Full Year 2024 Moleculin Biotech Inc Earnings Call
Hello, and welcome to the molecular and biotech fourth quarter and full year 2024 update conference call and webcast.
Unknown Executive: A question and answer session will follow the formal presentation.
A question and answer session will follow the formal presentation.
Unknown Executive: As a reminder, this conference is being recorded.
As a reminder, this conference is being recorded.
Unknown Executive: At this time, I'd like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations, or future projections. These are forward-looking statements and involve risks and uncertainties. Forward looking statements on this call are made pursuant to the safe harbor provisions of the federal securities laws and are based on Moleculin's current expectations and actual results could differ materially. As a result, you should not place undue reliance on any forward looking statement. Some of the factors that could cause actual results differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports, moleculin files with the Securities and Exchange Commission.
At this time I'd like to remind our listeners that remarks made during this webcast may state managements intentions beliefs expectations or future projections.
These are forward looking statements involve risks and uncertainties.
Looking statements on this call are made pursuant to the safe Harbor provisions of the federal Securities laws and are based on molecular and its current expectations and actual results could differ materially.
As a result, you should not place undue reliance on any forward looking statements.
Some of the factors that could cause actual results to differ materially from these contemplated by such forward looking statements are discussed in the periodic reports, but let give them files with the securities and Exchange Commission.
Unknown Executive: These documents are available in the investor section of the company's website and on the Securities and Exchange Commission's website.
These documents are available on the investors section of the company's website and on the Securities and exchange Commission's website.
Unknown Executive: We encourage you to review these documents carefully.
We encourage you to review these documents carefully.
Unknown Executive: Additionally, certain information contained in this webcast relates to or is based on studies, publications, surveys, and other data obtained from third-party sources in the company's own estimates and research. While the company believes these third-party sources to be reliable as of the date of this presentation, it does not independently verify and makes no representation as to the adequacy, fairness, accuracy, or completeness. or that any independent source have verified any information obtained from third-party source.
Additionally, certain information contained in this webcast, where they used to or is based on studies publications surveys and other data obtained from third party sources and the company's own estimates from research.
While the company believes he started parties sources to be reliable as of the date of this presentation. It does not independently verify it makes no representation as to the adequacy of fairness accuracy or completeness of.
Or that any independent source of verified any information obtained from third party source and.
Unknown Executive: Any data discussed regarding clinical trials and progress are considered preliminary and subject to change.
Anytime to discuss regarding clinical trials in progress are considered preliminary and subject to change.
Unknown Executive: Joining us on today's call from Moleculin's leadership team are Walter Klemp, Chairman and Chief Executive Officer, Dr. John Paul Waymack, Senior Chief Medical Officer, and Jonathan Foster, Executive Vice President and Chief Financial Officer.
Walter Clements: Joining us on today's call from electrodes leadership team or Walter Clements, Chairman and Chief Executive Officer, Dr. John Paul Layne.
Speaker Change: Chief Medical Officer, and Jonathan Foster Executive Vice President and Chief Financial Officer, I'd now like to turn the call over to Walter Clements Chairman and CEO Walt <unk>. Please proceed.
Walter Klemp: Now let's turn the call over to Walter Klemp, Chairman and CEO. Wally, please proceed. Thank you, operator. Good morning, everyone. And thanks for joining us today.
Walter Clements: Thank you operator, good morning, everyone and thanks for joining us today.
Walter Klemp: I'd like to kick things off with a brief overview of where we are. The entire Moleculin team has been laser focused on the launch of the Miracle Phase 3 Pivotal Trial for Anamycin. Now, this is a study designed to win approval for anamycin in combination with cytarabine for the second-line treatment of relapsed and refractory AML patients. This is a global study with sites planned for the U.S., Europe, and the Middle East. Twenty-five sites have been selected to date, and we've already announced regulatory and ethics approval in our first European country, and we expect several more in second quarter.
Walter Clements: I'd like to kick things off with a brief overview of where we are.
Walter Clements: The entire molecular team has been laser focused on the launch of the Miracle phase III pivotal trial randomized them. Yeah. This is a study designed to win approval for random Istent in combination with cytarabine for the second line treatment of relapsed and refractory AML.
Walter Clements: Patient.
Walter Clements: This is a global study with sites planned for the U S Europe and the Middle East twenty-five sites had been a selected to date and we've already announced regulatory and ethics approval and our first European country and.
Walter Clements: And we expect several more in second quarter.
Walter Klemp: Patient screening has already begun, and we still expect our first patient to be treated yet this quarter. Now in terms of managing expectations, I should point out that the U.S. will likely be one of the last countries to begin enrolling in this trial. Now that's not unique to our trial, but rather it's a function of the fact that the approval process between institutional review boards, ethics committees, and hospital contract negotiations just takes longer than in most other countries. We do already have our first IRB approval in the U.S., but in terms of overall timelines, you should expect the non-EU and Middle Eastern countries like Ukraine, Egypt, and Georgia to start first, followed by the more traditional EU member states, and then finally the U.S.
Walter Clements: Patient screening has already begun and we still expect our first patient to be treated yet this quarter.
Walter Clements: Now in terms of managing expectations.
Walter Clements: I should point out that the U S will likely be one of the last countries to begin enrolling in this trial now that's not unique to our trial, but rather it's a function of the fact that the approval process between institutional review boards ethics committees and hospital contract negotiations just takes longer than.
Walter Clements: And in most other countries, we do already have our first IRB approval in the U S. But in terms of overall timelines.
Walter Clements: I would expect the non EU and middle Eastern countries like Ukraine, Egypt in Georgia to start first.
Walter Clements: Followed by the more traditional EU member States and then finally the U S.
Walter Klemp: One of the most important and exciting aspects of the MIRACLE trial is the amount and timing of visibility that Moleculin stakeholders will have. Unlike most pivotal phase three trials, we will have multiple unblindings of data so that there is line of sight to exactly how we're tracking. The first of these will be when we reach 45 subjects, and we expect to achieve that before the end of this year. Then there will be a second unblinding at the end of Part A of the trial at between 75 and 90 subjects. That should be in the first half of 2026.
Walter Clements: One of the most important and exciting aspects of the Miracle trial is the amount and timing of visibility that molecular and stake holders will have.
Walter Clements: Unlike most pivotal phase III trials, we will have multiple unblinded of data. So that there is line of sight to exactly how we're tracking.
