Q3 2023 Moleculin Biotech Inc Earnings Call

Speaker 1: Greetings and welcome to the Molecular and Biotech third quarter 2023 conference call and webcast. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the call, please press star zero on your telephone key.

Greetings and welcome to the Milwaukee land biotech third quarter 2023 conference call and webcast. At this time all participants are in a listen only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the call. Please press star zero on your telephone.

Speaker 1: As a reminder, this conference is being recorded. At this time, I'd like to turn the call over to Jeanine Thomas, Investor Relations. Thank you. You may begin.

Pat.

As a reminder, this conference is being recorded at this time I'd like to turn the call over to Janine Thomas Investor Relations. Thank you you may begin.

Speaker 2: Good morning and welcome everyone. At this time, I would 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 molecular current expectations and actual results could differ materially.

Thank you Darryl good morning, and welcome everyone. At this time I would like to remind our listeners that remarks made during this webcast may state managements intentions beliefs expectations or future predictions. These are forward looking statements and involve risks and uncertainty.

And that's on the 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.

Speaker 2: As a result, you should not play undue reliance on any forward-looking statement.

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 those contemplated by such.

Speaker 2: Some of the factors that could cause actual results to differ materially from these contemplated by such foreign statements are discussed in the periodic reports molecular files with the Securities and Exchange Commission.

Statements are discussed in the periodic reports <unk>.

One files with the Securities and Exchange Commission. These documents are available in the investors section of the company's website and on the Securities and exchange Commission's website. We encourage you to review these documents carefully. Additionally, certain information contained in this web cast relates to or is based on studies publication surveys and other data obtained from.

Speaker 2: These documents are available in the investors section of the company's website and on the Securities and Exchange Commission's website. We encourage you to review these documents carefully. Additionally, certain information contained in this webcast relates to or is based on studies, publications, surveys, and other data obtained from third-party sources and the company's own estimates and research.

Third party sources and the company's own estimates and research while the company believes these third party sources to be viable as of the date of this presentation. It does not independently verify it makes no representation as to the adequacy and accuracy or completeness I'm worried that any independent source verified any information.

Speaker 2: 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, accuracy, or completeness of or that any independent source of verified any information obtained from third-party sources.

Obtained from third party source any day to discuss regarding clinical trials in progress are considered preliminary and subject to change, but joining us on todays leaders are Walker, chairman and Chief Executive Officer, Dr. John Paul We not cheap senior Chief Medical Officer, and Jonathan Foster Executive Vice President and Chief financial.

Speaker 2: Any data discussed regarding clinical trials and progress are considered preliminary and subject to change. So, joining us on today's call from the leadership team are Walter Klint, Chairman and Chief Executive Officer, Dr. John Paul Wehm, Senior Chief Medical Officer, and Jonathan Foster, Executive Vice President and Chief Financial Officer. I'd now like to turn the call over to Walter Klint, Chairman and CEO . Wally, please proceed.

With that I'd now like to turn the call over to Walter Clinton, Chairman and CEO Walid. Please proceed.

Speaker 3: Thanks Janine, and hello everyone. I'm Wally Clem, founder, CEO , and chairman of Molecular Biotech.

Thanks, Judy and Hello, everyone, I'm Waleed club founder CEO and chairman of molecular in biotech.

Speaker 3: We are really excited to welcome you to this Q3 earnings call. We've been saying for some time now that this would be our year of data. And we are finally able to deliver on the phase 2 data we've been hoping for.

We are really excited to welcome you to this Q3 earnings call.

We've been saying for some time now that this would be our year of data.

And we are finally able to deliver on the phase II data, we've been hoping for.

Speaker 3: To be clear, this is preliminary and subject to change, and there's a lot more data to come in the next few quarters. But we have a start, and it's a good one. We're going to share it with you on this call.

To be clear this is preliminary and subject to change and there's a lot more data to come in the next few quarters, but we have a stark and it's a good one.

We're going to share with you on this call.

Speaker 3: As we walk through the data today, I'd ask you to keep in mind one of our core beliefs.

As we walk through the data today I'd ask you to keep in mind, one of our core beliefs.

Speaker 3: that is that the most important therapeutic tool for both AML and advanced STS has been and continues to be an anthracycline.

That that is the most important therapeutic tool for both AML and advanced S. T. S has been and continues to be in.

Anthracycline.

Speaker 3: Despite the fact that there had been more than a dozen new drug approvals in these indications over the last five or so years, the first line therapy for both indications and the best hope for a positive outcome remains with the use of anthracycline.

Despite the fact that there had been more than it doesn't new drug approvals in these indications over the last five or so years. The first line therapy for both indications and the best hope for a positive outcome remains with the use of Anthracycline.

Speaker 3: Unfortunately, today's anthracyclines have major limitations that prevent most patients from sharing in this benefit.

Unfortunately, today's anthracycline have major limitations that prevent most patients from sharing in this benefit.

Speaker 3: But those days are about to be over. Moleculin intends on making this indispensable tool available to those patients who have, until now, been excluded from their use.

But those days are about to be over Malek.

Molecular intends on making this indispensable tool available to those patients who have until now been excluded from their use.

Speaker 3: And of course, the drug we intend to do this with is anamycin, our lead program in a pipeline that is both deep and broad with a long list of potential additional high value targeted indications.

And of course, the drug we intend to do this with <unk> our lead program in our pipeline that is both deep and broad with a long list of potential additional high value targeted indications.

Speaker 3: As many of you know, we're doing this with a highly efficient capital structure by exploiting a global network of preeminent collaborators.

As many of you know we're doing this with a highly efficient capital structure by exploiting our global network a preeminent collaborators.

Speaker 3: Now, our pipeline is robust and too complicated to capture in just one slide. After all, between the trials that we've completed, are currently running, and are approved to begin, we're talking about 11 clinical trials for our technologies. Today,

Now our pipeline is robust and too complicated to capture in just one slide after all between the trials that we've completed are currently running and are approved to begin we're talking about 11 clinical trials for our technologies.

Today, we will focused on just two of them.

Speaker 3: our European trial in acute myelod leukemia and our US trial in advanced soft tissue sarcoma.

Our European trial in acute myeloid leukemia, and our U S trial in advanced soft tissue sarcoma.

Speaker 3: As a reminder, we have orphan drug designation and fast track status in both indications, and we have a strong patent position for anamycin and a range of potential indications.

As a reminder, we have orphan drug designation and fast track status in both indications and we have a strong patent position for animation and a range of <unk>.

Potential indications.

Speaker 3: For those of you who are new to the story, it's critical to understand why the use of anthracycline has been limited for so long.

For those of you who are new to the story, it's critical to understand why the use of Anthracycline has been limited for so long.

Speaker 3: Far and away, the greatest limitation to current anticyclines is cardiotoxicity.

Foreign away the greatest limitation to current Anthracycline is cardio toxicity.

Speaker 3: This is the primary reason patients either can't receive anthracyclines or have to terminate treatment before receiving the desired benefit.

This is the primary reason patients either can't receive answered anthracycline or have to terminate treatment before receiving the desired benefit.

Speaker 3: As well, there are also limitations resulting from tissue organ distribution and multi-drug resistance mechanisms. As a result, there are many patients who simply don't get to benefit from today's anthracycline.

As well there are also limitations, resulting from tissue organ distribution and multi drug resistance mechanisms. As a result, there are many patients who simply don't get to benefit from today's anthracyclines.

Speaker 3: Now, when it comes to cardiotoxicity, the data are quite surprising.

Now when it comes to cardio toxicity the data are quite surprising.

Speaker 3: Anthrocyclines are so cardiotoxic, in fact, that the FDA has established a lifetime maximum allowable dose of 550 milligrams per square meter.

Anthracycline or so cardio toxic in fact that the FDA has established a lifetime maximum allowable dose of 550 milligrams per square meter.

