Q4 2024 Plus Therapeutics Inc Earnings Call
Please.
Speaker Change: Good afternoon, ladies and gentlemen. Welcome to Plus Therapeutics, Force Quarter, and Full Year 2024 Results Conference Call.
Speaker Change: All such statements are subject to risk and uncertainties, including the risk and uncertainties described under the risk factors section included in Plus Therapeutics Annual Report on Form 10K and quarterly reports on Form 10Q, filed with it.
Speaker Change: Securities and Exchange Commission from time to time. Plus Therapeutics advises you to review these risk factors in considering such statements.
Speaker Change: 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.
Speaker Change: President and Chief Executive Officer. Sir, you may begin.
Speaker Change: Thank you, Sherry. Good afternoon, everyone. Thank you once again for taking the time to join us today, as we provide an overview of recent business highlights and discuss our fourth quarter and full year 2024 financial results and go forward guidance.
Speaker Change: Joining me for the call today is Mr. Andrew Sims, our Chief Financial Officer.
Speaker Change: I'll begin the call by providing more detail on four important recent corporate announcements.
Then I'll discuss progress in our most advanced clinical programs.
Speaker Change: and then discuss progress and plans for sea insight and its commercialization.
Speaker Change: After that, I'll turn the call over to Andrew to review our financials.
So, first of all, in early March, [inaudible]
Speaker Change: on an underwritten equity financing of $15 million in gross proceeds with new stockholders.
This was preceded by a smaller financing from existing stockholders.
Speaker Change: We also received about that time 2 million in its accelerated grant proceeds from secret.
Speaker Change: This capital, in combination with further anticipated grant funds, strengthens our balance sheet and provides funding through key milestones into mid-2026.
Speaker Change: Additionally, the Financings enabled Plus to regain compliance with NASDAQ's minimum stockholders equity listing requirements.
Speaker Change: Andrew will, in fact, provide additional details on the transactions, future grant availability and cash run rate.
Speaker Change: On a personal note, and on behalf of our Board of Directors and our dedicated management team, I would like to express our collective gratitude to our current and new stockholders for their support of and confidence in plus in our mission.
Speaker Change: We're also grateful to those organizations with which we have substantial financial and grant support, specifically the US NIH.
Speaker Change: and that's the NCI National Cancer Institute, the U.S. Department of Defense, in the state of Texas, specifically secret.
Also, moving on, we recently-
We've taken to strengthen our senior leadership team.
specifically for Plus Therapeutics [inaudible]
Speaker Change: Dr. Mike Russell joined us as Chief Development Officer, responsible for leading our pre-clinical and clinical development activities, including clinical operations.
Speaker Change: Mike has extensive experience in oncology, radiotherapy, therapeutics, and biomarker development all highly germane to Plus's pipeline.
Speaker Change: Great Field, previously holding top management positions in both major and smaller diagnostic companies as well as related board positions.
Russ: Russ has a deep knowledge of diagnostic operations, fast growing commercial diagnostics, market access activities and business development.
Russ: Additionally, I'm pleased to welcome Dr. Jonathan Stein to the team at sea inside as its medical director. Jonathan has extensive experience in all aspects of diagnostic operations, compliance, and regulatory affairs.
[inaudible]
Russ: Now, I'm excited to introduce you to ReoBik. We now have an FDA-accepted proprietary name, which is ReoBik. And that goes alongside the USAAN adopted, and IAN recommended non-proprietary name or generic name, Rinium RE186 Avisbameda. All of these are required for a future marketing application with the FDA.
Russ: Working with the leader in pharmaceutical brand name creation development, we are striving to develop a powerful brand identity for Ray Obick, and then all begins with its global name.
Russ: In parallel, we will be rolling out comprehensive branding materials that will strengthen and shape the Rayobic brand identity and going forward. We'll use Rayobic to refer to our lead drug now in mid-stage clinical trials.
Russ: for use in patients with glioblastoma, leptomaninial cancer, and soon in children with pediatric brain cancer.
Russ: Finally, we recently received approval by the U.S. FDA on our application for orphan designation for the use of reobick in patients with L.M. due to lung cancer. This adds to our previously received orphan designation for L.M. due to breast cancer and a fast track designation for reobick.
This is reflective of our strategy to focus on
Russ: on the top two causes of LM, specifically breast and lung cancer, which represents two-thirds of the LM market.
Russ: Now, let the switch gears and focus on our left-to-manential metastasis clinical development program.
in which we are investigating our lead radio therapeutic reobach.
Russ: in the Respect Elim Trials, which are substantially funded by the state of Texas.
