Q2 2021 Aptose Biosciences Inc Earnings Call

August 3, 2021

[music].

Good afternoon. My name is Mary and I will be conference operator today I would like to welcome everyone to ask those of other Sciences conference call.

For our second quarter ended June 32000, and and so I need 1 at this time all participants are in a listen only mode. After the Speakers' remarks, there will be a question and answer session.

If you would like to ask a question and you're in this time simply press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question. Please press the pound key.

As a reminder, this conference call may be recorded I would like to introduce Ms. Susan that they're Paolo. Please go ahead.

Thank you Mary good afternoon, and welcome to the <unk> Biosciences conference call to discuss financial and operational results for the first quarter ended June 30th 2021, joining me on today's call are Dr. William G Rice, Chairman, President and CEO, Dr. Yoder them around those senior Vice President and Chief Financial Officer, and Chief business Office.

And Dr. Rafael Bejar, Senior Vice President and Chief Medical Officer before we proceed I would like to remind everyone that certain statements made during this call will include forward looking statements within the meaning of U S and Canadian Securities laws forward looking statements reflect apoptosis current expectations regarding future events, but are not guarantees of performance and it is possible.

And that actual results and performance could differ materially from these stated expectations. They involve known and are known and unknown risks uncertainties and assumptions that may cause actual results performance and achievement to differ materially from those expressed to learn more about these risks and uncertainties. Please read the risk factors set forth and apoptosis. Most recent annual report on form 10-K and F C.

C and Cedar filings all forward looking statements made during this call speak only as of the day, they're made up for US undertakes no obligation to revise or update the statements to reflect events or circumstances. After the date of this call except as required by law I will now turn the call over to Dr. Rice, Chairman, President and CEO of apoptosis Amtrust Biosciences Dr.

Ice.

Thank you Susan.

And welcome everyone to our call for the second quarter ended June 32.

2021.

And while the continued progress on our clinical trials, especially with interest.

And patients with acute myeloid leukemia, or AML patients with B cell cancers, we continue to move through dose escalation and our Chief Medical Officer Dr. Rafael.

And we'll bring you through that and a moment.

Because we have observed clinical activity and our early cohorts for clinical sides are highly engaged and we're pleased with the brisk patient flow to bolt on b cell cancer and.

And no cancer trials.

I'll turn it over to Dr. Bejar.

I'd just like to emphasize the continued need for therapies and these hematologic cancers.

There are a number of drugs on the market and in development for <unk>.

Losses are often insufficiently durable and most patients will relapse or develop resistance.

Let's just and it is our oral highly potent non covalent inhibitor on the <unk> III driver kinases and.

It is like no other commercialized or drug under development.

I'll remind you that losses more than just a typical flit 3 or <unk> inhibitor as.

Is it not only inhibits wild type and mutant forms of <unk> Dk and <unk>.

It's selectively targets clusters and related timing and.

Suppresses the mutations that occur and AML and CML sales that render such sales resistant to other agents.

And it has been found remarkably safe and well tolerated to date.

Thus far looks to have been shown clinically to target. The primary drivers on b cell malignancies, and AML, including <unk> and played through yet.

Yet with the precision that avoids known targets such as <unk> Egfr and <unk> that are often associated with toxicities.

This selectivity is what sets <unk> apart from other hematology drugs on the market or in development and what makes it compelling.

I'll also remind you and at this point.

And sometimes gets lost.

Patients and both of our trials are relapsed and refractory patients who already have been treated with and sales by the best available therapies. So.

So the progress, we're observing and our ongoing clinical trials and these very difficult to treat patient populations is encouraging and we are hopeful that loves will prove to be valuable and to our momentum of therapies for a diversity of hematologic cancers.

With that I'll ask Dr. Rafael Bejar, our chief Medical officer to provide an overview of our clinical activities.

Thank you Bill.

<unk> has 3 ongoing clinical trial 2 studies other kinase inhibitor will accept and then our Lux, 1 and patients with acute myeloid leukemia or AML and the other in patients with B cell cancers and.

And the third trial without make rhopressa after <unk>, III and patients with AML and Mds and.

And certainly there b cell cancer study.

This includes chronic lymphocytic leukemia, or CLO, and non Hodgkin's lymphoma, or NHL, who have failed or intolerant to 2 or more lines of established therapies, including drug such as Rituxan and <unk> from <unk>.

No other treatment options are available and the patients in our trials on previously received from 2% to 12 regimen and it failed them, which also may include failure of other investigational agents.

As we mentioned and our last call, we completed for desktop and our phase 1 trial and accepted and Lexus and well tolerated and patients treated at 150 milligrams 300 milligrams 450 milligrams and 650 milligrams twice daily over multiple cycles.

Evaluable patients at these dose levels, 2 thirds of them experienced dose related reductions and lesion size or IGN measurements compared to baseline demonstrating anti tumor activity.

Since our last update and you're well into the expanded 750 milligram dose cohort and is fully enrolled at this time.

Dr. Rice mentioned, our recruitment has picked up nicely and we expect to complete the 750 milligram dose level with the currently enrolled patients.

Generally we described before and we've observed encouraging on target activity, including tumor reductions and but the aggressive and indolent cancers.

Corporate events held in conjunction with the European Hematology Association of EHS and early June we reported from phase 1 data highlighting our it looks at net activity and B cell malignancies.

Intermediate dose levels as of June 7 had delivered all leading indicators of clinical activity, including target engagement with dose dependent and addition of also be T. K.

And related lymphocytosis and patients with any of the classic CLO and.

Tumor reductions across different b cell malignancies, including Follicular lymphoma.

Chronic lymphocytic leukemia small lymphocytic leukemia.

And welcome since Maverick lobby linear and type of non Hodgkin lymphoma.

We've observed cases, and clear reversal of aggressively growing disease on intra patient dose escalation and longer times on drug, suggesting that even aggressive disease may be successfully challenged with higher exposure levels and extended dosing duration of accepting them.

Pet scans and 1 relapsed follicular lymphoma patient revealed lesion growth during treatment with like sets a net 450 milligrams PID for 7 and cycles, yet after dose escalations at 600 milligrams PID and cycle 8 lesion measurements demonstrated continuous reduction and by cycle 15 day, 1 and target lesions shrank by 43% when compared with peak.

Tumor side.

We continue to spotlight the case for this patient from the first half of this year as a reminder, and moving to higher and longer exposures for effectiveness as we expect and the second half of this year may successfully challenge relapsed and refractory disease.

And it's also important to point out that the data reported during the day, except nib has been generally well tolerated and 'twenty 2 relapsed refractory b cell cancer patients in dose escalation and continue with no concerning drug related safety trends to date.

And so it is our intention, especially as we have begun to observed dose dependent anti tumor activity can you further dose escalation to the 900 milligram dose level for extended duration to tackle and increasingly treatment refractory presenting population and to get as many patients as possible on these higher dose levels.

For more specific information on the trial and the clinical sites and enrolling patients. Please visit clinical trials Dot Gov.

Now, let's turn to <unk> and AML acute myeloid leukemia, or AML is a particularly difficult to treat hematologic cancer, because <unk> potently suppresses split 3 and additional oncogenic signaling pathways upon and which AML cancers rely for survival and drug resistance treating AML patients has always been a priority for answers.

And as Bill mentioned all of the patients and our AML trial have already been treated with and have been found by the best currently available therapeutics, which can include <unk> inhibitor, such as go through it and it might've store and granola net art and if its sorafenib as well and <unk> other treatments and investigational drug and so this is an extremely tough to treat patient population and.

And our EAA corporate event in June and reported promising anti leukemic activity from accepting them.

The first dose cohort received 450 milligrams PID delivered encouraging anti leukemic activity and multiple patients, including a durable <unk> negative complete response, and a flip <unk> ITD AML patient, who had relapsed after 2 allogeneic stem cell transplants multiple lines of chemotherapy and prior for <unk> inhibitor therapy.

To date, we only have presented data on patients at the 450 milligram dose level. We also have completed the 600 milligram dose level for some patients remaining on treatment at 450 milligram and 600 milligram dose level and we expect to complete the 750 milligram dose level with currently enrolled patients.

We are pleased that our sites are very engaged and then we have a vigorous flow and diverse patients on.