Speaker 3: As you can see from the chart on the left, if you only accumulate 100 milligrams per square meter, your risk of cardiac impairment is negligible.

As you can see from the chart on the left if you only accumulate 100 milligrams per square meter your risk of cardiac impairment is negligible.

Speaker 3: But if you go up to that maximum, there's a 65% chance you will experience some form of cardiac impairment. And if you go up to 850 milligrams, it's 100% certain you will have some kind of impairment.

But if you go up to that maximum there's a 65% chance you will experience some form of cardiac impairment.

And if you go up to 850 milligrams, it's 100% certain you will have some kind of impairment.

Speaker 3: Now, to make this even more graphic, the chart on the right shows that 600 milligrams per square meter, there's an 8% chance you'll have full-on heart failure during treatment.

Now to make this even more graphic the chart on the right shows the 600 milligrams per square meter.

There's an 8% chance you'll have full on heartfelt failure during treatment.

Speaker 3: When you translate this reality to our lead indications, you see that more than half of all patients diagnosed with AML cannot receive currently prescribed anticyclines because they're deemed unfit due to age or poor health.

When you translate this reality to our lead indications you see that more than half of all patients diagnosed with AML cannot receive currently prescribing anthracycline, because they're deemed unfit due to age or poor health.

Speaker 3: Likewise, in advanced soft tissue sarcoma, even though the standard of care therapy is always anchored around an anthracycline, usually doxorubicin, only about 30% of patients will respond, and all of those will relapse. And once they're at the lifetime maximum allowable dose, they're relegated to a range of drug cocktails that do little or nothing to extend their lives.

Likewise in advanced soft tissue sarcoma, even though the standard of care therapy is always anchored around an anthracycline usually doxorubicin.

Only about 30% of patients will respond.

And all of those will relapse and once they're at the lifetime maximum allowable dose. They are relegated to a range of drug cocktails that do little or nothing to extend their lives.

Speaker 3: The best answers currently available are simply not enough.

The best answer is currently available are simply not enough.

Speaker 3: In AML, that is a drug called venetoclax, most often used in combination with azacytidine.

In AML that is a drug called Vineeta clocks, most often used in combination with a decidedly.

Speaker 3: This Venaza combination is capable of generating a complete response in 37% of patients, which is good for that 37%. And this drug generates a half a billion dollars a year in revenue for AbbVie.

This then as a combination is capable of generating a complete response and 37% of patients which is good for that 37% and this drug generates a half a billion dollars a year in revenue for Abbvie.

Speaker 3: But there's a strong consensus among clinicians that Venazia is just too hard on patients. It's very difficult for patients to tolerate, and it's clear there needs to be a better answer.

But there's a strong consensus among clinicians that then as it is just too hard on patients, it's very difficult for patients to tolerate and it's clear there needs to be a better answer.

Speaker 3: In advanced STS, the best fallback treatments appear to be decarboxine and trabectin, but the best they can offer is about a three-month PFS to around half the patients with no appreciable improvement in overall survival. There simply must be a better answer.

In advanced S. T S. The best fallback treatments appear to be Dacarbazine enter back then but the best I can offer is about a three month PFS to around half the patients with no appreciable improvement in overall survival.

They're simply must be a better answer.

And now there is.

Speaker 3: Animicin is what we call a next generation anthracycline that's designed to be non-cardiotoxic and appears to be improving outcomes in both AML and STS.

Animation is what we call. Our next generation Anthracycline, that's designed to be non cardio toxic and appears to be improving outcomes in both AML and S. T S.

Speaker 3: In AML, we've completed phase one testing and are now in phase two. And in STS, we've not only completed phase one, we've also completed enrollment in our phase two study and are preparing for a pivotal approval trial.

In AML, we've completed phase one testing and are now in phase two and S. T. S. We've not only completed phase one we've also completed enrollment in our phase two study and are preparing for a pivotal approval trial.

Speaker 3: Animicin does have orphan drug and fast track status in both indications and importantly strong patent protection through 2040.

Adam ice and it does have orphan drug and fast track status in both indications and importantly, strong patent protection through 'twenty 40.

Speaker 3: So when we say anamycin is non-cardiotoxic, we mean 100% non-cardiotoxic. It's important to stress this as there are other players out there with anthracycline technologies that they claim are less cardiotoxic than doxorubicil.

So when we say animation is non cardio toxic we need 100% non cardio toxic it's important to stress. This as there are other players out there with Anthracycline technologies that they claim are less cardio toxic and doxorubicin, but to our knowledge.

Speaker 3: But to our knowledge, no one is capable of making the claim we make because we're the only ones testing every aspect of cardiotoxicity and then submitting our data to an independent cardiology expert at the Cleveland Clinic.

No one is capable of making the claim we make because we're the only ones testing every aspect of cardio toxicity, and then submitting our data to an independent cardiology expert at the Cleveland clinic.

Speaker 3: And in addition to being completely non-cardiotoxic, we appear to be easier on patients than currently approved anthracycline. As a small example, 65% or more patients treated with doxorubicin will lose their hair.

And in addition to being completely non cardio toxic we appear to be easier on patients than currently approved anthracycline as a small example.

65% or more patients treated with doxorubicin will lose their hair.

Speaker 3: we're seeing less than 10% of patients having any hair loss with anamycin.

We're seeing less than 10% of patients, having any hair loss with animation.

Speaker 3: But despite the fact that anamycin is easier on patients, it is actually more potent than doxorubicin in most tumor models. And it's able to avoid the multidrug resistance mechanisms that limit the efficacy of doxorubicin in many patients.

But despite the fact that animation is easier on patients. It is actually more potent than doxorubicin in most tumor models and it's able to avoid the multi drug resistance mechanisms that limit the efficacy of doxorubicin in any patients.

Speaker 3: And that means even though we're concentrating on AML and STS, anamycin should be relevant to 10 times as many patients once expanded to additional education.

And that means even though we're concentrating on AML and S. T S and eisen should be relevant to 10 times as many patients once expanded to additional indications.

Speaker 3: As it relates to expanding our pipeline, by the way, we are very effectively utilizing non-dilutive institutional funding for clinical development. In addition to our sponsored research at both MD Anderson and UTMB, we've benefited from clinical development funding from MD Anderson, Emory University, and the Madame Curie Institute in Poland. And we're expecting several clinical trials to benefit from outside funding this coming year.

As it relates to expanding our pipeline by the way we are a very effectively utilizing non dilutive institutional funding for clinical development. In addition to our sponsored research at both MD Anderson and U T. M. B, we've benefited from clinical development funding from MD Anderson, Emory University and the Madame Curie instead.

In Poland.

And we're expecting several clinical trials to benefit from outside funding yet this year and this coming year.

Speaker 3: And our sponsored research has paid some big dividends thus far. In addition to demonstrating the synergy between anamycin and cytarabine that's now playing out in our Phase II AML trial, this ongoing research also eliminated the fact that anamycin is 30 times better at accumulating in the lungs.

And our sponsored research has paid some big dividends thus far in.

In addition to demonstrating the synergy between anime and cytarabine, that's now playing out in our phase III AML trial. This ongoing research also eliminated. The fact that animation is 30 times better at accumulating in the lungs.

Speaker 3: than doxorubicin, making it an ideal candidate for advanced STS, which is most commonly what is the point of metastasis is to the lung.

Then doxorubicin, making it an ideal candidate for advanced S. T S, which is most commonly the test what what that is.

Is the point of metastasis is as to the lungs.

Speaker 3: So with that as background, I'd like to invite our Senior Chief Medical Officer, Paul Wehmach, to give you the specifics on the new data.

So with that as background I'd like to invite our senior Chief Medical Officer, Paul way back to give you the specifics on the new data.

Thanks Wally.

Speaker 4: It has taken a long time to get to the point of generating phase 2 clinical data for AML, but we are finally there.

It has taken a long time to get to the point of generating phase two clinical data for AML.