Russ: We recently announced the completion of the Respect LM Phase I single administration dose escalation trial.
Russ: In that trial, we have determined a recommended phase two dose of 44 milicuries, as well as the maximum feasible dose of 75 milicuries.
Russ: To identify the most expedited path to market for patients that are in desperate need for options. We think given the promising phase one data a single dose of 44 note curious warrants further valuation for FDA approval.
Russ: For <unk> related to breast cancer.
Russ: In parallel.
Russ: With respect to all the multiple dose escalation trial of re <unk> will begin enrollment soon for the purpose of dose optimization key.
Russ: Key details for the trial are as follows.
Russ: A single dose at the recommended phase II dose of 44 militaries will be fractionated into three doses of approximately 13 militaries.
Russ: Based on the PK and PD data derived from the phase one single dose trial three doses will be given at diminishing intervals are first every two months.
And every month and then every 15 days.
Russ: There are options to expand the size of the treatment cohorts and extend the number of treatments beyond three to six doses total.
Russ: Besides the pharmacokinetic and Pharmacodynamic data.
Russ: And dose optimization, the trial will assess safety and efficacy.
Russ: <unk> trial will be a basket trial, initially and Thats been approved previously by the FDA and site startup is ongoing.
Russ: The plan to pursue both single and multiple doses and an accelerated clinical development approach is based on the positive clinical data specifically presented at the end of last year at the society for Neuro oncology annual meeting and the San Antonio breast cancer Symposium in December.
Russ: As well as data that has been obtained subsequently.
Russ: Those conference presentations included important new data on PK PD safety clinical response and survival.
Russ: Key highlights of the conference presentations and some of the more recent data that we will present in detail at upcoming conferences include 29 patients with <unk>.
Russ: We received a single intraventricular dose of <unk> between six 6% and 75 militaries.
Russ: In terms of safety data there was one <unk>, which is a great for platelet count reduction that was observed at the cohort five dose of $66 one four militaries.
Russ: And <unk> were observed in one patient in cohort six that was a great for platelet and neutrophil count reductions, indicating at least some bone marrow exposure.
Russ: <unk> with the PK analysis data.
Russ: Notably there were no SAE that occurred in cohort four patients and what it's determined.
Russ: To be the RP QD PK.
Russ: PK and PD analysis showed target to off target radiation absorbed dose ratios of greater than 100 to one.
Russ: To put that in perspective, such racy ratios are impressive because they mean the dose is much more effectively delivered to the area of interest the tumor in this case then to the other areas of the body, where one desire is to keep the doses as low as possible in other words, our drug design and formulation strategy works.
Russ: Clinical response to a single dose of <unk> was assessed.
Russ: Four.
Russ: Months or 112 days post treatment to deliberately exclude the effect on patients receiving money.
Russ: Under a compassionate use protocol.
Russ: Who survived well beyond the published median overall survival specifically.
Russ: Specifically in these patients we assessed change in CSF tumor cells via our <unk> inside tumor cell enumeration assay, which is the best measure of tumor cell bulk or prevalence also we looked at radiographic response.
Russ: And survival benefit was also assessed.
Russ: Through cohort five at the time of data cutoff for the conference presentations data was available for 16 patients.
Russ: <unk> five or <unk>, 31% of those patients showed a radio graphic response based on investigator.
Russ: We also used clinical benefit rate or CBR as an outcome measure and is very fragile patient population as it encompasses complete response partial response and stable disease outcomes in.
An additional seven of the 16 patients I just mentioned showed stable disease through four months for radio graphically determined clinical benefit rate, we can get by combining.
Russ: Combining the five I just mentioned before of 75%, so 75% CPR related to imaging analysis.
Russ: Additionally, in terms of clinical responses or decrease the disease symptoms was noticed in two of 14, evaluable patients or 14% with 10, showing stable symptoms through four months for a clinical benefit rate of 86%.
Russ: Lastly, when looking at the cerebral spinal fluid or the CSF tumor cell enumeration assay again are seeing side assay, which is the most sensitive measure we have.
Russ: We're assessing tumor volume, which has also been shown to correlate with survival. This decreased up to a 100% by day 28, following <unk> treatment with four of the 15 evaluable patients showing a response.
Russ: Translating to a clinical benefit rate of 93%.
In terms of survival median overall survival was nine months, which compares favorably to the historically reported consensus in the literature of about four months supporting the potential efficacy of <unk> for <unk>.
Russ: The full presentations from snow in San Antonio breast cancer meetings are available on our website for further review.
