Q3 2024 Plus Therapeutics Inc Earnings Call
Not that I care, but people might think I lost my license or something.
Speaker Change: Good afternoon, ladies and gentlemen, welcome to plus Therapeutics third quarter 2024 results conference call before we begin we want to advise you that over the course of the call including any question.
Speaker Change: And the answer session I'm sorry good.
Speaker Change: Good afternoon, ladies and gentlemen, welcome to the plus Therapeutics third quarter 2024 results conference call before we begin we want to advise you that over the course of the call, including any question and answer session forward looking statements will be made regarding events trends.
Speaker Change: Ms prospects and financial performance, which may affect plus therapeutics future operating results and financial position.
Speaker Change: 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-K, and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time plus.
Speaker Change: Plus therapeutics advises you to review these risk factors in considering such statements.
Therapeutics assumes no responsibility to update or revise any forward looking statements to reflect events trends or circumstances. After the date. They are made it is now my pleasure to turn the floor over to Dr. Marc Hedrick, plus therapeutics, President and Chief Executive Officer, Sir you may begin.
Speaker Change: Thank you Sri good afternoon, everybody and thank you once again for taking the time to join US today as we provide an overview of recent business highlights and discuss our third quarter 2024 financial results joining.
Speaker Change: Joining me for the call today is Mr. Andrew Sims, our Chief Financial Officer.
I'll begin the call by reviewing our recent clinical and corporate progress in the third quarter, and then turn the call over to Andrew for a review of our financials and then we'll come back for Q&A.
Speaker Change: Okay.
I'll begin this afternoon with an overview of our Leptomeningeal metastases program in which we are investigating our lead Radiotherapeutic radium 186, Obispo Meda and the respect L M trial.
Speaker Change: No going forward for this call I'll refer to really add 186 Obispo Meda is arnelle, which is its research name for the sake of brevity.
Speaker Change: Part one of our development program, our ongoing respect I'll, then phase one single administration dose escalation trial.
Speaker Change: It's perhaps closing in on a maximal color.
Five and which we administer a very substantial dose of arnelle approximately 66 militaries.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Data safety monitoring board the board.
Recommended proceeding to a modified lesser cohort six dose of 75 no curious.
Speaker Change: And the first patient has been treated.
Speaker Change: To date 21 of them.
Speaker Change: Including a subset of three patients who responded well to the initial dose and have received multiple doses under compassionate use.
Speaker Change: Part two of our integrated development plan is to expand the phase one respect L. M trial to a multiple dose administration trial.
Speaker Change: Radio Relatedly in Q3, we reached agreement with the FDA to proceed under a multiple dose escalation protocol and we are currently in site startup phase for that trial.
Speaker Change: I'll review that trial design more fully in a moment.
Speaker Change: In terms of clinical data from the respect of EM single Administration trial, we presented an interim update at the Snow ESCO conference in August through cohorts one through four.
Speaker Change: Here are the key highlights from that presentation.
Speaker Change: Doses of earn out up to 44 militaries were found to be safe and well tolerated with no dose limiting toxicities.
Speaker Change: Pharmacokinetic data demonstrated a very high therapeutic index, specifically about a 50 to 100 target the off target ratio.
Speaker Change: <unk> cohorts one through three means circulating tumor cells were reduced on average 53% at day 28 post treatment.
Speaker Change: And median overall survival for cohorts one to four was 12 months, which is quite favorable compared to historically reported consensus of approximately four months with treatment and breast and non small cell lung cancer.
Speaker Change: The full presentation from that meeting is available on our website.
Speaker Change: Later this month at the Snow Society for Neuro oncology annual meeting, which is going to be November 21 to the 24th in Houston we.
Speaker Change: We will provide a comprehensive update on the phase one single administration dose escalation trial through cohort five with important new data, including PK PD response and survival data.
Speaker Change: We will also host a luncheon symposium to discuss the data in greater detail with leading subject matter experts Dr. Priya can take car, Dr. Jonathan Yang and Dr. Andrew Brenner.
Speaker Change: Okay.
Speaker Change: As I've mentioned before we have reached agreement with the FDA to initiate enrollment in a phase one trial.
Speaker Change: At multiple dose administrations of arnelle for treating patients with Atlanta.
