forward and said, hey, we want to be a part of this. Talk a little bit about those milestones and more that you can share today, because that's what this podcast will be for, is for you to come on later—come on again, right, Peter, to talk about the excitement and new announcements later on. But we can talk about some now.

Well, yeah. So, I mean, some of the key marks that we have to look at is really overcoming sort of the putting this technology, all this new equipment, all these new ideas, all these components that we're pushing forward—they all have to be assembled and then have to work. But I think the biggest, and that's a technological issue that TibaRay has solved, I would say.

The next milestone that we have to look into is really, you know, having, again, independent verification of our milestones, of our beam characteristics and our, you know, our technology, what the technology can deliver. So that has to be independently verified.

And then I think the one big hurdle is to actually show that in some human clinical trial, in a well-designed clinical trial, that delivering the radiation is as good, if not better, than what we can do currently. So once these milestones have been demonstrated, again, that would be the, you know, sort of a mandatory shift towards delivering the radiation very, very fast.

That's great. So thinking about, you know, right now you're in the midst of raising capital via the community and using WeFunder as the platform for that. Talk a little bit about what it means to have the right capital at this stage of development and share your thoughts on going through and actually including the community—some people who have been affected by cancer—in this investment round so that they can participate in the success of the company.

Yeah, yeah, no, absolutely. So, you know, medical devices itself, whether it's a radiation device like we're building, generally medical devices have a well-known valley of death between promising, you know, prototype and then production at industrial scale conforming to all regulatory requirements.

Federal grants that we obtained in the past were great. They were an excellent vehicle, you know, for discovery and for prototyping and making initial progress and proof of concept progress, if you will. But, you know, building something on a commercial scale, adhering to all the regulatory requirements, that will require quite a different amount of investment, you know, to do this on an industrial scale.

So what we're seeking through the WeFunder platform or other investment possibilities is, you know, help us to bridge from the idea, from the prototype, I think, to really commercialization, to really industrial-scale manufacturing of these devices that unfortunately the government cannot fund in that perspective. So that is something that we are eager to work with investors for.

Are you still having fun with this?

It has been a privilege for me to be part of this journey. It has been a very gratifying process to see that some ideas that we came up with many, many years ago as young, energetic faculty at Stanford to take this really to the next level and actually really see the benefit that patients will be treated with this as we wanted that 10 plus years ago.

So it's a tool that we're building for ourselves. This is a tool that, you know, if we would have right now we would treat our cancer patients with that. So yes, the enthusiasm is still there and I cannot wait for that day when we're treating the first patient with this new technology.

I can't wait either. I think so many lives have been touched so deeply and personally by cancer and this not just gives hope to those today but also a path forward in the future. And I think what you have been able to do with your colleagues is nothing short of incredible. And so I thank you for sharing your journey today, talking about the technology, what your vision for this is and the mission for TibaRay.

I think this is just the start of something great where we get to have you on as a regular part of this to share your perspective, to answer questions from investors and to talk about the different milestones that are building, you know, through this technology. So I'm really excited about it. Thank you so much for joining me today, Peter.

Yeah. Thank you, Justin.

On behalf of my guest today, Dr. Peter Maxim, one of the co-founders of TibaRay, you've been watching the FLASH Effect podcast. Until next time.

Okay.

How did it go?

I thought that was good.

What did you think, Lisa?

Excellent. Excellent. That was great. I mean, I was glued to my—I was starting to do something else. I wasn't kind of listening with the left ear, but Peter, I was just glued in on every word you said. And this is the first time I've actually heard you speak. And I've been at TibaRay for a while.

Yeah. You know, I mean, so the one thing, Justin, just really quick is, you know, medical physics, radiation oncology—because it's so technically involved, the medical physicists are the guys that are in the background. So think about that, the movie Avatar: you know, without the effect, you would see two guys in their blue costumes running around, but the effect is what makes the movie, right?

And so the medical physicist is always sort of in the background, is the guy behind the stage that makes it all work. The doctor is always in the forefront. So Bill was always the face of it because, you know, he's the treating physician. He's the guy that actually treats the patients. You know, I'm in the background making sure that everything goes well. So, Lisa, to answer your question, that's why Bill was always sort of, and, you know, obviously Bill is Bill, you know, the smartest guy that I know. But, you know, it's always the physician. They're the actors, right?

They're the protagonists in this game. Yeah. No, it was beautiful. It was beautiful. So I'd love to hear more from you. We got to get more people later on for little things here and there too.

So this was great. Yeah. I thought so too. I thought you did a great job. I stayed within the outline, but asked them a little bit different. And I thought you did a great job meeting me right there. I thought the conversation flowed really well. And this was a little bit on the shorter side, but I also didn't want to drag it out. I felt like I left some meat on the bone. So we can come back to this and ask more questions.

Yeah. No. And obviously, Lisa, Justin, I'm available anytime. So there's a little vested interest in you too.

And Justin, like the way it was like a conversation because you wanted clarification on something and it sounded like you were actually, you know, just talking to him normally. Like, oh, okay, wait. So you're saying—so it just went really well. I like the way you do these, Justin. They're just very natural, even though it's Zoom, and you're in two different places. I think it's just, it's like a conversation, you know, with two friends. And I like it. I like the style of this.

So well, thank you very much.

You'll be an expert in radiotherapy, Justin, after going on with this.

And it's amazing. So Lisa, thank you. That's one of the nicest compliments I've ever gotten in doing this. Because at the end of it, I don't know the answers to the questions that I'm asking. And so sometimes the best thing I can do is just get out of the way. And I always feel like I was never shy about asking questions. Like I always thought that I should be the one that sounds dumb for 30 seconds so that everybody else could hear it because they were afraid of asking the question.

Man, it was great. I'm so thankful to get this new knowledge. Yeah, no, and thanks for doing this for us, Justin. This is really great. You know, what I hear from Thinh, this podcast and the other interviews that we conducted have generated a little bit more enthusiasm. So I always see this little spike in WeFunder.

Yeah, we're going to be launching these next week, and then yours will be following the first two. So we'll get them edited up so that they will also pull out some great clips. So you had a lot of really good information to share there. So we'll pull those out to be able to use for social posts and updates and thinking about the website, you know, all that stuff later on.

Sure. Yeah.

So we call them foundational assets because it starts to create, you know, pillars from which to build to look at this long term because, of course, you're going to be raising money for a while, but we look at this as something that can be used forever.

Yeah. No, thank you, Justin. Really, thank you for your help. This is great.

Well, thank you very much, Lisa. Thank you for coordinating this. And I'll catch up with you guys later this week.