Russ: In terms of guidance for our integrated development plan for <unk>, we anticipate an FDA meeting likely a type b end of phase one meeting as soon as possible to align on the following first a path to a registrational trial for a single dose of <unk> in patients with <unk> and resulting for breast cancer primaries that.
Russ: It includes a single dose expansion trial that would provide an expeditious path to registration.
Russ: Key issues to resolve in this meeting if possible are things like endpoints comparator tumor subtypes that will study and so forth.
Russ: Second we seek to align on the integration of our future multiple dose strategy given the promising data we have seen with compassionate use treatment in a single dose phase one.
Russ: And anticipated data data expected later this year and the former former formal multiple dose escalation trial.
Russ: In the second half of 2025, we anticipate completion of the first and longest duration of the multiple dose expansion cohorts.
Russ: By then we anticipate having FDA alignment a definitive clinical plan for a single dose expansion trial and site onboarding should be ongoing.
Speaker Change: Furthermore, on May nine 2025, plus will be presenting response data from their respect single dose <unk> trial, essentially the full phase one data set as it exists at that time at the nuclear Medicine <unk> Symposium in Vienna, Austria.
Other data presentations are anticipated throughout the remainder of 2025, and we will update on acceptance.
Speaker Change: Our agreement to participate.
Speaker Change: Now switching gears a bit to glioblastoma.
Speaker Change: In terms of respect.
Speaker Change: GBM in those trials.
Speaker Change: The phase one trial results results were recently published in nature Communications, a prestigious high impact journal.
Speaker Change: We have made that publication open access and is now available on <unk> website or directly through nature.
Speaker Change: The results show, a strong safety and efficacy signal that has been further confirmed through the first half of the phase III trial as previously reported.
Speaker Change: For the program as a whole a total of 52 patients have been enrolled through both both phase one and two.
Speaker Change: And we anticipate phase two completion in 2025.
Speaker Change: And the respect trial continues to benefit from a grant from the NCI.
Speaker Change: An offshoot of the adult Glioblastoma trial as our pediatric brain cancer program. We previously announced that we have received a U S Department of Defense Award of a $3 million grant substantially support a phase one trial for children with pediatric high grade Glioma independent woman.
Speaker Change: Yeah.
Speaker Change: Approximately 90000.
Speaker Change: $900000 payment was received in September 2024, as part of this award and we anticipate an additional $1 1 million payment in 2025.
Speaker Change: Interactions with the FDA are ongoing towards final IND approval, we anticipate obtaining that approval in 2025 with Larry Children's hospital associated with northwestern in Chicago, serving as the initial clinical trial site.
Speaker Change: Now regarding <unk> radio therapeutic drug production and supply chain management. This remains an important an active focus.
Speaker Change: Ongoing behind the scenes.
Speaker Change: Recently, we announced partnerships with spectrum Rx ISO therapeutics radio medics and AVX the details of which can be found in previous press releases and earnings earnings calls.
Speaker Change: Furthermore to ensure our ability to meet the demands of expedited or accelerated late stage clinical trials as I've mentioned before and future commercial production requirements for <unk>. We continue to expand key partnerships in 2025 as we have in previous years, but now with the focus geared more towards <unk>.
Speaker Change: <unk> chain redundancy and backup supply.
Speaker Change: Now fundamentally switching gears I'd like to update you on our <unk> business, but I think it's important to give a brief background on C. Insights for those of you that may not be as familiar with it and frankly, we haven't talked much about it over the last few.
Speaker Change: See inside is a CNS cancer testing platform, we have been utilizing in our respect <unk> clinical development programs as a biomarker and exploratory endpoint since 2022.
Speaker Change: Since then and over that time.
Speaker Change: Extremely high conviction of the value of CN side for <unk> future commercial success, and specifically I mean, increasing the total addressable market by two to four times for reopening.
Speaker Change: The immense value also for hundreds of thousands of cancer patients at risk for LTM, but are in a diagnostic quandary and then finally the substantial value of <unk> insight is a commercial diagnostic platform.
Speaker Change: In of itself.
Speaker Change: Given this we seized on the opportunity last year to acquire outright.
Speaker Change: Since then we have been investing thoughtfully in the people the means and the materials to bring C inside back to market in a manner that can unlock its full value for patients providers and stockholders.
Speaker Change: <unk> is C inside what does it do <unk>.
Speaker Change: <unk> side.
Speaker Change: In a brief way brief description, it's a cerebral spinal fluid or CSF assay platform that accomplishes three core things first diagnosis, specifically I can confirm or importantly, reject the clinical suspicion doctors may have that a patient with almost any type of solid.