Speaker Change: Favorable outcomes observed in compassionate use patients receiving multiple doses of <unk> from a single administration dose escalation trial reinforce the safety and potential value of multiple dose administration regime to obtain long tail survival in patients with ALS.
Speaker Change: More specifically the phase one respect all the multiple dose administration trial is an open label two part study aimed at evaluating the safety dosing intervals and efficacy of administering multiple doses of <unk> to patients with <unk>.
Speaker Change: Primary objectives are to assess safety and tolerability and to identify both the maximum tolerated and the maximum feasible doses at various dosing intervals and frequencies.
Speaker Change: Secondary objectives include evaluating response and survival.
Speaker Change: The first part of this study will treat up to 24 patients administering at minimum three doses of <unk> at.
Speaker Change: At $13 two militaries at progressively shorter intervals, starting at 56 days and then every 28 days and finally every 14 days and then potentially up to six doses in a subsequent cohort.
Okay.
Speaker Change: The trial is expected to begin enrollment in Q1 2025 with the aim to utilize current seven active U S trial sites.
Being enrolling patients in our respect earlier in phase one single administration dose escalation trial.
Speaker Change: We plan to provide further details on the integrated development plan and path to approval for Leptomeningeal cancer at the 2020 for Snow annual conference in Houston.
Speaker Change: Sure.
Speaker Change: Yeah.
Speaker Change: Now for a discussion around our diagnostic.
Speaker Change: Increasingly we are recognizing the importance of our C inside cerebral spinal fluid assay platform in both the investigation of <unk> for <unk> and the assay has commercial value as a standalone diagnostic product in a broader group of patients at risk for L M or other CNS malignancies.
Speaker Change: The C inside cerebral spinal fluid.
Speaker Change: As a platform consists of four lab developed test or <unk>. It.
Speaker Change: It may be used by neuro oncologist, your immunologist medical oncologist or other practitioners for the diagnosis treatment selection and monitoring of patients with or at risk for <unk> as well as other CNS malignancies.
Speaker Change: In terms of market access activities related to the planned <unk> launch in January.
Speaker Change: As you May recall step one was tech transfer and initiating lab testing, which was completed earlier this year.
Speaker Change: Step two at our wholly owned sub based in Houston, Texas, We obtained the CLIA certificate of registration in Q3, and we intend to obtain a clear certified certificate of compliance in Q1 2025 following inspection by CMS.
This quarter, we will apply for expanded reimbursement with a Z code to the diagnostics exchange, which helps ensure that both healthcare providers and payers understand which test is pink.
Speaker Change: Thrilled.
Speaker Change: And it also allows payers to automate the preauthorization or adjudication of claims.
Speaker Change: Specifically, the Zeke the Z code as required by well known payers such as Medicare Unitedhealthcare Humana.
Speaker Change: Blue Cross Blue shield and so forth.
Next quarter following receipt of the CLIA certificate of compliance we intend to apply for a CPT proprietary laboratory analysis code or a PMA code with the American Medical Association.
Speaker Change: This code is required by Medicare and certifies labs for complex testing, ensuring that meet federal standards for quality accuracy and safety and the Pls code further specifically identifies the test.
Speaker Change: In parallel to these activities mentioned above we are negotiating with a number of commercial payers, which previously had agreements in place for the <unk> assay.
Speaker Change: Specifically, we are informing them that we acquired the assets of <unk> inside when the previous owner and plan to make the test platform commercially available again and new agreements will be put in place.
Speaker Change: So we are focused on payers that cover regions containing the highest number of <unk> patients.
Speaker Change: Currently the C inside tumor cells numeration LDP continues to be used in their respect <unk> clinical trial. We are on track to commercially reintroduced the test as part of a limited market release in the U S. In January of 2025.
Speaker Change: At the same time, we are expanding the <unk> test menu on a rolling basis to include specific cellular biomarker assays in molecular assays. It we'll talk more about that in 2025.
Speaker Change: Aggregate 2020 for investment in the tests will remain limited as test costs are offset in a meaningful way by our current secret grants and.
Speaker Change: In 2025 post expanded market access we will guide more specifically towards forecasted diagnostic diagnostic growth ramp and related economics.
Speaker Change: Now shifting gears to our respect GBM trial, which evaluates a single dose of <unk> in patients with recurrent glioblastoma.
