Q1 2022 Aptose Biosciences Inc Earnings Call

May 9, 2022

Welcome to the <unk> Biosciences incorporated reports results for the first quarter 2022 Conference call. My name is Daryl and I will be your operator for today's call. At this time all participants are in listen only mode. Later, we will conduct a question and answer session. During the question and answer.

Session. If you have a question. Please press zero one on your Touchtone phone.

As a reminder, this conference is being recorded I will now turn the call over to Dan Ferry, Dan you may begin.

Thank you.

Good afternoon, and welcome to the <unk> Biosciences conference call to discuss financial and operational results for the first quarter ended March 31 two.

2022.

Earlier today <unk> issued a press release relating to these financial results.

News release as well as related SEC filings.

Our accessible on <unk> website.

Joining me on today's call are Dr. William G Rice, Chairman President and CEO .

Dr. Rafael Bejar, Senior Vice President 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.

Looking statements reflect apoptosis current expectations regarding future events.

But are not guarantees of performance.

It is possible that actual results and performance could differ materially from these stated expectations.

They involve 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 in apoptosis. Most recent annual report on Form 10-K, and SEC and SEDAR filings. All forward looking statements made during this call speak only as of the date they are made.

<unk> 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 <unk> Biosciences, Dr. Rice.

Thank you Dan.

I want to welcome everyone to Oracle for the first quarter ended March 31 2022.

Our last call was only a month and a half ago and because we plan to hold our kols corporate update a bit around the European Hematology Association or <unk> conference in just a few weeks.

He will provide you with a brief update.

I want to emphasize that <unk> is in the best position we've ever been.

With two well differentiated well tolerated and active <unk> inhibitor drugs, ATM or three $2 million to $3 million or just $2 million to $3 million and looks at it.

<unk> as we call. It we continue to thoughtfully execute on our corporate vision and we're entering a new stage of maturity.

<unk>, our Chief Medical Officer, Dr. Rafael Bejar will discuss why we believe our lead candidate to three nine.

Best in class oral kinase inhibitors.

And to treat the disease of AML, not just treat a particular target.

The superior to competitors for the treatment of AML patients with adverse mutations.

And looks which is mechanistically and pre clinically remains a well differentiated agent has demonstrated clinical activity in <unk> and AML cancers, plus we continue to make strides with a new formulation with Lux in an effort to achieve greater plasma exposures with lower doses of logs and we've recently highlighted.

Its activity on it.

<unk>, III inflammatory and potential applications for inflammatory and autoimmune diseases.

Dr Hart will deliver the updates on both product candidates.

Before I turn the microphone over to him I want to make a few remarks about three nine.

The upcoming <unk> conference.

And about our new Chief commercial officer.

Let's begin with two or $3 million.

Totally yet a bit to highlight is our recent news that the FDA granted fast track designation to <unk> three nine for the treatment.

<unk> of patients with relapsed or refractory AML, who have flip three mutations.

<unk> previously received orphan drug designation from the FDA for the treatment of AML.

Destination of fast track status certainly is welcome news as it codifies the recognition of $2 three nine.

Already demonstrated meaningful clinical benefit to flip <unk> mutated AML patients.

As most of you are aware fast track status acknowledges <unk> potential to fill an unmet need for AML patient populations.

And supports our efforts as we advance it towards a potential Registrational study.

Fast track designation also helps facility and potentially expedite the drugs development, which allows us to have early and frequent communication with the FDA.

Questions and issues are resolved more quickly.

Now, let's discuss our plans for the upcoming <unk> conference that is just a few weeks away.

We recently were notified that an abstract we submitted to <unk> and.

Encompassing preclinical research on $2 million to $3 million has been accepted for a poster presentation in Vienna.

But just prior to Ehealth, we plan to hold our Kols corporate event during which we plan to present available clinical data from all patients in all dose levels enrolled in our clinical trials for both to three nine and look we.

We will continue to collect PK PD.

Efficacy and pet scan data up until the time of the Kols corporate event and such data will not be embargoed.

For <unk>, we also plan to update you on the clinical data with our new <unk> formulation and email and detailed cancer patient.