But we are finally there.

Speaker 4: Part of the challenge from a regulatory standpoint was needing to demonstrate the safety and the efficacy of animicin as a single agent before combining it with cytarabine for AML patients.

Part of the challenge from a regulatory standpoint was needing to demonstrate the safety and the efficacy of minimize some as a single agent before combining it with cytarabine for AML patients.

Speaker 4: Given that we also had to demonstrate that patients could be safely dosed at well above the FDA's maximum allowable anthracycline dose.

Given that we also had to demonstrate that patients could be safely dosed at well above the F. D. A maximum allowable anthracycline dose.

Speaker 4: This also meant we had to work with patients who were receiving 3rd, 4th, 5th line, or 1st line.

This also meant we had to work with patients who were receiving third fourth fifth line or worst therapies.

Speaker 4: which are the most difficult patients to treat and expect any impact.

Which are the most difficult patients to treat and expect any impact.

Speaker 4: Now, notwithstanding all these challenges, we are now finally treating AML patients in a phase two study with anamycin in combination with cytarabine.

Now notwithstanding all these challenges we are now finally treating AML patients in our phase two study with animation in combination with cytarabine.

Speaker 4: A combination our preclinical testing suggested would be even more effective for AML patients.

A combination of our preclinical testing suggested would be even more effective for AML patients.

Speaker 4: And this appears to be the case. We now have data from the first eight patients.

This appears to be the case, we now have data from the first eight patients.

Speaker 4: Who incidentally entered our trial with a median of four prior therapies?

Who incidentally Internet trial with a median of four prior therapies.

Speaker 4: We are very pleased to report that among patients who have completed their antimicin dosing, we have three complete responses. This represents a 38 percent response rate, something that would not be expected in such heavily pretreated patients.

We are very pleased to report that among patients who have completed their analyses and dosing. We have three complete responses. This represents a 38% response rate bumps.

Something that would not be expected in such heavily pretreated patients.

Speaker 4: For comparison, you may recall that Wally mentioned the approval of Veneza was based on a 37% complete response rate. So, we are already performing at a level that we believe will support marketing approval of Anamycin.

For comparison, you may recall that while he mentioned the approval of venues was based on a 37% complete response rate.

So we are already performing at a level that we believe will support marketing approval of animals.

Speaker 4: And what's more, we are doing this in heavily pre-treated patients.

And what's more.

We are doing this in heavily pretreated patients.

Speaker 4: Whereas the Vaneza trial for approval was in first-line therapy patients.

Whereas the benet's, though.

Vanessa trial.

The approval was in first line therapy patients.

Yeah.

Speaker 4: When you look at the specifics relating to our complete responders, there are some valuable insights that are now apparent.

When you look at the specifics relating to a complete responders. There are some valuable insights that are now apparent.

First.

Speaker 4: One of them responded to Vanessa, but then relapsed.

One of them responded to the news, but then relapse.

Speaker 4: One was refractory to Venaza and the other had no prior exposure to Venaza.

One was refractory to the news.

And the other had no prior exposure to Vanessa.

Speaker 4: The first two responders are now confirmed as durable.

The first two responders and now confirmed is durable.

Speaker 4: with one at eight months of remission and climbing, and the other having just received a bone marrow transplant three months after treatment with animal isin.

One of the eight months of remission.

Climbing.

And the other having just received a bone marrow transplant.

Three months after treatment with animals.

Speaker 4: We can't yet declare a durability for the third patient simply because not enough time has passed since their treatment and remission.

We can't yet declared durability for the third patient.

Because not enough time has passed since their treatment in remission.

Speaker 4: It's also worth pointing out that all three of these patients were treated well above the lifetime maximum allowable anthracycling dose of 550 mg per meter square.

It's also worth pointing out that all three of these patients were treated well above the lifetime maximum allowable anthracycline dose of 550 milligrams per meter square.

Speaker 4: Again, this is what we were hoping to see in AML, and if we continue to see this level of activity, we think we will be in a very good position to establishing a marketing approval pathway.

Again. This is what we were hoping to see in a M L.

And if we continue to see this level of activity. We think we'll be in a very good position, establishing a marketing approval pathway.

Now turning to our soft tissue sarcoma.

Speaker 4: We now have complete enrollment of the Phase II arm of our U.S. clinical trial and are able to present some preliminary data from the trial as a whole.

We now have complete enrollment of the phase two arm of our U S clinical trial and are able to present, some preliminary data from the trial as a whole.

Speaker 4: There's a lot to process here, but in total, we believe this trial's data bodes well for an ultimate approval in advanced soft tissue sarcoma.

There's a lots of process here, but in total.

We believe this trials data bodes well for an ultimate approval.

In advanced soft tissue sarcoma.

Speaker 4: The unmet need here is so great that most of the recent approvals have been based on the very modest improvements in progression-free survival, or PFS.

The unmet need here is so great that most of the recent approvals have been based on the very modest improvement in progression free survival or PFS.

Speaker 4: It took us a while in this trial to zero in on the optimal dosing regimen.

It took us a while in this trial to zero in on the optimal dosing regimen.

Speaker 4: and it turns out that the most productive dosing regimen is not the highest dose we tested. When you isolate four...

And it turns out that the most productive dosing regimen is not the highest dose we test it.

When you isolate for the optimum dose.

Speaker 4: which turned out to be around 330 milligrams per meter square. The column on the.

Which turned out to be around 330 milligrams per meter square.

The column on the far right shows.

Speaker 4: shows that we had a 78% response rate, with 56% of the patients reaching three months or higher progression-free survival among patients who had received one or two prior therapies.

Joseph we had a 78% response rate.

With 56% of the patients, reaching three months or higher progression free survival among patients who had received one or two prior therapies.

Speaker 4: That compares favorably with other approvals for the indication, but it's only half the story.

That compares favorably.

With other approvals for the indication.

But it's the only half the story.

Speaker 4: One of the shortfalls of second-line therapies is delivering extended overall survival.

One of the shortfalls of second line therapies is delivering extended overall survival.

Speaker 4: Although we haven't had enough elapsed time in the phase two group to reach the medium overall survival.

Although we haven't had enough elapsed time in the phase two group to reach the medium overall survival.

Speaker 4: Since 12 of the 17 patients receiving antimycin are still alive and the median overall survival won't be reached until the number still alive falls all the way down to eight, we can look to the phase one cohorts data where we see overall survival at 11 months and climbing.

Since 12 of the 17 patients receiving <unk> are still alive and the median overall survival won't be reached until the numbers still alive falls, all the way down to eight weeks.

We can look to the phase one cohort data, where we see overall survival of 11 months and climbing.

Speaker 4: Considering that the median number of months from diagnosis for patients entering the phase two portion of our trial was 20

Considering that the median number of months from diagnosis of patients entering the phase II portion of our trial was once he.

Speaker 4: The overall survival that we appear to be headed for could be an even stronger basis for a marketing approval.

The overall survival, we appear to be headed for could be an even stronger basis for marketing approval.

Speaker 4: We had the pleasure of sharing these data with a group of soft-tissue sarcoma key opinion leaders at the recent CTOS, that's Connected Tissue Oncology Society Conference in Dublin, and the Enthusiasts.

We had the pleasure of sharing these data with a group of soft tissue sarcoma key opinion leaders at the recent SITA, that's connective tissue Oncology Society conference in Dublin.

The enthusiasm was hot.

Speaker 4: As a result, we now have two different groups proposing to run their own versions of a pivotal approval trial which we expect to be kicking off next year.

As a result, we now have two different groups.

To run their own versions of a pivotal approval trial, which we expect to be kicking off next year.

Speaker 4: I'll now hand it off to our Executive Vice President and Chief Financial Officer, John Foster, to wrap up the call. John ?

I'll now hand, it off to our executive Vice President and Chief Financial Officer, Jon Foster.

We're up to call it.

John.

