Plus Therapeutics (PSTV) 14 Nov 242024 Q3 Earnings call transcript

Good afternoon, ladies and gentlemen. Welcome to Plus Therapeutics Third Quarter 2024 Results Conference Call.

Before we begin, we want to advise you that over the course of the call, including any question answer session -- sorry.

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics Third Quarter 2024 Results Conference Call.

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. and uncertainties, including the risks and uncertainties described under the Risk Factors section included in Plus Therapeutics' Annual Report on 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 afternoon, everybody, and thank you once again for taking the time to join us today as we provide an overview of recent business highlights and discuss our third quarter 2024 financial results.

Joining me for the call today is Mr. Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent clinical and corporate progress in the third quarter and then turn the call over to Andrew for a review of our financials, and then we'll both come back for Q&A.

I'll begin this afternoon with an overview of our leptomeningeal metastases program in which we are investigating our lead radio therapeutic Rhenium (186Re) Obisbemeda in the ReSPECT-LM trial.

As now, going forward for this call, I'll refer to Rhenium (186Re) Obisbemeda as RNL, which is its research name for the sake of brevity. Part of our development program our ongoing respect LM Phase I single administration dose escalation trial, is perhaps closing in on a maximum [indiscernible] in which we administer a very substantial dose of RNL for approximately 66 millicuries.

Data Safety and Monitoring Board, the Board recommended proceeding to a modified lesser Cohort 6 dose of 75 millicuries, and the first patient has been treated. To date, 21 [indiscernible] including a subset of 3 patients who responded well to the initial dose and have received multiple doses under compassionate use. Part 2 of our integrated development plan is to expand Phase I ReSPECT LM trial to a multiple dose administration trial. Relatedly, in Q3, we reached agreement with the FDA to proceed under a multiple dose escalation protocol, and we are currently in site start-up phase for that trial. I'll review that trial design more fully in a moment.

In terms of clinical data from the ReSPECT-LM Single Administration Trial, we presented an interim update at the SNOW ASCO Conference in August through Cohorts 1 through 4.

Here are the key highlights from that presentation. Doses of RNL up 44 millicuries were found to be safe and well tolerated with no dose-limiting toxicities. Pharmacokinetic data demonstrated a very high therapeutic index, specifically about a 50 to 100 target to off-target ratio. Through Cohorts 1 through 3, means circulating tumor cells were reduced on average 53% at day 28 post-treatment. And median overall survival for Cohorts 1 through 4 was 12 months which is quite favorable compared to the historically reported consensus of approximately 4 months with treatment in breast and non-small cell lung cancer. The full presentation from that meeting is available on our website.

Later this month, at the SNOW; Society for Neuro-Oncology Annual Meeting, which is going to be November 21 through 24 in Houston, we will provide a comprehensive update on the Phase I single administration dose escalation trial through Cohort 5 with important new data, including PK, PD response and survival data.

We will also host a symposium to discuss the data in greater detail with leading subject matter experts, Dr. [ Priya Kumathekar ], Dr. Jonathan Yang and Dr. Andrew Brenner.

As I mentioned before, we have reached agreement with the FDA to initiate enrollment in a Phase I trial of multiple dose administrations of RNL for treating patients with LM. Favorable outcomes observed in [indiscernible] patients receiving multiple doses of RNL from our single administration dose escalation trial reinforced the safety and potential value of multiple dose administration regime to obtain long-tail survival in patients with LM. More specifically, the Phase I ReSPECT-LM multiple dose admiration trial is an open-label 2-part study aimed at evaluating the safety, dosing intervals and efficacy of administering multiple doses of RNL to patients with LM. Primary objectives already assess safety and tolerability and to identify both the maximum tolerated and the maximum feasible doses at various dosing intervals and frequencies.

The secondary objectives include evaluating response and survival.