Data from patients receiving G. III will continue being collected over the next few weeks and we plan to present the available data at the Kols corporate event.

Regarding to three nine.

Regard that during the Ash conference in December we presented five complete remissions.

With the 80 milligram cohort four of which advanced to the potentially curative allogeneic stem cell transplant.

In addition, one patient who was unfit for transplant harbored wall type split three and Holly adverse T. P 53 mutations.

This patient experienced a durable response, including a CR for more than one year.

These data illustrate that to three nine meaningfully and safely extended the life of multiple patients with relapsed or refractory AML that already had been filled by other therapies.

More recently, we reported that.

At the 200 at the 120 milligram dose.

One patient had experienced a partial remission or PR and another patient with <unk> and <unk> mutations experienced a complete remission or CR.

Adding to this yards from the 80 milligram dose level reported in December .

Consequently, we already have identified two dose levels 80, milligram and 120 milligram.

Payer complete remissions with Tolerability.

And we know we're exploring a higher dose by expanding at the 160 milligram dose level.

By methodically testing different doses with numerous patients during this phase one trial.

One manner.

Optimize our chance to select the best doses to maximize safety and to minimize regulatory risk.

Boarding a dose that could exhibit toxicity.

Also I want to be clear that as we approach our focus with two or three nine is to recruit AML patients with a diverse array of mutations in our ongoing phase one trial.

We already have demonstrated crs and multiple patients with flip <unk> email and the FDA has recognized that capability by awarding up dose with fast track designation for <unk> three nine and these patients how's.

However, we are not attempting to focus solely on flit three mutated patients in this trial.

This is a phase one trial designed to explore doses and the range of activity of $2 million to $3 million.

Because we also have seen <unk> in patients with wild type III and a host of other adverse mutations.

We want to further our understanding of the full breadth of activity of 239 in patients with diverse mutation profiles.

While this may result, in lower and a lower percentage of Crs in the near term inpatients with adverse co mutations. We believe this approach should allow us to select the appropriate population to treat and those populations to avoid and future studies as part of our goal to deliver the greatest value to patients physicians and the <unk>.

<unk>.

To be clear our focus is to select genetically defined AML patient populations with unmet medical need that appear to have sensitivities to three nine.

And then to initiate fixed dose expansion trials in these patient populations.

The first step is to identify the appropriate patient populations and we believe the ongoing phase one trial already is delivering this information.

For these expansion trials, we must identify an efficacious and well tolerated dose selected.

Selected expansion for go forward dose in.

In fact, the ongoing phase one already identified at least two go forward doses.

Both safe and efficacious that we can use to explore and optimizing our expansion trials in specific patient populations and.

In the second half of the year, we plan to present the selected expansion dose.

Along with the safety and efficacy packages to the FDA and request allowance to initiate the expansion trials soon thereafter.

Data from those trials are successfully are sufficiently compelling.

We then would request an accelerated risk registrational pathway of course. This is the desired path for two or three nine there is much work ahead of us, but two to three nine to date delivered results that pointed us in this direction.

We plan to speak more about this plan during the Kols corporate events.

As an FYI, we plan to announce formally the Kols corporate event.

And its logistics later this week along with the <unk> abstract.

Now, let me turn to my last subject with the maturation of the Companys products comes to the task of building the right team and so I'm very pleased that we recently added a chief commercial officer, Dr. Felipe leadership to our executive management team.

<unk> comes to that.

Toast with exceptional pharmaceutical industry experience in the U S and Europe most.

Most recently he served as associate Vice President and head of oncology new products at Merck, where he was responsible for commercial leadership over the Merck oncology pipeline over 25 assets from discovery to mid stage clinical development across major solid tumors and hematologic malignancies at.

At Merck also provided commercial leadership on all licensing and M&A activities, including the peloton therapeutics and <unk> acquisition in 2019.

Prior Dr. <unk> spent a 20 plus year career at Novartis in the U S and France. Most recently a senior director of early commercial strategy focused on oncology products.

He also was a member of the brand team any held early commercial development and global marketing responsibilities for several new compounds, including the <unk> three inhibitor modest store.

Earlier on Novartis oncology.

