Moleculin Biotech Inc. Q1 2023 Earnings Call
Speaker 1: C C to and.
Speaker 1: Hundred.
Speaker 2: Hello and welcome to the Molecular Biotech Q1 2023 quarterly update conference calling webcast. If anyone should require operator assistance, please press star zero on your telephone keypad. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded.
Speaker 2: It's not my pleasure to throw the call over to your host, Janine Thomas and Best of Relations. Please go ahead Janine. Thank you Kevin, good morning and welcome everyone. At this time I would like to remind our listeners that remarks made during this webcast may state management intentions, beliefs, expectations or future projections.
Speaker 3: These are for looking statements and involve risks and uncertainties. For looking statements on this call are made pursuant to the state's hardware provisions of the federal securities laws and are based on molecular current expectations and actual results could differ materially. As a result, you should not place undue reliance on any for looking statements.
Speaker 3: Some of the factors that could cause actual results to differ materially from these contemplated by such board-looking statements are discussed in the periodic reports molecular and files with the Securities and Exchange Commission. These documents are available in the Investor Section of the Companies' Website and on the Securities and Exchange Commission's Websites.
Speaker 3: 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. While the company believes these third-party sources to be reliable as of the date of this presentation.
Speaker 3: It is not independently verified and makes no representation as to the adequacy, fairness, accuracy, or completeness of, or that any independent source has verified any information obtained from third-party source. Any data discussed regarding clinical trials and progress are considered preliminaries and subject to change.
Speaker 3: Joining us on today's call from the molecular leadership team are Walter Klem, Chairman and Chief Executive Officer, Dr. John Paul Waymak, Senior Chief Medical Officer, and Jonathan Foster, Executive Vice President and Chief Financial Officer. I would now like to turn the call over to Walter Klem, Chairman and CEO . While we please proceed.
Speaker 4: Thanks, Danine. We're going to keep this call relative with brief and highly focused on clinical results.
Speaker 4: First, though, I'd like to add some context here. We think there's a serious disconnect between today's share price and what is actually happening with our clinical data. So I'd like for us to take a deeper dive into both AML and soft tissue socoma.
Speaker 4: In yesterday's press release on clinical activity, we provided a very important detail about the final cohort in our MB105 clinical trial. That's the single agent trial in AML and the final cohort had five patients treated at 240 milligrams.
Speaker 4: per square meter. The official clinical study report or what we call the CSR listed one CR, that's a complete response, and three PRs or partial responses.
Speaker 4: But as we point out in the release, two of those subjects listed as PRs actually cleared their bone marrow blast below 5%, which per the protocol and per industry standards constitutes a complete response, not a partial response.
Speaker 4: By the time the CSR was audited for publication, the clinician who had labeled those subjects as PRs instead of PRs had already left for another institution in position.
Speaker 4: But based on the analysis of our CMOs, we believe that these were both truly complete responses. So why am I focused on this detail? It's because in accordance with our protocol and with the industry norm for AML, we believe we didn't just have five of the last eight patients treated respond.
Speaker 4: Four of them were complete responses and to have a 50% complete response rate in mostly elderly and heavily pre-treated fourth and fifth line AML patients, well, we think that is remarkable.
Speaker 4: And we want you to understand why the entire Molecular Team is so excited about the progress we're making. Another important nuance in our data is playing out in soft tissue sarcoma.
Speaker 4: with nearly half of our MB107 trial and rolled, we're seeing a preliminary median progression free survival or a PFS approaching three months.
Speaker 4: half of our MB-107 trial enrolled, we're seeing a preliminary median progression free survival or PFS approaching three months. While that is
Speaker 4: significant improvement over historical norms for untreated patients and other clinical trials. We believe it's actually much better than it appears.
Speaker 4: And that's because most prior clinical trials of, quote, unquote, advanced soft tissue sarcoma patients.
Speaker 4: include a spectrum of patients from those who are simply no longer receptive, resectable, those are patients whose PFS is expected to be much better than average.
Speaker 4: to those who have lung metastases. And those are the folks with PFS that is expected to be much, much worse. In MB107, we are only enrolling the latter. And that's to say only patients with lung metastases.
Speaker 4: and with the worst possible prognosis. So for us to be nearly doubling the historical media and PFS expected in untreated, advanced.