Thanks, Paul.

Speaker 3: We ended the quarter with roughly $25 million in cash.

We ended the quarter with roughly $25 million in cash on hand, and our balance sheet remains clean with what no debt and a little overhang with warrants.

Speaker 3: and our balance sheet remains clean with no debt and little overhang with

Speaker 3: with our current burn rate, this cash will get us into the third quarter of 2024. A runway that we've been consistent in our discussion since our last major equity raise in 2021. We have just short of 30 million.

With our current burn rate.

This cash will get us into the third quarter of 2020 for a runway that we've been consistent in our discussions since our last major equity raise in 2020 one we.

We have just short of 30 million shares outstanding.

Speaker 3: This runway allows us, we believe, to deliver these milestones in the 2023, early 2024 and set the table for delivering the milestones later in 2024. Regarding Annamite.

Okay.

This runway allows us we believe to deliver these milestones into 2023 early 2024 and set the table for delivering the milestones later in 'twenty 'twenty four.

Regarding antibodies for the treatment of AML.

Speaker 3: with MB-106 being an open label trial.

And then B 106, being an open label trial.

Speaker 3: We will continue our quarterly clinical trial updates and also concurrently with other events.

We will continue our quarterly clinical trial updates and also concurrently with other events.

Speaker 3: such as scientific conferences or other public presentations.

Such as scientific conferences or other public presentations.

With us delivering the efficacy discussed.

Speaker 3: Recruitment has picked up, and we expect recruitment to be fulfilled in early 2024, if not sooner, in engaging with the FDA and the EMA within the Phase 2 meeting.

Recruitment has picked up and we expect recruitment to be fulfilled in early 2024, if not sooner and engaging with the FDA and the EMA with end of phase two meeting.

Speaker 3: From that, we expect to identify the next steps for the next pivotal clinical trial and begin that at the earliest in the second half of 2024.

From that we expect to identify the next steps for the next pivotal clinical trial and began that at the earliest in the second half of 'twenty 'twenty four.

Speaker 3: Regarding treatment of advanced soft tissue sarcoma, we will continue to monitor subjects for OS and PFS, and we expect to report in the second quarter of 2024 that final readout.

Regarding treatment of advanced soft tissue sarcoma, we will continue to monitor subjects for OS and PFS and we expect to report in the second quarter of 2020 for that final readout.

Speaker 3: But that's not stopping us from moving forward with discussions with investigators for a possible investigator funded trial, either partly or fully in first line treatment advanced STS just as Paul.

But that's not stopping us from moving forward with discussions with investigators for a possible investigate investigator funded trial.

Either partly or fully in first line treatment of advanced S. T S. Just as Paul discussed.

Speaker 3: The response to our meetings with investigators at CEPAS leads us to believe that the next program could be identified in either the U.S. or the E.U. in the first half of 2024 and initiated in the second.

The response of our meetings with investigators see pods leads us to believe that the next program could be identified in either the U S or the EU in the first half of 'twenty 'twenty four and initiated in the second half.

Speaker 3: All of these milestones are building upon the efficacy data that we just discussed.

All of these milestones are building upon the efficacy data that we just discussed.

Wally.

Thanks, John.

Speaker 3: For quite some time now, we've been touting the non-cardiotoxic nature of animison, but there is just no substitute for data.

For quite some time now we've been touting the non cardio toxic nature of animation, but there is just no substitute for data.

Speaker 5: We've now treated 66 patients, most of whom were taken well above the lifetime maximum allowable dose.

Well, we've now treated 66 patients most of whom were taken well above the lifetime maximum allowable dose.

Speaker 5: And not a single one has exhibited any signs of cardiotoxicity.

And not a single one has exhibited any signs of cardio toxicity.

Speaker 5: But the absence of cardiotoxicity is meaningless without efficacy. And up until now, that's been the big unanswered question. Could anamycin actually deliver enough activity in a phase two setting to be worthy of marketing approval? Well, that question.

But the absence of cardio toxicity is meaningless without efficacy and up until now that's been the big unanswered questions could Anna mice, and actually deliver enough activity in a phase two setting to.

To be worthy of marketing approval.

Well that question is now being answered.

Speaker 5: Yes, the data are preliminary and we need to substantiate what we've shown you with a few more patients.

Yes, the data are preliminary and we need to substantiate what we've shown you with a few more patients.

Speaker 5: But with those caveats in mind, anamycin is delivering, and it has everything it needs in order to become what we believe will be a multi-billion dollar fraud.

But with those caveats in mind animation is delivering and it has everything it needs in order to become what we believe will be a multi billion dollar truck.

And it all comes back to our core belief.

Speaker 5: The most important tool for AML and advanced STS, as well as a host of other hard to treat cancers, is an anthracycline.

The most important tool for AML and advanced S. T S as well as a host of other hard to treat cancers is N and recycling.

Speaker 5: those anthracyclines haven't been improved in decades.

Those anthracycline haven't been improved in decades.

Speaker 5: Anamycin finally represents a real improvement in anthracyclines, and we're going to make this tool available to those patients who until now have been denied this opportunity.

And Iceland finally represents a real improvement in Anthracycline and we're gonna make this tool available to those patients who until now have been denied this opportunity.

Speaker 5: So that wraps up our prepared presentation for the quarter to mean. We'd be happy to handle any questions folks have.

So that wraps up our price our prepared presentation for the quarter Janine, we'd be happy to handle any questions folks have.

Speaker 1: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the

Thank you we will now be conducting a question and answer session.

To ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue. You May press star two if he would like to remove your question from the queue for participants using speaker equipment, it might be necessary to pick up your handset before pressing the star keys.

Speaker 1: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for your question.

Please while we poll for your questions.

Speaker 1: Our first questions come from the line of Jonathan Ashkoff with Roth MKM. Please proceed with your question.

Our first question is come from the line of Jonathan Aschoff with Roth Capital. Please proceed with your questions.

Speaker 5: Thanks. Good morning. Congrats on the data, but what I wanted to ask about it, you know, can you really exclude from the percent CR rate analysis in AML, you know, the cytarabine, SAA, SAE, as well as the stroke patient, shouldn't that denominator be 10?

Hi, Thanks, good morning, Congrats on the data, but what I wanted to ask about it.

Really exclude from the percent CR rate analysis in AML.

Oh, the cytarabine S I.

I see as well as the stroke patients that shouldn't that denominator 10 and 19.

Speaker 5: Paul, I think you're probably best to address the statistical basis for establishing CR rates, so you want to tackle this one?

Paul I think you're probably best to address the AR the key statistic statistical.

Statistical basis for establishing CR rates. So you want to tackle this one.

Speaker 4: Yes, certainly in a pivotal trial with the intent to treat analysis, you would include them all.

Yes.

Certainly in a.

The pivotal trial with the intent to treat analysis you would include the mall.

Speaker 4: And as a phase 2 study, we do things differently. In a pivotal trial, because the person had an allergic reaction to cytarabine, we would have just continued treating with anamycin alone. Since in the 105 monotherapy trial, we were getting similar results of a

And as a phase II study, we do things differently in a pivotal trial because the person had an allergic reaction to cytarabine, we would've just continue treating with analyzing alone since in the 105 monotherapy trial, we were getting similar results of a.

Speaker 4: CR rate around 40%, so we just wanted to present here patients who had finished. I would point out we've got another patient in this trial who finished their therapy.

So you are right around 40%. So we just wanted to present here patients who had finished I would point out we've got another patient.

This trial, who finished their therapy, we have <unk>.

Speaker 3: verbal confirmation from the site that they had a CR, but we don't put that in the slide deck until we have the written documentation. So we are trying to be very specific in a phase two study with patients who have documented data and who exactly followed the protocol, whereas in the pivotal phase three trial, it would be more broadly in the intent to treat analysis.

Verbal confirmation from the site that they got to see our <unk>, but we don't put that in the slide deck until we have the written.