Speaker Change: Enrollment in the phase one portion for patients with recurrent glioblastoma tumors greater than 20 MLS.
That's been completed and we will be evaluating that data into 2025 and completing the final phase one clinical study report.
Speaker Change: Enrollment continues for the respect GBM phase II trial limited to patients with tumors less than or equal to 20 MLS.
Speaker Change: The last respect GBM trial update what's at the Congress for neurological Surgeons annual meeting in October of this year.
Speaker Change: As a reminder, key highlights include a total of 42 patients had been enrolled across three sites at that time.
Speaker Change: In phase II, most adverse events were mild or moderate with over half deemed unrelated to the study drug.
Speaker Change: Only two of the nine severe adverse events were related to the study drug and systemic radiation exposure remains low.
Speaker Change: Moreover.
Speaker Change: The average absorb radiation dose the tumors in phase two was 300 gray.
Speaker Change: Well above the 100 great.
Speaker Change: Fair pre clinically and in phase one that is highly correlated with increased overall survival.
Speaker Change: Furthermore, approximately 90% of patients achieved critical drug delivery parameters also correlated with improved survival.
Speaker Change: Finally objective tumor response analysis using both cerebral blood volume.
And volumetric analysis analysis showed a statistically significant relationship between tumor control and absorbed dose specifically patients receiving doses above 100 gray showed effective tumor control within the treated areas.
They respect GBM trial continues to benefit from substantial NIH support and we are pleased to announce we have added two new large volume clinical trial sites to support phase III enrollment and.
And potentially a pivotal trial.
Speaker Change: We've added Ohio State University, which provides us coverage in the upper Midwest and North Shore Hospital part of the North well analytics cell network in the Greater New York Metropolitan area.
Speaker Change: With these two new additional sites activated in screening patients for enrollment we expect phase two completion with 34 total patients by mid year 2025, and a data readout in the second half of 2025.
Speaker Change: Additionally, we would like to announce that we recently entered into a research collaboration agreement with brain lab, a software driven medical technology company.
Speaker Change: To develop and implement optimize case planning software for convection enhanced delivery of R&R for brain cancers brain.
Speaker Change: <unk> software married to their C. C. D device ecosystem will enhance treatment planning procedure execution and more precise drug delivery for GBM patients anticipated to further improve patient outcomes.
Speaker Change: Yeah.
Speaker Change: Now just a bit about our pediatric brain cancer program.
Speaker Change: Recall, we previously announced that we have received a U S Department of Defense Award of a $3 million grant to substantially support a phase one trial for children with pediatric high grade Glioma independent moment.
Speaker Change: Approximately $900000 payment was received in September of 2024 as part of this award.
Speaker Change: We anticipate obtaining approval in the first half of 2025 at Lurie Children's Hospital in Chicago, serving as the initial clinical trial site.
Speaker Change: And moving onto drug production and manufacturing.
Speaker Change: Okay.
Speaker Change: We are expanding our GMP manufacturing capabilities and building redundancy in terms of materials and intermediates to support Registrational trials and future commercial demand projections.
Speaker Change: To ensure a reliable supply of Arnelle, we recently announced our second GMP manufacturing partnership this time with spectrum Rx.
Speaker Change: Through this partnership we have completed process qualification to trends transition from single dose single batch production to a pilot scale process capable of producing multiple doses per batch with a potential opportunity for scale up at capacity of approximately 15000 doses per year.
Speaker Change: Around the time of anticipated FDA approval.
Speaker Change: So Andrew can turn it over to you for a discussion about the financials 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 third quarter ended September 2024.
Andrew: The cash and investments balance was $4 8 million at September 24, compared to $8 6 million at December 23.
Andrew: In addition, we received our first advanced from the Doj Grant in October 24.
Andrew: Is there a <unk> 9 million and are on track to receive the next secret advance a $3 9 million within 90 days of today.
Andrew: The company recognized $4 4 million in grant revenue year to date 24, compared to $3 6 million in the same period of 'twenty three.
Andrew: This represents secret shares of the cost incurred to Arnelle development for the treatment of patients with <unk>.
Andrew: We expect 2024 grant revenue to be in the range of $6 million to $7 million.
Andrew: The total operating loss year to date 2024 was $10 8 million compared to $9 5 million in the same period of 2023.