He helped lead the launches of several oncology products, including the kinase inhibitor Imatinib brand name Gleevec, a landmark drug pioneered by Dr. Brian <unk> that has transformed outcomes for patients with chronic myelogenous leukemia.

Proactively joining up towards our drug to three nine lit up on his radar screen of priority agents and he actually approached us with this interest in joining up to us to work on the development and commercial strategy for 239.

I'll say more about what a timely videos for <unk> and we're delighted to have him join our team.

Let's have Dr. Bexar it give us a brief commentary on two or three nine and logs right.

Thank you Bill we.

We are in the fortunate position of having two well differentiated oral kinase inhibitors for the treatment of hematologic malignancies, <unk> 39 for AML.

For both AML and B cell cancers.

First let's talk about 2009, our lead product candidate <unk>.

<unk> has demonstrated multiple complete remissions for Crs.

2019, the highly effective <unk> three inhibitor <unk>.

Wild type and all other forms of with recasting in fact, it may be best in class superior three inhibiting competitors such as Guthrie.

The single agent and when combined with <unk> are you decided it.

It is important to highlight that 2019 is more than just an inhibitor. Three is it also inhibits other oncogenic signaling pathways and validated kinase targets, including sick mutant forms of C kit as well as GAAP, one Jack to among others can disrupt proliferation and emergence of resistance.

2009 inhibits all tested systems concurrently forms of <unk>, including forms with the ITD TKD activation gatekeeper mutation as well as the wild type training.

And it demonstrated inhibition of resistance confirming growth factor pathways in particular.

JAK stat and map kinase or erk pathway.

Simpler language 2019 interfere with the rescue pathways that may lead to resistance from treatment with <unk> inhibitors, while avoiding targets that may compromise safety.

As we have reported the kinase inhibitory profile of 2009 already has translated into strong durable and broad anti leukemic activity and a diverse array of relapsed or refractory AML patients with a striking a range of highly <unk> commutation delivering multiple complete remissions in the phase one trial, thus far.

I'll remind you. This includes patients with mutations in the <unk> hundred 53, NPM one ranks at each two gene as well as with wild type <unk> three and in patients.

ITD or tyrosine kinase forms.

We already have shown 2009, as an active and well tolerated drug at 80 milligrams and 120 milligrams or we have efficacy paired with tolerability.

An extensive preclinical animal model suggests 2009 can be paired with other drugs to create drug combinations that are even more effective in treating disease.

Now we are exploring the 150 milligram dose and an expansion cohort to characterize the therapeutic window to reduce regulatory risk and to ensure we leave no efficacy on the table.

We're often asked about the full breadth of activity of 239 different subpopulations of AML patients our observations to date illustrating anti leukemic activity at multiple dose levels.

<unk> hundred nine appears to have the potential to treat with <unk> three mutant patient.

Compromising about a third of new AML as well as with the wild type patients the other two thirds.

Both fit and unfit patients since it had been so well tolerated that active dose of keybanc.

In the relapse refractory population as well as the newly diagnosed frontline AML population.

Additionally, we expect that it can be successfully in combination with other drugs.

In the ongoing phase one trial designed for extensive dose exploration. According to do where FDA guidelines, we are dotting, the i's and crossing the Ts and exploring all types of AML patients in our dose expansion arms as Dr. <unk> mentioned, we are not seeking to focus only on treating patients in our current trial already have validated <unk> hundred 90 active patients even.

If they previously received <unk> three inhibitors, which is minus story.

So we now seek to define the mutation profile susceptible to 39, so we can better treat an appropriate patient.

We are seeking to undercover.

That breadth of the AML patients responding to 2019, we're encouraged by what we're seeing.

<unk> in patients with challenging highly enriched mutations growing or at least a adverse AML genotypes would appear to respond or capable of responding to 2009.

This includes a recent patient with the CR reveal 2009 can deliver responses in patients harboring abnormalities of the MLM gene mutations.

Mutations in <unk>.

We believe this deliberate thorough approach will help us define the subgroups of AML patients that are likely to respond to 2009 and those less likely to respond by guiding the path forward in our next phase of clinical development.

As we discussed in our last call. We already have identified two well tolerated and active doses 80 milligrams and 120 milligrams and could serve as the go forward dose to take into expansion trials we.