Speaker 4: STS patients, but to do so while treating only lung meds patients, what we think, again, we think that is remarkable.
Speaker 4: And yes, these data are preliminary and we have more patients to recruit, but thus far, we are performing above expectations in arguably the worst possible patients. And we're doing this without the cardiotoxicity expected from currently prescribed anthracyclines.
Speaker 4: If you're an investor in Moleculin or considering an investment, we think this is where you should be focused.
Speaker 4: This is where the most immediate opportunity for success can be envisioned. And it's why I'm eager to have our Senior Chief Medical Officer, Dr. Paul Weimack, expand further on our clinical progress. Paul?
Speaker 5: Thank you, Wally.
Speaker 5: As Wally noted, we at Moleculin are extremely pleased at our progress to date.
Speaker 5: Our lead candidate, Anna Mison, has now reached the phase two stage of clinical development for our soft tissue sarcoma indication.
Speaker 5: And we expect to reach phase two stage for acute myelogenous leukemia later this year.
Speaker 5: This slide summarizes our current status with animycin and soft tissue sarcoma. And as you can see, we have successfully completed Phase 1b with the identification of 330 milligrams per meter squared as the recommended dose for Phase 2 development. We are now just over halfway through enrollment.
Speaker 5: for the Phase 2 component.
Speaker 5: In this phase two portion of the trial, animisement is demonstrated a progression-free response of 60% of subjects.
Speaker 5: showing stable disease through two or more cycles of therapy.
Speaker 5: with three subjects continuing with the study drug.
Speaker 6: continuing with the study drug. One subject.
Speaker 7: has exhibited stable disease after their end of cycle 4 scan and has now received six full cycles of therapy.
Speaker 8: For the three subjects with stable disease not continuing with study drug, they are still being followed for progression-free survival. And for all subjects, overall survival is being monitored.
Speaker 9: These data are preliminary and are of course subject to change.
Speaker 10: are preliminary and are, of course, subject to change. finally
Speaker 11: As has been true of all clinical trials of anemysin.
Speaker 12: And despite prospective, methodical search plans, we have yet to identify any cardiac toxicity from manamycin in this or in any study.
Speaker 13: Moving on to our acute myelogenous leukemia development.
Speaker 14: We have now completed their two Phase 1 monotherapy trials. These were standard dose escalation Phase 1 studies.
Speaker 15: Not shown on this slide is their US trial, MB104.
Speaker 16: And our European 105 study, we were able to dose escalate up to a dose of 240 milligrams per meter squared.
Speaker 17: administered on three consecutive days. Now, although this dose did not fulfill criteria for stopping dose escalation due to any newly identified dose-limiting toxicities in the patients,
Speaker 18: We nevertheless chose not to dose escalate further for three reasons.
Speaker 19: First, this was a monotherapy trial, and we recognize that it is highly probable that if and when anamycin is approved for marketing for acute myelogenous leukemia, it will be as combination therapy.
Speaker 20: The reason our initial trials were not as combination therapy but rather as monotherapy were routine standard FDA demands for new drug testing.
Speaker 21: The second reason for stopping the monotherapy trial was that newly finished animal studies documented that significant efficacy for animicin existed when combined with cytarabine when treating acute myelogenous leukemia.
Speaker 22: The final reason was that as they shown on this slide, at the 240 milligram per meter square dose,
Speaker 23: Four of the five patients had either a partial or a complete response.
Speaker 24: That's an 80% response rate.
Speaker 25: Of these four responders, one was created as a complete response by the investigator.
Speaker 26: and the other three were graded as partial responses.
Speaker 27: But as Wally mentioned, it should be noted that two of the three patients rated as partial responders had their bone marrow blast percentages fall to less than 5%
Speaker 28: which is the standard definition of a complete responder.
Speaker 29: However, since the investigator classified these two cases as partial responders, they are so recorded in the clinical record, despite they're having met the laboratory criteria for a complete responder.
Speaker 30: In light of these three factors, we have therefore moved forward to the combination therapy stage of clinical development.
Speaker 31: in patients with acute myelogenous leukemia.
Speaker 32: In this study, patients with refractory or relapse to acute myelogenous leukemia are being treated with anomycin in combination with cythera-bein.
