Plus Therapeutics Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 14, 2023

There are 5 speakers on the call.

Operator

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, 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 on Form 10 ks 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.

Operator

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 Doctor. Mark Hedrick, Plus Therapeutics' President and Chief Executive Officer. Sir, you may begin.

Speaker 1

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 recent business highlights to discuss our 2023 Q2 financial results. Joining me for the call today is Doctor. Norman LaFrance, our Chief Medical Officer and Mr. Andrew Sims, our Chief Financial Officer.

Speaker 1

I'll begin the call by reviewing our recent clinical and regulatory progress with a focus on the Q2 and then turn the call over to Andrew to review our financials. And Norman will then be joining us for Q and A. I'll begin with updates on our 2 lead CNS cancer programs. First, an update on our RESPECT lm trial for patients with leptomeningeal metastases or lm. In Q2, we completed enrollment in the Phase 1 Part A That's cohorts 1 through 3.

Speaker 1

And as is called for in the protocol, we reviewed the safety data with the FDA And they approved us to continue the Part B of the Phase 1, specifically dose escalation from Cohorts 4 and beyond until a DLT is observed. At the SNO ASCO CNS Cancer Conference last week in San Francisco, we reported the results from our RESPECT Lm Phase 1 Part A trial. Recall that we've Treated 10 patients with a single administration except for 1 patient that received a second treatment off trial under compassionate use. It is mentioned that was in 3 dose escalation cohorts. Thus far, we found that rinium obisimatas circulated fully in the CSF space within minutes of injection and remain concentrated in the CSF space for at least 7 days following administration.

Speaker 1

Critical organs outside the central nervous system, including blood, spleen and liver showed de minimis absorbed radiation doses well below critical safety levels. In contrast, target organs in The spinal CSF showed linear increases in absorbed dose that correlated with administered dose. In Part A, we dosed from 6.6 millicuries up to 26.4 millicuries And we achieved absorbed doses of up to 102 gray to the ventricles and cranial subarachnoid space. 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 3. In terms of safety, consistent with the low off target absorbed doses, no dose limiting toxicities Furthermore, the overall safety profile was favorable.

Speaker 1

Approximately 83% of adverse events were mild or moderate And the majority were not related to treatment. The favorable safety profile provided the basis for moving forward into Part B of Phase 1. However, we've also assessed whether there were disease target effects by measuring tumor cell counts, survival and symptomatic improvement. Recently, a highly specific and sensitive CSF tumor cell enumeration technology called CNS side assay has been approved and we are employing it in the RESPECT LN trial. In our view, the technology is a significant advance in CSF tumor assessment over standard of care.

Speaker 1

In Part A, we found that tumor cell counts trended lower immediately after treatment and were sustained through day 28 post treatment. At 28 days, tumor cell counts were reduced on average of 53% and up to 91% over preoperative baseline. And then generally, we noted a rebound in tumor cell counts at 56 days. Our view is that effective therapies in the management of Lm such as potentially rhenium obisimeta Can disrupt the care of LM, but the addition of a reliable tumor cell enumeration technology can magnify that therapeutic and commercial impact. Current means of LM diagnosis, specifically the triad of imaging, clinical symptomatology and CSF analysis of cells, We use now the old stalwarts of protein, glucose and cytology, both lack sensitivity and specificity.

Speaker 1

Specifically, tumor cell enumeration may allow earlier diagnosis, diagnosis of subclinical cases and Lm is about 2 to 4 times under diagnosed and then support decisions on redosing patients through their treatment course. 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 of approximately 3 to 9 months observed with standard of care. As a note, as part of the SNO ASCO meeting in San Francisco in which the Phase 1 data was presented, Plus co hosted a KOL roundtable with Doctor. Justin Waltz, which also included 2 Respect LM investigators Doctor.

Speaker 1

From the University of Texas Health Sciences at San Antonio and Doctor. Priya Kumtikar from the Neurology and Medicine departments at Northwestern University's Feinberg School of Medicine. This KOL roundtable is available for replay on our website During the KOL roundtable, doctors Brenner and Kumtikar provided a comprehensive discussion about the ongoing Respect LM Phase IIIa dose escalation clinical trial with emphasis on epidemiology, Diagnosis, Safety and Tolerability, Dosing and Efficacy. We urge everyone that's interested to watch the webinar for a deeper look at LM and the respect to clinical trial findings thus far. In terms of next steps for LN, the clinical development plan is to continue to dose escalate to the maximum tolerated dose and in parallel expand the Phase 1 dose escalation trial to explore multiple dosing.