Speaker Change: <unk> cancer.
Speaker Change: They have LTM. It does so at a much higher sensitivity or said differently, a true positive or true negative rate that's much better that can be done with existing technology, which is essentially cytology.
Speaker Change: It also accomplishes treatment monitoring in patients with <unk> monitoring of CSF tumor cells has been shown to correlate with survival and is now recommended and the NCC and clinical guidelines I E.
Speaker Change: One can address whether a patient is responding to treatment do.
Speaker Change: Do they need a different therapy therapeutic of choice.
Speaker Change: Perhaps can therapy be pause potentially.
Speaker Change: Perhaps they may have safety issues related to their current course of therapy.
Speaker Change: And then finally as a treatment selection tool <unk> cancers, often exhibit a drift in bio molecular signal that may influence treatment approaches and drug selection decisions in the future once drugs are approved by the FDA.
Speaker Change: Clinical data has shown that <unk> can be important and its clinical decision making process.
Speaker Change: Users of see inside our neuro oncologist newer immunologist and medical oncologists are other practitioners caring for patients with common cancers, such as breast and lung cancers, as well as melanoma and others, it's not strictly limited to patients that are there.
Speaker Change: Or have all of them are highly suspect suspected of having <unk>.
Speaker Change: Now, let me talk about the status of the business in brief.
Speaker Change: As mentioned, we have hired a seasoned <unk> to both launch and manage the business day to day, specifically, Mr. Bradley Dr. Stein, who I mentioned previously, but other key hires have been made on boarded in the past 12 months.
Speaker Change: We have also established a CLIA registered centralized laboratory for test operations in Houston, Texas that.
Speaker Change: It is actively testing patient samples from our clinical trial and ongoing pre commercial pilot testing.
Speaker Change: Key market access activities have been ongoing for nine months in the areas of medical affairs and reimbursement this.
Speaker Change: This includes negotiations with commercial payers as well as seeking expanded coding approvals and NCC in CNS cancer change requests for LLM diagnosis.
Speaker Change: Furthermore, key marketing corporate and product branding and sales planning activities have been completed.
Speaker Change: In terms of guidance.
Speaker Change: First of all the company will be exhibiting see inside a key medical conferences in 2025 and plan to submit abstracts and publications as we move forward this year.
Speaker Change: Commercially the CSI tumor cell and emigration test is on track to launch fully this year beginning in a geographically limited manner expanding over the course of the year as market access activities, such as state licensure key payer agreements at medical system contracts or expand it.
Speaker Change: Specific financial guidance will be forthcoming later this year as visibility improves and finally see inside product offerings will also evolve in 2025 and up more on that over the next few quarters and with that I'll now turn the call over to our Chief Financial Officer, Andrew Andrew.
Andrew 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 fourth quarter and full year ended December 2024.
Andrew Andrew: The cash and investments balance was $3 6 million at December 31, 2024, compared to $8 6 million at December 31 2023.
Andrew Andrew: The company recognized $5 8 million in grant revenue in 2024 compared to $4 9 million in 2023.
Andrew Andrew: This represents <unk> share of the costs incurred for our reopening development for the treatment of patients with <unk>.
Andrew Andrew: We expect 2025 craft revenue to be in the range of $6 million to $8 million of which we've already received.
Andrew Andrew: Sure.
Andrew Andrew: The total operating loss in 2024 was $14 7 million compared to $30 3 million for the full year 2023.
Andrew Andrew: The increase is primarily due to increased spend relating to the respect to Alan trial.
Andrew Andrew: Net loss in 2024 was 13 million.
Andrew Andrew: <unk> 95 per share compared to a net loss of $13 3 million or $4 24 per share for full year 2023.
Andrew Andrew: I would also like to provide an update on our runway based on the previously announced private placement and provide guidance on a grant funding for 2025.
Andrew Andrew: There are two additional sources of cash to which process access beyond the balance disclosed in cash on hand, and liquid investments on our Q4 2024 balance sheets.
Andrew Andrew: The first source is the cash from the recently announced private placement closed on March four with gross proceeds of $15 million.
Andrew Andrew: The second source of cash remains a continued funding through three grants.
Andrew Andrew: Firstly, the separate grants to support their respective <unk> trial.
Andrew Andrew: Coming into 2025, we have $7 2 million remaining to be received on the grounds of which we received $2 million in Q1 2025, and they are on track to receive $1 6 million in Q2.
Andrew Andrew: And the balance to be received in late Q3 or early Q4 2025.
Andrew Andrew: Plus also is just over $2 million remaining.
