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

Good morning, and welcome to the Plus Therapeutics, Inc. Annual Meeting of Stockholders. I'd now like to introduce Dr. Marc Hedrick, President and Chief Executive Officer. Dr. Hedrick?

Thank you. Good morning, ladies and gentlemen, I'm Marc Hedrick, President and Chief Executive Officer of Plus Therapeutics, and it's my pleasure to welcome all of you. It is now 9:00 a.m. Central time on the 17th day of May 2021 and in accordance with the notice of the meeting, I hereby call to order the 2021 Annual Meeting of Stockholders. I will be acting as the Chairman of this meeting. In this meeting, we will consider the proposals set forth in the proxy statement for the annual meeting dated May 17, 2021. After the votes are counted, the meeting will be adjourned. But first, though, I'd like to share a brief corporate update since our last public presentation, and I'll be presenting a few slides, and then ultimately, I'll make those available on our website as soon as possible. And of course, remember, my comments should be considered in light of our forward-looking statement language. As shareholders, I know you are very familiar with our focus on developing innovative treatments for patients battling rare and CNS cancers. But why go after CNS and rare cancers? Most important, they represent very significant unmet medical needs. And even though these diseases are rare individually, in aggregate, they represent a sizable patient population, and also they have biological similarities. Meaning many of these cancers may be treatable with the same agent or approach, and therefore, they're inherent economies of scale. Glioblastoma is a type of brain cancer and is a prime example of a serious rare disease that is incurable without good treatment options. [Presentation]

In our currently open clinical trial called ReSPECT, the doctors that are treating these patients with our lead drug, RNL186, are seeing promising clinical outcomes. For example, here is a patient treated with RNL. And on the left image, it's a pre-op showing the large recurrent brain tumor in white. And then on the right side is an involuted or shrunken tumor in gray at 56 days after treatment with RNL. And this is exactly what you would want to see in a patient like this after a treatment. But achieving an improvement in clinical outcomes in these patients has been really challenging for the medical community and [indiscernible] across many medical specialties in areas of engineering and scientific innovation. But the drug for us commercially is a critical element for the company. Our lead drug, as I mentioned, is RNL186. It's a nanoscale drug, much [indiscernible] big high dose of radiation that overwhelms the DNA repair mechanisms of cancer cells, causing mitotic catastrophe and cell death, while seeming to spare more normal tissues and cells. It is also unique in that besides cancer killing, it also emits a low energy imaging particle that [indiscernible] this pipeline contains 4 investigational drugs. Our lead drug, Rhenium NanoLiposome is in Phase I for recurrent GBM. With new additional CNS indications that are in development, and we have received feedback from the FDA on 2 of those, and I'll discuss those in a moment. And we also have an earlier stage development program for a therapeutic combination of isotopic Rhenuim, combined with the potent chemotherapeutic. And then finally, we have 2 other clinical stage chemotherapeutics for which we are seeking licensing partners. [indiscernible] specifically, the liposomal encapsulation of the isotopic Rhenium increases its half-life from about 5 hours to 90 hours, such that it is retained at the tumor site for weeks. Additionally, our formulation provides predictable dispersion characteristics and very high doses of radiation were tolerated with no maximum dose reached. RNL was then shown to significantly enhance survival in both the U87 and U251 xenograft models, and importantly, no residual disease to the treated animals had a loss of bioluminescence activity back to background levels, suggesting complete eradication of the tumor. And that was consistent with the blinded histological evaluation by a neuropathologist showing no residual disease in RNL treated animals. On a practical level, translating RNL into the clinical setting and achieving precise targeted delivery is only possible because of recent advances in the modern clinical workflow, leveraging advances in imaging and computer and AI-based software algorithms, updates in the neurosurgical operating rooms, such as geospatial stereotactic catheter placement and advances in convection enhanced delivery. Furthermore, the benefits over traditional external beam radiation therapy, which is the closest comparator to RNL are substantial. [Presentation]