Speaker 1

This approach is critical to enhancing the potential for the clinical benefit of rinium obisimatum in these patients, which will require further FDA discussions. As mentioned, we did treat in Part A one patient with a second dose of ritium obisperimata 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 Called Respect GBM for patients with recurrent glioblastoma or GBM, we continue to enroll for both our active Phase 1 and Phase 2 trials. Our Phase 1 now has enrolled 4 patients in Cohort 8 With tumor sizes being treated in that greater than 20 milliliters and they were treated with an administered radiation dose So 41.5 millicuries in a treatment volume of 16.4 milliliters. We have now successfully used up to 5 catheters per treatment in multiple patients and no DLTs have thus far been observed.

Speaker 1

We plan to treat 6 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 2 protocol. Our Phase 2 continues to enroll patients with tumor sizes of 20 cc's or less using an administered radiation dose of 22.3 millicuries and treatment volume of 18.8 8.8 milliliters. We remain on track to complete Phase 2 enrollment by the end of 2024. 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 and beyond.

Speaker 1

As a respect to GBN trials or open label We are analyzing the data in an ongoing manner and I would like to highlight the GBM data readouts going forward. First, we intend to publish the Phase 1 data in of equal to 21 patients in peer reviewed literature and that's in process. 2nd, we continue to evaluate the feasibility, safety and efficacy in the ongoing Phase 1 trial. The extended Phase 1 trial evaluating the safety at these higher dosages and volumes as mentioned and the impact of these higher doses and volumes on R and L distribution and tumor coverage and then also finally on the effects on large tumors. And I think it should be obvious from some of the data I mentioned before in terms of volume and administered 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 1

And that data will be presented at Society For Neuro Oncology meeting in November. 3rd, we continue to periodically assess the actively enrolling Phase 2 alone and in a pooled fashion with representative data from the Phase 1 and that data will also be presented at the SNO meeting in November. 4th, we have recently reported top line data from a propensity matched real world data analysis of recurrent GBM patients receiving either bavucizumab or convection enhanced delivery. That data will be used as a real world control comparator arm for the Phase 1 and Phase 2 trials and also for regulatory purposes, including as it relates to potential pivotal trial design. More detailed data will be presented on the real world propensity MATCH trial at SNO in 2023 as well.

Speaker 1

I think we have 5 posters or presentations at SNO this year. 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 presented before. One thing I just wanted to highlight beyond the safety profile is what we've observed relating to the dose response data, specifically the correlation between overall survival And both increasing radiation absorbed dose to the tumor and increasing percent coverage of the tumor volume. 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 percent. 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.

Speaker 1

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 trial, we have formally responded to the FDA request for additional safety data from adults And assuming no new request, we anticipate IND approval and then moving forward with our pediatric brain cancer trial in the second half of twenty twenty three. As mentioned in the past, management's practice is to rely heavily on grants or other third party funding through Phase 2 for each active program. We currently have a number of grant submissions in excess of $1,000,000 under review, including 2 specifically Our second radiotherapeutic drug is making steady Regulatory and development progress. We recently received feedback from the FDA on our pre request for designation.

Speaker 1

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 embolic product will be regulated as a device primarily by CDRH. This is consistent with the 2 Generation 1 products that are now on the market that collectively share A market opportunity of about $1,300,000,000 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 Pyramal Pharma Solutions that produce additional to meet the forecasted increase in demand for RINIUM-one hundred and eighty six of bisperemata for ongoing and planned clinical trials.

Speaker 1

Our view is that we are where we should be today in terms of our supply chain and we are executing on a longer term plan to stay ahead of the curve as we move our radiotherapeutic products closer to market. 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?

Speaker 2

Thank you, Mark. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the 2022-three 2nd quarter ended June 30, 2023. 1st, regarding the balance sheet. As of June 30, 2023, Cash and cash equivalents were $10,900,000 compared to $18,100,000 as of December 31, 2022.