Andrew: The increase is primarily due to increased spend related to the respected <unk> trial.
Andrew: Net loss year to date, 2024 was $9 1 million or $1 46 per share compared to a net loss of $9 5 million or $3 54 per share for the same period in the prior year.
Andrew: I would also like to provide an update on that runway and cash position based on the previously announced private placement and provide guidance on a grant funding for the remainder of 2024 and in 2025.
Andrew: There are three additional sources of cash plus has access to the on the balance disclosed in cash on hand liquid investments on our Q3 2024 balance sheet.
Andrew: First as a reminder.
We announced in May that we closed a private placement financing of up to $19 5 million from new healthcare focused institutional investors and company insiders.
A total of $705 million received at closing with up to $12 million remaining available under this financing.
Andrew: The second source of cash remains a continued funding through now three announced grants.
Andrew: Firstly, the separate grants to support the respected Allen trial.
Andrew: As reported we received $3 3 million from secret.
Andrew: In Q2 at this time of $7 8 million remains due on the grants and we remain on track to receive the next advanced some secret of $3 9 million within the next 90 days from today, an additional $3 9 million as expected from separate in Q3 2025.
Andrew: Secondly, as reported on April 22nd Pluses received an award recommendation from the United States Department of defense for $3 million to support the upcoming respect pediatric brain cancer trial. The first advances received in October, but just under $1 million.
Andrew: Plus also continues to benefit from the NIH grants to support the respect GBM phase one two trial.
Andrew: Although we expect it to be completes in the next six months. It currently covers approximately 90% of the overall trial costs.
Andrew: We also continued to source other non dilutive sources of capital with a target of applying for at least $10 million a year.
Andrew: We will continue to only report on individual grounds for narrow awarded.
Andrew: Taken in total this cash on hand financing warrants, if fully exercised and committed or contractual grant revenue is approximately $27 million.
Andrew: And now I'll turn it back to Marc Great. Thank you Andrew <unk>.
Appreciate it before we move on to Q&A I will take a moment to provide a specific summary of guidance for anticipated key events and milestones taking us through the remainder of 2024.
First in terms of conferences, we will have a substantial presence at the snow at the society for neuro oncology annual meeting.
Andrew: From November 21 to the 24th this year.
Andrew: There we will present three abstracts hosted an educational symposium on <unk> in GBM.
Andrew: Conduct our annual investigator meeting and showcase our key insights triple spinal fluid assay platform in our booth.
Andrew: As our as we will showcase our investigational drug <unk> for <unk> GPM in pediatric brain cancer more.
More specifically in terms of the three abstracts.
Andrew: As mentioned for <unk> therapeutic program, we will present data on the safety and feasibility of respect <unk> phase one single administration dose escalation trial through cohort five including important PK PD response and survival data will also provide an update on our integrated development plan for both single dose and multiple dose.
Andrew: <unk> programs and linking them to an FDA approval plan and timeline.
Andrew: For our <unk> side.
Andrew: As a platform we will present data on first the <unk> clinical trial data on CSF tumor cell detection, including its clinical utility and accurately diagnosing <unk> patients with high sensitivity and specificity compared to the gold standard cytology and also its clinical utility.
Enhancing clinical management of patients with.
Second we will show the results of a retrospective analysis of <unk> insights real world ability to detect a variety of gene mutations in CSF tumor cells offering insights into potential treatment strategies and also ways Alvin patients may benefit from complementary regional therapies, such as our enel and other treatments.
As mentioned the company will host an educational symposium featuring three subject matter experts Dr. <unk> can take car Yang and Brenner, who will provide updates on our <unk> and GBM programs and our <unk> insight platform.
Andrew: Lastly, we will showcase our investigational therapies as well as the <unk>.
Andrew: C&I side diagnostic at our booth.
Andrew: Later in the year.
Andrew: In December we will also attend the San Antonio breast cancer Symposium.
Andrew: San Antonio, Texas, where we will present.
Andrew: The data on the safety and feasibility of the respect our phase one single administration trial through cohort five with a focus on the breast cancer patients and related data that.
Andrew: Happens to be the primary cancer with the highest incidence of patients without lab.
Andrew: In addition to those upcoming events and conferences mentioned above the company also anticipates completing our respect Lam's single administration dose escalation trial by year end.