Documentation. So we are trying to be very specific in a in a phase two study.

With patients who had documented data and who exactly follow the protocol, whereas in the pivotal phase III trial, it would be a more broadly in the intent to treat analysis.

Speaker 5: Okay, is it fair to say that for the STS-LM data set in today's press release that it is no new data compared to the update a week ago?

Okay is it fair to say that for the U S. Yes.

And then you said in today's press release that it is no new data compared to the update a week ago.

Speaker 5: Yes. John , you're most familiar with what's been publicly shared. So do you want to dial that in?

Yes, it's Sean.

John Your John you're most familiar with what's been publicly shared.

Sure. So do you want them do you want to dial that in.

Speaker 3: No, I would disagree, Jonathan. If you if you look at the chart that that we presented on slide 19 and also in the queue and also believe the press release when you start. Remember, we took all comers into this trial. We took up to people with up to 11 prior therapy.

No I I would disagree Jonathan if you if you look at the chart that we presented on slide 19 and also in the Q.

I also believe the press release when you start remember we took all comers into this trial, we took up to people with up to 11 prior therapies.

Speaker 3: And if you look at the right hand side of that chart, you get down to where we're looking at second and third line therapies, add a dose that we zeroed in on, and we're getting substantially better data.

And if you look at the right hand side of that chart, you get down to where were we.

When you're looking at second and third line therapies at a dose that we zeroed in on and we're getting substantially better data.

Yeah.

Speaker 6: I'd look at that waterfall.

So as long as they can look at that waterfall.

I look at that waterfall I'd look at that waterfall data.

Speaker 5: But it's the same N of patients that was prior reported on as just greater duration data, correct?

But it's the same.

Ah patients that was prior reported on is just greater duration data correct.

Speaker 3: No. Well, we reported the phase 1B, the 67% was phase 1B, and then we moved on, and now we're presenting the phase 2 data. And so, what we did was we added 17 patients. And you can see the waterfall data, how it goes across that chart. And so, we end up, once we start looking at the 330 milligrams and below patients, we found out that 360 and 390 was just too much.

No well, we reported the phase one beat the 67% was phase one be and then we moved on and now we're presenting the phase two data and so what we did was we added 17 patients and you can see the waterfall data how it goes across that chart.

And so we end up once we start looking at the 330 milligrams and below patients we found out that $3 60, and 390, but it's just too much and.

Speaker 3: and people with less prior therapies. We got better results. We got results compared to dicarzavine and trabecu...

And people with less prior therapies, we got better results, we got results.

Parents have to die cars are being a trabecular.

Speaker 5: And worse to be fair to me, though, I mean, I've written up notes in the past of three phase 1 patients at the recommended phase 2 dose and 14 phase 2 patients, all of whom must be taking the recommended phase 2 dose, and that adds up to 17.

And in worst or to me, though I mean I've written up notes in the past the three phase one patients at the recommended phase two dose and 14 phase two patients all of whom must be taking the recommended phase two dose and that adds up to 17.

Speaker 5: Yeah, I think the point here, Jonathan, is since that last report, we now have updated PFS, updated OS, as well as segment data that just hadn't been elucidated. So, I take your point, but I think there's important new information that we're sharing for the first time in this release.

Yeah, I think the point here Jonathan is since that last report, we now have updated PFS updated O S. As well as segment data that just hadn't been elucidated.

So so you know I.

I take your point, but I think there's important new information that we're sharing for the first time in this release.

Speaker 5: All right, lastly, how many patients do you expect to have to enroll in a pivotal trial for both AML and...

Alright. So lastly, how many patients do you expect to have to enroll in a pivotal trial for both AML.

And S T S L M.

Speaker 5: So, Paul, you spent more time than anybody focusing on the proposed pivotal trial protocols, and I know you've had lengthy discussions both with investigators and statisticians, so you want to tackle that one?

So Paul you you spent more time than anybody focusing on the propose a pivotal trial protocols and I know you've had lengthy discussions both with investigators and statisticians. So you want a you want to tackle that one.

Speaker 4: The ultimate answer is whatever the FDA demands. For soft tissue sarcoma, the

The ultimate answer is whenever the FDA demands for soft tissue sarcoma.

We have not.

Speaker 4: finalize the plans for the pivotal trial yet because as I mentioned, patients are still going on and we have not reached median overall survival and the like. We would anticipate it will be in the few hundreds, but we can't give you an exact number yet because that trial, the efficacy data are still coming in. For the AML, as we have mentioned before, we would like to go for first-line therapy.

Finalized the plans for the pivotal trial, yet because as.

As I mentioned patients are still going on and we have not reached the median overall survival and the like we would anticipate it will be in the in the in the few hundreds, but we can't give you an exact number yet because that trial the efficacy data are still coming in.

For the AML as.

As we have mentioned before we would like to go for first line therapy.

Speaker 4: The 106 trial we're doing now, we are now enrolling first line therapy patients to get data to make sure that the results are similar, if not better than what we have seen to date.

The 106 trial, we're doing now we are now enrolling a first line therapy patients to get data to make sure that the results are similar if not better than what we have seen them to date.

Speaker 3: Based on FDA guidance documents, we would propose going to the FDA and getting approval based on a single trial. There is a pathway for a single trial with single-arm therapy through accelerated approval with subsequent confirmatory trial through the accelerated approval process. We would propose that a single-arm trial would take about 100 patients. If we're required to do a randomized trial, it would be about 300.

Based on FDA guidance documents, we would propose going to be F. D E and getting approval based on a single trial. There is a pathway for a single trial with single arm therapy through accelerated approval with subsequent confirmatory trial through the accelerated approval process, we would propose.

Is that a single arm trial would take about 100 patients. If we're required to do a randomized trial would be about 300.

Speaker 4: And Paul, let me add on to that. You mean elderly and unfit first line, correct? Yeah, for elderly, for our first line therapy in elderly and unfit patients, we would do a single arm study, which is not that far off from what Vanessa was doing, and get approval on a...

Okay, Paul let me add onto that you mean elderly unfit first line correct.

Alright for elderly and for a first line therapy in elderly unfit patients. We would do a single arm study, which is not that far off from what <unk>.

But Asia was doing.

And get approval on a.

Speaker 3: single arm steady accelerated approval. And then again, if you do accelerated approval, you need a confirmatory trial, more of a traditional randomized trial where we would go broader indication, randomized versus an active people alarm.

Single arm study of accelerated approval and then again if you do accelerated approval you. The confirmatory trial in more of a traditional randomized trial, where we'd be go broader indication a randomized versus an active control arm.

Speaker 5: Okay, just to make it clear that it's somewhere in the lower triple digits of patients per trial is helpful, thanks. Can you lastly answer, what kind of progress have you made in finding funding or getting an investigative sponsored trial going with the other two products, 1066 and 1112?

Okay, well just to make it clear that its somewhere in the lower single digits of patients per trial as is helpful. Thanks, I'm, taking you lastly.

Cancer have you what kind of progress have you made.

Finding funding or getting an investigator.

Sponsored trial going with the other two products 10, 66 to 11 and 12.

Speaker 5: So, let me start there, but, John , you may have some nuance that you want to add to this. Probably one of the most prolific areas of outside funding has been with our STAT-3 inhibitor 1066.

So let.

Let me, let me start there, but John you may have some some nuance that you want to add to this.

One of them.

One of the most prolific areas of outside funding has been with our statutory inhibitor 10 66.

Speaker 5: And just a quick recap, MD Anderson sponsored a trial there, then Emory University in pediatric brain tumors, and then the investigator that was at MD Anderson moved to Northwestern University. And we've been in ongoing discussions with that investigator. It's very likely that that investigator will come through with another externally funded trial for brain tumors in 1066. And we know that the folks

And just a quick recap.

MD Anderson sponsored trial, there then Emory University in pediatric brain tumors and and then the investigator that was at M. D. Anderson moved to northwestern University.