Speaker 2

In addition, this month we were notified that Seapri released approximately $1,900,000 in additional cash anticipated to flow to the company's balance sheet in August. As a reminder, the company benefits from both a $3,000,000 NIH award for the RESPECT GBM clinical trial through Phase II and a $17,600,000 award from CPRIT for the RESPECT Lm trial through Phase 2. Going forward in years 23, grant funding is forecast to be $6,700,000 $7,100,000 respectively, likely split into 2 or more advance 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 $49,000,000 Now on the income statement, the company recognized 1,900,000 Grant revenue in the Q2 of 2023, which represents Seapriq's share of costs incurred to fund a portion of our LM clinical program. Total operating expenses for the Q2 of 2023 was $3,300,000 compared to total operating expenses of $5,100,000 for the same period the prior year.

Speaker 2

The decrease is due primarily to the company completing one off investments in the GMP development of the company's lead drug, renium-one hundred and eighty six abysmal mater in Q3 2022. In addition, we incurred lower legal and professional fees in 2023 versus the prior year. Interest expense decreased from $181,000 for the Q2 of 2022 to $112,000 for the Q2 of 2023. This decrease reflects the continued principal pay down on the company's Oxford debt. Net loss for the quarter of 20 23 was $1,500,000 or $0.59 per share compared to a net loss of $5,300,000 or $3.56 per share for the same period of the prior year.

Speaker 2

And now I'll turn it back to you, Mark.

Speaker 1

Thank you, Andrew. Before we move on to Q and A, let me provide some guidance on anticipated milestones through the remainder of the year. We are on track to initiate the Phase 1 Part B of the RESPECT L M trial in the second half of this year and we plan to expand dosing to multiple doses for each We also published the RESPECT GBM Phase 1 data and provide a comprehensive trial update at the Society For Neuro Oncology meeting in November 2023. We are on track to initiate the Phase I RESPECT pediatric brain cancer trial for pediatric patients with ependymoma and high grade glioma in the second half of twenty twenty three. We intend to finalize the device designation for our BAM product and expand our activities accordingly.

Speaker 1

Finally, in general, management has internal targets around portfolio and business development opportunities and additional non dilutive grant funding, both are progressing and we will update on those when appropriate to do so. At this point, Abigail, I'll now turn the call back over to you for Q and A.

Operator

Thank you. At this time, we'll conduct a question and answer session. Our first question comes from Justin Walsh with Jones Trading. Your line is open.

Speaker 3

Hi. Thanks for taking the questions and congrats on the progress. My first question, I'm wondering about your current thoughts about Potentially approvable endpoints for LM in the context of the data you presented. Overall survival obviously could make sense, particularly given the 10 month median overall survival you saw in 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 radiopharmaceuticals were approved for

Speaker 1

Hey, Justin, it's Mark. I think At this point, it's a bit too early to say definitively as you sort of hinted in your question. But Beyond the gold standard of overall survival, I do think quality of life or symptomatic improvement Our potentially approvable endpoints will be implementing and expanding a QLL Metric in the trial and there are some that are out there that would be appropriate. Relative response rate is difficult because imaging can be difficult. And however, I think there might be an opportunity in terms of Reducing CNS tumor cell count with the SI I mentioned before.

Speaker 1

So I think that's less likely, but I do think that As you mentioned, QLL or symptomatic improvement are also possible endpoints. It's certainly not primary endpoints would be secondary endpoints.

Speaker 3

Got it. And then one more question. I'm just sort of wondering if you can comment on just some more Broad thoughts on why LM is so under diagnosed? And I guess how much of that comes from the challenges of having effective diagnostics for it And how many come from maybe the fact that there may be is not a lot out there that can currently be used to specifically treat LM? So just some thoughts on that, maybe a little bit of a chicken and 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 perspectives on that.

Speaker 1

Yes. It's a good question. The mortality is high. Patients that are non treated live 4 to 6 weeks and just a few months with treatment. So with better treatment, it's likely the incidence will be higher.

Speaker 1

Patients will live longer and also with better primary tumor treatment patients who can live longer as well. The 2 to 4 times increased incidence is based on autopsy studies. So I think there are a lot of subclinical Infections that are out there, patients may die of their primary disease, but they die of their primary disease with CNS mets Or 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?

Speaker 1

Probably not. Are we likely to be see kind of a near term improvement in our ability to image these patients? Not so sure, Doubtful, but I do think there's a real possibility with a highly sensitive and specific CSF assay to evaluate patients that 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 as well at some point.