The first part of the study will treat up to 24 patients administering at minimum 3 doses of RNL at 13.2 millicuries at progressively shorter intervals, starting at 56 days and then every 28 days and finally, every 14 days and then potentially up to 6 doses in a [indiscernible] cohort. The trial is expected to begin enrollment in Q1 2025 with the aim to utilize current 7 active U.S. trial sites being -- enrolling patients in our ReSPECT-LM Phase I single administration dose escalation trial. We plan to provide further details on the integrated development plan and path to approval for leptomeningeal cancer at the 2024 SNOW Annual Conference at Houston.

Now for a discussion around our diagnostic Increasingly, we are recognizing the importance of our see inside cerebrospinal fluid assay platform in both the investigation of RNL for LM and the assays commercial value as a stand-alone diagnostic product in the broader group of patients at risk for LM or other CNS malignancies. The CNSide cerebrospinal fluid assay platform consists of 4 lab developed tests or LDTs, and may be used by neuro-oncologists, neuro-immunologist, medical oncologists or other petitioners for the diagnosis, treatment selection and monitoring of patients with or at risk for LM as well as other CNS malignancies.

In terms of market access activities related to the planned CNSide launch in January.

As you may recall, Step 1 was tech transfer and initiating lab testing, which was completed earlier this year. Step 2; fully owned sub based in Houston, Texas, we obtained a CLIA certificate of registration in Q3, and we intend to obtain a CLIA certificate of compliance in Q1 2025 following inspection by CMS.

This quarter, we will apply for expanded reimbursement with a Z-code to the Diagnostics Exchange which helps ensure that both health care providers and payers understand which test is being drilled, and it also allows payers to automate the pre-authorization or adjudication of claims. .

Specifically the Z-Code is required by well-known payers such as Medicare, UnitedHealthcare, Humana, Blue Cross Blue Shield and so forth.

Next quarter, following receipt of the CLIA certificate of compliance, we intend to apply for a CPT Proprietary Laboratory Analysis Code, or PLA code with the American Medical Association. This code is required by Medicare and certifies labs for complex testing, ensuring they meet federal standards for quality, accuracy and safety and the PLA code further specifically identifies the test. In parallel to these activities mentioned above, we are negotiating with a number of commercial payers, which previously had agreements in place for the CNSide assay.

Specifically, we're informing them that we acquired the assets from CNSide, from the previous owner and plan to make the test platform commercially available again and new agreements will be put in place. Also, we are focused to payers that cover regions containing the highest number of LM patients. Currently, the CNSide tumor cell and enumeration LVT continues to be used in the ReSPECT-LM clinical trials.

We are on track to commercially reintroduce the test as part of a limited market release in the U.S. in January of 2025.

At the same time, we are expanding the CNSide test menu on a rolling basis to include specific cellular biomarker assays and molecular assays and we'll talk more about that in 2025. Aggregate 2024 investment in the test will remain limited as test costs are offset in a meaningful way by our current secret grant. In 2025, post expanded market access, we will guide more specifically toward forecasted diagnostic growth ramp and related economics.

Now shifting gears to our ReSPECT-GBM trial which evaluates a single dose of RNL in patients with recurrent glioblastoma. Enrollment in the Phase I portion for patients with recurrent glioblastoma greater than 20 mls, has been completed, and we will be evaluating that data into 2025 and completing the final Phase I clinical study report. Enrollment continues for the ReSPECT-GBM Phase II trial limited to patients with tumors lesser than or equal to 20 mls. The last ReSPECT-GBM trial update was at the Congress for Neurological [indiscernible] Annual Meeting in October of this year.

As a reminder, key highlights include a total of 42 patients had been enrolled across 3 sites at that time.

In Phase II, most adverse events were mild or moderate with over half deemed unrelated to the study drug. Only 2 of the 9 severe adverse events were related to the study drug and systemic radiation exposure remains low. Moreover, the average absorb radiation dose to tumors in Phase II was 300 gray, well above the 100 gray [indiscernible] served preclinically and in Phase I that is highly correlative with increased overall survival. Furthermore, approximately 90% of patients achieved critical drug delivery parameters also correlated to improved survival.