Walter Clements: The first of these will be when we reached 45 subjects and we expect to achieve that before the end of this year.
Walter Clements: And then there will be a second on blinding at the end of part a of the trial at between 75 and 90 subjects that should be in the first half of 2026.
Walter Klemp: Part of the reason we expect this to happen so quickly is that the primary endpoint is complete remission after just one cycle, which is approximately one month. So roughly 30 days after the 45th subject is treated, we will be able to see how the drug is performing.
Walter Clements: But part of the reason we expect this to happen. So quickly is that the primary endpoint is complete remission. After just one cycle, which is approximately one month. So roughly 30 days after the 45th subject is treated we.
Walter Clements: It will be able to see how the drug is performing.
Walter Klemp: The other really exciting part of this is how much we already know about anamycin in second-line AML patients. As Paul will discuss in his segment, our phase two data just keep getting better. Overall, survival keeps climbing at 11 months and durability has reached nine months and is still climbing. As a reminder, the performance of Anamycin in our latest Phase 2 trial was better than any drug ever approved for second-line AML patients. Also, as we discussed, as disclosed recently, our latest analysis shows that anamycin overcomes resistance to venetoclax in AML and is delivering durable, complete remission in patients where venetoclax has failed.
Walter Clements: The other really exciting part of this is how much we already know about atomizer in second line AML patients.
Walter Clements: As Paul will discuss in his segment our phase two data just keep getting better.
Walter Clements: Overall survival keeps climbing at 11 months and durability has reached nine months and is still climbing.
Speaker Change: As a reminder, the performance of animal I sit in our latest phase two trial was better than any drug.
Speaker Change: <unk> approved for second line AML patients.
Speaker Change: Also as we discuss as disclosed recently, our latest analysis shows that animas and overcome resistance to the need of clocks in AML and is delivering durable complete remission in patients where the <unk> has failed and.
Walter Klemp: And through all of this, we continue to see a complete absence of drug related cardiotoxicity. As I mentioned at a recent conference. The latest Anamycin results were frankly, so good that a lot of industry players simply didn't believe. But I can say with confidence that that is beginning to change. A number of key opinion leaders in the U.S. and Europe have now reviewed the data in detail and have even discussed the results with the investigators in the trial, who, by the way, span seven sites in two different countries. These experts are now recognizing the significance of the data and the potential importance of antamycin for AML patients.
Speaker Change: Through all of this we continue to see a complete absence of drug related cardio toxicity.
Speaker Change: As I mentioned at a recent conference.
Speaker Change: The latest analyzing results were frankly, so good that a lot of industry players simply didn't believe them.
Speaker Change: But I can say with confidence that that is beginning to change.
Speaker Change: Number of key opinion leaders in the U S and Europe have now reviewed the data in detail and have even discuss the results with the investigators in the trial, who by the way spans seven sites in two different countries.
Speaker Change: These experts are now recognizing the significance of the data and the potential importance of animation for AML patients and they're now speaking out about the game changing implications of what if approved will be the first ever non cardio toxic anthracycline.
Walter Klemp: And they are now speaking out about the game changing implications of what, if approved, will be the first ever non-cardiotoxic anthracite.
Paul Waymack: Let me now hand the call over to our Senior Chief Medical Officer, Dr. Paul Waymack, to discuss our clinical activity in more detail. Paul. Thank you. Thank you, Wally.
Speaker Change: Let me now hand, the call over to our senior Chief Medical Officer, Dr. Paul way Mac to discuss our clinical activity in more detail Paul.
Speaker Change: Thank you Wally.
Paul Waymack: Well, as we have noted during prior updates, there is an incredible unmet need in AML. And especially for those patients who either don't respond to initial therapy, that is, they are refractory to current therapy. or quickly relapsed after first line induction therapy. And you can see from our phase two data obtained in our MV106 clinical trial, this is where anamycin excels. As we have previously reported, we achieved a 50% complete remission rate in these second-line patients. We treated with anamycin plus high-dose cytarabine, which is more than double the performance you would expect from existing therapy.
Speaker Change: Well as we have noted during prior updates there is an incredible unmet need in AML.
Speaker Change: And especially for those patients who either don't respond to initial therapy.
Speaker Change: That is their refractory to current therapies.
Speaker Change: We're quickly relapse after first line induction therapy.
Speaker Change: And you can see from our phase II data obtained in RMB 106 clinical trial.
Speaker Change: This is where Anna milestone itself.
Speaker Change: We have previously reported we achieved a 50% complete remission rate in these second line patients.
Speaker Change: Treated with antibodies, some plus either cytarabine, which is more than double the performance you would expect from existing therapies.
Paul Waymack: And the durability of our responses continues to improve. As Wally mentioned, our median progression-free survival has now increased to nine months. with their overall survival amongst second-line therapy patients at 11 months. And as we previously reported, 78% of them were recorded as negative in terms of measurable residual disease.
Speaker Change: And the durability of our responses continues to improve.
Speaker Change: As Wally mentioned, our median progression free survival has now increased nine months.
Speaker Change: With their overall survival amongst second line therapy patients at 11 months and.
Speaker Change: As we previously reported 78% of them were recorded as negative.
Speaker Change: In terms of measurable residual disease.
Paul Waymack: So for second line therapy patients, we believe that our durability is shaping up as truly a game changer. This 50% CR rate in second-line therapy with anamycin plus high-dose cytarabine compares very favorably to a 17 to 18% CR rate reported in two large recent clinical studies in patients with refractory and relapsed AML. And I should note that in both of these studies, The control arm used hydrocytarabine. the exact same control arm we intend to use in our phase three study.
Speaker Change: No.
Speaker Change: Second line therapy patients, we believe that our durability is shaping up is truly a game changer.
Speaker Change: This 50% CR rate in second line therapy, with animals, and plus high dose cytarabine compares very favorably to a 17% to 18% CR rate.
Speaker Change: Reported in two large recent clinical studies in patients with refractory in relapsed AML.
Speaker Change: And I should note that in both of these studies.
Speaker Change: Control arm used high dose cytarabine.
Speaker Change: The exact same control arm, we intend to use and Eric Phase III study.