And we've been in ongoing discussions with that investigator, it's very likely that that investigator will come through with another externally funded trial for brain tumors, and 10, 66, and we know that the folks at Emory.

Speaker 5: are awaiting some additional data to come from the adult progress before they kick off. They've already indicated they want to kick off another pediatric brain tumor trial. So they're symbiotic, they're comparing information. There's essentially a consortium of folks across the U.S. that have now recognized.

Are awaiting some additional data to come from the adult progress before they kick off they've already indicated they want to kick off another pediatric brain tumor trial. So there there are symbiotic they're there they're comparing information.

There's essentially a consortium of folks across the U S that are now recognized there's clearly some potential for activity of 10, 66, and brain tumors, especially when it comes to pediatrics.

Speaker 5: there's clearly some potential for activity of 1066 in brain tumors, especially when it comes to pediatrics.

Speaker 5: And then finally, we continue to grind away on an IV formulation for 1066.

And then finally.

We are we continue to grind away on the IV formulation for 266 and the.

Speaker 5: And the investigators I've just described have all made it clear the instant that we have an IV formulation, they intend to switch to that.

The investigators I've just described have all made it clear the incident that we have and I E formulation, they intend to switch to that.

Speaker 5: because we all recognize that the PK characteristics are probably going to be better with an IV delivery of that drug. On the 1122 side, we continue to right now just be moving at what I call grant speed on the basis of U.S. government grant funding of.

Because we all recognize that the PK.

The characteristics are probably going to be better with an IV delivery of that of that drug on the 11 22 sides. We we continue to right now just be moving at what I called grant speed on the basis of U S. Government Grant funding of Virology research as it relates to 11 22, so that's our primary.

Speaker 5: Virology research as it relates to 1122. So that's our primary focus there. But I you know, let's face it that that stuff is

We focus there, but I I mean, let's face it that that stuff is highly.

Speaker 5: It's highly speculative and it's slow-moving, so I would say that the slowest program we have in the portfolio right now is $11.25.

It's highly speculative.

And it's slow moving so I would say that the slowest program we have in the portfolio right now it's 11 22.

Speaker 5: And then I would add to that, I would add that the Northwestern trial is already listed on clinicaltrials.gov. It's 1066 in combination with radiation against GBM. Okay, thank you. And the Q will come out later today?

Alright, Thanks, and then I would add to that that I would add.

I would add that the northwestern trials already listed on clinical trials Dot Gov. It's 10 66 in combination with radiation against G. P M.

Okay. Thank you and they are Q will come out later today.

But the Q should have already been filed.

Okay.

Thank you guys.

Thanks, Jonathan.

Speaker 1: Thank you. Our next questions come from the line of Jason McCarthy with Maxim Group. Please proceed with your question.

Thank you. Our next question is come from the line of Jason Mccarthy with Maxim Group. Please proceed with your questions.

Speaker 7: Hi guys, thanks for taking the questions. In the STS data, with the median PFS looks like it's 3.4 months for patients who are less than

Hi, guys. Thanks for taking the questions and the S. T. S data with the median PFS looks like it's 3.4 months for patients who are less than.

Speaker 7: 330 megs per meter squared. You mentioned that the overall survival median so far has reached

We entered 13 migs per meter squared.

You mentioned that the overall survival median so far has reached 11 months and 15 patients from phase one b, what what was the share back that in.

Speaker 7: 11 months and 15 patients from phase 1b. What was the trabec to be?

Speaker 3: OS before it was approved. I know it didn't move the needle much on OS, but it did. It must have had an OS. That's the first. Yeah, okay. I'll jump in there because I looked at the paper they're referencing. They really don't go into PF, I mean OS data. They really focus on PFS data. That's why we're so excited.

Oh S. Before it was approved I know it doesn't really move the needle much at all that but it did it must have had and all that.

Yeah Okay.

I'll jump in there because.

It looked at the paper, they're referencing they really don't go into Pea or PFS OS data, they really focus on PFS data.

That's why we're so excited about the median OS that we're receiving.

Speaker 7: Okay, and mechanistically...

Okay and and Mechanistically.

Speaker 7: from for Adam Iason, what do you think the differences are?

From for Adam I ads and what what do you think the differences are.

Speaker 7: where you're having to go 330 meg per meter squared or less in the STS trial but you're going higher in the AML trial.

Where you're having to go 330, Meg per meter squared or less and the S. T S trial, but youre going higher and the AML trial.

Speaker 5: Well, let me let me let me start that off and Paul, fill in wherever you think I maybe haven't covered it adequately, but.

Well, let me let me, let me start that off and Paul fill in wherever you think I, maybe haven't covered it adequately but.

Speaker 5: I think there are two dynamics here at work. One of them is the specter of thrombocytopenia in patients. And so we know that even though we can technically

There I think there are two dynamics here at work one of them is the specter of thrombocytopenia in patients and so we we know that.

Even though we can technically.

Speaker 5: the hurdle that of not reaching a DLT and keep we in fact we never we never did establish an MTD in that trial.

Cross the hurdle of of not reaching a D. L T and we in fact, we never we never did establish an M T D in that trial.

But as we bumped up against $3 90. It was the handwriting was on the wall that the thrombocytopenia.

Issue with patients.

What was going to become a barrier to ongoing treatment and and so we felt like okay. We're seeing.

Speaker 5: similar activity at lower dose levels, so let's not push the envelope here. Let's work in the center of the therapeutic window, if you will. More specifically to your, because I understand your question, you know, why do we think that we might not get any more benefit out of higher dosing? Because classically speaking, higher is better with an anthracycline. You go to the maximum.

Similar activity at lower dose levels, so, let's not push the envelope here, let's let's work at in the center of the therapeutic window, if you will.

More specifically to you because I understand your question.

You know why do why would why do we think that we might not get any more benefit out of higher dosing because classically speaking hires better with an anthracycline. If you go to the maximum.

Speaker 5: There's a scientific analysis that the inventor has gone through whereby there are some mechanistic reasons when you get to a certain level, this as you know is a topoisomerase II poison, there appears to be the potential for a point of diminishing returns where you simply can't get any more.

There is a scientific analysis that the inventor has gone through whereby there there are some mechanistic reasons when you get to a certain level is this as you know is a turbo I summarized to poison.

There appears to be the potential for a point of diminishing returns where E U.

You you simply cant get any more.

Speaker 5: cell kill benefit out of increasing the dosage, but you can actually start to have some sort of counter-effective results, and we don't have the specific mechanism data to support that argument, but it's a theory.

I'll kill benefit out of increasing the dosage, but you can you can actually start to have some some sort of counter effective results and and that's we don't have the specific mechanism neck mechanism data to support that argument, but it's a theory, but the original theory.

Speaker 5: But there is a theory out there that says there's a point where you can go too far with the topo2 poison and not get any additional benefit out of it. But Paul, do you want to add anything to that?

We're out there that says there's a point where you.

You you can go too far with the telco to poison and not get any additional benefit out of it Paul do you want to add anything to that.

Speaker 4: Yeah, let me just add just the indications. You are correct, and that's a good point. The 330 we're doing for soft tissue sarcoma is actually lower than the 230 we're doing for AML, because the 230 is for three straight days, which becomes 690.

Yeah, Let me just add just the the indications you're correct and that's a good point. The 330, we're doing for soft tissue sarcoma is actually lower than the $2 30, we're doing for AML, because the 230 years for three straight days, which becomes six nine.

Speaker 4: If you look at the soft tissue sarcoma, our number one by far.

If you look at the soft tissue sarcoma, our number one by far.

Speaker 4: Adverse event is low blood counts, especially plate.

Adverse event is low blood counts, especially platelets.

Speaker 4: And that forces us at times to stop. We could go up to 390. We didn't have a DLT, but we had to delay therapy because of the low.

And then.