The first in-man trial of RNL is called ReSPECT, and it's a Phase I/II trial assessing the safety, tolerability and distribution of RNL in recurrent or progressive malignant glioma and funded to a significant degree by the NIH or National Cancer Institutes where up to 55 patients and 3 clinical sites are now on board. Thus far, we have now treated 21 patients. No treatment-related serious adverse events have been observed and promising efficacy signals noted when adequate dosing and tumor coverage were achieved. As mentioned, thus far, we have treated 21 patients in 7 cohorts. In the most recent cohort, 8.8 milliliters and 22.3 millicuries were delivered at a rate of -- maximum rate of 20 microliters per minute. The rationale behind increasing the flow rate in cohort 7 is that we believe we are likely delivering sufficient tumorcidal radiation, but desire to increase the distribution and speed the delivery time. Thus far, RNL appears to be safe and well tolerated without dose-limiting toxicities. And there are, thus far, no observed correlations in the treatment-emergent adverse events, and notably, the incidence and severity does not appear to increase with increasing doses of RNL. One reason we've not seen systemic serious adverse events or SAEs, such as marrow ablation is that, as we've shown preclinically as well, the radiation stays in the tumor and surrounding abnormal brain and exposure outside the brain is negligible. This table summarizes the delivery characteristics through cohort 7 with a few exceptions where Dosimetry data is not yet available for assessment. So as mentioned, we're now up to 22.3 millicuries of radiation, 8.8 milliliters of volume, a concentration of 2.5 millicuries per milliliter and a flow rate maximum of 20 microliters per minute. Thus far, here, the averages we can report, and these are largely averages. Number of catheters used 1.8, tumor volume 9.4 milliliters, tumor coverage 66%, absorbed dose 239 Gray, average prior treatments 1.7, and then there were 7 patients included in the trial thus far that were Avastin or bevacizumab failures. I can report a key delivery finding is that patients receiving prior bevacizumab convect poorly. In other words, the drug doesn't perfuse through the brain tumor properly at the present delivery parameters and only an average of 43% of the tumor volume was covered in these patients. Whereas in the bevacizumab-naive patients, they had almost double the average tumor coverage at 81%. And tumor coverage is critical and seems to correlate with survival as one would intuitively suspect. For reference, average overall survival in recurrent GBM patients, shown in a recent meta-analysis, was only eight months. And in respect, through cohort 6, overall survival in bevacizumab-naive patients is 15.1 months, with 4 patients still alive and another 3 patients are still alive from cohort 7. And here I'll show you a couple of representative cases. These are images for patient 14, showing good tumor coverage, 5 days after treatment with greater than 90% coverage, and an absorbed dose of radiation of 419 gray. In that same patient, MRI scans show first an increase in the size of the tumor image, which peaked at day 118 because of edema, not tumor growth, then shrinked after a year post-op and the patient remains alive. Pseudoprogression is not unusual in these patients, because of the amounts of radiation delivered, and therefore, imaging is not the optimal way to follow and assess biological effect. These are images for another patient, #17, showing 87% coverage and a dose of 336 gray. And again, also in patient 17, one can see clearly the ablative tumor response and change in perfusion, going from left to right, at 56 days after surgery and 2 different tumor cuts through the brain. Also, the company has data showing RNL is promising for a number of other cancers and 4 are listed here. 2 very difficult-to-treat cancers, leptomeningeal carcinomatosis and pediatric brain cancer, we feel are interesting targets for RNL. Leptomeningeal disease or LMC affects about 110,000 patients in the U.S., and there is no clear standard of care. And these patients die rapidly despite what care we provide to them. Pediatric brain cancers, though much rare, carry an equally poor prognosis. The treatment approach for pediatric brain cancer would mirror our approach in adults with glioblastoma using convection enhanced delivery. However, LMC is a disease of the lining of the spinal fluid space and nanoliposomes of 100 nanometers seem to circulate freely if injected there and preclinical studies thus far look promising. We [indiscernible] and this is highly dependent on forthcoming feedback from the DSMB, further data assessment and our ongoing analysis of imaging and clinical response. Our DSMB meeting is slated for June, and depending on that feedback, we will likely seek an FDA meeting regarding our CMC package for Phase III. And if a Phase II dose is recommended at that meeting, despite the lack of dose-limiting toxicities, we may seek to keep the Phase I open and continue to dose escalate and take the recommended Phase II dose into a Phase II trial funded by the NIH, while we complete the CMC activities for a potential registrational trial. As to the 2 new indications, we plan to file an IND this year for LMC and potentially for a pediatric indication, if possible, to follow an LMC IND and hope to treat LMC patients as soon as the end of this year. As to forthcoming milestones over the next year or so, we intend to complete enrollment and report data from the US ReSPECT Phase I trial for RNL in recurrent GBM; have our DSMB meeting and hopefully, FDA CMC meeting; complete