Andrew: Initiating enrollment in our respect and multiple administration dose trial in Q1 of 2025.
Andrew: Launching a limited commercial release of our CNS side platform as an LDC in early 2025.
Andrew: To pay completing enrollment and are expect to be in phase III trial by mid 2025 and for our pediatric brain cancer trial, obtaining IND acceptance initiating enrollment for our respect trial for pediatric opinion moment in high grade glioma and patients in 2025.
Andrew: So sherri with that I'll turn it back over to you for any questions.
Sherri: Thank you if you would like to ask a question. Please press star one 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: And our first question will come from the line of Justin Walsh with Jones trading your line is open.
Hi, Thanks for taking the question congrats on all the progress.
Speaker Change: Im wondering how you view the opportunities for cm side and are now in <unk> as a complementary products versus on their own.
Justin Walsh: Hi, Justin.
Justin Walsh: Great question.
Justin Walsh: What.
Justin Walsh: We continue to see more and more synergies you may recall when we first considered this acquisition.
Justin Walsh: It made sense solely on one factor and that is it could potentially increase the total addressable market for <unk> by two to four time, just by improving diagnostic sensitivity.
Justin Walsh: But since then.
As more and more data.
That shows that.
Justin Walsh: Using circulating tumor cells can be a proxy for survival and for disease monitoring and there as we see more and more papers coming out.
Justin Walsh: Related to that.
Justin Walsh: And then.
Justin Walsh: We are now increasingly relying on it as an exploratory endpoint in the phase one.
And we're going to be.
Justin Walsh: <unk> more insight into that data next week I think it's highly relevant supporting the other.
Justin Walsh: Sure.
Justin Walsh: Signals, we've seen in terms of response and efficacy.
Justin Walsh: I think there.
Justin Walsh: There's a recent publication by actually one of the.
Justin Walsh: Key opinion, leading doctors and our symposium Dr. Yang.
Who treated patients with targeted radiation and in that case from proton being creative spinal radiation, but showed in that trial targeted radiation therapy.
Justin Walsh: It correlated very highly to see inside assay actually RSA correlated very highly with survival and progression. So I think over time, we will see more and more reliance on that is it ready to be used as a primary endpoint in the pivotal trial I don't think so but I think as a secondary endpoint it provides substantial.
Justin Walsh: Collaborative data to other progression data and survival.
Speaker Change: Great. Thanks for taking the question looking forward to the presentation.
Justin Walsh: Thanks, Justin.
Speaker Change: Thank you one moment our next question.
Speaker Change: And that will come from the line of Edward Woo with <unk> capital. Your line is open.
Speaker Change: Yes, congratulations on the progress I was just wondering.
Speaker Change: What does the landscape look four grams has it changed in terms of the opportunities that are available and do you anticipate any change I guess with the change in the incoming government. Thank you.
Speaker Change: Hi, Ed.
Speaker Change: Yeah.
Speaker Change: To answer your latter question.
Speaker Change: I don't know.
It's hard to tell.
Speaker Change: I think.
Speaker Change: We're in a good pretty good spot through the next year as it relates to grants, we think they're being in Texas, Insulates us a bit from what's going on at the federal level, we have been.
Speaker Change: We've been very successful.
Aaron.
Speaker Change: It's separate.
I think we have almost 80 million active grants.
Speaker Change: From them in an aggregate $25 million total and active grants.
Speaker Change: What we're hearing no guarantees, but what we're hearing from separate is that there from time to time, there is additional capital that they can deploy.
Speaker Change: And there they tend to reach out to companies, who are executing and we are executing.
Speaker Change: Precisely to our our proposed and planned timeline. So we're kind of hoping there might be some opportunities there.
Speaker Change: But but also will continue as Andrew said that.
Speaker Change: <unk>.
Speaker Change: To talk about <unk>.
Speaker Change: Grants as they come in but we think there's continued opportunity in Texas, if things change at the federal level.
Speaker Change: Great well, thanks for answering my questions and I wish you guys. Good luck. Thank you.
Speaker Change: Thank you.
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.
Speaker Change: Hey, good afternoon, guys and thanks for taking my questions I just have two quick ones.
Speaker Change: One is first is on the.
Speaker Change: How on a multi dose study.
Speaker Change: How did you guys come out with 13 <unk> dose to be used in that study and how does that compare to what patients have received so far through the compassionate use program.