Paul Waymack: Moving on to our new Phase 3 study, the MIRACLE trial. It was designed after an end of Phase 1-2 meeting with FDA. It is to be a randomized study comparing the dosing regimen with which we had great success in our NB106 study, that is anamycin plus high-dose cytarabine, with the control arm of placebo plus high-dose cytarabine. We chose this design because FDA encouraged it and because Two recent large randomized clinical trials in refractory and relapsed AML patients. that is the MIROS and CLASSIC-1 clinical trials. which are the ones we mentioned in the prior trial. used it, and both achieved approximately a 17.5% CR rate among patients randomized to receive high-dose cytarabine plus placebo.
Speaker Change: Moving on to our new Phase III study the Miracle trial.
Speaker Change: It was designed after an end of phase one two meeting with FDA.
Speaker Change: It has to be a randomized study comparing the dosing regimen with which we had great success in our N B one of those six study.
Speaker Change: That is <unk> plus high dose cytarabine.
Speaker Change: With the control arm of placebo plus high dose cytarabine.
Speaker Change: We chose this design because FDA encouraged and because.
Speaker Change: Two recent large randomized clinical trials in refractory relapsed AML patients.
Speaker Change: That is the mirrors and classic one clinical trials.
Speaker Change: Which are the ones we mentioned in the prior trial.
Speaker Change: We used it and both achieved approximately a 17.5% CR rate among patients randomized to receive high dose cytarabine plus placebo.
Paul Waymack: To that end, we can expect we will need for our anamycin plus high-dose cytarabine treatment arm to beat a 17.5% CR rate to a statistically significant degree for our drug to be approved by FDA for marketing. And again, in our MB 106 study. This combination of high-dose citarabine plus anamycin achieved a 50% CR rate. For our phase 3 study, as I noted, we will be comparing anamycin plus high-dose cytarabine against placebo plus high-dose cytarabine. During Part A of the study, we will have two different anamycin treatment arms, a 190 milligram per meter square treatment arm and a 230 milligram per meter square treatment arm.
Speaker Change: To that end, we can expect we will need for animation plus high dose cytarabine treatment arm.
Speaker Change: To beat a 17, 5% CR rate to waste the stickley significant degree where our drug to be approved by FDA for marketing.
Speaker Change: And again in our M. B 106 study.
Speaker Change: This combination of high dose cytarabine, plus Santa mice and achieved a 50% CR rate.
Speaker Change: For our phase III study as I noted, we will be comparing antibodies, some plus high dose cytarabine against placebo plus high dose cytarabine.
Speaker Change: During part a of the study we will have two different analyses and treatment arms, a 190 milligram per meter square treatment arm in a 230 milligram per meter square of treatment arm.
Paul Waymack: There will be unblinding of the data in Part A after the first 45 patients that completed their efficacy analyses. And the second unblinding after between 75 and 90% of patients have completed their efficacy analysis. These interim looks at the data are in part. to determine which of the two anamide-inducing regimens will be taken to completion of the study. And the primary efficacy endpoint is the rate of complete remission of leukemia at approximately day 35. All patients will be eligible for standard treatments after completion of their experimental therapy. We have already had one site that has been activated and believe that we may begin treating our first patient before this quarter is over.
Speaker Change: There will be unblinded of the data in part a.
Speaker Change: After the first 45 patients have completed their efficacy analyses.
Speaker Change: And the second on blinding after between 75 and 90% of patients have completed their efficacy analyses.
Speaker Change: These interim looks at the data.
Speaker Change: In part.
Speaker Change: Determine which of the two analyzed and dosing regimens will be taken to completion of the study.
Speaker Change: And the primary efficacy endpoint is the rate of complete remission of leukemia and approximately <unk> 35.
Speaker Change: All patients will be eligible for standard treatments after completion of their experimental therapy.
Speaker Change: Yeah.
Speaker Change: We have already had one site that has been activated and believe that we may begin treating our first patient before this quarter.
Speaker Change: Over.
Paul Waymack: As I previously noted, Part A of the study will determine which of the two anamizing dosing regimens to take all the way through to completion of Part B. Part D will randomize 222 patients to receive placebo plus high-dose citerabine. or anamycin plus hydrocytarabine using whichever anamycin dosing regimen RDA found to be superior.
Speaker Change: As I previously noted part a of the study will determine which of the two antibodies being dosing regimens.
Speaker Change: All the way through to completion of part B.
Speaker Change: Part B will randomized 222 patients who received placebo plus high dose cytarabine.
Speaker Change: Or and a Madison plus high dose cytarabine, using whichever randomized dosing regimen or they found to be superior.
Paul Waymack: The next slide documents our timeline. I should note, as shown on this slide, that there is a small possibility that the results from our analyses at the end of Part A could be so definitive so as to confirm the efficacy of anamycin plus high-dose citarabase. If this were to happen, then we might be able, for ethical reasons, to complete Part B as a single-arm study.
The next slide documents our timelines.
Speaker Change: I should note as shown on this slide that there is a small possibility that the results from our analysis at the end of the par a day could be so definitive so as to confirm the efficacy of minimizing plus side those cytarabine.
Speaker Change: If this were to happen.
Speaker Change: Then we might be able for ethical reasons to complete part D is a single arm study.
Paul Waymack: Finally, Let me note that although we have had no major clinical updates since our MV106 study completed enrollment last year, We have been quite busy. Clinically designing our Phase 3 study, obtaining regulatory approval for conducting the study on multiple continents, and signing up various hospitals and investigators to participate. As of today, we have approximately 25 sites selected to participate in the study. and another approximately 45 who are in the process of completing the selection process. And we still believe that we can begin treating the initial patient in our MB-108 study in this order.
Speaker Change: Finally.
Speaker Change: Let me note that although we have had no major clinical updates since RMB one of those six study completed enrollment last year.
Speaker Change: We have been quite busy.
Speaker Change: Politically designing our phase III study.
Speaker Change: Pending regulatory approval for conducting the study on multiple continents.
Speaker Change: And finding up various hospitals and investigators to participate.
Speaker Change: As of today, we have approximately 25 sites selected to participate in the study.
Speaker Change: And another approximately 45, who are in the process of completing the selection process.
Speaker Change: And we still believe that we can begin treating the initial patient in our <unk>.
Speaker Change: M B 108 study.
Speaker Change: In this quarter.
