Q2 2023 Plus Therapeutics Inc Earnings Call
Speaker 1: Good afternoon, ladies and gentlemen. Welcome to the PLUS Therapeutics second quarter 2023 results conference call. Before we begin, we want to advise you that over the course of the call and question and answer session, forward-looking statements will be made regarding events, trends, business prospects, and financial performance.
Speaker 1: 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. Mark Hedrick, Plus Therapeutics' President and Chief Executive Officer. Sir, you may begin. Thank you, Abigail. Good afternoon, everyone, and thank you once again for taking the time to join us today as we provide an overview of the COVID-19 pandemic.
Speaker 2: with a focus on the second quarter, and then turn the call over to Andrew to review our financials. And Norman will then be joining us for Q&A.
Speaker 2: I'll begin with updates on our two lead
Speaker 2: First, an update on our RESPECT-LM trial for patients with leptomeningiometastasis, or LM.
Speaker 2: In Q2, we completed enrollment in the Phase 1 Part A, that's cohorts 1 through 3.
Speaker 2: And as is called for in the protocol, we reviewed the safety data with the FDA and they approved us to continue to part B of the phase one, specifically dose escalation from cohorts four and beyond until a DLT is observed.
Speaker 2: At the snow, ASCO CNS Cancer Conference last week in San Francisco, we reported the results from our respect LM phase one part A trial.
Speaker 2: Recall that we've treated 10 patients with a single administration except for one patient that received a second treatment off trial under compassion at use.
Speaker 2: It is mentioned that was in three dose escalation cohorts.
Speaker 2: Thus far, we found that Rineum Obispermaid has circulated fully in the CSF space within minutes of injection and remained concentrated in the CSF space for at least seven days following administration.
Speaker 2: Critical organs outside the central nervous system, including blood, spleen, and liver, showed the minimus absorbed radiation doses well below critical safety levels. In contrast,
Speaker 2: Critical organs outside the central nervous system, including blood, spleen, and liver, showed the minimus absorbed radiation doses well below critical safety levels. In contrast, target organs and...
Speaker 2: Ragnoid P.S. Final CSF showed linear increases in absorbed dose that correlated with administered dose.
Speaker 2: In part A, we dose from 6.6 milicuries up to 26.4 milicuries. And we achieved absorbed doses of up to 102 gray to the ventricles and cranial subarachnoid space.
Speaker 2: So to summarize the dosing or dosimetry findings, the radiation is clearly getting to the target organs and the off-target effects thus far are minimal through cohort three.
Speaker 2: In terms of safety, consistent with the low off target absorbed doses, no dose limiting toxicities have been observed. Furthermore, the overall safety profile was favorable. Approximately 83% of adverse events were milder moderate and the majority were not related to treatment.
Speaker 2: The favorable safety profile provided the basis for moving forward into Part B of Phase I. However, we've also assessed whether there were disease target effects by measuring tumor cell counts.
Speaker 2: Survival and Symptomatic Improvement.
Speaker 2: Recently, a highly specific and sensitive CSF tumor cell enumeration technology called CNS-SIDE-ASA has been approved and we are employing it in the RespectLM trial. In our view, the technology is a significant advance in CSF tumor assessment over standard of care.
Speaker 2: In part A, we found that tumor cell counts trended lower immediately after treatment and were sustained.
Speaker 2: through day 28 post treatment.
Speaker 2: At 28 days, tumor cell counts were reduced on average of 53% and up to 91% over preoperative baseline.
Speaker 2: And then generally we noted a rebound into Marcel counts at 56 days.
Speaker 2: Our view is that effective therapies in the management of LM, such as potentially RINIMO Obisbameda, can disrupt the care of LM, but the addition of a reliable tumor cell and the MIRATION technology can magnify that therapeutic and commercial impact.
Speaker 2: Current means of LM diagnosis, specifically the triad of imaging, clinical symptomatology, and CSF analysis of cells.
Speaker 2: specifically the triad of imaging, clinical symptomatology, and CSF analysis of cells.
Speaker 2: We use now the old Star Wars of protein glucose and cytology, both lack sensitivity and specificity.