Speaker Change: Hey, Sean.
Thanks for the question, it's a good one so as we were.
Speaker Change: We are increasingly taking a bayesian approach to clinic.
Speaker Change: Clinical development, and we'll talk more about that in our integrated development plan.
Speaker Change: Both next week in an ongoing manner, but we found as we were getting into cohort four which is approximately 44 militaries that we were seeing excellent safety.
And.
Speaker Change: And also strong response.
Horton.
Speaker Change: And.
And so we as we began our negotiations with FDA.
Speaker Change: On the multiple dose approach.
Speaker Change: We felt like.
Speaker Change: We could we could support.
Speaker Change: Taking that cohort four dose.
Speaker Change: And then fractionated and that that follows approaches that FDA is very comfortable with so we are able to get them to go along with that.
Speaker Change: And so.
Speaker Change: Think that because of <unk>.
Speaker Change: So what we're seeing clinically.
Speaker Change: That that debt earlier compression of doses will be.
It will be very important.
Speaker Change: And getting that long tail survival.
Speaker Change: That.
Speaker Change: I'd mentioned.
Speaker Change: In terms of the compassionate use that we've had I think.
Two patients that have received three aggregate doses were actually.
Speaker Change: Giving them the.
Speaker Change: Whatever dose is.
Speaker Change: Whatever dose is currently enrolling.
Speaker Change: So theyre getting actually.
Speaker Change: In the neighborhood of 40 or more higher dose, but their dose frequency is much longer they are being treated.
Speaker Change: When they come back with symptoms in other words patients are responding to the initial dose and then there they are doing well for extended period of time, maybe up to a year. So they are coming back with symptoms or progression and asking to be retreated and so we treat them with that dose that's available so.
Speaker Change: Back to my original point.
Speaker Change: Think increasingly recognize the Bayesian design as appropriate we're modeling that right now that's integrated into the multiple dose trial and then as well as we'll talk about over time, how we how do we leverage that to get to approval.
Speaker Change: Great. Thanks, that's very helpful.
Speaker Change: My second question is on the fee.
Speaker Change: Side I'd say so in the prepared remarks, you mentioned that.
Speaker Change: He needed to get the.
Speaker Change: Unclear compliance followed by our CMO inspection as well as getting the Z code MPLA coats.
Speaker Change: Yes.
Speaker Change: Card loan for the approximate timeline for these two steps.
Im sorry, its John just to clarify the timeline for getting.
Speaker Change: Additional reimbursement.
Speaker Change: Yes, so getting the inspection done as well have been good.
Speaker Change: The reimbursements online so when can we expect in that side too.
Speaker Change: Selling commercially and marketing.
Speaker Change: Not getting reimbursed.
Speaker Change: Yes.
Speaker Change: So.
So I think we're on track to being able to.
Speaker Change: Two.
Speaker Change: Commercialize the test.
Speaker Change: Q4 of this year I think the issue is going to be.
Speaker Change: That we need to.
We're more likely to get reimbursed if we have a CN CN side clear compliance in that inspection is not.
Speaker Change: Not been scheduled but it is going to be Q1, and we are pushing to make that as early in Q1 as possible because we want to try to accelerate that timeline.
Speaker Change: And then and then number two I think some of these.
Speaker Change: Some of the laboratory services agreements, which were I think there are approximately $10 is that right Andrew 10 in place.
With with <unk>.
Speaker Change: We've hired a market access team that is actively negotiating with those 10 institutions on a on a.
Speaker Change: Regionally focused basis based on my comments, you know, where the patients and where the highest level of reimbursements.
Speaker Change: Prioritizing those areas.
Speaker Change: Being practical obviously.
Speaker Change: I think we're going to have some more.
Speaker Change: Things to talk about in Q1 as it relates to reimbursement and I think once those reimbursement.
Speaker Change: Dominoes fall.
Speaker Change: Then I think we'll feel more comfortable talking about pricing ramp.
Speaker Change: Margins and so forth.
Speaker Change: Right now, it's just a bit premature until we get those things in place we want to be really cautious in terms of guiding.
Speaker Change: In the early phases until we until we get comfortable that we can stand behind the guidance I can tell you that we're.
Speaker Change: At the time that biceps.