Also it's important to note that at these doses. We continue to find that box is generally well tolerated with no toxicity signals or trend to date that we believe would prevent further dose escalation and <unk>.

Colorability profile is critical because it is allowing us to reach the higher dose levels and will permit future use it looks at and <unk> in combination with other agents.

And finally, I will mention that based on our clinical observations to date data from our dose escalation studies are guiding the planning of our dose expansion studies to explore select disease phenotypes under monotherapy and combination therapy programs, we expect to select and expansion dose cohort strategy for AML around year end for.

For more information on the AML trial, and the clinical sites that are recruiting patients. Please visit clinical trials dot Gov.

Now let me quickly bring you up to date on the status of after 253, our second clinical candidate currently in phase 1 trials for AML and Mds.

Some of these data are reported and a poster presented and DHA.

To remind you after 2.5 series and Mick repressor, and and make oncogene is a major driver of cancer cell proliferation, including hematologic cancers.

And as 1 of the most coveted drug targets and cancer. However, there are substantial challenges that have impeded direct make targeted drug development and has been considered undruggable on the past.

As a direct inhibitor of MC transcription. After 250 <unk> represents a novel approach for targeting this oncogenic pathway.

And.

Inhibitor. After 2.5 years III currently being tested in a phase <unk> trial in relapsed or refractory AML and Mds patient currently dosing patients at our sixth dose level of 210 milligrams per meter squared.

And the ongoing phase <unk> study and patients with relapsed and refractory AML and high risk Mds after 2 factories and well tolerated and the patients treated at $20.40.66, 100, and 150 milligrams per meter squared over multiple cycles.

Thus far there is no evidence of drug related adverse events and importantly, no evidence of myeloid suppression.

And the peripheral blood of patients after 2 factory amount of a rapidly transforms to and coexist with the mechanistically active.

And 2 phase III conjugate and significantly higher concentrations of the iron conjugate are sustained for day, suggesting that further dose escalations may provide more sustained pressure on the net target gene and also the biology of the tumor cells.

Collectively the findings from the ongoing phase <unk> study support continued dose escalation and after 2 months III study is currently enrolling patients with AML and Mds at the sixth dose level of 210 milligrams per meter squared and several subsequent dose escalations are anticipated.

Of note we are expanding the trial to include other mix driven hematologic cancers based on after 2 factories and mechanism of action. We also plan to treat.

Patients with buckets lymphoma, and other b cell malignancies that are driven by Nick rearrangements.

We are pleased by the progress across our clinical programs and at the safety and Tolerability of both drug candidate for assessment and after the 2 phase III are allowing dose escalation and all 3 of our ongoing trials as.

As we treat more patients at higher doses, we're generally and for.

Pharmacological and pharmacokinetic data and we hope to provide further updates at the Ash meeting later this year.

I'll now turn the call over to Dr. <unk>, <unk>, our Chief Financial Officer, and Chief Business Officer, who will review financial results for the second quarter Jody.

Thank you Ross and good afternoon, everyone, let's now turn to the quarterly results.

We ended the second quarter was approximately $103 million and cash cash equivalents and investments.

During the quarter, we utilized approximately $8.8 million on cash and operating activities, which were attributable to activities surrounding our pipeline candidates as well as general and administrative purposes.

Based on current operations cash on hand at June 30th provides the company with sufficient resources to fund planned operations, including research and development into the first half of 2023.

Moving on to the income statement, we had no revenues for the quarter research and development expenses were $9.8 million for the quarter and attributable to clinical trial costs for our pipeline candidate manufacturing of drug product for our clinical trials, including continuing development on improving formulations.

So for our pipeline candidates and personnel costs for head count and supporting clinical trials and manufacturing activities and research studies.

G&A expenses for the quarter was $3.7 million and our net loss for the quarter was $13.5 million or <unk> 15 per share.

More detailed information can be found in our filings on Edgar and SEDAR.

I will now turn the call back over to Dr. Right Bill.

Thank you Jody and as you open the call for questions. Please feel free to pose a question to any of us and Dr. <unk>, Dr Bejar or muscle operator, if you could please introduce the first question.

At this time I would like to remind everyone that if you would like to ask a question. Please press star.

And the number 1 on your thoughts on Keybanc. Please limit your questions from 1 question for pricing.

Pause for just a moment to compile the Q&A roster.

Your first question comes from the line of Dan said Pandev.

From Piper Sandler Your line is open.

And thank you very much.

Our credit and care about the progress with from.

Blocks and AML.

AML and pillow and I'm wondering just looking back at the preclinical data was the earnings from that.

So that might start to accrue towards.

Upper level or dose limiting toxicities to look for.

Quick follow up question, if I may 2 for 253.

Good to see that data really like on mechanism did you have a plan.

And to ultimately pursue that beyond hematologic malignancies, and thanks, so much guys.

Alright, thanks for thanks for so much for coming on.

I'll start with the first question on it looks up data and the preclinical data associated with any pointing to any potential DLT.

What I can tell you.

Lux was extraordinarily well tolerated and all the preclinical studies.

And it would be and mouse roadmap for dogs and the GOP talks and what we did observe and this is all of our studies up until that point once a day dosing and all the animal models and we had great anti tumor activity, but we had not seen any toxicity associated with our model with the with Lux and those models. We therefore.

And went into the GOP talks and decided to dose twice a day.

We were trying to drive toxicity and the GOP Tox studies and both the other roads and the dogs.

Even with that going up to the maximum feasible dose in both species, we saw no effects on on the rodents, but if the dogs after 2000 and ease of twice per day dosing, we did see a very slight reduction and neutrophil count it was not considered sufficient to be adverse. So it was not listed as an adverse event.

And.

But it gave us signaled that at the very highest doses there may be a trend towards some of the.

Neutrophil reductions and.

And that's what we are we will continue to look for in the clinical trial.

And a moment I'll ask Dr. Bejar, if he wants to add to that but also you mentioned 253.

Therefore, II <unk> III or MC repressor.

And we agree with you it is exciting to say it.

Find a molecule that actually Ken and EBIT mix, we have seen <unk> inhibition in patients, but at this point, we have not seen any overt toxicity.

Beyond this as we continue to dose escalate through the heme malignancies, we did start with AML and Mds. We are now also including the B cell malignancies that are associated with vickery arrangements and Dr. From my heart, maybe want to add to that and just a moment, but we also would like to look beyond the heme malignancies, and possibly go towards some of the solid tumors.

A good example is that and.

And non human studies of pancreatic cancer, it's been shown that even transient reductions and Mick will highly sensitized to those tumors.

To your classic chemotherapy, and that's a real need and the pancreatic cancers and humans and so once we get to a dose in humans and which we believe we can show consistent E transit or even prolonged inhibition of MC exploration, we'd like to be able to move that into first possibly the dose escalation.

Ladies and excuse me into the drug combination studies and some of those solid tumors and look for the.

The combined effect of drugs with chemotherapy pancreatic cancers, and perhaps the other solid tumors. So did that answer your questions and perhaps I can ask mark from a hard at CIT.

We're very thoroughly.

And then just 1.

1 quick follow up so if we're not looking for.

We may not see dose limiting tox.

Our other markers, including even may be just a plateauing.

And that we would look for for <unk>.

Dose selection or how do you think about that and the good good position that you're in.

So I'll start on that and then I'll ask Dr. <unk> to expand on it. So 1 other things that we look for is are we achieving exposure levels in humans as we dose escalate to inhibit the target kinases.

On the way to do that the accepted ways to take the plasma from the patients bring it back for laboratory place. It on a quarter sales and then ask after treating the sales with the drug did you have enough drug exposure, there and the plasma to inhibit the pathway.

And we have some very nice inhibition of the parcel for 3 of the sick and Egfr office CSF on our <unk>.

<unk> pathways as we continued to dose escalate further and so as we get to the 750 milligram dose level and we hope to get even greater exposure and greater hammering and some of those key oncogenic pathways as we dose escalate. So that's what we look for in terms of Biomarkers and so I'm going to ask Dr. Bexar Alt.

And so to expand on this a bit and to.

To tell us to tell you how we're thinking about selecting that those going forward for expansions.