We continue to explore the 160 intuitive milligram dose level. So we make sure like the optimal expansion dose and select genetically defined AML patient populations to initiate our fixed dose expansion studies with an eye towards accelerated registrational pathway.

While we are not providing further detail to the patients at this time, we are continuing to collect data over the next few weeks, we plan to disclose with all available data to date at our Halo corporate event next month.

Okay now on to a quick review of accepting it.

Just a reminder, <unk> is the only known clinical agent that Potently inhibits both <unk> III and <unk> with the precision that avoids known targets that are often associated with toxicity.

Preclinical orally administered box demonstrated potent anti tumor activity in animal models of disease Clint.

Clinically the drug has thus far demonstrated clear target engagement PDK for the three and anti tumor activity, including dose and exposure dependent tumor reductions observed in multiple patients.

The original formulation does not absorb well enough to achieve exposure levels consistently and effectively treat these aggressive cancers.

And the one CRE, we did report for Lux relapsed AML patient the patient had achieved greater exposures in the drug even at the 450 milligram dose level.

As we mentioned in our last call. We've made significant progress with our new formulation of <unk>, which we call at G III, and which may be able to enable greater exposures across patients.

Im pleased to report that we have now dosed in Q3 at two different dose level safely competing dosing three patients 50 milligram dose level and recently escalating the dose to 100 milligrams in our ongoing clinical program.

After patients received a single dose samples are collected for PK valuation and then patients go on to the original formulation of <unk> for the direct comparison.

As mentioned in our last call. The PK data to date are encouraging and we plan to discuss further at our upcoming cable corporate event.

We expect the ongoing single dose <unk> three studies will allow us to define a single dose PK profile and from those data we can model that continuous dosing PK profile if.

If that PK modeling data are sufficiently compelling we plan to take those data to the FDA requested transition fully to continuous dosing with the GP formulation, which will allow us to continue with dose escalation.

In addition to potentially delivering higher exposures that may result in greater responses. We expect the GP formulation may reduce significantly the pill burden the amount of drug substance administered to patients and thereby the amounts of drug substance and drug product manufacturing to support the trial.

Finally, let me close out the lesser view by drawing attention to the recent press release, highlighting three publications in flux.

Under those papers as related to inflammation autoimmune disease, and providing novel insights into the mechanisms by which less than your peers with the <unk> III plant is up and <unk> and reduce inflammatory signaling pathways along with its protective effects against inflammation induce toxicity in murine models.

The ability to what's happening to inhibit inflammatory pathways of concentrations, which are well tolerated and patients makes it a potential clinical candidate for the treatment of inflammatory and autoimmune diseases as well as inflammation associated resistance in cancer.

We're very pleased with the progress in <unk> and $2 nine clinical programs, we remain steadfast in our discipline to reduce regulatory risk and we look forward to providing further updates to you next month.

For more information on all of our ongoing clinical trials and clinical sites that are treating patients. Please visit clinicaltrials Gov.

Now I'll turn it back to you Dr. <unk> to review the financials Bill.

Thank you Rob.

We take a disciplined approach to our cost management to ensure cash is deployed to the high impact agents and studies and as we reported last quarter, our cash runway extends well into the fourth quarter of 2020 through so let's review our cash position.

We ended March 31, 2022, with approximately $69 5 million in cash cash equivalents and investments during.

During the quarter the net loss was approximately $11 5 million.

Translating into approximately <unk> 12 per share.

Provided in the income statement, we had no revenues for the first quarter of 2022.

Research and development expenses were approximately $7 4 million for the quarter down from $8 2 million during the same quarter of 2021.

G&A expenses were $4 1 million for the quarter down from $8 million from the same quarter of 2021. The decrease was primarily due to a reduction in stock based compensation during the first quarter of 2020 relative to 2021.

We will turn to the Q&A session. So operator, if you would please introduce the first question.

If anyone has a question you can press zero one on your Touchtone phone. Once again, if you have a question. It's zero one on your Touchtone phone and our first question comes from Greg <unk> go ahead Greg.

Yes, Hey, good afternoon, Bill and team and congrats on the progress and thanks for taking my question.