Speaker 3

Got it. And maybe just a follow-up on that. That assay, it requires a lumbar puncture, Right. 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's It could be pretty reasonable to get patient compliance there.

Speaker 1

Yes, good point. So For patients that are suspected or been diagnosed with LM, Almost all of them have what's called an OMAIA reservoir, which is a small subcutaneous port with a little pigtail coming off of it that goes into the ventricle that allows the physician real time access, which is how our LN treatment is actually infused in the patient. But 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 We'll generally be required because there's no other way to get the excuse me, the CSF out.

Speaker 1

So but it's still it's a common part of the workup. It's CSF analysis via lumbar puncture is part of working up little kids with fevers oftentimes or Patients that come in with neck stiffness and photophobia. So in these patients that have Oncologic primaries, who are at risk potentially of LM, A lumbar puncture is a very reasonable procedure to do those and they're frankly very well tolerated.

Speaker 3

Got it. Thanks. That makes a lot of sense.

Speaker 1

Thanks.

Operator

One moment for our next question. Our next question comes from Sean Lee with H. C. Wainwright. Your line is open.

Speaker 4

Good afternoon, Mark and Andrew, and thanks for taking my questions. My first question is on the recent LN results. I was wondering, because you guys saw a linear trend with the I missed your dose to the absorbed dose. I was wondering any relationships you've seen so far between the absorbed dose and Decreases in tumor cell counts or relative survival?

Speaker 1

No, we haven't. I think it's still early. That's something we'll look 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.

Speaker 4

Great. Thanks. My second question is also on that study. Yes. You mentioned that you're going to be looking at repeat dosing for some of these patients.

Speaker 4

Would that be done on the context of a different study? Or would you You're looking to expand this study protocol to include a separate repeat dosing cohort?

Speaker 1

I think that will be pending decision will 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, You look at the overall survival signal even at low doses, but when you incorporate the safety profile and the reduction tumor cell counts that we've seen, I think that it makes complete sense to continue to dose escalate to a maximum tolerated dose, but then add Additional doses, we're working on that right now. So my guess is it will be part of the current trial, not a separate protocol.

Speaker 4

I see, I see. Thanks. Then moving on to the GBM side, in the prepared remarks, you mentioned that the FDA has approved To be device and not a drug. So would you be looking at the 510 de novo pathway for Yes, it's

Speaker 1

a great question. Right now, it's hard to say. I think A 510 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.

Speaker 1

Obviously, if it's a 510 that's a pretty quick path to market. The PMA would be a bit longer, but either way it is going to be a faster path than a drug related pathway. So We're parallel paths right now. Number 1 is to just the process now with FDA is to do a pre RFP evaluation and then submit your The final RFP, which we're in the process of doing that and then in parallel, we're looking at the device based Regulatory opportunities including 510 and PMA in parallel. And then once we have the final designation, then we'll be ready to move.

Speaker 4

Great. Thanks for your thoughts on that. And that's all I have questions about that.

Speaker 1

Thank you, Sean.

Operator

Thank you. We have a question from the line of Edward Wu with Ascendiant Capital. Your line is open.

Speaker 4

Yes. Thank you for Yes. Thank you for taking my question. My question is on the grants that you guys are working on. Is it only with CPRIT or are you guys doing stuff with NIH?

Speaker 4

And also because you guys already Got a major contract from Seaport. Does it make it easier for you to get future grants? Thank you.

Speaker 1

Hey, Ed. Thanks for the question.

Operator

There's

Speaker 1

no prevention for us going back The secret for additional grants, we know of one company that has 3 secret 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 Grants and go through the process and so forth. So it's going to be both. We're going back to CPRIT for additional grant opportunities, But we're also going to the NIH and other sources of funding here in the U.

Speaker 1

S. 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 Pay for it through Phase 2 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, pediatric 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 Seapret.

Speaker 4

Great. Thank you for answering my question. I wish you guys good luck. Thank you.

Speaker 1

Thank you, Ed.

Operator

Thank you. That concludes the question and answer session. At this time, I would like to turn it back to Doctor. Mark Hedrick for closing remarks.

Speaker 1

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. In the meantime, have a nice evening. Thank you.

Operator

Thank you all for your participation in today's conference. This does conclude the program. You may now

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