Finally, of the tumor response analysis using both cerebral bud volume -- volumetric analysis showed a statistically significant relationship between tumor control and absorb dose, specifically patients receiving doses above 100 gray, showed effective tumor control within the treated areas. The ReSPECT-GBM trial continues to benefit from substantial NIH support, and we are pleased to announce we have added 2 new large volume clinical trial sites to support Phase II enrollment and potentially a pivotal trial.

We've added Ohio State University, which provides us coverage in the Upper Midwest and North Shore Hospital, part of the Northwell and Lenox Hill Network in the New York metropolitan area.

With these 2 new additional sites activated and screening patients for enrollment we expect Phase II completion with 34 total patients by midyear 2025 in a data readout in the second half of 2025.

Additionally, we would like to announce that we recently entered into a research and collaboration agreement with Brainlab, a software-driven medical technology company to develop and implement optimized case planning software or convection-enhanced delivery of RNL for brain cancers. Brainlab's software married to their CED Device Ecosystem will enhance treatment planning, procedure execution and more precise drug delivery for GBM patients, anticipated to further improve patient outcomes.

Now just a bit about our pediatric brain cancer program. Recall, we previously announced that we have received a U.S. Department of Defense Award of a $3 million grant to substantially support a Phase I trial for children with pediatric high-grade glioma and [indiscernible]. Approximately $900,000 payment was received in September of 2024 as part of the award. We anticipate obtaining IND approval in the first half of [indiscernible] Children's Hospital in Chicago serving the -- as the initial clinical trial site. And moving on to drug production and manufacturing.

We are expanding our GMP manufacturing capabilities and building redundancy in terms of materials and intermediates to support registrational trials and future commercial demand projections. To ensure a reliable level supply of RNL, we recently announced our second GMP manufacturing partnership, this time with SpectronRx. Through this partnership, we have completed process qualification to transition from single dose, single batch production to a pilot scale process capable of dosing multiple doses per batch with the potential opportunity for scale up at capacity of approximately 15,000 doses per year around the time of anticipated FDA approval.

So Andrew, Can i turn it over to you for a discussion about the financials. Andrew?

Thank you, Mark. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the third quarter ended September 2024.

The cash and investments balance was $4.8 million at September '24 compared to $8.6 million at September '23.

In addition, we received the first advance from the DoD grant in October '24 of $0.9 million and are on track to receive the next [indiscernible] advance of $3.9 million within 90 days of today. The company recognized $4.4 million in grant revenue year-to-date '24 compared to $3.6 million in the same period of '23. This represents separate shares of the cost incurred for our RNL development for the treatment of patients with LM.

We expect 2024 grant revenue to be in the range of $6 million to $7 million. The total operating loss year-to-date 2024, $10.8 million compared to $9.5 million in the same period of 2023. The increase is primarily due to increased spend related to the ReSPECT-LM trial. Net loss year-to-date 2024 was $9.1 million or $1.46 per share compared to a net loss of $9.5 million or $3.54 per share for the same period in the prior year. I'd also like to update on our runway and cash position based on the previously announced private placement and provide guidance on our grant funding for the remainder of 2024 and into 2025.

The 3 additional sources of cash, that Plus has access to beyond the balance disclosed in cash on hand and liquid investments on our Q3 2024 balance sheet.

First, as a reminder, we announced in May that we closed a private placement financing of up to $19.5 million from new health care-focused institutional investors and company insiders with a total of $7.25 million received at closing with up to $12 million remaining available under this financing.

The second source of cash remains our continued funding through now 3 announced grants.

Firstly, the CPRIT grant to support the ReSPECT-LM trial, as reported, we received $3.3 million from CPRIT in Q2, at this time, $7.8 million remains due on the grant, and we remain on track to receive the next advance from CPRIT of $3.9 million within the next 90 days from today. An additional $3.9 million is expected from CPRIT in Q3 2025.

Secondly, as reported on April 22, Plus has received an award recommendation from the United States Department of Defense for $3 million to support the upcoming RESPECT pediatric brain cancer trial.