the CMC activities for RNL for Phase III drug supply; potentially proceed with Phase II, and ongoing dose escalation at the same time. We also intend to move RNL into Phase I for LMC and pediatric brain cancer indication, as mentioned; complete additional preclinical studies we have slated for RNL and dRNL, and then continue to pursue potential new in-licensing and out-licensing opportunities. The company finished Q1 2020 with $14.4 million and 10.2 million outstanding shares. In our most recent 10-K, we noted that in Q1, we raised an additional $9.4 million in part due to warrant exercises. And we continue to carry a small residual loan balance maturing in 2024. So with that, we will move on to the remainder of our agenda. So this annual meeting is held pursuant to the proxy materials mailed on or about April 5, 2021, to each stockholder [indiscernible] there were 9,221,902 shares of common stock outstanding and entitled to vote. A list of stockholders entitled to vote at this meeting has been available at company headquarters for the past 10 days and is available at this meeting for examination [indiscernible] the proof of mailing of the notice of this meeting will be filed with the minutes of the meeting. Christine Amarine has been appointed to act as Inspector of Elections for this meeting. Christine is present, has taken the oath of office, which will be filed [indiscernible] preliminary count indicates that a majority of the shares entitled to vote at this meeting are present via live webcast or present by proxy, and therefore, I declare a quorum is present for the purpose [indiscernible]. The rules of conduct for this meeting have been posted on the Q4 Inc. website. Following adjournment of the formal business of the annual meeting, the company will address appropriate questions from stockholders regarding the company. Such questions may be submitted in the field for the questions and it will help us if questions are succinct and cover only one topic per question and the Q&A session will be limited to 20 minutes. When submitting questions, please include your name and whether you are a stockholder or a proxy holder or both. If you are a proxy holder, please include the name of the stockholder or stockholders that gave you the proxy. Please keep your statements brief and limited to the specific item for discussion. The company does not intend to address any questions that are not appropriate for this meeting [indiscernible] if you wish to vote via the Internet at this meeting, you will have an opportunity to do so momentarily. I now declare the polls for voting are open. To vote via the Internet at this meeting, you will need the control number included on your notice or your proxy card, if you received a printed copy of the proxy materials. Proposal 1 is the election of 6 directors to serve as directors until the 2022 Annual Meeting of Stockholders or until their successors have been duly elected and qualified. The present Board of Directors has nominated and recommends the following nominees: Howard Clowes, An van Es-Johansson; Richard J. Hawkins, Marc H. Hedrick, Robert Lenk and Greg Petersen. The company has an advanced notice provision in its bylaws and given that we have not received any other nominations, I hereby declare the nominations for election of Directors of the company to be closed. Directors will be elected by a plurality of the affirmative votes cast by those shares present or represented by proxy and entitled to vote at this meeting. If you are voting via the Internet at this meeting, please submit your vote now. Proposal 2 is to ratify the selection of Audit Committee of the Board of Directors of BDO USA LLP, independent registered public accounting firm, to audit the financial statements of the company for the 2021 fiscal year. Approval of the proposal requires the affirmative vote of a majority of the common stock present in person or represented by proxy at the annual meeting. If you are voting via the Internet at this meeting, please submit your vote now. Proposal 3 is the approval of the company's amendment and restatement of the company's 2020 Equity Incentive Plan. Approval of the proposal requires the affirmative vote of the majority of the common stock present in person or represented by proxy at the annual meeting. If you are voting via the Internet at this meeting, please submit your vote now. Proposal 4 is to provide a nonbinding advisory vote on the compensation of our named executive officers. Approval of the proposal requires the affirmative vote of a majority of the common stock present in person or represented by proxy at the annual meeting. Once again, if you're voting via the Internet at this meeting, please submit your vote now. [Voting]

That concludes the voting on the proposals. Again, if you have already voted by proxy, you need not vote today unless you would like to change your vote. As there are no questions, we will move on to the preliminary results of voting. The vote -- excuse me, the Inspector of Elections has reported that, based on a preliminary count of the votes, stockholders have approved all four proposals. Following confirmation of the preliminary voting results, the voting tabulation report of the Inspector of Election will be filed with the records of this meeting. This now concludes today's annual meeting. I declare the meeting to be adjourned. [indiscernible] attended the meeting as well as those, who submitted their proxies, but were unable to attend or present in person. Thank you, and have a great day.

This concludes the Annual Meeting of Stockholders for Plus Therapeutics, Inc. Thank you so much for attending. You may now disconnect.