Jonathan Foster: John, let me pass the baton off to you now. Thanks, Paul. Well, as we've moved forward with the miracle trial, as Paul just made. So have we with our market cap and our capital. With our cash on hand at the end of the year, plus the roughly $9 million that we raised in February of this year, 2025, that combined cash balance for approximately $13 million takes us into the third quarter of 2025.
John: John Let me pass the Baton off to you now.
John: Thanks, Paul.
John: As we move forward with the Miracle trial as Paul just mentioned, so happy with our market cap and our capital raises.
John: With our cash on hand at the end of the year plus the roughly $9 million that we raised in February.
John: This year 2025.
John: That combined cash balance of approximately $13 million takes us into the third quarter of 2025.
Jonathan Foster: Our focus in 2024 and into 2025 was and remains on the development of animizing. while relying on externally funded programs on WP-1066 and WP-1100.
John: Our focus in 2024 and into 2025 was and remains on the development of animation.
John: While relying on externally funded programs on W. P 66, and WP 11 22.
Jonathan Foster: Overall, we reduced our operating expenses in 2024 over 2023 by about $3 million. Our current market cap is $16.2 million with 14 million shares outstanding. This is up from year-end due to the issuance of equity in February of 2025. And our trailing one-year trading volume is 1.4 million shares per day. We remain focused on operational execution and meeting our milestones. It's been very important. We've delivered on successfully contracting CROs and CITES and early country approvals as we had planned for the MIRACLE trial. and we're looking forward to the next upcoming milestone. And first quarter through the third quarter of this year, we'll be updating you on Miracle Trial Site selection and approvals by country.
John: Overall, we reduced our operating expenses in 2024 over over 2023 by about $3 million.
John: Our current market cap is $16 $2 million with 14 million shares outstanding.
John: This is up from year end due to the issuance of equity in 2020 in February of 2025, and our trailing one year trading volume is one 4 million shares per day.
John: We remain focused on operational execution and meeting our milestones it's been very important to us.
John: We've delivered on successfully contracting ciros insights and early country approvals as we had planned for the Miracle trial.
John: And we're looking forward to the next upcoming milestones.
John: The first quarter through the third quarter of this year, we'll be updating you on miracle trial site selection and approvals by countries.
Jonathan Foster: The first quarter of this year, as Wally and Paul have discussed, the first subject enrolled and treated in our miracle trial. We'll also be doing the data readout. and Unblinding of Efficacy and Safety Data. by the end of this year. And then in the first half of 2026, we'll have The remaining patients, given us a total, as Paul mentioned, between 75 and 90 subjects' data, we'll unblind that, we'll share that safety and efficacy data with you, and we'll also set the optimum dose for Part B of the MIRACLE trial. And then the milestones that follow these readouts, and almost just within a year from today, this speed of milestones, we believe, is exceptional for Phase III trials.
Speaker Change: In the first quarter of this year as Huawei and Paul discussed first subjects enrolled and treated in a miracle trial.
John: We'll also be doing the data readout.
John: And then blinding of efficacy and safety data.
John: By the end of this year.
John: And then.
John: In the first half of 2026, we'll have the.
Paul: The remaining patients, giving us a total as Paul mentioned between 75 and 90.
Paul: Subjects data will unblock that we'll share that safety and efficacy data with you and we will also set the optimal dose for part B of the Miracle trial.
Paul: And then the milestones that follow these readouts and almost just within a year from today.
Paul: The speed of the milestones we believe is exceptional for phase III trial.
Jonathan Foster: Additionally, we expect to publicly release the data readout from MB-107, which is our clinical trial of anamycin and monotherapy treating advanced soft tissue sarcoma metathesis to the lungs in April. And we hope to use that data to develop a pivotal investigator-initiated trial in Europe later in 2020.
Paul: Additionally, we expect to publicly release the data.
Paul: Readout from M. B 107, which is our clinical trial with <unk> monotherapy treating advanced soft tissue sarcoma metastasize to the bonds in April.
Paul: And we hope to use that data to develop a pivotal investigator initiated trial in Europe later in 2025.
Unknown Executive: So as one can see, we expect to be extremely busy in 2025. Thanks, John.
Paul: So as one can see we expect to be extremely busy in.
Paul: In 2025.
Paul: Wally.
Paul: Thanks, John.
Walter Klemp: Again, we want to thank everyone for your support throughout 2024. But now it all comes down to this truly pivotal year in 2025. Look, anamycin isn't just disruptive. It has the opportunity to change history. becoming the first ever non-cardiotoxic anthracycline. and its unique patented structure is designed to be not just safer and more tolerable, but its lack of cross resistance with traditional cancer therapies means it truly has the opportunity to fill a huge unmet need, not only in AML, but in a wide range of cancer. The clinical advancement of anamycin is now in extremely rare territory.
Paul: Again, we want to thank everyone for your support throughout 2024.
Now it all comes down to this truly pivotal year in 2025.
Speaker Change: Look animation isn't just disruptive.
Paul: It has the opportunity to change history.
Paul: Coming the first ever non cardio toxic anthracycline.
Paul: And its unique patented structure is designed.
Paul: To be not just safer and more tolerable, but its lack of cross resistance with traditional cancer therapies means it truly has the opportunity to fill a huge unmet need not only in AML.
Paul: But in a wide range of cancers.
Paul: The clinical advancement of anti <unk> is now in extremely rare territory.
Walter Klemp: you just don't find small biotechs that go into a pivotal phase three trial with data better than any drug ever approved in the space, and then have the opportunity for an early look at approval data. And in our case, the approval bar is extremely low. And we expect everyone will have a chance to confirm that before this year is out.
Paul: You just don't find small biotechs that go into a pivotal phase III trial with data better than any drug ever approved in the space and then have the opportunity for an early look at approval data and in our case. The approval bar is extremely low and we expect to everyone will have a chance to.
Paul: Confirm that before this year is out.
Walter Klemp: Moleculin has a diverse, exciting pipeline and is guided by one of the most experienced development teams in biotech. 2025 is our year to bring this all together. You won't wanna miss what's about to unfold.
Paul: Molecular has.
Paul: Diverse exciting pipeline and as guided by one of the most experienced development teams in biotech.
Paul: 2025 is our year to bring this all together you won't want to Miss what's about to unfold. So thanks again, everyone and have a great day.
Unknown Executive: So thanks again, everyone, and have a great day.
Unknown Executive: Now open for questions.
Paul: Now open for questions.