Andrew Andrew: The gross proceeds from a reward from the United States Department of Defense.
Andrew Andrew: The $3 million in total to support the upcoming respect pediatric brain cancer trial.
Andrew Andrew: Thus the first advances received in 2000 to 2024, but just under 900000.
Andrew Andrew: Plus also continues to benefit from the NIH grants to support to respect GBM phase one two trial.
Andrew Andrew: They are expected to be completed in 2025 currently covers approximately 90% of the overall trial costs.
Andrew Andrew: We also continue to source other non dilutive sources of capital we will continue to only report on individual brands when they are awarded.
Andrew Andrew: In addition in Q1 2025, we consolidated our operations into a CN site facility in Houston.
Andrew Andrew: Dreamliner operations and reducing costs.
Andrew Andrew: Taken in total the cash runway as well.
Andrew Andrew: And then as Mark laid out being fully funded.
And now I'll turn it back to you Mark Thank you Andrew.
Andrew Andrew: Before we move on to Q&A I'll make take a moment to provide a summary of guidance unanticipated key events and milestones for the remainder of the year.
Andrew Andrew: First of all in terms of data and related presentations, specifically at the nuclear medicine in neuro oncology Symposium in May we will provide a comprehensive respect LLM data review of the single dose phase one trial, including new key safety and efficacy data.
Andrew Andrew: In terms of in terms of other targeted meetings for the remainder of the year, we plan to contribute abstracts and presentations along the way at a minimum to our core constituencies in oncology specifically at the society for Neuro Oncology American Society of clinical oncology joint meeting.
Andrew Andrew: In August and the society for Neuro oncology annual conference in November and.
Andrew Andrew: In addition, besides a submitted abstracts the company plans to host educational seminar at Snow ASKO, featuring Kols presentations on both <unk> and <unk> inside and potentially at the snow annual meeting more on that to come later.
Andrew Andrew: In terms of clinical and regulatory milestones. This year, we are on track to initiate the respect El Limn phase one multiple dose escalation trial.
Andrew Andrew: And complete the first cohort of multiple doses at the two month intervals.
We're also on track to meet with the FDA. This year following completion of the respective phase one clinical study report, which is in process to seek agreement with the FDA on a few things first the broad issues around the clinical development of <unk> through approval first for breast cancer and other cancers.
Andrew Andrew: Also we intend for these meetings to provide us with substantial agreement on key issues such that we can optimally design a phase three registrational trial for both a single dose of <unk> for breast cancer and later to integrate dosing optimization thereafter, as additional multiple dose data becomes available.
Andrew Andrew: And then finally as a result of these meetings, we will be better able to design a single dose expansion trial in agreement with the FDA and be in startup mode in the second half of 2025.
Andrew Andrew: Also we intend to complete enrollment of the final patients in respect GBM phase II trial by the end of the year. We also plan to obtain approval for the respect PVC.
Andrew Andrew: Phase one trial of <unk> for pediatric brain cancer.
Andrew Andrew: We're also push to.
Speaker Change: To get enrollment started there as well this year at Lurie Children's hospital.
Speaker Change: Regarding C. Inside this will be a very important year for plus with many commercially oriented milestones planned specifically CN site is on track to launch fully this year.
Speaker Change: This is beginning with a geographically limited introduction introduction.
Speaker Change: Now, but with building steam over the course of the year as CN site as an assay platform initial commercial.
Speaker Change: So on tumor cell enumeration or tumor cell number counting to be followed with additional testing capabilities thereafter market access activities are ongoing and state license.
Speaker Change: Spittle in bellwether medical system contracts will be announced as completed.
Speaker Change: Geographically since lab testing is centralized market expansion will be driven as market access objectives are met.
Speaker Change: Most important commercially related financial guidance is planned to begin later in this year as key milestones are achieved and visibility improved.
Speaker Change: Additionally, the company will be exhibiting inside at key medical conferences and plan to submit a variety of abstracts and publications as we move forward. This year, so with that Sherry I will turn it back over to you for Q&A.
Speaker Change: To ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw your question Press Star One again, one moment, while we compile the Q&A roster.
Speaker Change: Okay.
Speaker Change: And our first question will come from Edward Woo with <unk> capital. Your line is open.
Edward Woo: Yes, congratulations on all the progress that you're making on the CN inside do you anticipate building up a major sales force or will you look for partners to commercialize this.
Edward Woo: Hi, yes. Thanks for the question appreciate it.
Edward Woo: So not a major sales force.
Edward Woo: Let me clarify that this is this is a niche offer opportunity so.