The first advance was received in October for just under $1 million. Plus also continues to benefit from the NIH grant to support the ReSPECT-GBM Phase I/II trial, although expected to be complete in the next 6 months, it currently covers approximately 90% of the overall trial costs.

We also continue to source other non-dilutive sources of grant capital with a target of applying for at least $10 million per year.

We will continue to only report on individual grants when they're awarded. Taking into [indiscernible] cash on hand, financing warrants that are fully exercised and committed to contractual grant revenue is approximately $27 million. And now I'll turn it back to you, Marc.

Great. Thank you, Andrew. Appreciate it.

Before we move on to Q&A, I'll take a moment to provide a specific summary of guidance for anticipated key events and milestones taking us through the remainder of 2024.

First in terms of conferences, we'll have a substantial presence at the SNOW -- at Society for Oncology Annual Meeting from November 21 to the 24 this year. There, we will present 3 abstracts, host an educational symposium on LM and GM, conduct our annual investigator meeting and showcase our CNSide cerebral spinal fluid assay platform in our booth as we will showcase our investigational drug, RNL for LM,GBM and Pediatric Brain Cancer. More specifically, in terms of the 3 abstracts.

As mentioned for our LM Therapeutic Program, we will present data on the safety and feasibility of ReSPECT-LM Phase I single administration dose escalation trial through Cohort 5, including important PK/PD response and survival data. We'll also provide an update on our integrated development plan for both single dose, multiple dose ReSPECT-LM programs and linking them to an FDA approval plan and time line.

For our CNSide, assay platform, we will present data on first, the 4C clinical trial data on CSF tumor cell detection, including its clinical utility and accurately diagnosing [indiscernible] with high sensitivity and specificity compared to the gold standard cytology, and also its clinical utility in enhancing clinical management of patients with LM.

Second, we will show the results of a retrospective analysis of CNSide's real-world ability to detect a variety of gene mutations in CSF tumor cells, offering insights in the potential treatment strategies and also ways LM patients may benefit from complementary regional therapies such as RNL and other treatments.

As mentioned, the company will host an educational symposium featuring 3 subject matter experts, Dr. [indiscernible] Yang and Brenner, who will provide updates on our LM and GBM programs in our CNSide platform.

Lastly, we will showcase our investigational therapies as well as the CNSide Diagnostic at our booth. Later in the year -- in December, we will also attend the San Antonio Breast Cancer Symposium in San Antonio, Texas, where we will present -- the data on the safety feasibility of the ReSPECT-LM Phase I [indiscernible] trial through Cohort 5 with a focus on the breast cancer patients related data. That happens to be the primary cancer with the highest incidence of patients with LM.

In addition to those upcoming events and conferences mentioned above, the company also anticipates completing our ReSPECT-LM single dose escalation trial by year-end, initiating enrollment in our ReSPECT-LM multiple administration dose trial in Q1 of 2025 and launching a limited commercial release of our CNSide platform as an LDT in early 2025. [indiscernible] completing enrollment in our ReSPECT-GBM Phase II trial by mid-2025, and for our pediatric brain cancer trial, obtaining IND acceptance, initiating enrollment for a ReSPECT trial for pediatric [indiscernible] and high-grade glioma in patients in 2025.

So Sheri, with that, I'll turn it back to you for any questions.

[Operator Instructions] And our first question will come from the line of Justin Walsh with Jones Trading.

I'm wondering how you view the opportunities for CNSide and RNL in LM as complementary product versus on their own?

Justin, great question.

You know what, we continue to see more and more synergies. And you may recall when we first considered this acquisition, it made sense solely on one factor and that is it could potentially increase the total addressable market for LM by 2x to 4x just by improving diagnostic sensitivity.

