Plus Therapeutics, Inc. (PSTV) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen. Welcome to the Plus Therapeutics business update on CNSide. Before we begin, we want to advise you that over the course of the call, including any question-and-answer session, forward-looking statements will be made regarding events, trends, business prospects and financial performance, which may affect Plus Therapeutics' future operating results and financial position. All such statements are subject to risks and uncertainties, including the risks and uncertainties described under the Risk Factors section included in Plus Therapeutics' annual report form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time. Plus Therapeutics advises you to review these risk factors in considering such statements. Plus Therapeutics assumes no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made. It is now my pleasure to turn the floor over to Dr. Marc Hedrick, Plus Therapeutics' President and Chief Executive Officer. Sir, you may begin.

Thank you, Sheri. Good morning, everyone, and thank you for taking the time to join us today, as we provide a business update on our CNSide Diagnostics platform acquired a little over a year ago and our related CNSide Diagnostics subsidiary. Joining me for the call today is Mr. Andrew Sims, Chief Financial Officer of Plus Therapeutics; and Mr. Russ Bradley, the President and General Manager of CNSide Diagnostics. And Russ first call and welcome aboard officially. Now as many of you who follow Plus already know, we have been using the CNSide diagnostic assay since 2022 in our ReSPECT-LM clinical trial, and it has become an increasingly compelling part of the overall clinical development story for our lead therapeutic candidate, REYOBIQ. Early on in the use of CNSide, it became clear that, one, CNSide had significant value for our REYOBIQ programs, but also two, that CNSide fills an essential gap in the broader diagnostics CNS cancer patients. And then Plus was in a unique and privileged position with first-hand experience with a product in an experimental therapeutic to recognize CNSide's potential to transform the current CNS cancer care paradigm. And in early 2024, we acted decisively to acquire the asset as part of a distress sale that was not related to the promising nature of CNSide. As part of that evaluation of the CNSide assets, we assess the commercial opportunity, the competitive landscape, the operational requirements, pricing and so forth. And based on a positive outcome of that analysis, including deriving attractive NPVs as part of our analysis, we began to put in place the key elements of our CNSide business plan. Now with that analysis complete, and the decision made to move forward commercially with CNSide, we wanted to formally update stockholders on the current status and next steps, hence, the rationale behind the CNSide business update call today. Now I'd like to begin with a bit more context around the acquisition and then turn it over to Russ Bradley to discuss the go-forward plan. CNS metastases, central nervous system metastasis represents a rapidly growing challenge, affecting approximately 30% of all cancer patients or potentially over 1 million individuals in the U.S. alone. This epidemic is largely driven by positive advancements in primary cancer treatments and longer patient survival, which have as a byproduct [indiscernible] to the incidence of CNS metastases. These metastases can occur in the brain or spinal tissue, the CNS fluid space also called the cerebrospinal fluid, or CSF, or both, posing significant diagnosis and treatment due to the highly protected nature of the CNS and the blood-brain barrier is a well-known and key part of that protective apparatus. However, the current standard of care for making a definitive diagnosis of CNS mets is outdated and wholly inadequate. In fact, the principal diagnostics used today, number one is cytology, which dates back to 1904 and the other MRI dates back to the '70s. So without accurate tools for diagnosis, let alone disease or treatment monitoring or treatment selection, patients and their providers face a slew of open questions or outright guesses and as a result, a bleak prognosis ensues. In fact, a therapeutic neolism has taken hold in the neuro-oncology community, such that approximately half of those ultimately diagnosed or suspected to have leptomeningeal metastases, which is a common form of CNS mets. Those patients transition just to palliative or hospice care and survive only a few weeks. So in that context, here's where CNSide comes into the picture. CNSide is a comprehensive CNS and CSF testing platform useful for both metastatic and primary CNS cancers. It's 4 tests in 1 from a single CSF sample that quantitates cancer cells and measures both cellular and molecular signals common in CSF mets. Recently published data shows that the CNSide testing platform offers a clinical specificity of 95% and sensitivity of 92%, which significantly exceeds the performance of the current standard of care methods, I mentioned earlier. CNSide's capability to detect tumor cells at a concentration of just a single cell per 5 ML sample of cerebrospinal fluid is a major advancement in tumor cell diagnosis and in the management of patients with CNS mets. Now with that preamble, I'm happy to introduce Mr. Russ Bradley, who recently came on board as the President and GM of CNSide Diagnostics. And I'd like him to provide more detail on plans for 2025 and thereafter, including the commercialization strategy. But first, I think it's appropriate to highlight Russ' background and why it's such a great fit for this role. Russ has decades of global experience in both the clinical diagnostic and life science tools markets where he evaluated, developed and successfully launched multiple market-leading technologies and applications. Most recently, he was the Head of the Hematology and Business Unit with the core diagnostics division of Abbott Laboratories, responsible for the global launch of Abbott's market-leading Alinity product line. Russ also spent over a decade at Luminex Corporation as a Corporate Officer, responsible for Luminex's commercial operations, global growth strategy, M&A and strategic partnership business model. And so with that, Russ, I'll turn it over to you.