Speaker Change: Quit offering the test they had 200 unique customers they were growing at about a 30% per year CAGR.
Speaker Change: And that was with no data no NCC in guidelines.
Speaker Change: No specific reimbursement.
Note four C clinical trial data so we have all those elements.
Find us at this point today, and Thats only going to grow their only more papers coming out and so forth. So I think.
Speaker Change: The environment continues to look really positive for that as a standalone product.
Speaker Change: Got it. Thank you for that I think for a lot more clear that's all the questions on that.
Speaker Change: Thanks, a lot John I appreciate it.
Thank you I'm showing no further questions in the queue at this time I would now like to turn the call over to Mr. Andrew Sims.
Speaker Change: Thanks, Jerry we have two written questions. So the first is.
Speaker Change: Can you elaborate on the therapeutic ratio youre seeing in your trials and safety data profile.
Speaker Change: Yes, so thats a good question, we'll talk more in detail, we will talk more in detail about that.
Speaker Change: Our next week at snow, but I think so.
Speaker Change: A key point.
Speaker Change: And that the therapeutic ratio.
Speaker Change: We are seeing and going out to court for is very high in particular for <unk>, we're thinking about.
Speaker Change: Our ratio of about 50, plus in cohort four.
Bob.
Speaker Change: In terms of.
Speaker Change: Therapeutic target versus off target.
Speaker Change: I can give you a preview of cohort five I think we're seeing that it's greater than a 100 to one ratio. So we're continuing to see a linear.
The dose.
Speaker Change: <unk> as we dose escalate, a higher and higher absorbed dose.
Speaker Change: And the spinal subarachnoid space and really relatively flat.
Speaker Change: Absorption and in.
Speaker Change: And the key critical organs bone marrow, starting to tick up a bit in cohort five and we will talk about that and that was part of the rationale for the DSM be to cut back the cohort six dose and I think we are.
Speaker Change: Increasingly.
Speaker Change: Becoming more comfortable that the cohort four dose will be the recommended phase II dose and the maximum tolerated dose will be cohort five but the FDA has been very insistent about us continuing to dose escalate to failure, hence the cohort six dose in terms of GBM I think the therapeutic ratio is really hard to calculate because.
Speaker Change: Seeing essentially very minimal systemic absorption and very high.
Yes.
Speaker Change: Delivery of radiation to the region of interest the tumor and the infiltrated margin.
Speaker Change: So yes, I think we're seeing what we're seeing is very favorable much higher than other companies are reporting with their systemically delivered.
Speaker Change: Technology, So I think thats really really strong part of the technology.
Speaker Change: Okay and then.
Speaker Change: Second question is can you provide details on your integrated development plan for <unk>.
Speaker Change: Yes, I think.
Speaker Change: I've mentioned some of the details and I think we will present more at snow and roll that out over the first part of 2000 22025.
Speaker Change: I think.
Speaker Change: Right now I think there is based on the data we're seeing in single dose there is clearly.
Speaker Change: Activity.
Speaker Change: And there is strong potential for advancing the single dose and an expansion cohort.
Speaker Change: Specifically focused on breast and lung cancer non small cell lung cancer as that data continues to look strong.
Speaker Change: We can use that data to help de risk.
Speaker Change: Pivotal phase III trial thereafter.
Speaker Change: And I anticipate getting that into the clinic.
Speaker Change: Pretty soon next year, but we'll talk more about that in terms of multiple dose.
Speaker Change: I think we could follow a similar pattern, where we pick as we complete each cohort.
Speaker Change: Promising dose cohort expand it.
Speaker Change: Confirm that there is there is an efficacy signal there as well as safety signal and then move that forward and that could potentially see taking two different doses to market a high single dose and a lesser multiple dose regime.
Speaker Change: And then so more on that.
Speaker Change: Next week, and then first half of next year.
Speaker Change: Are there any other questions. Okay. Thank you Andrew.
Speaker Change: Well just to conclude thank you shari and thank you everyone I appreciate you.
Speaker Change: On the call.
On behalf of the board just like to thank our employees and team members and the physicians we work with.
Speaker Change: Very much. Thank you to the patients who continually trust us to enter into these trials. Thank you for your participation and have a good evening.
Speaker Change: This concludes today's program. Thank you all for participating you may now disconnect.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: [music].