Speaker 2: Specifically, tumor cell enumeration may allow earlier diagnosis of subclinical cases, and LM is about two to four times underdiagnosed, and then support decisions on redosing patients through their treatment course.
Speaker 2: Finally, in terms of survival, as of today, 5 of the 10 treated patients in the Phase 1 Part A are alive, and the median overall survival is at 10 months. This compares favorably with the published overall survival rates at approximately 3 to 9 months observed with standard of care.
Speaker 2: As a note, as part of the snow, ASCO meeting in San Francisco, in which the phase one data was presented, plus co-hosted a KOL roundtable.
Speaker 2: with Dr. Justin Walsh, which also included two.
Speaker 2: RespectLMInvestigators.com
Speaker 2: from the University of Texas Health Sciences at San Antonio and Dr. Priya Kumtekar.
Speaker 2: from the
Speaker 2: Neurology and Medicine Department at Northwestern University Spineberg School of Medicine.
Speaker 2: This KOL roundtable is available for replay on our website.
Speaker 3: out of the hour.
Speaker 2: During the KOL Roundtable, Drs. Brenner and Kumtekar provided a comprehensive discussion about the ongoing RESPECT-LM Phase I-IIa dose escalation clinical trial, with emphasis on epidemiology, diagnosis, safety and tolerability, dosing, and efficacy.
Speaker 2: We urge everyone that's interested to watch the webinar for a deeper look at LM and the respect clinical trial findings thus far.
Speaker 2: In terms of next steps for LM, the clinical development plan is to continue to dose escalate to the maximum tolerated dose, and in parallel expand the phase one dose escalation trial to explore multiple dosing.
Speaker 2: This approach is critical to enhancing the potential for the clinical benefit of RINIUM abyspamada in these patients, which will require further FDA discussions.
Speaker 2: As mentioned, we did treat, in Part A, one patient with a second dose of rhenium obispomata outside the trial under compassionate use, and that patient continues to do quite well and is over a year out from her initial treatment. Now, with respect to our...
Speaker 2: called Respect GBM for patients with
Speaker 2: called RESPECT-GBM for patients with recurrent glioblastoma or GBM. We continue to enroll both our active phase 1 and phase 2 trials.
Speaker 2: Our Phase 1 now has enrolled four
Speaker 2: with tumor sizes being treated in that greater than 20 milliliters, and they were treated with an administered radiation dose of 41.5 millicuries in a treatment volume of 16.4 milliliters.
Speaker 2: We have now successfully used up to five catheters per treatment in multiple patients and no DLTs have thus far been observed.
Speaker 2: We plan to treat six total patients in this cohort in case it's the last cohort, but we will also assess whether to continue dose escalation or make other dosing changes with an eye toward any potential amendments we might deem to make in the Phase II Protocol.
Speaker 2: Our Phase 2 continues to enroll patients with tumor sizes of 28 CCs or less using an administered radiation dose of 22.3 milicuries in treatment volume of 18.8 mililiters. We are made on track to complete Phase 2 enrollment by the end of 2024.
Speaker 2: In order to continue to meet our clinical trial enrollment goals, we have expanded our internal clinical team, including adding a VP of clinical operations, and also adding additional select CROs to support the trials. The impact of these decisions are already being felt, and will become increasingly more apparent as we end 2023 and go into 2024.
Speaker 2: If you have a peer-reviewed literature, that's in process.
Speaker 2: Second, we contend to evaluate the feasibility, safety, and efficacy in the ongoing phase one trial. The extended phase one trial is evaluating the safety at these higher dosages and volumes as mentioned and the impact of these higher doses and volumes on RNL distribution and tumor coverage and then also finally on the effects on large tumors.
Speaker 2: And I think it should be obvious from some of the data I mentioned before in terms of volume and minister dose that we're really pushing the limits in terms of what's achievable in convection enhanced delivery in the brain in terms of targeted radiation and volume.
Speaker 2: And that data will be presented at the Society for Neuro-Oncology meeting in November .
Speaker 2: Third, we continue to periodically assess the actively enrolling phase two alone and in a pooled fashion with representative data from the phase one. And that data will also be presented at the snow meeting in November .