Sure. Thanks, Bill I think your point about the TIAA assays as best as you. Just described is really important because I think that that's a necessary, but not sufficient cash.

Test to see if youre at the right dose I think if we don't see inhibition and that assay and we certainly need to go higher but design and offsetting in particular to start with a dose of and already shows inhibition and that's also for 3 at the lowest dose level and that study. So we're seeing that already I think like I said I think it is not sufficient.

And not sufficient if necessary, we need to see other activity as well before we decided that we are at the right dose level and Fortunately toxicity permitting we're able to continue to dose escalate and pushed into these higher dose levels to observe that ultimately given the variability of AML patients and some that may have sensitizing patients from that may have more resistant mutations it may not be 1.

On dose level and that applies to all comers and we will have to continue to dose escalate to explore that but we're in a good position as you mentioned, where the toxicity profile is allowing us to do that.

Perfect. Thank you Dr. Paul and thank you very much.

Okay. Thank you too.

Next question comes from Gregory Relenza from <unk>.

RBC Your line is now open.

Hi, This is in 1 for Greg and thank you for taking my questions.

And I was wondering if you could for.

And more color around the dose dependent antitumor activity that was mentioned and that press release is now and what is your latest thinking around dose escalation and beyond the 900 <unk> dose level. Thank you.

Alright, so again I'll start on it and I'll ask Dr by hard too.

To provide a bit more color around it and as you asked for.

As we have especially in the B cell malignancy patients as we have.

Continued to dose escalate at some of the lower dose levels. We are seeing some of the what we call the markers or the indicators of activity inhibition of <unk> and <unk>.

And of on target lymphocytosis, and some levels of tumor inhibition.

But as we went to higher and higher doses, we started seeing greater levels of tumor inhibition and in particular in patients on.

And when we would see we would start out at 1 dose and then we would expand or increase them to a higher dose level. So I'll ask Dr. Bexar, 2 step and at that point and talk about what we've seen there.

Yes, I think your example is exactly the 1 that we're referring to.

Where do you have a patient that starts at a lower dose level does not see the kind of activity and you would hope to see and then upon dose increasing the dose then begins to see improvements and as we've gone to higher dose levels. We are also seeing higher exposures and so we're hopeful that will translate into greater activity. We have seen the phenomenon that we described at the ehi, meaning where some patients who are on it should come.

On study and will see initial tumor growth and then a couple of these examples patients were allowed to dose escalate and actually have seen some reduction and that tumor growth and net peak, whether it be below baseline or not and so.

But there is some activity as we get to those higher dose levels I think it's a good motivator for continuing to dose escalate and see if we can get greater exposure and individuals and therefore greater likelihood of response.

Yes, So let me play off that because she had also asked about possibly increasing beyond the 900 milligram dose level. So we're at the 750 now we have plans to go to the 900 milligram dose level thereafter.

We hope that we get increased exposure as we go to the higher dose levels.

And we also hope it continues to be tolerated well, if we see that the pharmacokinetics exposures continue to increase its tolerated well, we would seek to to increase.

On the 900 milligram dose level, if the PK and plateauing all for if we see some safety signals.

That may take us and a different direction.

Did that answer your question.

Yes. Thank.

Thank you and I just have a quick follow up if I may on the TIAA assay.

And I was wondering based on the data so far what's your expectation around the serum level that will be needed to inhibit III and resistant mutations and where does that translate in terms of dose level.

For you.

What's interesting is Dr. Bernhard just mentioned just a moment ago how diverse these patients are with AML and we've actually presented some of the data with the Pis and <unk> looking at Blue tree and it is clear when you get to <unk> 5 micro molar you're inhibiting essentially all of the activity the flip III and <unk>.

Particular, when you have the <unk> ITD.

But.

And these patients flit 3 is only part of the what's driving these tumors. So you'll have to flow through as well as and number of other tumors. So it is essential for us to show that we're inhibiting the flip 3 activity.

But we also want to get as high as we possibly can to hit as many pathways as possible. So you want to achieve the highest.

Exposure levels that are tolerated and humans to try to hit the pathway as much as you can.

And Trumpf and what else Owen and as we look to wild type and typically it takes a little bit more of a drug to inhibit the wall type flip 3.

But we are seeing inhibition of that too we have our pis and <unk> I think we're the only company that does this we look at we have 2 different sale reported sales and 1 is split 3 well type 1 and split 3 IGD and.

And we've already shown that we also inhibit the wall type flow III at sub micro molar levels and we do so very effectively.

But again you need to inhibit the other receptors and for cell service PDGF are almost CSF 1 on track.

As well as some of the internal.

<unk> 6 <unk>.

<unk> 6 as.

As well as maybe the <unk> and some of the awards and some of the others. So we need more drug or we always want to try to get more drug in as much as we'll be tolerated.

<unk> be hard to do you want to add to that.

Yes, I'll point out that it's tempting to look at the drug like deluxe and call. It a <unk> inhibitor and that is an accurate description on what it does what it does and so many other things and I think irrelevant to which activity and we have to take those into account and you asked specifically about the inhibition of the resistance mutations that for example could arise and the setting of prior treatment with 1 other agents 1 other.

Resistance mutations can be the resist the mutations that occur and the tyrosine kinase domain certain credit <unk> inhibitors that are out there don't target that very effectively and we know from preclinical data that like I said and that is very effective at targeting those kinds of mutations that could arise and setting and resistance the other.

And mutation that can arise as the gatekeeper mutation and <unk> and.

And our preclinical data again suggests that we have low and animal or activity against that mutation also.

We haven't had the opportunity to to explore that using the pis and <unk> specifically.

We believe that we are well above the concentrations that should be able to do that and that type of in vitro assay.

Thank you. Thank you very much.

Next question comes from the line of John Your line from.

Canaccord Your line is now open.

Hi, guys. Thanks for taking my question.

Other question on the type of patients that you are now enrolling for exceptional and the AML study specifically at the 750 milligram cohort.

Just curious if you are looking to enrich for flit 3 here for example.

Or if you are taking all patients and also.

Wondering if youre getting any patients with prior successful transplants.

And if you can talk a little bit about.

How much follow up you might have on this cohort as we reached the end of 2021 for thanks.

Alright.

So the types of patients while we have not disclosed the types of patients definitively that are on the 750 milligram dose level, but I'll remind you. It is an all comer and which we have both flip through wall type and flip 3 mutated patients.

It is clear that we have shown activity already against it.

<unk> mutant patients, we clearly want to get additional patients like that on the study to be able to prove that we can we can have activity against multiple <unk> ITD patients because again every 1 of those represent a different patient.

Different almost a different disease, because they have such a wide diversity of other mutations and they've been treated with different drugs coming into them at the same time, we absolutely want to have put 3 wall type patients and what I will say that okay. It may be volatile for the 3 it may be over expressed wild type <unk> 3 but again you have all these other mutations.

And there that gives rise to the disease.

So we.

We want to provide balance and we've talked about that all the way through we clearly want to have the <unk> 3 mutated as well as as well.

<unk> type patients.

In terms of patients that have received successful transplants.

We highlight 1 patient and particular, the patient and which we.

We reported the complete response and Marty negative complete response.

Patients had had 2 successful transplant and then and relapsed after several years after the successful transplant.

So perhaps Dr bejar, we'd like to add a bit more to that to talk about the data coming.

Yes, we do allow patients who have had prior transplant on study and then subsequently and relapsed and several other patients have met those criteria.

We do also try to.

Our balance our cohorts to include wild type and for patients.

And with sites selecting the patients that they believe are more likely to respond to help us with that so we are not trying to.

Enrollment in any way, we want to get a clean picture for for both wild type and switch patient because we make decisions about how they go on to expansion.

And then you asked about how much follow up we will have by year end.

You can gauge from from when we have announced progress.

Eddie how many how much time it will be from that point and as we mentioned, we believe that we'll be able to complete the 750 milligram dose escalation cohorts for AML with the patients that we currently have enrolled.

Great. Thank you a little bit.

Yes, okay. Thank you for.

Yes.

Yeah.

Next question please.

Next question comes from the line of Alethia Young from Cantor Fitzgerald. Your line is open.