There's other times to stop we could go up to $3 90.

We didn't have a D L T, but we have to delay therapy because of.

The low platelet counts because it was hitting the bone marrow well with AML, that's where you get out of it that's where the cancer is it is the blood cells in the bone marrow. So you've got a blast the hell out of them essentially and wipe them out for a while so the toxicity that is forcing us to hold and delayed dosing in soft tissue sarcoma.

Speaker 4: because it was hitting the bone marrow. Well, with AML, that's where you gotta hit. That's where the cancer is. It is the blood cells in the bone marrow. So you've gotta blast the hell out of them essentially and wipe them out for a while. So the toxicity that is forcing us to hold and delay dosing in soft tissue sarcoma if we go too high, that's not an issue with AML because in AML, here the safety location is also the efficacy location. So it's just...

If we go too high that's not an issue with AML, because then a M. O here. The safety location is also the efficacy of location. So it's just what's in a adverse event for one indication for the other that's efficacy. So I think that's the primary reason for the difference in why we were keeping it a little lower.

Speaker 4: With an adverse event for one indication for the other, that's efficacy. So I think that's the primary reason for the difference in why we're keeping it a little lower than soft tissue sarcoma than an AML.

Sure than soft tissue sarcoma and in AML.

Does that makes sense to you.

Speaker 7: Got it. Last question, you had mentioned potentially selecting another indication next year. Can you provide a little bit more detail as to what you may be thinking perhaps along the lines of where an anthracycline may be a key therapy or a go-to therapy? Kind of what the PFSOS might look like in whatever set indication.

Got it last question you had mentioned potentially selecting another indication next year can.

Can you provide a little bit more detail as to what you may be thinking perhaps along the lines of awareness and Anthracycline, maybe a key therapy or a go to therapy.

Sure what the PFS all that might look like in whatever set of indications.

Speaker 5: Yeah, we can't speak to speculating on what the human PFS OS implications of this would be, but we've got

Yeah, we I mean, we can't speak to it too.

Speculating on what the human PFS OS implications that this would be but we've got very compelling data in a number of indications.

Speaker 5: very compelling data in a number of indications. For example, triple negative breast cancer mets to the lungs. Also, renal cell carcinoma met to the lungs.

For example, the triple negative breast cancer matched to the lungs.

Also renal cell carcinoma met to the lungs.

Speaker 5: but the one that probably gets the most excitement out there is pancreatic cancer and specifically pancreatic cancer mets to the liver. And as I'm sure you know, Jason, most pancreatic cancer patients present with liver mets. And so it's the most common site of metastasis.

But the one that probably gets the most excitement out there is pancreatic cancer and and specifically pancreatic cancer matched to the liver and as you all know I'm sure you know, Jason most pancreatic cancer patients present with liver Mets.

And so it's it's it's the most common side of metastasis and <unk>.

Speaker 5: We've talked for now a long time about the fact that we can hyperaccumulate in the lungs. It turns out we also hyperaccumulate in the liver as compared to doxorubicin. I think the ratio's like six to nine times more than doxorubicin. So it might be the first opportunity to actually bring an anthracycline to the table in pancreatic cancer. So,

We've talked for now a long time about the fact that we can hyper accumulate accumulate in the lungs. It turns out we also hyper accumulate in the liver as compared to doxorubicin.

I think the ratios like six to nine times more than doxorubicin. So it might be the first opportunity to actually bring in anthracycline to the table in pancreatic cancer.

So if we were if we were to kind of pick and choose and say who what investigator funded study would we be most enthusiastic about its probably that one.

Speaker 5: If we were to kind of pick and choose and say who, what investigator funded study would we be most enthusiastic about? It's probably that.

Speaker 7: Okay, just to follow up to that then.

Okay, just a follow up to that then.

Speaker 7: Because you're accumulating in the liver, does that reduce the potential for healthy tissue talks in the liver? Because a lot of chemotherapies are just not used in the liver because the liver's already weakened because it has either liver mets or primary tumors there.

Because you're accumulating.

In the liver does that reduce the potential for.

Healthy tissue talks in the liver because a lot of chemotherapies or just not used in the liver because deliveries already weakened because it has.

Either liver Mets are our primary tumors there.

Well I mean, we.

Speaker 5: What we know from the animal data is that

What we know from the animal data is that.

Speaker 5: we don't see any disproportionate increase in liver toxicity in animals vis-a-vis doxorubicin even though we appear to accumulate it nine times the level. Paul, you've been monitoring liver toxicities in human patients. What's your perspective there?

We don't see any dip.

Disproportionate increase in liver toxicity in animals needs to be done.

So even though we saw a period of accumulated nine times the level.

Paul you've been monitoring liver toxicities and in <unk>.

Human patients.

What's your perspective there.

To date, we have.

Speaker 3: We have seen no indication of liver toxicity. You look for what's liver toxicity based on what's called PI's criteria, that's H-Y-E-Z.

I've seen no indication of liver toxicity, you look for.

Liver toxicity based on what's called is a criteria that's H Y. He's a famous the physician in liver disease. We've seen them. We have not seen bilirubin go up we have seen liver enzymes fluctuate a little but they never go up to a clinically significant degree so as of now I guess were.

Speaker 3: famous physician in liver disease. We've seen that. We have not seen Billy Rubin go up. We have seen liver enzymes fluctuate a little, but they never go up to a clinically significant degree. So as of now, I guess we're approaching 70 patients being treated in all of our studies. We don't have evidence of liver toxicity.

Approaching 70 patients being treated in all of our studies, we don't have evidence of liver toxicity.

Great. Thank you guys.

Speaker 1: Thanks, Jason. Thank you. Our next questions come from the line of Jeff Jones with Oppenheimer. Please proceed with your question.

Thanks, Jason.

Thank you our next questions come from the line of Jeff Jones with Oppenheimer. Please proceed with your question.

Speaker 1: Thanks for taking the question, guys, and congrats on the quarter and the updated data.

Thanks for taking the question guys.

That's on the quarter and the updated data.

Speaker 1: A couple of questions, following on from what's been discussed already. My understanding of your path forward in STS lung MIPS is that you're looking at, similar to Trevectadine, a PFS endpoint for approval. Is that correct?

A couple of questions following on from what's been discussed already.

My understanding of your path forward in STS alone. That's is that you're looking at similar to her back to that in a PFS endpoint for approval is that correct.

Speaker 5: Well I think we would modify that to say we really think that we've got a shot at moving the needle materially on OS. So correct me if I'm wrong Paul but I think of our our window of opportunity here to be the combination of both PFS and for the first time ever PFS that actually translated into increased OS.

Well I think we would modify that to say, we really think we've got a shot at moving the needle.

Materially on OS So correct.

Correct me, if I'm wrong, Paul, but I I think of our our window of opportunity here to be the combination of both PFS and for the first time ever PFS that actually translated into increased O S.

Speaker 4: Again, from a regulatory standpoint.

Again from a regulatory standpoint.

Speaker 3: We would, in any clinical trial, would be measuring both variables, PFS and OS. We would prefer to have PFS since it would be quicker approval, obviously, but as Wally said, the data are becoming very impressive for OS, so we would probably, at an end-to-phase 2 meeting, propose to the FDA initial approval on PFS and then add OS into the product labeling just for better marketing opportunities.

We would in any clinical trial would be measuring both variables PFS and OS.

We would prefer to have PFS since it would be quicker approval, obviously, but as Wally said the data are becoming very impressive for O S.

So we would probably at an end of phase II meeting and propose to the F. D. A initial approval on PFS and then add OS into the product labeling Ah just for better marketing opportunities.

Speaker 1: Okay. That makes sense. And then I guess as I look at the PFS data across the subgroups that you've provided, you know,

Okay that makes sense and then I guess as I look at D O S state or at the PFS data across the subgroups that you've provided you know.

Yeah.