Well, thanks, Marc, and good morning, and thanks for joining us. One of the several things really that drew me to this opportunity is that CNSide is a combination of a sizable opportunity unto itself, but it's also substantially derisked. And what I mean by that is that in the previous owner's hands, over $300 million was invested in advancing the core technology of CNSide prior to Plus' acquisition last year. Since the initial launch in 2020, CNSide has gained significant traction in the market with over 11,000 tests ordered by more than 200 unique physicians across 120 different institutions. Furthermore, the clinical utility of CNSide and its core technology is reinforced by 8 peer-reviewed publications and a clinical trial that was completed in 2024. And as part of that, we've established support for the technology from key opinion leaders in neuro-oncology. Finally, CNSide testing is offered at a centralized laboratory under the regulatory oversight from the centers of Medicare and Medicaid Services or CNS, ensuring a more predictable regulatory pathway exempt from FDA premarket review requirements. So perhaps a little more about what makes CNSide such a unique platform. CNSide employs several proprietary technologies and processes for the sensitive detection and enumeration of tumor cells. The core technology is protected by 14 patents and 10 trademarks, including a couple of key technology patents around the sample collection process and preservation of the samples that really facilitates the centralized testing business model, which I'll expand upon a little later in the call. We also have some apparatus patents around the microfluidic cell capture technologies that are used and have demonstrated high sensitivity and specificity for tumor cells. This results in a diagnostic process that provides clinical clarity, and -- but also treatment guidance, therapeutic monitoring and prognostic insights through a personalized report that we create and send back to the health care provider. We believe CNSide has the potential to dramatically impact the standard of care in the CNS cancer diagnostics market and consequently, improve therapies and ultimately, patient outcomes. By virtue of our specific market sizing knowledge, courtesy of Plus Therapeutics analysis, we estimate there are more than 500,000 CNS metastases patients per year that could benefit from better diagnostic alternatives like CNSide. This translates into a total addressable market of approximately $6 billion just in the U.S. Some background information on the regulatory environment that we are operating in as well. As I said earlier, the CNSide business model is to produce a laboratory developed test and is, therefore, regulated under the centers for Medicare and Medicaid services and their clear accreditation program. We have put in place the infrastructure, the testing processes and quality systems at our centralized testing lab in Houston, Texas, that ensures the quality control of our testing process. We anticipate receiving clear accreditation for the lab in Houston, in Q3 of this year, which will open up our regional access program before we launch more broadly in the U.S. subject to gaining appropriate state licensure. From a commercial perspective, since coming on board at CNSide, we've been validating the commercial assumptions around the test launch, refining our business strategy and developing a go-to-market plan for the relaunch of CNSide. We've optimized CNSide's coding and pricing model, facilitating a simplified billing process, which we believe will be accepted across both commercial and government payers. Our commercial road map will begin in Texas later this year, capitalizing on established local relationships we have and a favorable market access dynamic. From late 2025 through to 2027, we intend to expand nationally, prioritizing leading cancer centers and simultaneously securing payer coverage. We have put the testing infrastructure in place within our centralized testing lab, and that will support the test processing for our planned rollout and our capacity to scale. In terms of what to expect in guidance for our plans to roll out. Our 2025 forecast is understandably conservative despite the initial commercial traction CNSide had already previously enjoyed. This is due to several factors, including what needs to be done still, which includes reestablishing the Medicare and private payer agreements. So we're in the process of reengaging, updating our lab services agreements previously in place and expanding into new geographic regions. And in parallel to this, we are planning to expand the breadth of our testing services that we offer. As we turn to 2026 and beyond, as our testing volumes grow in line with our current expectations, we anticipate meaningful revenue and margin contributions that will review when appropriate. So to close out this part of the update, I'm excited to reintroduce CNSide testing at a time when there is such a strong clinical demand for better tools to detect, enumerate and support the management of patients with CNS metastases. We have a proprietary and highly sensitive technology solution that has been clinically accepted, it's been published, it's been validated and previously utilized by many of our target health care providers. We are addressing an unmet clinical need in a large and growing market, but we believe we can also significantly improve both outcomes and quality of life for those impacted by CNS cancers. So with that, I'll turn it back to Marc.