Hi, This is Emily on for Alethia, Thanks for taking our questions I am curious if you have any updates on potential combination approaches for AML and do you plan to maybe combination cohorts and the dose expansion portion of the phase 1 study and if so what agents would you potentially consider and then I'm also curious.

And you said that you would have the dose.

And sadly by year, and how does the 900 and make the dose cohort.

And to that do you think you could potentially and rolled out by the end of the year or if not on what are your thoughts about that thank you.

Alright, Emily So again, we'll tag team this 1 I'll start out.

In terms of the combination approaches we absolutely want to pursue combination approaches. We've shown this drug has activity as a single agent we want to prove that and expansions with specific either genotypic are definitively defined patients that is as a single agent monotherapy, we are pursuing net but in parallel we do what we do.

And to perform drug combination studies, we haven't disclosed exactly which ones that we're going to pursue yet we will continue to collect data throughout the remainder of this year with the current study the patient populations, and then see which which types of combinations would be appropriate and the particular patient.

And <unk> by that I may see it maybe relapsed refractory and more first line and depending on what we see and the patient types that we look at we will choose the drug combinations appropriately and.

And then in terms of the 900 milligram and how does that fit into the process well again, we're going into the 900 milligram. If it is tolerated well if we're getting greater exposure and we will continue to dose escalate that will be and impacted the timing of the of the <unk>.

Expansion cohorts and we may decide to move on with the 700, 5900, or possibly a higher dose level.

We will follow the data, which is what we always do and try to make rational decisions and then provide you with additional information towards the year end and Dr. Bexar any additional.

Nothing additional to your comment about the 900 milligram cohort and if thats.

Accurate with regard to combination.

Want to be able to combine with other agents, because we think that the future of the treatment of and that will be and combination just as it has been for other hematologic malignancies, where they have several therapeutic options available.

For myeloma for example, and.

I think 1 of the keys to that and to have a drug that doesn't bring added toxicity to the table. So that you are able to combine more cleanly and other agent not necessarily exacerbate toxicity and be able to push the doses that are likely to be therapeutic for post.

Yes, great point I should've brought it up thank you Dr Reinhardt.

Alright, and thank you Emily.

Next question comes from the line of Matthew Cross from Alliance Global Partners. Your line is from telephone.

Hey, guys hope, everyone is doing well and and thanks for taking a couple of questions from me.

I think you've kind of laid out well the rationale for for dosing Haier and <unk>.

Both of these trials on that we're getting up to <unk>.

<unk> hundred 50, and potentially going on to 900, it sounds like I.

I was curious how much of a priority you feel it is also to either backfill or dose escalate.

2 dose levels, where we've seen pretty substantial exposure.

For the 600 and 750 milligram dosages.

And whether that differs based on the indication we're talking about.

And kind of the second part similarly, as we're getting higher up and to the dosage here.

I guess, you were talking about and the preclinical setting.

Moving from from QD to I was.

Curious if we're moving into potentially 900 by the end of this year, then and probably early next.

And Youre, giving I guess.

5 pills twice a day 906 twice a day.

And I was curious if you could speak to whether pill burden has been a problem at all for these patients or if there's a way to circumvent that.

And I believe there was some maybe trends and commentary about about formulation work. So it was just curious to get.

And so there is a dosing higher thanks.

Alright, Thanks Mark.

To have somebody on the phone and it looks down on me.

So.

So let me start with talking about as we dose escalate the pill burden. So yes, you are correct in the past we have mentioned formulation development activity, but we really havent said that much about except that we continue to pursue it.

At 750, we do have 5 capsules twice a day and 900 it will be 6 capitals twice a day. So we would look to reduce that fuel burn and there were a couple of ways that we can do that.

But what other things that we are doing is as with.

And most drugs.

And phase 1 and phase 2 efforts continued in to improve the formulation as you move towards the later stage development as well as commercialization and we are often asked about the potential for new formulations for <unk> given that our formulation does require administration of such high doses.

We have been developing a new oral formulation that we believe it may significantly improve absorption of looks and the new.

<unk> has been successful in non human models to date, it's very encouraging.

Actually preparing it for GMP manufacturing stability testing and preparation for advancement to the clinic.

What I would say is.

And we're happy with what we're seeing we're happy with what we've seen in animal models multiple animal models to date.

We as I said, we are moving it forward toward.

Towards GMP manufacture, but also remind you that the manufacturing stability regulatory risks still remain there are no guarantees that this will actually work in humans and at the ports that we will show improved properties.

But we feel like it's getting to the stage now that we can actually talk about it a bit I. Appreciate you asking the question. So it is promising it may reduce the pill burden. It may reduce the amount of milligrams that we have to give each day to humans and.

And so we're keeping our fingers crossed everything looks good thus far but we're not quite there yet and we hope to get it into humans as soon as we can.

So good question, Okay. So what was the follow up.

I can take the bank for a question to that though.

Okay. Thanks.

You mentioned about <unk> and then further dose escalating patients I think the actual and provides us with several advantages.

And just fairly straightforward advantages that it can be frustrating to enroll patients for a phase 1 study and dose escalation for a limited number of slots patients can't wait necessarily until the next dose cohort is open so having a mechanism for better patient on study and a backfill when the dose escalation cohort is closed.

Often and welcome by sites and <unk>.

Can you stay on it to favor ongoing site engagement, but from our standpoint, where we're trying to learn more about the safety and efficacy and the drug and it gives us the opportunity to explore and more patients and to get some of that diversity and AML and by putting patients on different genotypes or phenotypes on non study and.

And we might otherwise.

And be able to do during dose escalation. So it is an opportunity to learn more about the agent and get more patients on so we think it's a win win it's really positive for us and understanding the drug is positive for patients who would like to get on study and it's positive for the sites, who are sometimes frustrated with the peso and dose 1 dose escalating phase 1 dose escalation study.

Thank you Dr.

Thanks Bill.

Okay very much did on.

Okay.

Yes.

Operator.

We have time for 1 more question, Matt Biegler from Oppenheimer. Your line is now open.

Oh, Hey, bingo and thanks for squeezing me in.

I'll add that net.

Don.

I definitely don't look down on you I have to look up to you I'm only 5.

Yes.

No.

And that's maybe a multi part question on on the evolving treatment landscape and <unk> and maybe how that.

Affecting demographics and you're paid on trial and.

Specifically are you noticing any uptick or are you getting any patients with.

Prior non covalent PTK exposure.

And I kind of wanted to hear your thoughts on the follow up on emerging resistance mechanisms and the non covalent class as a whole and whether you think lux might be able to show some effectiveness here. Thanks.

Alright, again I'll start and then we will start to be hard to come in so in terms of evolving landscape and cielo and <unk> in particular, we're seeing patients that are getting treated with non covalent <unk> inhibitors and the answer is yes.

And we're seeing patients that have been treated with effectively every type of treatment out there and they failed those and then they come to us. So it is many of these are very heavily pretreated patients whether it's the covenant and beauty case, non covalent <unk> inhibitors, venetic, Lex Rituximab PR for U K and.

<unk>.

For <unk> and Dr. <unk> can talk a little bit about more of that but let me just mentioned very quickly in terms of the resistance that we're beginning to see and a lot of these patients.

Yes of course, you will get some patients coming forward that have mutations and be dk, but those are actually quite rare most of them that were seeing emerge now or and the Ras and the ppt 3 pathways.

So we think that is in an area that's key for us.

Because once you start getting the rest of the <unk> 3 mutations most other drugs you don't see activity or you lose sufficient activity that you just cannot achieve those exposure levels in the bloodstream, we've actually done studies.

Brian <unk> studies with.

With various sales that had Ras and <unk> 3 mutations and they maintain sensitivity for Lux. So we're hoping that as patients fail. The other types of molecules out there and the vast array of other molecules that it's actually driving the sales towards sensitivity to our drug but again these are very experienced patients Dr.

Dr. Bexar would you please.

Yes, no I think that's key.

Correct I think that we are seeing patients that have had that kind of prior exposure and some of our sites.

And I don't think we entirely understand what the patterns there isn't going to be for them, but obviously the patterns of business and so we've seen for Ibrutinib arent just implementation business.

On that.

And as I am itself PTK and also include other pathways like plc gamma too and so on so unclear to me.