Just to come.

Come.

The tier three nine strategy certainly your mention of looking at those diverse mutation profiles I'm. Just curious if you could just touch on the inputs involved here, how we should think about really studying the molecule up for success looking at the commercial inputs and maybe.

And if you could just believes presence in determining that path forward and then lastly, just how it pertains to the timing and even if I add the patients that youre alluding to with respect to getting the end results. Thank you so much.

Thanks, Greg.

That's an expansive question. So I'll begin and then I'll ask Dr. Bejar also to jump in so it's clear that we've been asked is this a flip <unk> inhibitor and we say well of course. It is it doesn't inhibit flip three inhibits all forms of flip three better been tested very well.

And so we feel confident we can move into patients that have <unk> three mutations, including those with a variety of mutations and including those who have already been filled by other <unk> inhibitors, such as auto sorting deal.

So that positions us well as a <unk> inhibitor to be very competitive.

But this molecule goes well beyond that.

Because of its ability to inhibit sick the JAK one Jeff to the mutant forms of C kit.

And allows it then too.

To inhibit those key pathways those rescue pathways that can compensate for let's say you inhibit flint flit three but these other pathways then can rescue the sale while the drug is able to also to suppress those pathways. So we've already seen that we have patients that are wild type in their phase III.

A variety of adverse mutations and we've actually seen Crs and such a group of patients there, but we wanted to understand kind of the full breadth of activity what all new patients are going to be covered by this drug.

We've said that a patient who had a <unk> three mutation responded to the drug that does not mean, our drug directly inhibits the <unk> 53. It just means that we're able to cover enough of the pathways to be able to kill those cells. The patient responded.

Our task right now is to.

To fully understand the breadth of activity against all of these different types of mutations.

Best we possibly can which means in our current phase one trial. We are really now trying to focus on getting as many of those drugs versus mutations as we can as Dr. <unk> mentioned, just recently, we had a patient with the CR had the MLR <unk> mutations as well as the <unk>, one well that brought on a new.

Group of co co mutations that are adverse.

A patient so we want to get as many of those we can now.

It is likely we will have a lower percentage of responses in these types of patients, but that's important for us to see now because we want to know which ones will respond which ones will not respond that then guides are our expansion trials going into the future. So we're collecting the data on these patients we want to be able to write that up get it to the FDA.

Identify the we'll call it the expansion dose that we're going to select and move forward.

And we hope we actually have maybe three doses that can be used in those expansion cohorts. So.

So at this point, let me turn it over to Dr. Bexar, if he can speak more about this in the patients.

Sure.

You can learn a lot from patients in the clinical study not only.

Which mutations.

Well.

<unk> learned a lot about the molecular basis of the disease and how their drug is affecting that so when patients get started on the study I understand with the genomic mutations are at baseline and then if a patient responds and then relapses, we can understand what mutation somehow control resistance for patients with particular mutations never responded we understand that those might be primary resistance.

<unk>.

So these are the kinds of things that we hope to learn from these patients beyond whether or not they respond what factors are actually driving that response or lack thereof.

And then used to identify patient populations that we might want to go after in a more narrower focus.

And as we've talked about before obviously the population is going to be a target of this drug.

Patients that have unfortunately adverse disease relapse and are not cured by available therapies out there short of stem cell transplant. So we will be focusing on that patient population, but there are others out there that may derive great benefit and allow us to.

One trial will allow us to mine, whom they arent, where you might focus on.

Yes.

Yes, just to add to that you know you see drugs out there being developed for patients with <unk> mutations <unk> 53.

Various other pathways and we wanted to see how many of these other pathways and targets. We can cover with this molecule. So that's our plan. Thank.

Thank you Greg I hope that answer your question.

Sure.

You very much guys and looking forward to the update in a few weeks.

Thanks for being here.

And our next question comes from.

Matt Biegler from Oppenheimer go ahead, Matt.

Oh, Hey, guys. Thanks for the question, maybe I can squeeze you in first.

Just maybe a sense for how many new patients we should expect for 293 Ehow.

Relative to what we saw at Ash.

That's number one and then I do want to.

One about acceptance outside of cancer.