Edward Woo: At <unk>, we're really we're beginning the sales process with academic neuro oncologist at major oncology centers call. It the 30 NCI designated cancer centers Thats, a relatively small group. They are only about 300 neuro oncologist in the country.
Edward Woo: There are a lot more medical oncologist and there are a lot more emergency room doctors, even that could use it but that will come later the key thing is to launch us into this narrow group of <unk>.
Edward Woo: The thought leaders and made major institutions that probably gets you to 80% of the market and then over time expand it out to the broader medical oncology market and perhaps even as mentioned the ER docs.
Edward Woo: That's well within our capability to execute.
Edward Woo: <unk> finance and.
Edward Woo: And I don't think it makes sense at this point the partner, although at some point partnering in the U S and our outside the U S will.
Edward Woo: We will be.
Edward Woo: Something that we're going to look at very closely and be predisposed to do.
Edward Woo: Great well, thanks for answering my questions and I wish you guys. Good luck.
Edward Woo: Thank you.
Speaker Change: Thank you one moment our next question.
Speaker Change: And that will come from the line of Jason Kolbert with Steve Boyle Capital. Your line is open.
Speaker Change: Hi, Dr. Hedrick. This is lindsey on for Jason first off I just wanted to say congratulations on the financing. We just have a few questions for you.
Speaker Change: First question is the recurrent GBM trial is the most advance are you able to lay out what must happen to meet the goal of data this year.
Dr. Hedrick: Hi, Lindsay, yes in a way it's most advanced although.
Speaker Change: Its really look at.
Speaker Change: In the integrated development plans for both.
Speaker Change: It's very likely that <unk> could get approved before.
Speaker Change: But Ah superficially, yes, GBM is in sort of late stage phase two.
Speaker Change: So as I mentioned, we've enrolled over 50 patients, including completing phase one completing the dose escalation over halfway through a phase III.
Speaker Change: The key thing is it's been adding new sites.
Speaker Change: We've got a flood of new sites that are interested on the heels of the nature communications.
Speaker Change: Publication, we really don't need more new sites. We now have five sites that are enrolling now in New York site and now a.
Speaker Change: Upper Midwest site, So we've got sort of Chicago area, and upper Midwest covered as well as the northeast really talking about 11 patients to complete that.
Speaker Change: And so that'll be a focus over the next year and I think that's that's going to be achievable.
Speaker Change: Thank you and just a follow up question can you remind me of the powering assumption behind the trial, 80% powered for what Delta and then.
Speaker Change: What would be exciting data for that.
Speaker Change: So.
Speaker Change: The.
Speaker Change: Powering on the so the phase II.
Speaker Change: It's comparator is essentially.
Speaker Change: Standard of care.
Speaker Change: We've actually conducted a two real world control arms that we've that we have.
Speaker Change: We funded.
Speaker Change: Through our partner meta data and we have.
Speaker Change: Look at two different comparator arms, one is patients that have been treated.
Speaker Change: With mono therapy with the only approved drug for recurrent GBM, that's bevacizumab in those patients.
Live under eight months.
Speaker Change: That's a relatively large trial that also compares with published.
Speaker Change: Publications as well in terms of meta analysis on recurrent GBM.
Speaker Change: At the behest of the FDA, who wanted to control for the effects of convection enhanced delivery.
Speaker Change: We also looked at.
Speaker Change: Patients that have received CEB, but we're also demographically mapped to our trial again median overall survival.
Speaker Change: Is about.
Speaker Change: It's about eight months, so kind of any way you cut it recurrent GBM patients no matter, what you do lift on average about about eight months. So that's our clinical hurdles hurdle rate in terms of powering assumptions. If you look at kind of cut to the chase here, if you kind of look at 80% powering.
Speaker Change: When you look at that as the.
Speaker Change: As the comparator and really I don't think it matters.
Speaker Change: As your comparator as all roads lead to eight months it seems.
Speaker Change: That you're really talking about a trial of somewhere in the neighborhood of.
Speaker Change: 100 to 150.
Speaker Change: Patients we've had discussions with the FDA.
Speaker Change: About using real world control data.
Speaker Change: Actually a real world control Phase III design has been approved by the FDA.
Speaker Change: And.
Speaker Change: If that were able to do that that will mean, the active patients are going to be much closer to maybe 100 patients to get that same level of powering.
Speaker Change: Such that we would.
Speaker Change: Have a have a randomization scheme that sort of looks like this.
Speaker Change: You would treat three three active patients would be compared to three control patients and of those three control patients to would be demographically matched real world control patients and one would be a true comparator of prospectively taken.