Non covalent inhibitors will having superior activity and those cases, where the BPA molecule itself isn't mutated, but they themselves may induce other mutations and PTK and we'll have to explore with regard to the activity of our drug I think it's too early to know yet.

And that makes sense thanks, guys.

Thank you Matt.

And I'm currently.

I'm showing no further question and I will now turn the call back over to Dr. Rice for closing remarks.

Alright, well and want to thank everyone for joining us this afternoon.

Barrett of various exciting stage here without towards development and.

None of this would be possible without the dedication of our employees investigators and more importantly, the patients who are helping advance our important work. We're also very first day of our shareholders and that research analysts and we thank you for your continued support and we look forward to keeping you on apprised of our progress and the second half of the year I don't want to thank you and have a wonderful evening.

Thank you ladies and gentlemen. This concludes today's conference you may all disconnect and have a wonderful day.

Thank you.

Okay.

[music].

And.

[music].

And.

[music] range.

[music].

Good afternoon. My name is Mary and I will be conference operator today I would like to welcome everyone wanted to ask those of ISI and such conference call for second quarter ended June 30, and 2021 at this time all participants are in a listen only mode. After just because its remarks there will.

A question and answer session.

If you would like to ask a question. During this time simply press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question. Please press the pound key.

As a reminder, this conference call may be recorded I would like to introduce for me since I've got you Paolo. Please go ahead.

Thank you Mary good afternoon, and welcome to the <unk> Biosciences conference call to discuss financial and operational results for the first quarter ended June 30th 2021, joining me on today's call are Dr. William G Rice, Chairman, President and CEO, Dr yard and morale and those senior Vice President and Chief Financial Officer, and Chief business.

And Dr. Rafael Bejar, Senior Vice President and Chief Medical Officer before we proceed I would like to remind everyone that certain statements made during this call will include forward looking statements within the meaning of U S and Canadian Securities laws forward looking statements reflect apoptosis and current expectations regarding future events, but are not guarantees of performance and it is possible.

And that actual results and performance could differ materially from these stated expectations. They involve known and unknown and unknown risks uncertainties and assumptions that may cause actual results performance and achievement to differ materially from those expressed to learn more about these risks and uncertainties. Please read the risk factors set forth and apoptosis. Most recent annual report on form 10-K and S.

D C and Cedar filings all forward looking statements made during this call speak only as of the date, they're made a post undertakes no obligation to revise or update the statements to reflect events or circumstances. After the date of this call except as required by law I will now turn the call over to Dr. Rice, Chairman, President and CEO of apoptosis after us Biosciences Dr.

Price.

Thank you Susan.

And welcome everyone for our call for the second quarter ended June 32021.

As highlighted on the continued progress of our clinical trials, especially with lunch afternoon for.

For logs and patients with acute myeloid leukemia, or AML and in patients with B cell cancers, we continue to move through dose escalation and our Chief Medical Officer, Dr. Rafael Bejar will bring you through that and a moment.

And we have observed clinical activity and our early cohorts. Our clinical sites are highly engaged and we're pleased with the brisk patient flow to both our b cell cancer and AML cancer trials.

Before I turn it over to Dr. Bejar.

Just like to emphasize the continued need for therapies and these hematologic cancers.

While there are a number of active drugs on the market and and development responses are often insufficiently durable and most patients will relapse or develop resistance.

Let's start and it is our oral highly potent non covalent inhibitor of the <unk> III dropper kinases, and it is like no other commercialized or drug underdeveloped.

I'll remind you that looks as more than just a typical flit 3 or <unk> inhibitor as it.

Not only inhibits wild type and mutant forms of beat Dk, and <unk>, III and selectively targets clusters and related kinases and suppresses the mutations that occur in AML and CML sales that renders such sales resistant to other agents.

And it has been found remarkably safe and well tolerated to date.

Thus far looks it's been shown clinically to target the primary drivers of B cell malignancies, and AML, including be Teekay and played through yet with the precision that avoids known targets such as <unk> Egfr and <unk> that are often associated with toxicity.

This selectivity is what sets <unk> apart from other hematology drugs on the market or in development and what makes it compelling.

I'll also remind you and at this point.

Sometimes gets lost but the patients and both of our trials are relapsed and refractory patients who already have been treated with and sales by the best available therapies.

So the progress, we're observing and our ongoing clinical trials and these very difficult to treat patient populations is encouraging and we are hopeful that loves will prove to be valuable and the our momentum of therapies for a diversity of hematologic cancers.

With that I'll ask Dr. Rafael Bejar, our chief Medical officer to provide an overview of our clinical activities breath.

Thank you Bill.

After this has 3 ongoing clinical trial 2 studies other kinase inhibitor and looks at net our MX, 1 and patients with acute myeloid leukemia, or AML and the other and patients with b cell cancers and net.

Third trial with our make Rhopressa after 253 and patients with AML and Mds.

Let's start with other B cell cancer study.

This includes chronic lymphocytic leukemia, or CLO, and non Hodgkin's lymphoma, or NHL, who have failed or intolerant to 2 or more lines of established therapy, including drug such as Ibrutinib Rituxan and <unk> are from nowhere.

Other treatment options are available and.

And these patients in our trial and previously received from 2 to 12 right on it.

Failed them, which also may include failure of other investigational agents.

You mentioned and our last call, we completed for desktop and our phase 1 trial and what's happening.

And looks at and well tolerated and patients treated at 150 milligrams 300 milligrams 450 milligrams and 650 milligrams twice daily over multiple cycles.

On the Evaluable patients at these dose levels, 2 thirds of them experienced dose related reductions and lesion size or IGN measurements compared to baseline demonstrating anti tumor activity.

Since our last update and you're well into the expanded 750 milligram dose cohort and is fully enrolled at this time.

And as Dr. Rice mentioned, our recruitment has picked up nicely and we expect to complete the 750 milligram dose level with the currently enrolled patients.

Generally and we've described before.

There are encouraging on target activity, including tumor reductions and both aggressive and indolent cancers and.

On a corporate event held in conjunction with the European Hematology Association on DHA and early June we reported from phase 1 data highlighting our it looks at net activity and B cell malignancies.

Intermediate dose levels as of June 7 and delivered all leading indicators of clinical activity, including target engagement with dose dependent inhibition of fossil PTK treatment related lymphocytosis and patients with any of the classic CLO.

And tumor reductions across different b cell malignancies, including Follicular lymphoma, chronic lymphocytic leukemia small lymphocytic leukemia.

And welcome from macro copy linear and type of non Hodgkin's lymphoma.

We've observed cases, and clear reversal of aggressively go out and disease upon intra patient dose escalation and longer times on drug suggestion that even aggressive disease may be successfully challenged with higher exposure levels and extended dosing duration of acceptance.

Could you pet scans and 1 relapsed follicular lymphoma patient revealed lesion growth during treatment with looks at the net debt 450 milligrams PID for 7 and cycles, yet after dose escalation that 600 milligram and PID and cycle 8 lesion measurements demonstrated continuous reduction and by cycle, a 15 day 1 for Targa.

And these and shrank by 43% when compared with peak tumor size.

We continue to spotlight the case of this patients from the first half of this year as a reminder, and then moving to higher and longer exposures for testing that as we.

And the second half of this year make successfully challenge relapsed and refractory disease.

And it's also important to point out that the data reported during the day like setting up has been generally well tolerated and 'twenty, 2 and relapsed refractory b cell cancer patients in dose escalation and continue with no concerning drug related safety trends to date.

And so is our intention, especially as we have begun to observed dose dependent anti tumor activity can you further dose escalation to the 900 milligram dose level for extended duration to tackle and increasingly treatment refractory presenting population and to get as many patients as possible on these higher dose levels for.

For more specific information on the trial and the clinical sites and enrolling patients. Please visit clinical trials Dot Gov.

Okay.

Now, let's turn to <unk> and AML acute myeloid leukemia, or AML is it particularly difficult to treat hematologic cancer, because lux Potently suppresses split 3 and additional oncogenic signaling pathways upon and which AML cancers rely for survival and drug resistance treating AML patients has always been a priority for optics as bill mentioned all of the patients.

And our AML trial have already been treated with and had been sales by the best currently available therapeutics, which can include slippery inhibitor such as go through it and it might've store and Granola net art and.