Speaker 2: Fourth, we have recently reported top line data from a propensity matched real-world data analysis of recurrent GBM patients receiving either devuSysMab or convection enhanced delivery.
Speaker 2: That data will be used as a real-world control comparator arm for the Phase I and Phase II trials and also for regulatory purposes, including as it relates to potential pivotal trial design.
Speaker 2: More detailed data will be presented on the real world propensity match trial at snow in 2023 as well. I think we have five posters or presentations that snow this year.
Speaker 2: In terms of the GBM program in general, we continue to demonstrate feasibility and safety without dose-limiting toxicities and promising efficacy signals as we've presented before.
Speaker 2: In summary, we have learned that for each 100-gray increase in total dose and distribution volume, the risk of death decreases by 45.6%. And for each 10% increase in the ratio of treated to total tumor volume, the risk of death decreases by 66.9% with neither a threshold for either. Both have very low p-values, and this provides us with gathering confidence that there is indeed a meaningful treatment effect. Now, in terms of our planned pediatric brain cancer trials,
cancer program. Our second radiotherapeutic drug is making steady regulatory and development progress. We recently received feedback from the FDA on our pre-request for designation. The question is whether that drug will be deemed a device, a drug, or combination product. Specifically, the FDA notified us that the BAM radioembolic product will be regulated as a device.
Our second radiotherapeutic drug is making steady regulatory development progress. We recently received feedback from the FDA on our pre-request for designation. The question is whether that drug will be deemed a device, a drug, or a combination product. Specifically, the FDA notified us that the BAM radio-embalic product will be regulated as a device, primarily by CDRH.
This is consistent with the two generation one products that are now on the market that collectively share a market opportunity of about $1.3 billion. Obviously the benefits of this device-based approach would be that there are established regulatory reimbursement pathways.
already out there and potential speed to market. In terms of drug production and manufacturing, we continue to expand and shore up existing supply agreements and work to build in supply chain redundancy, including as it relates to isotope availability.
For example, we recently contracted with Pyramol pharma solutions that produced additional CGMP like some intermediate products to meet the forecasted increase in demand for RINIUM 186 of this tomato.
With that summary on our clinical development programs and other important company updates, I'll turn the floor over to our Chief Financial Officer, Andrew Sims, who will review 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 2020-23, second quarter, and the June 30, 2023. First, regarding the balance sheet, as of June 30, 2023, cash and cash equivalence with 10.9 million compared to 18.1 million as of December 31, 2022.
from both a 3 million NIH award for the respect GBM clinical trial through phase two, and a 17.6 million award from Superit for the respect LM trial through phase two.
Going forward in years two and three, grant funding is forecast to be 6.7 million and 7.1 million respectively.
likely split into two or more advanced payments each year.
Furthermore, the company has discretionary or stockholder approved access to capital from its ATM and equity line of credit of at least 49 million.
Now, a new-come statement that can be recognized 1.9 million of grant revenue in the second quarter of 2023, which represents the secret share of cost and curd to fund the portion of our LM clinical program.
Total operating expenses for the second quarter of 2023 were 3.3 million, compared to total operating expenses of 5.1 million for the same period the prior year.
The decrease is due primarily to the company completing one off investments in the GMP development of the company's lead drug, Renium 186 Abysmometer in 2,3, 2022.
In addition, we incurred lower legal and professional fees in 2023 versus the prior year.
Interest expense decreased from 181,000 for the second quarter of 2022 to 112,000 for the second quarter of 2023.
This decrease reflects the continued principal paydown on the company's Oxford debt.
That loss for the quarter of 2023 was 1.5 million or 59 cents per share compared to a net loss of 5.3 million or $3.56 cents per share for the same period of the prior year. And now I'll turn it back to you Mark.
Thank you, Andrew. Before we move on to Q&A, let me provide some guidance on anticipated milestones through the remainder of the year.
We are on track to initiate the Phase I Part B of the Respect LM trial, the second half this year. We plan to expand dosing to multiple doses for each patient more to come on that.