Thank you, Russ. So to finish up prior to Q&A, I would just like to reiterate key CNSide milestones and guidance for the remainder of 2025. First of all, we anticipate to launch CNSide in Texas in Q3 2025 with additional regions added in a state-by-state fashion for the remainder of 2025 and through 2026. Some states are pretty simple to enter and some states require a bit more paperwork and/or validation and hence, the staging of that. Second, we also anticipate payer and laboratory services agreements to track in a similar fashion starting in late 2025 through 2026, and we're also -- we're right now in communication with many of those legacy payers. Our plan is to announce the more material of these commercially oriented milestones when consummated. Third, while we intend to comment generally on test economics periodically, we fix CNSide financial guidance until Q1 2026. And our thought is, by then, we should have greater quarter-to-quarter visibility that we would need to confidently provide guidance. As the cash impact, we have budgeted for CNSide related spend for the remainder of 2025, but of course, reserve the option to seek additional capital in order to accelerate achievement of commercial milestones and capture greater and greater market share. So with that, I'll turn the call back over to Sheri and we'll address any questions that you may have. Thank you.

[Operator Instructions] And our first question will come from the line of Michael Okunewitch with Maxim Group.

Congrats on the progress at CNSide. I guess just to kick things off, could you just elaborate a little bit on what steps you need to take to gain coverage? And then what sort of reimbursement level would you be expecting, in particular now that you do have clinical data in hand, which the previous developer did not?

Michael, thanks for the question. I'm going to turn that over to Russ to talk about both our kind of payer strategy and kind of building off of what the prior company had done and what -- how we've sort of taken it to the next level, and also maybe comment generally on pricing and margins, which I think is kind of the second part of your question. Russ, do you mind taking that?

Yes. Sure, Marc. No problem. Thanks for the question. So yes, we aren't really at a stage to disclose what our reimbursement is. We're currently in the process of reengaging with the payers. We have developed what we would call value-based pricing based on the fact that the technology is a lot more validated and mature. And it also has -- what's been backed now by a clinical publications. So we have come up with pricing strategy. Where we're reengaging the payers that were contracted with the previous owner of CNSide, and we're also looking at -- going after some new agreements with that as well. So that's our fundamental go-to-market from a reimbursement point of view. The other thing I would say that is different is that we're -- because of the CNSide technology is such a unique offering, it's a combination of technologies in the market. We are pursuing specific codes for CNSide. So we intend to get specific reimbursement coding both for Medicare and for the private payers in association with our value-based pricing that we think is looking at comparable technologies in the marketplace and what they reimbursed that, we think that we'll be successful in pursuing the pricing and the coverage. So I think we're poised to start getting some of those payer agreements in place. We've already engaged with the previous payers that covered CNSide prior, but now as you mentioned, we have a lot more clinical data to go in there and stayed okay. So we're confident of getting a very favorable reimbursement decision once we go through that process.

Just for benchmarking, could you remind us what it was reimbursed at previously?

Yes. Actually, not sure it was publicly disclosed. What the reimbursement was for the product before. It was -- yes, it was -- obviously, it's dependent payer-by-payer and what you negotiate. I would say it was -- based on my knowledge of what they were seeing, it was pretty attractive, but it was also kind of sporadic. So -- maybe that question is best asked to the previous owners.