And if it's wrap on it.

And <unk> other treatments and investigational drug and so this is an extremely tough to treat patient population.

And our EAA corporate event in June we reported promising anti leukemic activity from accepting them.

The first dose cohort received 450 milligrams PID delivered encouraging anti leukemic activity and multiple patients, including a durable MRV negative complete response, and the flip <unk> ITD AML patient, who had relapsed after 2 allogeneic stem cell transplants multiple lines of chemotherapy and prior for <unk> inhibitor therapy.

We are pleased that our sites are very engaged and that we have.

The vigorous flow and diverse patients also important to note that at these doses. We continue to find that box is generally well tolerated with no toxicity signals are trends to date, we believe that prevent further dose escalation. This tolerability profile is critical because it is allowing us to reach the higher dose levels and will permit future use it looks at and it would be in combination with other agents.

Finally, I will mention that based on our clinical observations to date data from our dose escalation studies are guiding the planning of our dose expansion studies to explore select disease genotype under monotherapy and combination therapy programs, we expect to select and expansion dose cohort strategy for AML around year end.

For more information on the AML trial and clinical sites that are recruiting patients. Please visit clinical trials Gov.

Now let me quickly bring you up to date on the status of after 253, our second clinical candidate currently in phase 1 trials for AML and Mds.

Some of these data were reported in the poster presented and DHA.

To remind you after 2.5 series and Nick Repressor, and and Nick Oncogene is a major driver of cancer cell proliferation, including hematologic cancers.

And it's 1 of the most coveted drug targets and cancer. However, there are substantial challenges that have impeded direct and make targeted drug development and has been considered undruggable on the past.

As a direct inhibitor of MC transcription after $2.50 represents a novel approach for targeting this oncogenic pathway.

<unk>.

Inhibitor after the 2 phase III currently being tested on phase 1 trial in relapsed or refractory AML and Mds patient currently dosing patients at our sixth dose level of 210 milligrams per meter squared.

And the ongoing phase <unk> study and patients with relapsed and refractory AML and high risk Mds after 2 factories and well tolerated and patients treated at 2040, 66, 100, and 150 milligrams per meter squared over multiple cycles. Thus far there is no evidence of drug related adverse events and importantly, no evidence of myeloid suppression.

And the peripheral blood of patients after 2 factory amount of a rapidly transforms to and coexist with the mechanistically active.

Collectively the findings from the ongoing phase <unk> study supported continued dose escalation and after 2 funds III and study is currently enrolling patients with AML and Mds at the sixth dose level of 210 milligrams per meter squared and several subsequent dose escalations are anticipated.

Of note we are expanding the trial to include other mix driven hematologic cancers based on after 2 factories and mechanism of action. We also plan to treat.

Patients with buckets on pharma and other b cell malignancies that are driven by Nick rearrangements.

We are pleased by the progress across our clinical programs and at the safety and Tolerability of both drug candidates.

After the 2 phase III are allowing dose escalation and all 3 of our ongoing trials as we treat more patients at higher doses, and you're generally and and pharmacological and pharmacokinetic data and we hope to provide further updates at the Ash meeting later this year.

I will now turn the call over to Dr. EBIT Marando, our Chief Financial Officer, and Chief Business Officer, who will review financial results for the second quarter Jody.

Thank you Ross and good afternoon, everyone.

Let's now turn to the quarterly results. We ended the second quarter was approximately $103 million and cash cash equivalents and investments.

During the quarter, we utilized approximately $8.8 million of cash and operating activities, which were attributable to activities surrounding our pipeline candidates as well as general and administrative purposes.

Based on current operations cash on hand at June 30, and provides the company with sufficient resources to fund all planned operations, including research and development into the first half of 2023.

Moving onto the income statement, we had no revenues for the quarter research and development expenses were $9.8 million for the quarter and attributable to clinical trial costs for our pipeline candidates manufacturing of drug product for our clinical trials, including continuing development and on improving formulation.

And so for our pipeline candidates and personnel costs for head count and supporting clinical trials manufacturing activities and research studies.

G&A expenses for the quarter was.

Were $3.7 million.

And our net loss for the quarter was $13.5 million or <unk> 15 per share more.

And more detailed information can be found in our filings on Edgar and SEDAR.

I will now turn the call back over to Dr. Right Bill.

Thank you Jody and as you open the call for questions. Please feel free to pose a question to any of US Dr. <unk>, Dr Bejar or muscle on.

And if you could please introduce the first question.

At this time I would like to remind everyone that if you would like to ask a question. Please best bars and the number 1 on your thoughts on Keybanc. Please go and meet your questions from 1 question for pricing.

Pause for just a moment to compile the Q&A and Washington.

Your first question comes from the line of Dan Doug Pandev.

From Piper Sandler Your line is open.

And thank you very much.

Heidrick and care about the progress with from blocks.

Blocks and.

AML and.

CLO and I'm wondering just looking back at the preclinical data was there.

And that might start to creep towards.

Upper level or dose limiting toxicities to look for.

Quick follow up question from May 2253.

And I did see that data really like on mechanism did you have plans to ultimately pursue that beyond hematologic malignancies. Thanks, so much guys.

Alright, thanks for thanks for so much for coming on.

I'll start with the first question on looks at.

And the preclinical data associated with any pointing to any potential deal.

What I can say is that.

Lux was extraordinarily well tolerated and all the preclinical studies.

It would be and mouse road and for dogs and the GOP talks and what we did observe and this is all of our studies up until that point once a day dosing and all the animal models and we have great anti tumor activity, but we had not seen any toxicity associated with our model with Lux and those models. We therefore.

And went into the GOP talks and decided to dose twice a day.

We were trying to drive toxicity and the GOP Tox studies and both the other roads and the dogs.

Even with that going up to the maximum feasible dose in both species, we saw no effects on the on the.

Rodents, but if the dogs after 28 days of twice a day dosing, we did see a very slight reduction and neutrophil count and it was not considered sufficient to be adverse. So it was not listed as on the adverse event.

But it gave us the signal that at the very highest doses there may be a trend towards some of the.

Neutrophil reductions and.

That's what we are we will continue to look for in the clinical trial. So in a moment I'll ask Dr. Bejar, if he wants to add to that but also you mentioned and 253.

For 2 for our 3 our MC repressor, we agree with you. It is exciting to say it to find a molecule that actually can and EBIT mix, we have seen <unk> inhibition in patients, but at this point, we have not seen any overt toxicity.

Beyond this as we continue to dose escalate through the heme malignancies, we did start with AML and Mds. We are now also including the B cell malignancies that are associated with mccurry arrangements and Dr. Bejar, and maybe when I add to that and just a moment, but we also would like to look beyond the heme malignancies, and possibly go towards some of the solid tumors.

A good example is debt and non human studies of pancreatic cancer, it's been shown that even transient reductions and Mick will always seem to target those tumors to to your classic chemotherapy and that's a real need and the pancreatic cancers and humans and so once we get to a dose in humans and.

And which we believe we can show consistent E transit or even prolonged inhibition of Nick exploration, we'd like to be able to move it into first possibly the dose escalation or excuse me into the drug combination studies and some of those solid tumors and look for the.

The combined effect of drugs with chemotherapy.

Cancers, and possibly other solid tumors. So did that answer your questions and perhaps I can ask Dr. Bejar.

Okay.

We're very thoroughly yet.

And then Jeff and Jim.

1 quick follow up so if we're not looking for where we may not see dose limiting tox.

And there are markers, including even may be just a plateauing on the fact that we would look for for dose selection or how do you think about that.

Good good position that you're on.

So I'll start on that and then I'll ask Dr. Bernhard and 2 to expand on it so as 1 of the things that we look for is are we achieving exposure levels in humans as we dose escalate to inhibit the target kinases and the most on the way to do that the accepted ways to take the plasma from the patients bring it back for laboratory place.

On a quarter sales and then ask after treating the sales with the drug did you have enough drug exposure, there and the plasma <unk> inhibitor pathways and we have some very nice inhibition of the parcel for 3 the sick PDGF our office CSF on our AK tube pathways as we continued to dose escalate.