We also published the respect GBM phase one data and provided comprehensive trial updates at the Society for Neuroncology Meeting in November 2023. We are in track to initiate the phase one respect pediatric brain cancer trial for pediatric patients with a pinnumoma and high grade glioma in the second half of the day.
Finally, in general, management has internal targets around portfolio and business development opportunities and additional non-deleted grant funding, both the progressing and we will update on those when appropriate to do so.
Thank you. At this time, we'll conduct the question and answer session. To ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. So with your all your question, please press star 11 again. One moment will be compiled by Q&A roster. Our first question comes from Justin Walsh with Jones Trading. Waiting your line is open.
Hi, thanks for taking questions and congrats on the progress. My first question, I'm wondering about your current thoughts about potential, potentially approval endpoints for LM in the context of the data you presented. Overall survival obviously could make sense, particularly given the 10 months median overall survival use on the first 10 patients.
but wondering if there are others you're thinking about. And in particular, I'm kind of just thinking about, like potential for using symptomatic changes, given that we know some of the earlier radio farm circles were approved for bone pain, palliation, and prostate cancer. 13th January 2020 which was a long time before the coronavirus outbreak.
Hey Justin, it's Mark. You know, I think at this point, it's a bit, you know, it's a bit cheerily to say definitively as you sort of hinted in your question, but, you know, beyond the gold standard overall survival.
I do think quality of life or symptomatic improvement are potentially approval endpoints will be implementing and expanding a QL metric in the trial.
And there are some that are out there that would be appropriate. Rural of response rates difficult because imaging can be difficult.
And however, I think there might be an opportunity in terms of...
reducing CNS to Marcel Count with the SI mentioned before. So I think that's less likely, but I do think that as you mentioned, QOL or symptomatic improvement are also possible in points. If certainly not, if primary in points would be secondary in points.
Got it and then 1 more question, I'm just sort of wondering if you can. Comment on on just some more broad thoughts on why is so under diagnosed and I guess how much of that. Comes from the, the challenges of having.
there that can currently be used to specifically treat LM. So just some thoughts on that. Maybe a little bit of a chicken in the egg thing that hopefully is being resolved with your work and some of the diagnostic stuff that's going on, but just curious for your perspective on that. Yeah, no, it's a good question.
The mortality is high. Patients that are non-treated live four to six weeks and just a few months with treatment. So with better treatment, it's likely the incidence will be higher. Patients will live longer.
but they've died their primary disease with CNS meds. Or some oftentimes the imaging is poor, the CSF analysis is indeterminate. And the symptoms are symptomatic pattern is not really clear. So they may have it, they may actually be symptomatic, but it's very difficult to nail down the diagnosis so they may have other issues. So that's why I think are we likely to have a near-term significant improvement in our ability to sort out the symptoms? Probably not. Are we likely to be kind of a near-term improvement in our ability to image these patients? Not so sure. Delfal, but I do think there's a real possibility with a highly sensitive and specific CSF assay to evaluate the symptoms. It may be asymptomatic, but that are at risk, triple negative breast cancer patients that are asymptomatic with normal imaging and so forth. And pick it up early. And then there's an opportunity for us, if we have a treatment on the market to treat them early, and then potentially substantially prolong survival in these patients. So that's how I think about it. And that's why I think the importance of a tumor cell enumeration assay could be really valuable, potentially in terms of a companion diagnostic too. As well at some point. Got it. And maybe just a follow-up on that. That assay requires a lumbar pun.
I'm just wondering how much of a concern there is that that might, I don't know, limit patients wanting to get on board with that, or do you think that by the time they get to the point where they have systematic LM that it could be pretty reasonable to get patient compliance there? Yeah, good point. So for patients that are suspected or been diagnosed with LM, almost all of them have what's called an AMAYA reservoir, which is a small subcutaneous port.
literally any point in time during the patient's course, CSF could be sampled and tumor cell enumeration performed. So once they have that in, it's really a non-issue. In patients that are at risk but haven't received a diagnosis, lumbar puncture will generally be required because there's no other way to get the, excuse me, the CSF out. So, but it's still, it's a common part of the workup. It's, you know, it's CSF analysis, via lumbar puncture is part of.
working up little kids with fevers oftentimes or patients that come in with you know neck stiffness and a photophobia so
oncologic primaries who you know are at risk potentially of LM, a Lamar puncture is a very reasonable procedure to do those and they're frankly very well tolerated. Got it, thanks that makes a lot of sense. Thanks. One moment for our next question. Our next question comes from Shawn Lee with HC Wainwright. Your line is open. Good afternoon Mark and Andrew and thanks for taking my questions. My first question is on the recent LM results. I was wondering...