I appreciate the preclinical data that you guys.

Shared with US a couple of weeks ago.

I guess given its strong tolerability so far.

B cell inflammatory disorders are obviously, you need a good therapeutic window.

That you're actively considering or is it something that you would only pursue with a partner.

Thanks, Matt good to hear your voice again.

Regarding how many patients we're going to have since December .

I don't have a good handle on exactly how many maybe Dr. Bexar can give you a sense in a second.

So let me just flipped into your second question looks outside of cancer.

Clear that some of these PTK inhibitors <unk> inhibitors are being developed for <unk>.

Inflammation and so because of the kinase that looks inhibits we began to look at these.

Inflammation and autoimmune types of diseases, and the timing issues that are hit there and we've actually seen quite remarkable activity. Both at the molecular level, we're able to pick apart the various pathways inside the cells.

And look at the pathways all the way from the cell surface of all the way down through.

Say three to four levels within the within the.

Signaling pathways and it really pointed to the fact that we should have activity in the animal models. We then initiated a series of animal models in which we were using originally the original formulation and we're delivering it orally and we started seeing activity and now we're trying to move forward with our new formulation in animal.

Models and expand out on these.

These inflammation and autoimmune diseases.

It's also important as you said in a disease like this youre going to be dosing for long term in these patients. So you want to have a drug that's well tolerated well. We know that look is very well tolerated and it appears as though lower doses could have an effect on these inflammation and autoimmune diseases lower dose.

Is that are required to kill these very aggressive malignant cells. So yes. We are pursuing this we're we've kept a pretty quiet up until now because we wanted to make sure. We have animal data, we're now extending that into additional animal models and then we'll see where it takes us but again as always we will follow the data.

So I'll flip it back to Dr. Bexar, if he wants to talk about.

<unk> between <unk> and <unk>.

And then also if he wants to add anything else to the luxe and inflammation.

Sure. Thanks, Paul.

I'll remind you that at ash the data cut for that.

Quite a bit before the actual ash meeting itself, so I think at ash.

It wasn't even a total picture of how many patients once that even at that time.

So after that meeting.

The trial accrued additional patients that we've reported already that we had completed 120 milligram dose expansion, we're now exploring 160 milligrams.

So you'll see all of that all of the patients that are filling out the 120 and good data that we have to date on the 116.

But I don't have a good number on the exact number of patients out there. So Matt sorry may well change between now and then as well it will change.

Changes daily.

Anything else you wanted to say about.

Inflammation.

I think it's exciting there is inflammation.

It appears in several different places, where I think there's an opportunity to address it and one is obviously in the areas, where we're talking about b cell inflammatory disorders.

And the inflammation is actually a factor in other conditions, we briefly mentioned.

Cancer therapies inflammation as a driver of that and even in disorders like quantum that polices inflammation plays a role.

We'd be interested to explore the potential applications of <unk> in that context.

Alright, guys Thats exciting stuff.

Thank you Matt.

And our next question comes from Lee <unk> from Cantor Fitzgerald go ahead Lee.

Hey, guys. Thanks for taking my questions I guess.

First on <unk>.

116 Mick.

Can you comment a little bit more on what you saw from the efficacy point of view.

For many patients do you have right now.

And so it seems like 239 has pretty well.

Broad activity, so I guess, what efficacy threshold that you have.

I guess for you to open.

<unk> expansion cohort in that particular patient population. Thank you.

Interesting question.

So clearly we've seen and we've reported.

<unk> efficacy and well tolerated status at both 80 milligrams in at 120 milligrams and based on that then we moved up to the expansion of the $1 60, we have not released yet the number of patients at the 160 and as Dr. Bejar that changes daily it takes several months.

To get a patient on.

To get them identified washed out of their prior drugs get them on study and then hopefully over time, you'll see responses merge and confirm those until that process takes months and so what we'll do is between now and <unk>. We will collect all the data that we have available we will present that all the numbers of patients to the types of patients.

That's known about their disease mutations.

And where we have with them.

In terms of the broad activity.

You are right its more than just <unk> three inhibitor.

And in terms of the threshold for selecting patient populations, you really want to see single agent <unk> in these patients.