And further and so as we get to the 750 milligram dose level and we hope to get even greater exposure and greater hammering and some of those key oncogenic pathways as we dose escalate. So that's what we look for in terms of Biomarkers and so I'm going to ask Dr. Bexar also to expand on this a bit and.

Tell us to tell you, how we're thinking about selecting that dose going forward for expansions.

Sure. Thanks, Bill I think your point about the PAF based on the best as you. Just described is really important because I think that that's a necessary but not sufficient.

Test to see if youre at the right dose I think if we don't see inhibition and that assay and we certainly need to go higher but we designed and offset in particular to start with a dose of and already shows inhibition and that's also for 3 at the lowest dose level and that study. So we're seeing that already I think like I said I think it's not sufficient.

And not sufficient if necessary, we need to see other activity as well before we decided that we're at the right dose level and Fortunately toxicity permitting we're able to continue to dose escalate and pushed into these higher dose levels to observe that ultimately given the variability of AML patients and some that may have sensitizing patients and that may have more resistant mutations it may not be.

1 dose level and that applies to all comers and we will have to continue to dose escalate to explore that but we're in a good position as you mentioned, where the toxicity profile is allowing us to do that.

Perfect. Thank you Darko and thank you very much.

Okay. Thank you Ted.

Next question comes from Gregory Forlenza from RBC. Your line is now open.

Hi, This is the easy 1 for Greg and thank you for taking my questions.

And I was wondering if you per.

<unk> more color around the dose dependent antitumor activity that was mentioned and that press release, just now and what is your latest thinking around dose escalation beyond the 900 make dose level. Thank you.

Alright, so again I'll start on it and I'll ask Dr hard too.

To provide a bit more color around that as you asked for.

And we have especially in the B cell malignancy patients as we have.

Continued to dose escalate at some of the lower dose levels. We are seeing some of the what we call the markers or the indicators of activity inhibition of <unk> and <unk>.

And of on target lymphocytosis, and some levels of tumor inhibition.

But as we went to higher and higher doses, we started seeing greater levels of tumor inhibition and in particular and patients.

Yes, I think your example, though is exactly the 1 that we're referring to.

Where do you have a patient that starts at a lower dose level does not see the kind of activity you would hope to see and that upon dose increasing the dose then begins to see improvements and as we've gone to higher dose levels. We have also seen higher exposures and so we're hopeful that will translate into greater activity. We have seen the phenomenon that we described at the AAD meeting, where some patients who are on it should come.

On study and will see initial tumor growth and then and a couple of these examples patients were allowed to dose escalate and actually have seen some reduction and that tumor growth and net peak, whether it be below a baseline or not and so.

But there is some activity as we get to those higher dose levels I think it's a good motivator for continuing to dose escalate and see if we can get greater exposure and individuals and therefore.

For greater likelihood of response.

Yes.

So let me play off that because she had also asked about possibly increasing beyond the 900 milligram dose level. So we're at the 750 now we have plans to go to the 900 milligram dose level thereafter, we hope that we get increased exposure as we go to the higher dose levels.

And we also hope it continues to be tolerated well, if we see that the pharmacokinetics exposures continue to increase its tolerated well, we would seek to to increase.

On the 900 milligram dose level, if the PK is plateauing all for if we see some safety signals.

That may take us on a different direction.

Did that answer your question.

Yes. Thank.

Thank you and I just have a quick follow up if I may on the TIAA assay.

And I was wondering and based on the data so far what's your expectation around the serum level there'll be needed to inhibit 3 resistant mutations and where does that translate in terms of dose level.

For you.

What's interesting is Dr. Bernhard just mentioned just a moment ago how diverse these patients are with AML and we've actually presented some of the data with the Pis and <unk> looking at flip 3 and it is clear when you get to <unk> 5 micro molar you're inhibiting essentially all of the activity of the flip III and <unk>.

Particularly when you have the <unk> ITD.

But.

And these patients flit 3 is only part of the what's driving these tumors. So you'll have to flow through as well as a number of other tumors. So it is essential for us to show that we're inhibiting the flip 3 activity.

But we also want to get as high as we possibly can to hit as many pathways as possible. So you want to achieve the highest.

Exposure levels that are tolerated and humans to try to hit the pathway as much as you can.

And Trumpf and what else Owen and as we look to wall type typically it takes a little bit more of a drug to inhibit the wall type flip 3.

But we are seeing inhibition of that too we have our pis and <unk> I think we're the only company that does this and we look at we have 2 different cell reported sales and 1 is split 3 well type 1 and split 3 ITD and.

And we've already shown that we also inhibit the wall type flow III at sub micro molar levels and we do so very effectively.

But again you need to inhibit the other receptors and to sell service PDGF for all the CSF 1 on track.

As well as some of the internal.

<unk> 6 <unk>.

<unk> 6 as.

As well as maybe the <unk> and some of the awards and some of the others. So we need more drug or we always want to try to get more drug in as much as we'll be tolerated.

<unk> be hard to do you want to add to that.

Yes, I'll point out that it's tempting to look at the drug like deluxe and cover the flip <unk> inhibitor and that is an accurate description on what it does but it does and so many other things that I think are relevant to its activity and we have to take those into account and you asked specifically about the inhibition of the resistance mutations that for example could arise and the setting of prior treatment with other agents 1 other.

Resistance mutations can be the resist the mutations that occur and the tyrosine kinase domain certain <unk> inhibitors that are out there don't target that very effectively and we know from preclinical data that like I said and that is very effective at targeting those kinds of mutations that could arise and sending a persistent the other.

And mutation that can arise as the gatekeeper mutation and <unk> and our preclinical data again suggests that we have low and animal activity against that mutation also.

And I haven't had the opportunity to explore that using the pis specifically.

We believe that we are well above the concentrations that should be able to do that and that type of in vitro assay.

Okay.

Thank you Don.

And you very much.

Okay.

Next question comes from the line of John Your line from Canaccord. Your line is helpful.

Hi, guys. Thanks for taking my question.

Just had a question on the type of patients that you are now enrolling for exceptional.

The AML study specifically at the 750 milligram cohort.

Just curious if you are looking to enrich for 3 here for example.

Or if you are taking all patients and also.

Wondering if youre getting any patients with prior successful transplants and.

And if you can talk a little bit about.

How much follow up you might have on this cohort as we reached the end of 2021 for thanks.

Alright.

It is clear that we have shown activity you're already against the <unk> ITD mutant patients.

We clearly want to get additional patients like that on the study to be able to prove that we can we can have activity against multiple <unk> ITD patients because again every 1 of those represent a different patient different almost a different disease, because they have such a wide diversity of other mutations and they've been treated with <unk>.

And with different drugs coming into that at the same time, we absolutely want to have put 3 wall type patients and what I'll say that okay. It may be volatile for the 3 it may be over expressed wild type <unk> 3 but again you have all these other mutations and there that gives rise to the disease.

So we we.

And we want to provide balance and we've talked about that all the way through we clearly want to have the flip 3 mutated as well as well.

<unk> type patients.

In terms of patients that have received successful transplants.

We highlight 1 patient in particular for patient and which we.

We reported the complete response day Mardi negative complete response.

Patients had had 2 successful transplant and then didn't relapsed after several years after the successful transplant.

So perhaps Dr. Bejar would like to add a bit more to that to talk about the data coming.

Yes, we do allow patients that have had prior transplant on study and then subsequently and relapsed and several other patients have met those criteria.

We do also try to balance our cohorts to include wild type and for patients.

With sites selecting the patients that they believe are more likely to respond to help us with that so we are not trying to.

Enrollment in any way, we want to get a clean picture for for both wild type of flow through.

Patient because we make decisions about how they go on to expansion.

And then you asked about how much follow up will have by year end.

You can gauge from from when we have announced progress on this.

Great.

Yes, okay. Thank you.

Okay.

And then.

Next question please.

Next question comes from the line of Alethia Young from Cantor Fitzgerald. Your line is open.

Hi, This is Emily on for Alethia. Thanks for taking my questions. I'm curious if you have any updates on potential combination approaches for AML do you plan to maybe combination cohorts and the dose expansion portion of the phase 1 study and if so what agents would you potentially consider and then I'm also curious.

And you said that you would have the dose.