But since then, there's more and more data that shows that using circulating tumor cells can be a proxy for survival and for disease monitoring. And there's -- we see more and more papers coming out related to that. And then we're now increasingly relying on it as an exploratory endpoint in the Phase I. And we're going to be providing more insight into that data next week -- I think is highly relevant supporting the other signals we've seen in terms of response and efficacy. And I think there's a recent publication by actually one of the key opinion-leading doctors in our symposium, Dr. Yang who treat patients with targeted radiation in that case -- from proton beam creating spinal radiation -- but showed -- in that targeted radiation therapy -- it correlated very highly. The CNSide assay, actually our assay correlated very highly with survival and progression.

So I think over time, we'll see more and more reliance on that. Is it ready to be used as a primary endpoint in a pivotal trial? I don't think so. But I think as a secondary endpoint, it provides substantial collaborate data to other progression data and survival.

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

I was just wondering what does the landscape look for grants? Has it changed in terms of the opportunities that are available. And do you anticipate any change with, I guess, the change in the incoming government?

To answer your latter question, I don't know. It's hard to tell.

I think we're in a good -- pretty good spot through the next year as it relates to grants.

I think there -- being in Texas insulates us a bit from what's going on at the Federal level. We've been -- we've been very successful in -- at CPRIT.

As I think you know, we have almost an $18 million active grant from them in an aggregate $25 million total in active grants.

What we're hearing, no guarantees. But what we're hearing from CPRIT is that there -- from time to time, there's additional capital that they can deploy and they're -- they tend to reach out to companies who are executing and we're executing precisely to our proposed and planned time line.

So we're kind of hoping there might be some opportunities there, but also will continue, as Andrew said, to -- to talk about grants as they come in, but we think there's continued opportunity in Texas if changes at the federal level.

One moment for our next question, and it comes from the line of Sean Lee with H.C. Wainwright.

I just have two quick ones. One is -- first is on the LM multi-dose study.

So how do you guys come up with the 13 millicuries dose to be used in that study? And how does that compare to what patients have received so far through the [ Compassionate Use Program? ]

Sean, thanks for the question. It's a good one.

So as we were -- we're increasingly taking a [indiscernible] approach to clinical development, and we'll talk more about that in our integrated development plan both next week in an ongoing manner.

But we found as we were getting into Cohort 4, which is approximately 44 millicuries that we were seeing excellent safety and also strong response cohort [indiscernible].

And so we -- as we began our negotiations with FDA on the multiple dose approach. We felt like we could support taking that Cohort 4 dose. And then fractionating it, and that follows approaches that FDA is very comfortable with.

So we're able to get them to go along with that.

And so I think that because of -- based on what we're seeing clinically, that earlier compression of doses will be very important and getting that long tail survival that I mentioned.

In terms of the compassionate use, I think to patients that have received 3 aggregate doses. We're actually giving them the -- whatever dose is -- whatever dose is currently enrolling -- so they're getting actually -- in the neighborhood of 40 or more higher dose, but their dose frequency is much longer. They're being treated when they come back with symptoms. In other words, patients seem to are responding to the initial dose, and then they're doing well for an extended period of time, maybe up to a year or so.

They're coming back with symptoms or progression and asking to be retreated.

So we treat them with that dose that's available.

So back to my original point, I think increasingly, we recognize the Bayesian design is appropriate. We're modeling that right now that's integrated into the multiple dose trial. And then as we'll talk about over time, how do we leverage that and get to approval.

My second question is on the CNSide assay.

So in the prepared remarks, you noted that you needed to get the CLIA compliance followed by a CMS inspection, as well as getting the Z-Code and PLA-Code.

Just -- do you have a rough guideline for the approximate time line for these steps?

I'm sorry, Sean, just to clarify, the time line for getting additional reimbursement?

Yes, getting the inspection done as well as have getting the reimbursement online.

So like when can we expect CNSide to start selling commercially and getting reimbursed?

So I think we're on track to being able to commercialize the test in Q4 of this year.

I think the issue is going to be that we need to -- we're more likely to get imbursed -- if we have a CNSide CLIA compliance and that inspection is -- it's not been scheduled, but it's going to be Q1 and we're pushing to make that as early in Q1 as possible because we want to try to accelerate that time line.