Unknown Executive: Thank you and I'll be conducting a question and answer session. If you'd like to be placed in the question queue, please press star one on your telephone keypad. Once again, that's star one to be placed in the question queue and star two if you'd like to remove yourself from the One moment, please while we poll for questions.
Speaker Change: Thank you, we'll now be conducting a question and answer session if you'd like to be placed in the question queue. Please press star one on your telephone keypad. Once again Thats star one to be placed in the question queue and start to if you'd like to remove yourself from the Q1 moment. Please hold your poll for questions. Our first question today is coming.
Jonathan Aschoff: Our first question today is coming from Jonathan Aschoff from Roth Capital Partners. Your line is now live. Thank you. Good morning, guys.
Speaker Change: From Jonathan Aschoff from Roth Capital Partners. Your line is now live.
Jonathan Aschoff: Thank you. Good morning, guys. So I was curious what efficacy is required to pick one animation dose at 45 patients rather than waiting till 90, if it doesn't happen at 45.
Walter Klemp: I was curious, what efficacy is required to pick one anamycin dose at 45 patients rather than waiting until 90 if it doesn't happen at 45? Well, it's That's a multivariable equation that we would be ill advised to speculate too in too much detail. But generally speaking, Let me let me start by saying this and I'm going to invite Paul to maybe give some additional thoughts. If we do as well in the, in part A. If anamycin does as well as it did in the phase two, you know, clinical trial, and HIDAC simply performs as prior clinical trials have indicated, then we probably hit that that number that statistical significance that's required to, to frankly, shorten the trial and accelerate approval, approval even faster.
Speaker Change: Yeah.
Speaker Change: Well it's.
Speaker Change: That's a multi variable equation that.
Speaker Change: We would be ill advised to speculate too in too much detail, but.
Speaker Change: Generally speaking.
Speaker Change: Let me, let me start by saying this and I'm going to invite Paul to maybe give some additional thoughts.
Speaker Change: If we do as well in the <unk>.
Speaker Change: And in part a.
Speaker Change: If <unk> does as well as it did in the phase two.
Speaker Change: Ah clinical trial and.
Speaker Change: <unk>.
Speaker Change: Hi deck simply performs as.
Speaker Change: Prior clinical trials have indicated than we probably hit that that number that statistical significance that's required to.
Speaker Change: Two two frankly shorten the trial and accelerate approval approval even faster.
Walter Klemp: That said, I mean, one, we don't have to be that good to win approval. But I know you're asking what would it take to accelerate? But there's another possibility here. And we would argue a probability. And that is that the HIDAC numbers are likely not to be as good as the historical numbers. And the reason is because those historical numbers were allowed multiple cycles of the drug to get their 17 to 18% CR rate. whereas our CR rate of 50% came with just one cycle. And that's all that HIDAC is allowed in this trial as well.
That said I mean, one we don't have to be that good to win approval, but I know you're asking what could excel at what would it take to accelerate and and but.
Speaker Change: Theres another possibility here and we would argue a probability and that is that the high deck numbers are not are likely not to be as good as the historical numbers and the reason is because those historical numbers were allowed multiple cycles of the drug.
Speaker Change: To take to get there, 17%, 18% CR rate.
Speaker Change: Whereas our CR rate of 50% came with just one cycle and that's all that high DAC is allowed in this trial as well. So we expect high Dax will probably underperform.
Paul Waymack: So we expect HIDAC will probably underperform published statistics because they're going to be limited. It's going to be limited to one cycle. So there are multiple ways to get to the point you're looking for, Jonathan. And, you know, obviously we can't speculate too much about, you know, which of those outcomes. That's why we got to run the trial.
Speaker Change: Statistics, because they're they're gonna be limited, it's going to be limited to one cycle. So there are multiple ways to get to the point you're looking for Jonathan.
Speaker Change: And obviously, we can't speculate too much about.
Speaker Change: Which of those outcomes.
Speaker Change: We got to run the trial, but Paul do you have additional thoughts there.
Paul Waymack: But Paul, do you have additional thoughts there? Uh, yeah. As Wally said, this is a multivariable equation with not only what is the efficacy, what is the safety, what is the pharmacokinetic data. There will be also the secondary endpoint. It is very difficult to predict. As I said, I think the odds are against us ending early, but it is it is a possibility. It is a definite possibility. Alright, thanks for that.
Speaker Change: Yes.
Paul: As Wally said this is a multi variable equation with not only what does the efficacy what is the safety what does the pharmacokinetic data.
Speaker Change:
Speaker Change: There will be also the secondary endpoints. It is very difficult to predict as I said I think the odds are against us ending early but it is part of it is a possibility it is a definite possibility.
Speaker Change: Alright. Thanks.
Unknown Executive: Towards the end of the trial, you know, what was the thinking that went into cutting off about 10% of patients from Part D? Was there much thinking behind that or not really? Well, that really came as a result of FDA, when they review protocols, will often comment and make suggestions.
Speaker Change: Towards the end of the trial you know what was the thinking that went into cutting off about 10% of patients from part D was there much thinking beyond that or not really that much.
Speaker Change: Well that that really came as a result of.
Speaker Change: F D a win when they review protocols.
Speaker Change: We'll often comment and.
Speaker Change: And make suggestions in this particular case.
Walter Klemp: In this particular case, they specifically requested or suggested that we follow a slightly different biostatistical scheme than originally planned. And that recommendation essentially allowed us to reduce the number of patients. Okay, that's straightforward enough.
Speaker Change: They specifically requested or suggested that we follow a slightly different bio statistical scheme than originally planned.
Speaker Change: <unk>.
Speaker Change: That recommendation essentially allowed us to reduce the number of patients.
Speaker Change: Okay straightforward enough on the other program what is the STS lung that efficacy bogey you need to hit to proceed to you know even if it's just a investigator sponsored pivotal trial.
Walter Klemp: On the other program, what is the STS long net efficacy bogey you need to hit to proceed to, you know, even if it's just a investigator sponsored pivotal trial? Well, I mean, we've, we've, we've frankly already hit that in, in, in, in really broad strokes. The STS patients we've treated turned out to be of much more, if you will, challenged than we originally expected, you know, with the the early part of the trial was focused on third and fourth line patients. But as the trial progressed, and we, and we got through the phase two part of the trial, that got even worse.
Speaker Change: Well I mean, we've.