This initial combination clinical trial will begin with the standard phase 1B dose escalation phase.
Once the Phase 1B component has identified the recommended Phase 2 dosing regimen, we will move on to the Phase 2 clinical investigation.
As of this time, we have six active sites in Europe participating in the trial.
And we anticipate other sites in Europe going active shortly. We have already completed the first cohorts in the dos-escalation part of the trial. Among the three patients treated at 190 mg per meter square in this initial cohort, one patient achieved a durable, complete response.
in our AML clinical trials.
in AML clinical trials for
as their blast counts fall to less than 50%, which again is the accepted definition of a complete responder.
We have now begun enrollment in the second dosing cohort in this study and we anticipate reaching the phase two stage of the trial later this year.
Finally, as was true in the soft tissue sarcoma study, we have yet to identify any cardiac toxicity. We have yet to identify any cardiac toxicity.
Moving on to the next slide.
Our immune transcription modulator, 1066,
is currently being tested in multiple phase one clinical trials in patients with various types of brain cancer.
primarily types of glioma and medulloblastoma. These clinical trials have been and are being conducted at various prestigious medical university hospitals including MD Anderson, Emory University and Northwestern University.
These phase one clinical trials have established that 8 milligrams per kilogram is a safe dose.
and have documented both clinical and radiological evidence of efficacy.
Although the dates of the data are limited.
We are currently evaluating possible strategic partnerships and collaborations to assist in the development of 1066.
And I should also note that we have received orphan drug designation for the treatment of brain tumors, as well as rare pediatric disease designation from the FDA for 1066. Finally, I would like to discuss our 1122 portfolio.
in normal volunteers.
This study established the safety of 1122 and defined its pharmacokinetics.
To that end, this drug is now ready to begin Phase II efficacy studies.
We believe there are two potential avenues for the 1122 portfolio.
First.
We have animal data suggesting it may have benefit in certain types of cancer.
which is believed to be due to the fact that cancer cells are heavily reliant on glucose for their metabolism.
In light of this possibility, we requested and were granted orphan drug designation from the FDA for the treatment of certain types of brain cancer. Those are glioblastomas.
We also have preclinical data suggesting that 1122 will be beneficial in treating certain types of potentially deadly viral diseases. Since many of the types of viruses that infect humans require modifications of the glucose molecules.
forward. We are currently looking for potential collaboration opportunities for our 1122 portfolio.
fall, research and development expense increased by roughly $1 million to $5.7 million for the first quarter.
This increase of just over a million dollars is mainly related to the acquisition of our technology rights in roughly 10% of the world via the termination of a sublicense.
Otherwise, we see our clinical costs are trending downward as we drop from three active internally funded trials to two compared to a year ago.
As we continue to focus our internal funds on animizing trials, we experienced an increase in G&A expense by roughly 8% for the first quarter versus 2022. This increase is related to legal services and consulting fees.
Win of the quarter was over $37 million in cash, which we believe comfortably.
Get this into the third quarter of 2024.
So where are we delivering on data? Well, for anamycin, we continue delivering data on the Phase 1b portion of our Phase 1b2 clinical trial for using anamycin in combination for the treatment of AML.
So where are we delivering on data? Well for anamycin we continue delivering data on the phase 1b portion of our phase 1b2 clinical trial for using anamycin in combination for the treatment of AML in Poland and Italy, in B106.
The last time we spoke we just started this first the first cohort.
We have now recently announced this Paul and Wally have pointed out. Conclusion of that first cohort and does in recruiting in the second cohort as we march towards a recommended phase two dose for our phase two expansion cohort. For AML trials, this is moving quickly for us.
And we hope to announce the safety and advocacy in the second cohort very soon.
We hope this cohort leads us to opening the Phase 2 expansion portion, which will bring along safety and efficacy data going from that point forward, which will be announced with each quarter's results.
We will publish the detail of the MD-105 clinical study report in the near term, expanding on the top-line data already presented. We will continue giving you quarterly updates on the STS trial here in the US and also on the STS trial in Europe .
We continue to expect to announce with regard to our other core technologies, the NIH study with our WP 1122 portfolio.
We also expect to further our collaboration, as Paul just mentioned, on treating GVM using WP 1066. And additionally, for WP 1066, we should see top line results for the phase one pediatric trial and later expansion into phase two.