Mike, I can just add to that. The challenge with the developer of the test is they were using generic codes and had not and [indiscernible] and developing proprietary coding strategy. And so I think there are a number of things that we learned from looking at their experience, and we won't be making those same decisions. So it would be remarkably different approach to pricing in our view.

Yes. I appreciate the clarity. And then I guess just what sort of criteria would lead a patient to qualify for CNSide in your initial label of tumor cell enumeration for LM?

Yes. It's a great question. I'll take that and perhaps Russ has some additional information. But this is where the epidemic in CNS mets is sort of becoming more and more apparent and being talked about at scientific meetings and conversation with leading neuro-oncologist in the U.S. And so if you look at -- and we're talking about patients that have both parenchymal brain mets or patients that have liquid mets, which are effectively LM. So there's LM take that as an example. So generally, you look at the data, and there's maybe you could triangulate a number of about 125,000 patients per year in the U.S. that have LM. If you look at autopsy studies, it's probably 2 to 4x that. So there's an established market of people that have LM, but that are significantly underdiagnosed is sort of underlie the foundation of the commercial opportunity. But on top of that, there are a number of patients, and we get right to the core of your question, that are walking around with metastasis or systemic cancer from other -- from primaries that are common like melanoma, gastrointestinal cancer, breast cancer, lung cancer and so forth. That, for example, present to their doctor or the emergency room with some complaints or neurologic findings that are peculiar abnormal. And that's where we get to the number that Russ mentioned earlier, perhaps some 1 million patients in the U.S. that are walking around that need a better diagnostic opportunity. And so the numbers are pretty staggering in the context of technology that's over 100 years old, that's being -- is commonly implemented. So I think that's one way of looking at it, sort of epidemiologically. So those patients that are at risk for LM is really the foundation of the market. And those patients need a highly sensitive and specific diagnosis, so they can pick either rule in the diagnosis or rule out the diagnosis, perhaps as importantly with a single test. And then layered on top of that, the market gets broader because we now know that the CNS test correlates with survival and can be used for both disease and treatment monitoring. We've seen that in our REYOBIQ trials and other trials have seen that as well with external beam radiation. So that -- the market gets much broader, and that's sort of how you build the market out and get to what Russ had mentioned of a TAM of about $6 billion in the U.S. It's a remarkably underserved market.

All right. And then one more for me and I'll hop back into the queue. You did mention you do have some expansion plans. Are these largely focused on other forms of brain mets or primary tumors or layering in additional analyses on to those tumor cells captured in LM beyond just the numeration?

Yes. Yes, it's a great question. And so what's fundamentally unique about the CNSide assay is the tumor cell enumeration test that you mentioned. And there is no quantitative high-fidelity, high dynamic range, way to tumor cells. And that's the core thing that is sort of the basis of the CNSide test. It really drives a lot of the things that I mentioned before in terms of utility of testing and broadening the market and so forth. So that's -- but once that the determination is done, then by virtue of the technology, you lock the cells at a microfluidic chip and now you can interrogate them until one heart is content. So we can look at those cells from a macular signaling internally or externally. We can make suggestions about therapeutic selection and therapeutic utility. And so that's sort of driven by the primary cancer type and when we talk about metastases. But then also glioblastoma, for example, much rare disease, but tumor cells that infiltrate the CSF in a gliominous GBM situation, are correlate with prognosis. And so one can think downstream when addressing the therapeutic challenge of glioblastoma, you have to treat the golf ball tumor in the brain, but many times, their cells in the fluid. And those treatments that we use today don't affect the fluid. And so this is a massive opportunity, in my view, to improve the treatment for these patients by opening up the fluid space as an indicator for diagnosis, disease management and therapeutic selection, both for mets and for primary brain tumors.

All right. Once again, congrats on the progress in CNSide exciting asset.

And that will come from the line of Sean Lee with H.C. Wainwright.

My first one is on the initial market. So based on the historical results that you see, where do you expect CNSide to be used first? Is it for the -- in clinical studies to monitor patients or for the diagnosis of difficult to treat tumors? Or just based on the 200 physicians that you mentioned that have used it before, where is it used primarily?