For instance, we found one patient we had one patient had a <unk> three mutation wildcard flip III.

If we got several of those patients and we saw responses that has a meaningful group that we can move forward with but right now the one that we're absolutely confident in is the flip <unk> mutated population to be able to move forward and again, we have the fast track for that and we're looking to identify additional populations, maybe a coupled with different mutations.

Dr. <unk> would you like to jump in on that too.

Yes, the only thing I would add there is I think that the context of the population really matters and so in terms of what your threshold for success should be in those patients that really have no. Other alternative therapies in the very short pregnancy.

For example, patients who were previously treated with tyrosine kinase inhibitors for example.

We don't have any additional options threshold for success, there was a lot lower than say, perhaps in a patient population earlier in <unk>.

Therapy, perhaps second line or even first line, where you want it to be greater activity.

Depending a bit on who we're talking about but some of those patients. We identified are truly the worst of the worst in terms of the prognostic risk TV 50 meter complex karyotype patients patients who have been failed by minus door and get written it as the only approved FDA approved therapies.

Those patient populations will have quite a low bar for success and hopefully.

And that will be able to meet and exceed that.

Okay, great. Thank you.

Thank you Lee.

Our next question comes from Matthew Cross from Alliance Global Partners go ahead, Matt.

Hey, guys. Good afternoon, thanks for taking a couple of questions from me.

One kind of a follow up related to this continued discussion about.

The broader market for 2009 I guess.

Trying to interpret the fast track designation grants.

Just kind of wanted to clarify I guess to the century what to say.

What data the FDA was able to see in order to.

<unk> received an order to base that decision on if that's anything that we haven't seen but if it was kind of as of ash just to get understanding of what theyre looking at.

And what other potential subgroups that may have responded that they had seen.

When granting that and I guess kind of on a related point just thinking about the potential regulatory paths would you expect it sounded like you might consider the idea.

Pursuing a couple of different specific mutation groups would you kind of expect to roll up a few different possible fast tracks or at what point could this just be kind of a broader.

Discussion of a relapsed refractory AML population with particular patients that you focus on clinical trials from a regulatory standpoint.

Well I'll try to filter through the so thanks for.

The question in terms of the broad market. So you were asking with first about the fast track what David we have so we've disclosed essentially all of the data.

Regarding we have many patients.

And then the 120 milligram that had crs as well as the euro that came in.

A number of those were flip three mutated.

Especially those that had failed the motto store and the guilt ridden them.

And we're talking about Crs at very well tolerated doses. So we applied for the faster I can then the FDA provided that to us in terms of the breadth of activity.

We'd love to be able to move this forward for yes, flit three mutated, but also patients who are flipped through Walter Dr. Bejar mentioned flit three mutated that's about one third of the population so you'd like to be able to target. The other two thirds is many of those as you can.

Also fit and unfit this is a well tolerated drug so we would hope to be able to include the administration of this drug in the patients who are unfit for chemotherapy no thats, a little bit of a longer path, but that's something we'd like to do and also reluct refractory and then moving it up towards the first line if you have a drug.

It truly is well tolerated gets yours. So those are the paths that wed like to take the data are pointing to that but we will follow the data and it will tell us the patient populations to go after and you mentioned the regulatory path again, it will depend entirely upon the data that we're seeing as we go into these expansion.

Charles currently we believe that the <unk> three mutated is a path and in particular, if you can identify those patients and have a reasonable response rate in patients who have failed modest torn and gilt to Britain and even in those who havent been pre treated with that we have the fast track broadly in flip through mutated not just the ones who have failed those drugs.

If we're able to see enough patients that are with three wild type, but yet are able to treat these patients with these other adverse mutations we're able to identify subgroups. There is Dr. Bejar was mentioning we'd want to pull those in possibly get fast track, but again, we will need additional data that's why we're doing all these pace.

<unk> in this current phase one get as much data as we can just say what to go after and what not to go. After you don't want to waste your money and waste patients going after the wrong mutation profile identify the ones that work take the day to take to the FDA Dr. Bexar, what else did I Miss.

That was well put.

Makes it exactly at this point that.

For <unk> the fast track.