Speaker Change: We've frankly already hit that.
Speaker Change: In.
Speaker Change: In really broad strokes.
Speaker Change: The the STS patients we've treated.
Speaker Change: Turned out to be a.
Speaker Change: Much more if you will.
Speaker Change: <unk> then.
Speaker Change: Originally expected.
Speaker Change: With the the the early part of the trial was focused on third and fourth line patients, but as the trial progressed and we and we got through the phase two part of the trial that got even worse. So we know we haven't published the officially published the results yet, but we're about to.
Walter Klemp: So, we now we haven't published the officially published the results yet, but we're about to, but what you'll see is we were really treating the bottom of the barrel and we were getting, we're seeing OS numbers that are what you would normally expect in first line patients who were treated with docs, for example, well, to get that kind of performance in third, fourth and beyond line.
Speaker Change: But what Youll see is we were really treating the bottom of the barrel and.
Speaker Change: We were getting were seeing OS numbers that are what you would normally expect in first line patients who were treated with docs for example.
Speaker Change: Well to get that kind of performance in third fourth and beyond line.
Walter Klemp: It has already gotten the attention of sarcoma experts, one of the most prestigious sarcoma institutes in Europe has looked at the data, they've looked at the data and said, we'd really like to, we think this thing is ready for a pivotal approval trial, and we'd like to be be leading that if possible. So, you know, we still need to get the clinical study report done and published. Like I said, that's coming, but but the data are very strong. investigator-sponsored idea for a pivotal trial that was pretty much entirely inbound and true. Yes, yes.
Speaker Change: It has already gotten the attention of sarcoma experts.
Speaker Change: One of the most prestigious sarcoma institutes in Europe has looked at that have they've looked at the data and said, we'd really like to we think this thing is ready for a pivotal approval trial and we'd like to be the leading that if possible. So we still need to get the clinical study report done and published what like I said that's coming.
Speaker Change: But the data are very strong.
Speaker Change: Full investigator sponsored idea for a pivotal trial that was pretty much entirely inbound interest.
Speaker Change: Yes.
Unknown Executive: Thank you very much, guys. Thank you.
Speaker Change: Thank you very much guys.
Speaker Change: Thanks, Jonathan.
Jason Mccarthy: Next question today is coming from Jason McCarthy from Maxim Group. Your line is now live. Hey, Jason. Hi, guys. Thanks for taking the questions. So first question. In terms of the overall cost of the trial, what are you guys thinking there? John, you want to handle that one? Yeah, I mean, it's a phase three trial. So if you go out to the full You know, the full patient load, you're talking upwards of, you know, $60 million, $70 million. Our cash burn for the next rest of 2025 is $5 million a quarter, we've been very public about that.
Speaker Change: Thank you. Your next question today is coming from Jason Mccarthy from Maxim Group. Your line is not a lot.
Speaker Change: Hey, Jason.
Jason Mccarthy: Hi, guys. Thanks for taking the questions.
Speaker Change: So first question just in terms of the overall cost of the trial.
Jason Mccarthy: What are you guys thinking there.
John: John you want to.
John: Handle that one.
John: Yeah, I mean, it's a phase III trial. So if you go out to the full.
John: The full patient load youre talking upwards of $60 million $70 million, but.
John: Our cash burn for the next.
John: Rest of $2025 $5 million a quarter with very public about that and then that goes up probably to seven or $8 million a quarter in 2026.
Jonathan Foster: And then that goes up probably to $7 or $8 million a quarter in 2026 as we begin filling out some of the CMC requirements for an NDA. And, you know, but what's very important to us is getting this data out so we can. Get back to conversations with BID and Big Pharma that are very, very interested in these midterm data readouts.
John: Began filling out some of the CMC requirements for an NDA.
John: And.
John: What's very important to us is getting the data out so we can.
John: Get back to the conversations with bid and big pharma.
John: That are very very interested in these mid term data readouts.
Paul Waymack: Okay, great. And then Just a more broad question here. I mean, we're seeing this theme emerging more in AML development of moving to frontline, you know, once showing activity in the relapse refractory setting. You guys just general general thoughts there.
John: Okay, Great and then.
John: Just a more broad question here I mean, we're seeing that.
John: In emerging more and they'll development of moving to frontline once showing activity in the relapsed refractory setting.
John: Hey, guys just general general thoughts there.
Paul Waymack: Yeah, I'm going to suggest that Paul tackle this question. But in general, we get that question a lot of, you know, once we get approval in second line, is it logical for this drug to be used in first line? But Paul, you want to expand on that? Yes, once we document that this drug works and file their NDA, we're going to be in multiple different areas. Now, one of which we have to be doing a pediatric study to comply with the pediatric requirements that are in place. We're going to be doing a third-line therapy study, which FDA requires.
John: Yes.
Speaker Change: And it suggests that Paul tackle this question, but in general we get that question a lot.
John: Of.
John: Once we get approval in second line does it is it logical for this drug to be used in first line.
Speaker Change: Paul you want to expand on that.
John: Yes.
John: Once we document.
John: This drug works in the file their NDA, we're gonna be in multiple different areas, one of which we have to be doing a pediatric study to comply with the pediatric requirements that are in place we're going to be doing a third line therapy study, which.
John: <unk> requires.
Paul Waymack: But I agree with you, ultimately, it's first-line therapy, which is the biggest market because you don't get the second or third line unless you were initially a first-line therapy patient. And we have clearly shown, I believe, that unlike all other anthracyclines, we are not cardiotoxic. Unlike other anticyclines, we don't have a problem with the multidrug resistance. And we do agree, however, that First line therapy patients should get seven plus three where the three is an anthracycline. So we should have that market plus Half of all first-line therapy patients should get 7 plus 3, but they don't because they're unfit, meaning they're over 65 or they have a heart problem.
John: But I agree with you ultimately as first line therapy, which is the biggest market because you don't get the second or third line unless you were initially a first line therapy patients.
John: And we have clearly shown I believe that unlike all other anthracycline, we're not cardio toxic.
John: Unlike other recycling, we don't have a problem with the multi drug resistance.
John: And we do agree however that.
John: First line therapy patients should get seven plus three were the three years and then recycling. So we should have that market plus.
John: Half of all first line therapy patients should get seven plus three but they don't because they are unfit, meaning they're over 65 or they have a heart problem well that doesn't apply to us we've treated people who are unfit and our 106 trial and we have no problem. So we agree eventually.