Pension strategy by year, and how does the 900 and make the dose cohort.

And to that do you think you could potentially and rolled out by the end of the year or if not on what are your thoughts about that thank you.

Alright, Emily So again, we'll tag team this 1 I'll start out.

And to perform drug combination studies, we havent disclose exactly which ones that we're going to pursue yet we will continue to collect data throughout the remainder of this year with the current study the patient populations, and then see which which types of combinations would be appropriate and the particular patient.

And <unk> by that I may see it maybe relapse refractory and more first line and depending on what we see and the patient types that we look at we will choose the drug combinations appropriately.

And then in terms of the 900 milligram.

Does that fit into the process well again, we're going into the 900 milligram. If it is tolerated well if we're getting greater exposure. Then we will continue to dose escalate that will be and impacted the timing of the.

The expense.

The expansion cohorts and we may decide to move on with the 700, 5900, or possibly a higher dose level.

We will follow the data, which is what we always do and try to make rational decisions and then provide you with additional information towards the year and Dr. Bexar any additional.

Nothing additional to your comment about the 900 milligram cohort I think if thats accurate with regard to combination.

For myeloma for example.

And I think 1 of the keys to that is to have a drug that doesn't bring added toxicity to the table. So that you were able to combine more cleanly and other agent not necessarily exacerbate toxicity and be able to push the doses that are likely to be therapeutic for post.

Yes, great point I should've brought it up thank you Dr Reinhardt.

Alright, and thank you Emily.

Next question comes from the line of Matthew Cross from Alliance Global Partners. Your line is powerful.

Hey, guys hope, everyone is doing well and and thanks for taking a couple of questions from me.

I think you've kind of laid out well the rationale for for dosing higher and both of these trials on that we're getting up to.

750, and and potentially going on to 900 it sounds like.

Was curious how much of a priority you feel it is also to either backfill or dose escalate.

2 dose levels, where we've seen pretty substantial exposure.

600, 750 milligram dosages.

And whether that differs based on on the indication we're talking about.

And kind of a second part similarly, as we're getting higher up and into dosage here.

I guess you were talking about in the preclinical setting.

Moving from from QD to I was.

Curious if we're moving into potentially 900 by if not the end of this year, then and probably early next.

And you're giving I guess 55 pills twice a day 906 twice a day.

I was curious if you could speak to whether pill burden has been a problem at all for these patients. So we're if there's a way to circumvent that.

And I believe there was some maybe trains and commentary about about formulation work. So I was just curious to get.

And so there are dosing higher thanks.

Alright, Thanks Mark.

To have somebody on the phone and it looks down on me.

So.

So let me start with talking about as we dose escalate the pill burden. So yes, you are correct in the past we have mentioned formulation development activities, but we really havent said that much about it except that we continue to pursue it.

At 750, we do have 5 capsules twice a day and 900 it will be 6 capitals twice a day. So we would look to reduce that fuel burn and there are a couple of ways that we can do that.

But 1 other things that we are doing is as with most drugs in phase 1 and phase 2 efforts continued in to improve and formulation as you move towards the later stage development as well as commercialization and.

And we are often asked about the potential for new formulations for <unk> given that our formulation does require administration of such high doses.

We have been developing a new oral formulation that we believe it may significantly improve absorption of looks and the new formulation has been successful in non human models to date, it's very encouraging.

Preparing it for GMP manufacturing stability testing and preparation for advancement to the clinic.

What I would say is.

We're happy with what we're seeing for.

We're happy with what we've seen in animal models multiple animal models to date.

And we as I said, we are moving it forward toward.

Towards GMP manufacture, but also remind you that the manufacturing stability regulatory risks still remain there are no guarantees that this will actually work in humans and supports that we will show improved properties.

And so we're keeping our fingers crossed everything looks good thus far but we're not quite there yet and we hope to get it into humans as soon as we can.

So good question, Okay. So what was the follow up.

I can take the backlog question for that.

Okay. Thanks.

You mentioned about vacuuming, and then further dose escalating patient I think it actually provides us with several advantages.

So it's fairly straightforward advantages that it can be frustrating to enroll patients for a phase 1 study and dose escalation with her and limited number of slots patients can't wait necessarily until the next dose cohort is open and so having a mechanism for better patient on study and a backfill when the dose escalation cohort is closed.

And welcome by sites and <unk>.

Can you stay on it to favor ongoing site engagement, but from our standpoint, where we're trying to learn more about the safety and efficacy of the drug and gives us the opportunity to explore and more patients and to get at some of that diversity of AML and by putting patients on different genotypes or phenotypes on non study and.

And we might otherwise.

And be able to do during dose escalation. So it is an opportunity to learn more about the agent and get more patients on so we think it's a win win and it's really positive for us and understanding the drug is positive for patients who would like to get on study and it's positive for the sites, who are sometimes frustrated with the peso and dose 1 dose escalate and phase 1 dose escalation study.

Thank you Dr <unk>.

Thanks Bill.

Okay. Thank you very much did on.

Okay.

We have time for 1 more question, Matt Biegler from Oppenheimer. Your line is open.

Oh, Hey, Thanks, guys for squeezing me in.

And that Nathalie Don.

Definitely don't look down on you I have to look up to you I'm only.

Yeah.

No.

And that's maybe a multi part question on on the evolving treatment landscape and CLO and maybe how that's affecting demographics and your case on trial.

Are you noticing any uptick or are you getting any patients with price.

Prior non covalent PTK exposure and.

And I kind of wanted to hear your thoughts on the follow up on emerging resistance mechanisms and the non covalent class as a whole and whether you think luck might be able to show some effectiveness here. Thanks.

Alright, again, I'll start and minimal and start to be harder to come in so in terms of evolving landscape and CLO you ask in particular, if we're seeing patients that are getting treated with non covalent <unk> inhibitors and the answer is yes, we're seeing patients that have been treated with effectively every type of treatment out there and they fill those and then.

And they come to us. So it is many of these are very heavily pretreated patients, whether it's the covenant and <unk> non covalent <unk> inhibitors, but net of clocks Rituximab <unk> inhibitors.

For <unk> and Dr. <unk> can talk a little bit about more of that but let me just mentioned very quickly in terms of the resistance that we're beginning to see and a lot of these patients.

Yes of course, you will get some patients coming forward that have mutations and <unk>, but those are actually quite rare most of them that were seeing emerge now or and the Ras and the ppt 3 pathways.

So we think that is in an area that's key for us.

And once you start getting the Ras and <unk> 3 mutations most other drug you don't see activity or you lose sufficient activity that you just cannot achieve those exposure levels in the bloodstream, we've actually done studies Dr.

Dr.

Brian <unk> studies with.

With various sales that had Ras and P 53 mutations and they maintain sensitivity for Lux. So we're hoping that as patients fail of the other types of molecules out there and the vast array of other molecules that it's actually driving the sales towards sensitivity to our drug but again these are very experienced patients Dr.

Dr. Bexar would you please.

Yes, no I think that's.

That's correct I think that we are seeing patients that have had that kind of higher exposure and some of our sites.

I don't think we entirely understand what the patterns there isn't going to be for them, but obviously the patterns of visit and so we've seen for ibrutinib arm just limitations of that.

And as I am itself PTK and also include other pathways like plc gamma too and so on so unclear to me.

Non covalent inhibitors will having superior activity and those cases, where the molecule itself isn't mutated, but day themselves may induce other mutations and PTK and we'll have to explore with regard to the activity of our drug I think it's too early to know yet.

That makes sense thanks, guys.

Thank you Matt.

And on its actually knows I'm showing no further question and I will now turn the call back over to Dr. Rice for closing remarks.

Alright, well and want to thank everyone for joining us this afternoon.

And a very exciting stage here without dose development and.

None of this would be possible without the dedication of our employees investigators and more importantly, the patients who are helping advance our important work. We're also very first day of our shareholders and research analysts and we thank you for your continued support and we look forward to keeping you on apprised of our progress and the second half of the year I don't want to thank you and have a wonderful evening.

Thank you ladies and gentlemen. This concludes today's conference you may all disconnect and have a wonderful day.

Q2 2021 Aptose Biosciences Inc Earnings Call

Request a DemoDemo

APS

Aptose Biosciences

Earnings