All of these efforts will be mostly externally funded. So you can see our continued focus with our funds internally is on providing clinical readouts for animizin.
All while progressing on our other two technologies via external funding.
on our other two technologies via external funding. Wally?
Yes.
Thanks, John .
So clearly we're encouraging everyone to pay close attention to animison. The reason is this is where we are expecting to deliver what we would call game-changing news flow over the coming quarters.
But we shouldn't forget about our other two technologies. As Paul pointed out, WP 1066 in combination with radiation is on the verge of a new round of clinical trial activity being paid for by, as he said, prestigious institutions in both adult and pediatric brain tumors.
We expect significant announcements here, by the way, before the end of the year. And WP 1122 has now begun receiving research support from the federal government, and we believe there's potential for still more external funding support for this new class of anti-metabolites.
The early indications are promising and the turning point phase 2 data are now imminent for molecular.
Now look, we know that the small biotech market is under tremendous stress and of course that has put
pressure on values across the board and we're seeing historic lows. But we also believe that strong phase 2 data and encouraging guidance from the FDA will transcend even this market dynamic. And if we're right, it just makes the upside potential that much greater for molecular.
So thanks for your time, and definitely stay tuned for our next upcoming announcements.
And with that, Janine, I'll hand it back to you to open up the questions. All right. Thank you, Kevin. Please, please proceed.
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 1 at this time. A confirmation tone will indicate your line is in the question queue. To remove yourself from the queue, please press star 2. One moment please while we poll for questions. Our first question today is coming from Jonathan Ashworth from ROP-MKM. Your line is now live. Good morning and thank you guys. I was wondering, are the second cohort phase 1B AML combo therapy patients, are they being dosed yet or have they still just been identified? And if yes, how many have been dosed?
So we have just begun dosing the first patient and that second cohort. Additional patients have already been identified. So Jonathan, our expectation is that this cohort is going to fill up quickly. You know, obviously you can always have screening failures and that kind of thing. So.
You know, we don't want to overstate it, but it looks like this cohort is going to fill up quickly. Okay, so we should still see the kind of updates. I mean, I'm assuming that if the data are more positive versus less positive, that you're not just going to be waiting until these quarterly calls to update data, you'll just come out with it like you always have.
So we do have the latitude, and John correct me if you feel I'm misstating this, but we have the latitude to announce.
vaulted to is to say at a minimum you can count on us giving updates on a quarterly basis even when we're not in a dose escalation environment. So John is that is that a fair summation? Correct.
Correct. Jonathan, we will announce the end of that cohort when it happens, and we'll announce the efficacy, whether it's good or bad. Hopefully, that will happen before the next quarter conference call.
Okay, I was going to ask you about granularity on other data release time, but the slides were more granular than the two press releases. So that's fine. But the one I would like to ask for is it really sounds like early 2024 for the US soft issue along that data.
Sounds reasonable, but a top line final data for that.
Well, I think it continues to recruit pretty rapidly, you know, in terms of the traffic we've seen we're technically a little past the halfway point now. So if it continues at that pace, I think we might beat that. Bit of it.
that timing estimate. And keep in mind that...
depending on the flow of the data and how consistent it is, we may, it's entirely possible that we could call a time out and go visit with the FDA even before filling out all 28 patients in the expansion. So I mean I think you're technically correct.
If this goes all the way to term, full 28 patients, probably the formal presentation of the completed data set would be early 24. But I think at the pace we're going and given the consistency of how patients are responding.
We might not have to wait that long before we ask for an audience with the FDA. If I can clarify one thing. When you say the top-line data, I would point out that there are two types of top-line data here. Progression-free survival is what the critical decision is.
And as Marley said, we may, and I think John , we may be there before the end of the year. The other is overall survival and there is no way we're going to be overall survival by the end of the year because overall survival, you have to have a 50% plus one of the patients die and that's not going to happen from what we're seeing before the end of the year.
could trump that and bring a good looking PFS down in relevance if the OS was unimpressive or is PFS stand alone? Okay for registration.
My answer is that's going to be data dependent, data driven. It will depend on what the data shows. Certainly we would like for both of them to be great, but if progression-free survival is adequate to justify approval, then we would go to FDA with just that.