And then number two, I think some of these some of the laboratory services agreements, which were -- I think they were approximately 10. Is that right, Andrew? 10 in place with [indiscernible]. We've hired market access team that is actively negotiating with those 10 institutions on a regionally focused basis based on my comments, where are the patients and where the highest level of reimbursement is? So we're prioritizing these areas -- just being practical, obviously.

I think we're going to have some more things to talk about in Q1 as it relates to reimbursement. And I think once those reimbursement Domino's fall, then I think we'll feel more comfortable talking about pricing ramp margins and so forth. And I think right now, it's just a bit premature until we get those things in place. We want to be really cautious in terms of guiding in the early phases until we get comfortable that we can stand behind that guidance. I can tell you that at the time that quit offering the test, they had 200 unique customers. They were growing at about 30% per year CAGR.

And that was with no data, no NCCN guidelines no specific reimbursement, no foresee clinical trial data.

So we have all those elements behind us at this point today, and that's only going to grow. There are only more papers coming out and so forth.

So I think I think the environment continues to look really positive for that as a stand-alone product.

I'm showing no further questions in the queue at this time. I would now like to turn the call over to Mr. Andrew Sims.

Thanks, Sheri.

We have two written questions.

So the first is, can you elaborate on the therapeutic ratio you are seeing in your trials and safety data profile?

Yes.

So that's a good question. We'll talk probably more -- in detail.

We will talk more in detail about that at next week at SNOW. But I think it's a key point is that the therapeutic ratio that we're seeing going out to the Cohort 4 is very high. In particular, for LM, we're seeing about a ratio of about 50-plus in terms of therapeutic to target versus off-target.

I can give you a preview of Cohort 5.

I think we're seeing that as greater than 100:1.

So we're continuing to see a linear dose -- as we dose escalate -- a higher absorbed dose and the spinal subarachnoid space and really relatively flat absorption in the key critical organs. Bone marrow is starting to tick up a bit in Cohort 5, and we'll talk about that, and that was part of the rationale for the DSMB to cut back the Cohort 6 dose. And I think we're increasingly becoming more comfortable that the Cohort 4 dose will be the recommended Phase II dose, and the maximum tolerated dose will be Cohort 5.

But the FDA has been very consistent about us continuing to dose escalate to failure, hence, the Cohort 6 dose.

In terms of GBM, I think the therapeutic ratio is really hard to calculate because we're seeing essentially very minimal systemic absorption and very high delivery of radiation to the region of interest, tumor in the infiltrated margin.

So yes, I think we're seeing -- what we're seeing is very favorable, much higher than other companies are reporting with their systemically delivered technology.

So that's really a really strong part of the technology.

And the second question is, can you provide details on your integrated development plan for LM?

Yes, I think I've mentioned some of the details, and I think we'll present more at SNOW and roll that out over the first part of 2025.

I think right now, I think there's -- based on the data we're seeing in [indiscernible], there is clearly activity and there's a strong potential for advancing the single dose in an expansion cohort for -- specifically on breast and lung cancer, non-small cell lung cancer, that continues to look strong. We can use that data to help derisk a pivotal Phase II/III trial thereafter.

And I anticipate getting that into the clinic pretty soon next year, but we'll talk more about that.

In terms of multiple dose, I think we could follow a similar patent where we pick -- as we complete each cohort promising dose cohort expanded confirmed that there's an efficacy signal there as well as safety signal and move that forward. And I can potentially see taking 2 different doses to market a high single dose and a lesser multiple dose regime. And then so more on that next week and then first half of next year. Are there any other questions?

Thank you, Andrew. Well, just to conclude. Thank you, Sheri, and thank you, everyone. I appreciate you being on the call. On behalf of the board, I'd just like to thank our employees and team members and the physicians we work with and very much thank you to the patients who continually trust us to enter into these trials. Thank you for your participation. Have a good evening.

This concludes today's program. Thank you all for participating.

You may now disconnect.