Speaker Change: <unk> taken and that would likely be either a comparator to bevacizumab or radiation or standard of care, which is essentially.
Speaker Change: Physician's choice.
Speaker Change: To answer your question.
Speaker Change: Yes. It does thank you so much for answering my questions and I just want to say congratulations on the progress in the quarter.
Speaker Change: Thank you thanks Lindsay.
Speaker Change: Thank you one moment our next question.
Speaker Change: And that will come from the line of Sean Lee with H C. Wainwright. Your line is open.
Sean Lee: Hey, good afternoon, guys and thanks for taking my questions.
Speaker Change: My first one is on the O&M study so you proposed a.
Speaker Change: Dose expansion at the 44 minute Curie dose I was just wondering is that going to be another additional cohorts of the phase one study or with that.
Speaker Change: Maintaining that as part of the.
Speaker Change: A phase II study that Youre planning.
Sean Lee: Hey, Sean Thanks for the question, yes. So.
Speaker Change: Let me tell you what I.
Speaker Change: My aspiration with that isn't subject to discussion with FDA and it's subject to subject it to there.
Speaker Change: Desire to move this.
Speaker Change: This program quickly.
Speaker Change: I think that.
Speaker Change: The ideal path here would be for the FDA to sign off on a on a phase II trial.
Speaker Change: With.
Speaker Change: Focused on breast cancer likely.
Speaker Change: Her two positive.
Speaker Change: Her two positive her two negative patients and equals 15 of each.
Speaker Change: At the 44 military.
Speaker Change: The phase one dose.
Speaker Change: As a basket trial includes lung patients.
Speaker Change: And.
Speaker Change: Breast patients gastrointestinal cancer patients and so forth so.
Speaker Change: The key in and.
Speaker Change: And segmenting the patients by molecular subtype is to the degree that.
Speaker Change: Overall survival as an endpoint mix, there likely will be a differential survival, depending on what kinds of patients one select based on a.
Speaker Change: Survival data that's been reported in patients with O&M. So I think we want to sort that out.
Speaker Change: From a statistical evaluation.
Speaker Change: This discussion with FDA I think will elicit.
Speaker Change: The proper endpoints.
Speaker Change: Our belief is that.
Speaker Change: While overall survival.
Porting the ultimate goal because these patients have essentially two cancers, a primary cancer in the breast.
Speaker Change: And in metastatic cancer that confounds the interpretation of overall survival data our view is that actually see inside.
Speaker Change: Is the best measure of response and correlates with survival and that could be an important.
Speaker Change: Primary endpoint co primary endpoint or secondary endpoint and that would change the trial design dramatically.
Speaker Change: No.
Speaker Change: Dissipation is if thats the way we go with the phase II.
Speaker Change: With 30 patients 15 of each hormonal subtype, we could analyze those individually and also collectively that could provide enough patients.
Speaker Change: And we can build this in upfront to roll directly into an approval trial.
Speaker Change: So that would be ideal that will take a little bit more negotiation with the FDA and likely a bit more time to get up and running.
Speaker Change: We could also do a phase one b, which is essentially a direct dose expansion.
Speaker Change: That would be quicker, but it likely would.
Speaker Change: Would not expedite the regulatory approval process.
Speaker Change: As much as going directly into kind of a phase II or a phase III pivotal design.
Speaker Change: Understood Thanks for that.
Speaker Change: With regards to the multi dose study that would you wait for the first data to come out from that study before you initiate a phase II or would you try to build that into a phase III program.
Speaker Change: I will need a second study afterwards.
Speaker Change: Yes, no I think we're going to move forward directly into <unk>.
Speaker Change: Into this phase II or phase one b that data will be important no matter, what we do in terms of increasing the.
Speaker Change: Yes.
Speaker Change: Performance data.
Speaker Change: The.
Speaker Change: Sure on the proper.
Speaker Change: The proper endpoints in the trial.
Speaker Change: Powering assumptions.
Speaker Change: And in expanding the PK PD data so that no matter, what we do with multiple doses, that's going to be important data to drive the overall program.
Speaker Change: Thank the phase one data is.
Speaker Change: Very promising.
Speaker Change: We've had multiple multiple multiyear survivors, which essentially had hurt us if you look at the survival.
Speaker Change: Kaplan Meier curve for median overall survival you see a lot of long tail survival, which is unheard of in the disease.
Speaker Change: Which is a very positive thing so.
Speaker Change: I do believe based on the data that <unk>.
Speaker Change: Proceeding with a single dose approval.
Speaker Change: As is <unk>.
Speaker Change: Very.