Speaker 1: you're, well, it's 3.4 in the 330 mg per meter squared with less than two prior lines of therapy. It's in the two to two and a half range when you look at the more intent-to-treat populations for both the phase Ib and II. And Trebectadine, the PFS, was somewhere on the order of two and a half months. So...

You're well, it's three four in the 330 Meg per meter squared with less than two prior lines of therapy. It's in the two to two and a half range. When you look at the team more intent to treat.

Populations for both the phase one being two and trip back to then the PFS was somewhere on the order of two and a half months.

So.

Speaker 1: even taking the 3.4 months, you're adding a month, a month and a half to PFS. And so it goes to the question of clinical meaningfulness.

Even.

Even taking that three four months, you're adding a month to month and a half to PFS and so it goes to the question of clinical meaningfulness.

Speaker 1: And as you probably know, there was a company that just dropped a trial or dropped a program with a PFS of 3.6 months.

And as you probably know there was a company that just.

Just dropped the trial or crop the program with the PFS.

Three six months.

Speaker 5: So, you know, they just abandoned the product with the 3.6 month PFS. So, that overall file is critically important.

So you know they just abandoned the product out with the $3 six months PFS. So.

So Jeff one thing critically important.

Speaker 5: Jeff, one thing I would point out that I think is a point of difference.

Jeff One thing I would point out that I think is as a point of difference.

Speaker 5: is, first of all, it's not greater than a first-line therapy, it's two or fewer prior therapies in that right-hand column, but it's important to note that we chose the most difficult subset of patients.

Is first of all.

It's it's it's not a it's not greater than a first line therapy. It's it's it's it's cheap it's too.

Two or fewer.

Prior therapies in that right hand column, but.

It is important to note that.

We chose the most difficult subset of patients.

Speaker 5: in our inclusion exclusion criteria here. So we're not taking all advanced, this was not an all-comers trial, this is not all advanced soft tissue sarcoma, this was only lung meds.

In our inclusion exclusion criteria here. So we're not taking all advanced this was not an all comers trial. This is not all advanced soft tissue sarcoma. This was only lung Mets.

Speaker 5: And in every trial we've ever seen published, while no one actually gives specific data for the subgroup of lung mat.

And in every trial, we've ever seen published while no one actually give specific data for the subgroup of walnuts.

Speaker 3: most of those trials will somewhere in their text acknowledge that the lung mets subgroup underperformed vis-a-vis the overall population. So because we accumulated in the lungs the way we do, we deliberately chose this worst possible select selection criteria. Now, having said that,

Most of those trials will somewhere in their tax acknowledge that the lung Mets subgroup underperformed vis vis the overall population. So we because we accumulate them along the way we do we deliberately chose this worst possible select selection criteria.

Now having said that we.

Speaker 5: We think the more likely approval trial design will be an all comers trial. And it's very likely to be first line patients.

We think that the more likely approval trial design will be an all comers trial and it is very likely to be first line patients. So.

Speaker 5: So we realize that the data we're talking about today is not precisely the target that we're setting for a likely approval trial, but everything gets easier for us, we think, as we design this approval trial structure.

We.

We realized that the data we're talking about today.

It is not precisely the target that we're setting for a likely approval trial, but everything gets easier for us we think.

As we designed this approval trial structure.

Speaker 1: Okay, that's helpful. Thank you. On the AML side, you're in sort of your timelines. You're talking about an end of phase two, the first half of 24, and a potential pivotal start second half of the year. And as you were talking about dead A's,

Okay. That's helpful. Thank you.

On the AML side, you were in sort of your timelines you're talking about an end of phase two the first half of 'twenty for the potential pivotal start.

Second half of the year.

And.

As you were talking about that as a yes.

Speaker 1: You know, depending on single arm or otherwise in a randomized study 100 to 300 patients, what did the cost look like for pivotal study, both frankly in AML and SDS at Lung Mets or SDS as you were just implying?

Depending on single arm or or otherwise in a randomized study 800 to 300 patients what did the costs look like for pivotal study.

Frankly in AML and STS.

STS along the map for STS as you were just implying.

Speaker 5: John , that's clearly in your ballpark, you want to handle that one?

John that's clearly in your your your ballpark do you want to handle that one.

Yeah.

Speaker 3: Sure, so a talking about a phase 2-3.

Oh sure so you're.

You're talking about a phase two three.

Speaker 3: study, pivotal study, you're talking roughly roughly $18 million. Talking

Study pivotal study you talked Iraq I mean.

Roughly roughly $18 million.

Drug included in which indication.

Hey M L.

Speaker 5: And Jeff, we might not have been that articulate about it, but it looks like there's enough, in Paul's segment he mentioned this, there's enough enthusiasm on the STS side among institutions that are specializing in this. It looks very likely that we're gonna have external funding for a PIPL trial on STS.

And Jeff.

We we we were not we might not have been that articulate about it but it looks like the there's enough impulse segment. He mentioned this.

There's nothing to lose he has them on the S. T S side among.

<unk> that are specializing.

It looks very likely that we're going to have external funding for a pivotal trial on on S. T S.

Speaker 1: OK, well, you know, what would the total funding be required for the STS pivotal study?

Okay well.

What would the total funding be required for the S. T S. A pivotal study.

Well I would say.

Speaker 3: from a stamp, well, it really depends how much we get from the externally funded.

From a stand well it really depends how much we get from the external externally funded trial.

Speaker 1: Exclusive of external funding, so all in, and then external funding would obviously

I need to take out about exclusive of external funding so.

All all in and then external funding with obviously.

Speaker 3: reduce your investment requirement? Yeah, a Phase IIB, not a pivotal, just to get it off the ground would be fairly cheap. We would estimate less than $5 million. That does not include the pivotal population.

Reduce your investment requirement.

Phase two b not a pivotal would probably just to get it off the ground would be would be fairly cheap.

We would estimate at less than $5 million that does not include the pivotal.

Pivotal population.

Speaker 5: I think practically speaking, it's not a lot different than the pivotal AML trial in terms of cost.

But I think practically speaking, it's Frank it's not a lot different than the pivotal AML trial.

Correct in terms of cost.

Okay.

Helpful.

Thanks, guys.

Thanks, Jeff.

Speaker 8: Thank you. We have reached the end of our question and answer session. I would now like to turn the floor back over to Mr. Klimt for closing remarks.

Thank you we have reached the end of our question and answer session I would now like to turn the floor back over to Mr. Clemmer for closing remarks.

Okay.

Speaker 5: Thanks, Gerald. Look, we're clearly excited about this data, having it for the first time, something real to talk about. I think we're finally at that point where we're able to see...

Thanks Darryl.

Look we.

We're clearly excited about this data having it for the first time something real to talk about I think where we're finally at that point, where we're able to.

Speaker 5: stop talking about what might happen in the future and start talking about what is happening right now you know look

[noise] stopped talking about what might happen in the future and start talking about what is happening right now.

Speaker 5: Our loyal supporters have been patient for a very long time, so we couldn't be happier to be finally delivering this kind of data.

We are.

Our loyal supporters, who have been patient for very long time, so we couldn't be happier to be finally, delivering this kind of data.

Speaker 5: And for those of you who are new to the story, frankly, your timing couldn't be better.

And for those of you who are new to the story frankly, your timing couldn't be better.

Speaker 5: You should expect more positive updates in the next few quarters because this data is building. And so, we're going to establish a pivotal pathway for anamycin and we'll communicate that as quickly as we can to the marketplace. This is what we've all been waiting for.

You should expect more positive updates in the next few quarters. Because this data is building and so we're going to establish a pivotal pathway for animation and we'll communicate that as quickly as we can to the marketplace.

This is what we've all been waiting for.

So thank you a lot and have a great week.

Speaker 8: Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.

Thank you. This does conclude today's teleconference. We appreciate your participation you may disconnect. Your lines at this time enjoy the rest of your day.

Okay.

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Okay.

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Yeah.

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