No, we haven't. I think it's still early. That's something we'll look at as we get to the later cohorts. But I think we may because there's a nice linear relationship between administered and absorbed dose. So I think that's definitely something we're going to look for. Great. Thanks. My second question is also on that study. You mentioned that you're going to be looking at repeat dosing for some of these patients.
Would that be done on just a context of a different study or would you be looking to extend this study protocol to include a separate repeat dose in court? I think that'll be pending decision-be pending discussion with the FDA. Our preference would be to incorporate the current protocol.
I think that's just simpler and more straightforward. I think based on what we're seeing now with a single administration, and look at the overall survival signal, even at low doses.
But when you incorporate the safety profile and the reduction to Marcel counts that we've seen, you know, I think that it makes complete sense to continue to dose escalate to a maximum tolerated dose, but then add additional doses. And we're working on that right now. So I have my guesses it'll be part of the current trial, not a separate protocol.
I see, I see. Thanks. Then moving on to the GBM side and the prepared remarks you mentioned that the FBI has removed it to be devised and not a drug. So would you be looking at the...
510kPenobl, for regulatory approval, or would you be, who is it going to be? What's it got? PMA.
Yeah, that's a great question. Right now, it's hard to say, I think...
A 510k pathway is possible, but I can't say it's likely. I think we just, this is kind of new information, so we'll need a bit more time to do our evaluation with our regulatory team.
Obviously, if it's a 510K, that's a pretty quick path to market.
PMA would be a bit longer, but either way it is going to be a faster path than a drug-related pathway. So, you know, we're parallel paths right now. Number one is to just the process now with FDA is to do a pre-RFD evaluation and then submit your...
the final RFD, which we're in the process of doing that, and then in parallel, we're looking at the device-based regulatory opportunities, including 510K and PMA in parallel. And then once we have the final designation, then we'll be ready to move.
Great, thanks for your thoughts on that. And that's all I have to question back up.
Thank you, Sean. Thank you. As a reminder to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced.
We have a question from the line of Edward Boo with the sendient capital, your line is open.
Thank you for taking my question. My question is on the grants that you guys are working on. Is it only with CPRET or are you guys doing stuff with NIH? And also because you guys already got a major contract from CPRET, does it make it easier for you to get future grants? Thank you.
Hey, hey, thanks for the question. You know, there's no prevention for us going back to separate for additional grants. We know of one company that has three separate awards.
So in some ways, now that we understand the process, there are a little bit of economies of scale in terms of how to formulate these graphs and go through the process and so forth.
It's going to be both. We're going back to secret for additional grant opportunities. But we're also going to the NIH and other sources of funding here in the US. So taking a broad approach, but following.
Our internal.
mantra I guess, which is, we want to, before we start a new program, we want to have the funding to pay for it through Phase Two.
in hand or nearly in hand. And so we think that there are opportunities for each new thing we bring forward, whether it's the BAM program, PDF.
to put funding in place so that once we have the asset, we're ready to invest in it clinically, or in some cases pre-clinically, we have the capital to do so. So it'll be a mixture of both, and that definitely includes secret.
Great, thank you for answering my question. I wish you guys good luck. Thank you.
Thank you, Ed.
That concludes the question and answer session. At this time, I would like to turn it back to Dr. Mark Hedrick for closing remarks. Thank you, Abigail. Thank you to everyone that is tuned in. And we appreciate your interest in the company. And thank you for the questions. And please be sure to refer to our website. Take a look at our KOL webinar that has been uploaded. And feel free to reach out to management if you have any questions. And the meantime, have a nice evening. Thank you. Thank you all for your participation. And today's conference does conclude the program. You may now disconnect.