Speaker Change: Very promising and possible and I think we should pursue it.
Speaker Change: As quickly as we can but either way, we win with that dataset and the multiple dose data I.
Speaker Change: I think we already know that multiple doses work we've treated patients in the phase one as you know Sean with multiple doses under compassionate use.
Speaker Change: We know on a small number of patients that we can do that safely at very high doses and patient seem to live longer.
Dose optimization can take a while so we think it's very important to get this.
Speaker Change: And in the market to patients to doctors as quickly as we can we think that pathway. It really goes to single dose first and then we will layer on dose optimization as the data comes back and then play read and react to the data.
Speaker Change: In consultation with the FDA.
Speaker Change: Okay great.
Speaker Change: Understood.
Speaker Change: And my final question is on the C&I side I was wondering if you could provide a bit of color on the <unk>.
Speaker Change: Market opportunity and.
Speaker Change: So how much.
Speaker Change: Where do you think youll be in the next 12 months or so.
Speaker Change: Yes. It is.
Speaker Change: Great question.
Speaker Change: In my view the market opportunity.
Speaker Change: And kind of a best reasonable case is 5 million tests per year in the U S.
Speaker Change: That leverage is.
Speaker Change: Ruling in the diagnosis.
Speaker Change: Ruling out the diagnosis in patients who might have breast cancer and suspicious neurological symptoms, but indeed don't have <unk>.
Speaker Change: And then the treatment monitoring data increasingly looks to be very promising.
Speaker Change: So you add up all those markets and you look at.
Speaker Change: When you look at the.
Speaker Change: Publications that are increasingly coming out showing there is an epidemic and LTM.
Speaker Change: Really drives that market number so it's a very sizable market opportunity in our view in prior companies can.
Speaker Change: <unk> data or.
Speaker Change: Over two and a half years really support the.
Speaker Change: Physician acceptance of that about half the major cancer centers in the U S. We are using the test.
Speaker Change: During that timeframe.
Speaker Change: So I think it's a very sizable market opportunity, where do I think will be a year from now.
Speaker Change: I think that the tumor cell enumeration test will be.
Speaker Change: Commercial rollout on a geographic.
Speaker Change: Scale.
Speaker Change: As we get state licenses and we get major payers onboard as.
Speaker Change: As well as Medicare, we've actually made great progress in the last nine months on those we will be able to talk about that more but we want to talk about those on a success basis not on a.
Speaker Change: On a on a forward looking basis.
Speaker Change: So I think we will.
Speaker Change: The ability to scale up operationally in Houston really to infinite tests. So the number I mentioned before 5 million tests, we can do that in our Houston facility scale up is really a matter of.
Speaker Change: Extra extra head count and.
Speaker Change: Extra capital equipment.
Speaker Change: The the devices involved in the test we actually make in Houston, So we control our destiny. There. So I think a year from now will be the TCE test will.
Speaker Change: We'll be expanding throughout the U S we'll be adding.
Speaker Change: Insight to hybridization immuno cited chemistry, and Ngls, along with that there will be we'll be rolling out later in the year.
Speaker Change: And we'll be building out.
Speaker Change: Sales team that will be focus is as I addressed ed's question before.
Speaker Change: On those major cancer centers and those.
Speaker Change: Those those physicians that are key opinion, leading doctors.
Speaker Change: I failed to mentioned.
Speaker Change: <unk> Bradley Russ has been there done this multiple times throughout her 25 30 year career in diagnostics, including a long stint at Abbott knows knows how to scale diagnostics. It has key relationships in the market and can do this operationally commercially so really be.
Speaker Change: Integrating him more and more in that business over that same timeframe.
Speaker Change: Thank you for the additional detail is very helpful and thanks again for taking my questions.
Thanks, Sean.
Speaker Change: Thank you I'm showing no further questions in the queue. At this time I would now like to turn the call back over to Dr. Marc Hedrick for any closing remarks.
Speaker Change: Yeah.
Speaker Change: Thank you Sherry and thanks to everybody that joined us on the call.
Speaker Change: Listening on the call and a recorded version.
Speaker Change: Just like to say on behalf of the board.
Speaker Change: I would like to thank our employees our team members.
Speaker Change: The physicians that we work with the key opinion, leading doctors that are in this area that.
Speaker Change: A real.
Speaker Change: Which ate their input.
Speaker Change: And then most of all the patients that trust us a number of which I've talked to and interfaced with them as they have been involved in our trial. Thank you very much for your participation on the call and have a good evening goodbye.
Speaker Change: This concludes today's program. Thank you all for participating you may now disconnect.