Yes, Sean, I'll provide an overview and let Russ chime in. So the way we think about kind of utility, it cuts across a few different parameters, but I'll highlight the most important. So number one is the more academically oriented larger medical centers. It's surprising oftentimes the people, but there are about 300 neuro-oncologists in the U.S., a very small number that are concentrated at academic centers. And I mentioned this concept of therapeutic neologism. So within the neuro-oncology community, even though there are no approved treatments for LM and the diagnostics are terrible. They do what they can to help these patients. And they're familiar with CNSide. They represent a large part of the customers that have used it in the past, and they are clamoring for the test to come back. And so that will be kind of the sort of anchor group of customers, and they use it to diagnose, to monitor and to select therapy. And we have in 1 patient actually had 38 tests as part of their management course to monitor the change in cells. So -- and on average, if you look back at the prior company's data, on average, they were doing about 4 tests per patient. So I think that's where we start. And then from there commercially, we will transition into the broader medical oncology market. And then we're talking about patients who take care of breast cancer, lung cancer and so forth. And Russ, I'll let you weigh in if you'd like.

Yes, sure. So I think, Marc, if you look at the trajectory of these types of -- in tools in diagnostics, they start getting used to help in the workup of a patient or to rule in or rule out a diagnosis. But when it's evident that you've got something that's more sensitive more accurate, then they start to be utilized more frequently to help manage the patient, not just for any initial diagnosis. And I think as Marc alluded to, we already have some evidence that a sensitive and accurate enumeration of tumor cells and cerebral spinal fluid leads to that result being frequently used to manage the patient and make decisions on options for therapy and the course of therapy and even monitoring the effectiveness of the therapy. So our plan right now is just to reintroduce the products by starting with those health care providers who are familiar with it and have been asking us to bring it back to market. But what we expect as it evolves is that it will become a really indispensable tool for not just diagnosis, but for management and monitoring as well.

Great. That's very helpful. My last question is on reimbursement. You mentioned you're in discussions with these payers to reestablish the reimbursement for CNSide. I was just wondering, what's the expected time line for these discussions?

Thank you, Sean. Russ, would you mind addressing that question, please?

Sure. We've already engaged with the payers. We're in the process of negotiating the contracts as we speak. That's actually moving forward quite rapidly because in some cases, in most cases, with the payers we've engaged with, they're already familiar with the technology, the work has already been done to show the clinical utility. And now it's a matter of really just freshening up the paperwork and putting our pricing in place, so that's happening. We've got contracts under negotiation now. So obviously, we expect to continue to do that. There's still payers that aren't familiar with CNSide that we'll start pursuing. But as you can imagine, it's more efficient for us. And then some of these payers are pretty sort of national coverage. So we're starting there first, but then obviously, we'll have a pareto of coverage, including regional payers that we will pursue to put the agreements in place.

One moment for next question, and that will come from the line of Edward Woo with Ascendiant Capital.

Congratulations on all the progress. My question is more of a longer-term question. Have you thought about the international opportunity for CNSide?

Ed, yes, thank you for the question. Russ, would you mind taking that question as well, please?

Sure. Yes. So yes, we have indeed thought about international expansion. We're very focused right now acutely focused on the U.S. market, which as we've already shown a substantial. But there are patients we know outside the U.S. that could benefit from a more sensitive and accurate diagnostic tool for CNS mets. So these types of -- because we have a centralized lab model, we've thought about potentially partnering outside the U.S. to bring this badly needed pool to other markets around the globe. So it's early for us. We've got plenty to do here in the U.S. to get the test reestablished. But yes, we are thinking about international expansion, and we plan to really start exploring that next year.

Thank you. That is all the time we have for our question-and-answer session. I would now like to turn the call over to Dr. Marc Hedrick for any closing remarks.

Thank you, Sheri, and thank you to everyone who joined the call. We really appreciate your interest in CNSide. And we want to wish you a good day, and we will continue to communicate as new developments happen. Thank you.

This concludes today's program. Thank you all for participating. You may now disconnect.