And you always, if you file an MDA, you give a four-month safety update, roughly, to the MDA while the FDA is reviewing. And for this type of trial, frequently the four-month safety update, if you didn't have overall survival when you filed, you will in the safety update.
That's helpful. Thank you guys. Thanks, Jonathan. Thank you. Next question is coming from Jeff Jones from Oppenheimer. Your line is now live. Thanks, guys. Good morning and thanks for taking the question. I guess two questions. In terms of the range of streamlines, can we go to the next slide, please?
The number of patients who are enrolled who are already about the lifetime maximum for docs, what does that look like in both the AML and STS studies?
beyond the EEO. Sure, sure, and thanks for the question.
I'm going to defer to John as the keeper of the head count data, but while he's maybe looking for that specific point in a couple of comments. One.
among the people that we've taken above the lifetime maximum, it's out getting to be a pre-substantial number. We've had a few of those people reach as high as 1800 mix per square meter, whereas the lifetime maximum is 550. And so...
you know, we're not just taking them slightly over that threshold, dramatically over that threshold. And historical data supports that 65% of all patients that are taken above the 550 lifetime maximum will exhibit some evidence of cardiotoxicity.
And again, in our case, 100% of them have exhibited no evidence of cardiotoxicity. So we're pretty proud of the track record here. John , do you have a current count on the total number of people that have been taken over that limit? No, not anything updated that's currently out on our, beyond what's on our...
I'm sorry, what was the second part of your question? The second question was on AML and discussions with the FDA. Discussion with the FDA. Sure. Paul, do you mind characterizing how you feel like that FDA discussion on AML would need to go? Yes. Well, first, just to remind everybody, this trial is unblinded. Everybody gets the drugs. So we see the data in real time.
And we were obviously not going to go meet with them after a dose escalation, would be after the expansion cohort. So we would be watching to see what effect we're having in the expanded cohort, which won't start until sometime later this year.
we would meet with FDA when we see enough efficacy, both in terms of the magnitude of it and as far as talking about the statistical confidence intervals in the data, where we think we have established that this drug works for AML and combination therapy.
As Wally mentioned, right now, recently, once we've gotten this drug up to around 200 or more milligrams per meter square, we're getting about a 50% complete response rate. That, in the patient population we are treating, that has got our attention.
And if such trends were to continue, then we would stop the expansion cohort. And whenever we feel we have enough data establishing efficacy, we would stop and have an end-to-phase-2 meeting with FDA. As far as the previous question, let me just point out one thing about how many people went over the...
515 milligrams of meter square antrocycling dose. Most of the patients, even before they started animaisin, had been on another antrocycling in strong dosages. So most of the patients have gone over the recommended limit. I don't have the exact numbers either, but almost all the patients had prior antrocycling.
the talks and discussions with FDA on AML, or not talks, but cardiotox specifically. You'll also be able to leverage the data you've been generating from the STS trial, as well as the AML trial when you fit down with the agency on that prompt. 100%.
all the clinical trials. So we think the data are becoming compelling that antimicem does not cause the cardiovascular toxicity typical of all other ranthropcycling. And I would just add to that to what Paul just described. You know, I think that we're aware of the fact that there are a few other ranthropcycling.
to the best of our knowledge, we're really the only ones that are thoroughly evaluating cardiotoxicity with every known measure, and then having it independently reviewed, in this case by the Cleveland Clinic. So we're really serious about, you know, about demonstrating this safety record. And, you know, you.
really the only ones that are thoroughly evaluating cardiotoxicity with every known measure, and then having it independently reviewed, in this case by the Cleveland Clinic. So we're really serious about demonstrating this safety record. And Jeff, I know we talked about this.
that the liquid tumor division at the FDA took a different view initially, years ago now, but took a different view about their confidence in the absence of cardiotoxicity. Then a bit later when we were dealing with the solid tumor division, they were more sanguine, they were more convinced by our data.
And of course at that time we had more data. And so now by the time we go back to the liquid tumor division, we're going to, by comparison to the conversation we had with them several years ago, we've got a mountain of data. So we're really optimistic that we're going to be able to make that point.
Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over for any further or closing comments. We think we really thoroughly covered it here. The main message obviously is that there's critical data that's going to be coming in.