Paul Waymack: Well, that doesn't apply to us. We've treated people who are unfit in our 106 trial, and we had no problems. So we agree, eventually, first-line is our ultimate objective in AML, and we will proceed there once we have shown that we're approvable for an NDA for second-line therapy.
John: First line is our ultimate objective in AML and we will proceed there once we have a <unk>.
Joan: Joan that were approvable.
John: For an NDA for second line therapy.
Unknown Executive: Okay, great. Thank you.
Speaker Change: Okay, Great. That's all for me thank.
John: Thank you.
John: Yeah.
Vernon Bernardino: Next question today is coming in from Vernon Bernardino from HC Wainwright. Your line is now live. Hey, Vernon. Hey, Wally. Thanks for taking my question. And hey, Jonathan and John, just want to follow up. Hey, on the questions about the miracle doses. Just wonder if you could walk us through the rationale for choosing the one 90 dose. Discussions with the FDA, and then also, what does the anticipate using for the soft tissue sarcoma trial.
Thank you. Your next question today is coming from Vernon Bernardino from H C. Wainwright. Your line is that a lot.
Speaker Change: Hey, Brian.
Vernon Bernardino: Hey, thanks.
Speaker Change: Thanks for taking my question and Hey, Jonathan.
Speaker Change: Just one follow up.
Speaker Change: Hey.
Speaker Change: On the questions about the medical doses.
Speaker Change: Just wonder if you could walk us through.
Speaker Change: The rationale for choosing the 190 dose.
Speaker Change: Discussions with FDA and then also what does do you anticipate using for the Hum.
Speaker Change: Soft tissue sarcoma trial.
Speaker Change: Alright.
Paul Waymack: This all relates to the Now, infamous project optimist that that FDA has embarked on, but I think Paul's probably in the best position to maybe comment on on the rationale and what we expect going forward, Paul. Yeah. Obviously, we chose 230 for this study because 230 got the great results we were seeing in our 106 study. For Optimus, FDA wanted us to go to a lower dose. We went to 190 because we had used that also in our 106 study and saw efficacy. And the FDA has not required us to go any lower. As far as which one I think will work.
Speaker Change: This all relates to the.
Speaker Change: Now.
Speaker Change: Infamous project Optimus that that FDA has embarked on.
Speaker Change: But I think Paul is probably in the best position to maybe comment on the rationale and what we expect going forward Paul.
Speaker Change: Yeah.
Paul: Obviously, we chose to 30 for this study because <unk> got the great results, we were seeing in our 106 study.
Paul: We are optimists FDA wanted us to go to a lower dose we went to 190, because we had used that also in our 106 study and saw efficacy.
Paul: And the FDA has not required us to go any lower.
Paul: As far as which one I think will work.
Paul Waymack: I actually think both of them will work to a reasonably similar degree. And so I think it's going to be a very close call. It's not an easy pick. If I did 230 versus 110, I'd pick 230. But 230 versus 190, I can't make you a prediction right now as far as which one we'll use. We'll see what all the data shows because it's going to be a lot of data. It's going to be efficacy, short-term, long-term. It's going to be safety. It's going to be PK. It's going to be a wealth of data, which we're going to have to go through very quickly.
Paul: I actually think both of them will work.
Paul: Two a reasonably similar degree.
Paul: And so.
Paul: I think it's going to be a very close call. It it's not an easy pick if I did $2 30 versus $1 10 to 30.
Paul: But $2 30 versus $1 90.
Paul: I can't make you a prediction right now as far as which one will use we will see what all the data show because it's going to be a lot of data that's going to be efficacy short term long term, it's going to be safety is going to be PK is gonna be a wealth of data, which we're going to have to go through very quickly.
Paul Waymack: As far as the sarcoma question, it's an entirely different dosing regimen. We have used monotherapy to get our results, but we've used a much higher dose. We've used just one, each cycle is just one dose. We're around 300 milligrams per meter square. We're getting good efficacy, reasonable safety. So I think we will be around there, but before we were to finalize a dosing regimen for a pivotal sarcoma study, we would request an end of phase one, two meeting with FDA to get their blessing on their entire plan. Okay, just thanks for that. And just one follow up regarding the 190 dose.
Paul: As far as the sarcoma question.
Paul: It's an entirely different dosing regimen, we have used mono therapy to get a result that we've used a much higher dose we've used just one.
Paul: Each cycle is just one dose were around 300 milligrams per meter square, we're getting good efficacy reasonable safety. So I think we will be around there, but before we were to finalize a dosing regimen for a pivotal sarcoma study, we would request an end of phase.
Paul: One two meeting with FDA to get their blessing on their entire plan.
Speaker Change: Okay, and just thanks for that and just one follow up regarding the.
Paul: 190 dose.
Paul Waymack: You know, I guess we could expect, you know, if it was 230, you're going to hit and be better than high dex CR rates for what was observed in MERS and classic one. But in the 190 dose, do you have to be superior to the 17, 18% that was observed to continue to perhaps apply for early or you still need to go to 230 if? Yeah. When we look at the interim results, one dose is clearly superior to the other. Let's say 230 has a much better complete response rate and similar safety, then the comparison would be the 230 dose versus placebo.
Paul: I guess, if we could expect if it was $2 30.
Paul: Youre going to hear can be better than <unk>.
Speaker Change: Hi Tech CR rates for what was observed in mirrors and classic one.
Paul: But in the 190 dose.
Paul: Do you have to be superior to the.
Paul: 2017, and 18% that was observed to continue.
Paul: To perhaps supply for early or you still need clarity.
Paul: Yes.
When we look at the interim results.
Paul: Yes.
Paul: One dose is clearly superior to the other let's say $2 30 is a much better complete response rate and similar safety.
Paul: Then the comparison would be the 230 dose versus placebo, we're gonna have to be better than whenever we get with the placebo plus either cytarabine in order for FDA to approve it.
Paul Waymack: We're going to have to be better than whatever we get with the placebo plus high-dose citarabine in order for FDA to approve it. If we go through all the way to randomized part B. If our data from 106 are anywhere close to resembling what we're going to get in 108, it's going to be an easy win. As far as if we document statistical significance just after Part A, it's a little complicated because of the fact that biostatisticians will tell you the alpha of O5 is for the entire trial, and so you save most of it for the end.
Paul: If we go through all the way randomized part B a.
Paul: It's our data from 106 or anywhere close to resembling what we're going to get in one of them is going to be an easy win.
Paul: As far as if we documents statistical significance just after car day.
Paul: It's a little complicated because of the fact that <unk>.
Paul: <unk> will tell you the alpha <unk> five is for the entire trial.
Paul: And so you say most of it for the end so Oh five would not get you approval.
Paul Waymack: So O5 would not get you approval after Part A. It would have to be a very statistically significant number. The P would have to be less than O1. How much less? That, again, it depends on the totality of the data, on the safety data, the PK data, and the efficacy data. So it's difficult to predict. It's easier to predict if we go through to Part B because there, unless something really bad happens, as long as you're... Improvement with Anamycin plus Cytarabine is significant compared to placebo plus Cytarabine and the P is less than it's going to be about something like 0.048.
Paul: Part, a we would have to be a very statistically significant number the P would have to be <unk>.
Paul: Less than one one.
Paul: How much less that again it depends on the totality of the data on the safety data the PK data and the efficacy data so it's difficult to predict.
Paul: It's easier to predict for we go through the part B.
Paul: Because there.
Paul: Unless something really bad happens as long as you are.
Paul: Improvement with <unk> plus cytarabine.
Paul: Is significant compared to placebo plus cytarabine and the P is less than it was going be able to send Michal <unk>, we lose a little of that because the interim look.
Walter Klemp: We lose a little of that because the interim look it's an easy call that we will win. After Part A, it's a very complicated process.
Paul: We call that we will win after part of it.
Paul: Very complicated process.
Walter Klemp: Let me add one insight here, Vernon, that might also kind of tie this together for you. Let's just say that we get to the 45 subject level, and it's just obvious that 230 is a better choice than 190. And we could shorten that by saying more effective, but it does have to meet all the safety requirements too, so safety and tolerability, and have a decent PK profile. So let's just assume that all those boxes are checked, and 230 is clearly a better choice than 190. At that point, we probably would just drop continuation of treatment at 190.
Paul: Difficult to do.
Paul: Let me, let me add one.
Paul: Insight here Vernon.
Paul: That might also kind of tie this together for you, let's just say that we get to the 45 subject level and its just obvious that $2 30 is a better choice than 190, and we would we could shorten that by saying more effective but it does have to be you have to meet all the safety requirements to so safety.
Speaker Change: <unk> Tolerability and and.
Speaker Change: Have a decent PK profile. So, let's just assume that all of those boxes are checked and <unk> is clearly a better choice and 190 at that point.
Speaker Change: We probably would just drop continuation of treatment at 190 now there's there's a timing problem here. It's a good problem, but it's still an issue and that is that once you get 25 sites up and running the rate of recruitment picks up dramatically and so.
Walter Klemp: Now, there's a timing problem here. It's a good problem, but it's still an issue, and that is that once you get 25 sites up and running, the rate of recruitment picks up dramatically. And so by the time we get the 45 patient data, scrub it, and lock the database, and disclose it, we could well be all the way to 90 patients anyway. But in a perfect world, if we saw the results at 45, and let's just assume that 230 was the winner, then we would stop recruiting the 190 arm because we don't need any more data.
Speaker Change: By the time, we get to 45 patient data scrub it and lock the database and disclose it.
Speaker Change: We could well be all the way to 90 patients anyway, but.
Speaker Change: In a perfect world. If we saw the results at 45, and let's just assume that $2 30 was the winner then we would stop recruiting the 190 arm because we didn't we don't need any more data and that's why when you look at our part a in the timelines and the disclosures that we say something.
Walter Klemp: And that's why when you look at our Part A in the timelines and the disclosures, that we say somewhere between 75 and 90 patients. And that's because we're anticipating the possibility that we may have a clear winner at 45, and therefore no need to keep recruiting at the other dosage. Does that make sense? Yes, will that be able to preserve the 190 though, such that, you know, should any safety signals appear? But that's, of course, that's always a possibility. And we don't want to sound overly confident here, but we've got enough experience with this drug, not just in MB-106, but in MB-105 and MB-104 that were, you know, the single agent trials in AML as well as the STS trials.
Speaker Change: We're between 75% to 90 patients and that's because we're anticipating the possibility that we may have a clear winner at 45, and therefore, no need to keep recruiting at the other dosage is that makes sense.
Speaker Change: Yes.
Speaker Change: Will that be able to preserve the 190, though.
Speaker Change: What's that.
Speaker Change: Should any safety signals appear.
Speaker Change: Yeah.
Speaker Change: Of course, that's always a possibility.
Speaker Change: And we don't want to sound overly confident here, but we've got enough experience with this drug not just in Andy 106, and a 105 and 100 for that.
Speaker Change: The single agent trials in AML as well as the STS trials, we've got a pretty clear picture of the safety profile of this drug even above 230. So we're.
Vernon Bernardino: We've got a pretty clear picture of the safety profile of this drug, even above 230. So we're I think that's a very unlikely event. But, of course, if we got down the road and it looked like 230 was all of a sudden surprisingly a problem, then we could revert to 190. But I believe we will have enough data, certainly by the end of Part A, that everyone will have a lot of confidence in that choice. Thank you. This is very helpful and insightful. Thanks for taking my You bet, Vernon.
Speaker Change: I think that's a very unlikely event.
Speaker Change: But of course, if if we got down the road and it looked like <unk> was all of a sudden surprisingly a problem then we could revert to 190, but.
Speaker Change: Yeah.
Speaker Change: I I believe we will have enough data certainly by the end of part a that everyone will have a lot of confidence in that choice.
Speaker Change: Thank you that's very helpful. Sighful, Thanks for taking my questions.
Speaker Change: You bet Farhan. So operator, I think I think we're done appreciate everybody's.
Unknown Executive: So operator, I think I think we're done. Appreciate everybody's time and attention. And again, thanks for joining us.
Speaker Change: And attention and again, thanks for joining us.
Unknown Executive: That does conclude today's teleconference and webcast. You may disconnect your lines at this time and have a wonderful day. We thank you for your participation today.
Speaker Change: Thank you that does conclude today's teleconference and webcast you may disconnect. Your lines at this time and have a wonderful day, we thank you for your participation today.
Speaker Change: Yeah.
Speaker Change: Yeah.