Very obvious choice since we have multiple patients with responses in that group and they are genetically identified subgroup, you'll take more patients that are not needing to identify the genetically.

Susceptible subgroups, but that would be another path forward once we do have that data.

Got it thanks, guys I appreciate you kind of gaming out the possible scenarios for me.

And then I guess, just one clarification on the G III work with locks.

Noticed that you were elevating I guess are beginning to look at patients with 100 milligram Q3, Luxe just wanted to kind of understand whether those patients would still be transitioning to 600 milligram <unk> one lux after which I think is basically equivalent to the 50 milligram.

From what we have.

Got it so far about the kind of PK equivalency. So just wanted to understand the plan there and why the kind of doubling of doses for the next step given the potency yet.

Okay.

So we haven't really talked about equivalency, yet in terms of the <unk> three versus <unk>. One we use do you want as a comparison, but we're putting patients on whatever dose, which one is appropriate for the dose level that they're being treated on so we're not necessarily selecting it based on the G. III dose. The reason to look at multiple doses of <unk> three is to make sure that we have dose proportionality there as we increase the dose we're also seeing greater.

Closures can you get a better understanding of how it is going to work and that's going to help us in doing the modeling that's going to be required to understand what multiple doses of GP would look like in the clinic. So we will continue to vary the dose of <unk> three based on the data that we see it we could go higher than 100, you could pull back if we needed to so youll see that theres more than one dose that's going to go into the beating that model that will then use to justify.

G III continuous dose down the road.

Yes.

Good points you mentioned.

The fixed dose here so.

So for instance, at 50 milligrams, we're going to get three or four or five patients. There because some of these may be 110 kilos or you may have a smaller 50 kilo person. So you want to make sure you have a good sense of what the exposure is going to be in these patients at a fixed dose of 50 move on up to a 100 word 100, we're going to collect as many patients here is we can very quickly and then.

Hopefully if its safe, we'll move up to another dose and as Dr. Bejar said, then do that modeling. So you can get the continuous dosing if all goes well and then the dose escalation. So that's the plan with books.

Understood. Thanks, again, Bill and look forward to talking with you guys in a few weeks at the corporate update.

Yes, Thanks, Andrew.

And we have no more questions at this time I would like to turn it back to Dr. Rice for closing comments alright.

Alright, well, let's wrap it up I want to thank everybody for joining us this afternoon.

Thank our shareholders and our analysts for your continued support and we look forward to keeping you all apprised of our progress.

And have a good evening.

And thank you ladies and gentlemen. This concludes today's conference. Thank you for participating you may now disconnect.

Okay.

Yes.

[music].

Welcome to the <unk> Biosciences incorporated reports results for the first quarter 2022 conference call. My name is Daryl.

And I'll be your operator for today's call at this time all participants are in listen only mode. Later, we will conduct a question and answer session. During the question answer session. If you have a question. Please press zero one on your Touchtone phone.

A reminder, this conference is being recorded I will now turn the call over to Dan Ferry, Dan you may begin.

Thank you.

Good afternoon, and welcome to the <unk> Biosciences conference call to discuss financial and operational results for the first quarter ended March 31 two.

2022.

Earlier today <unk> issued a press release relating to these financial results.

This release as well as related SEC filings are accessible on apoptosis website.

Joining me on today's call are talking of William G Rice, Chairman President and CEO .

Dr. Rafael Bejar, Senior Vice President 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.

Not guarantees of performance.

It is possible that actual results and performance could differ materially from these stated expectations.

They involve 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 in apoptosis. Most recent annual report on Form 10-K.

And SEC and SEDAR filings.

All forward looking statements made during this call speak only as of the date they are made.

<unk> 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 <unk> Biosciences, Dr. Rice.

Thank you Dan.

I want to welcome everyone to Oracle for the first quarter ended March 31 2022.

Because our last call was only a month and a half ago and because we plan to hold our kols corporate update a bit around the European Hematology Association or <unk> conference in just a few weeks. They will provide you with a brief update.

Today I want to emphasize that in the best position we've ever been.

With two well differentiated well tolerated and active titled inhibitor drugs AGM for three two to three nine or just two or three nine and looks at it locks as we call. It we continue to thoughtfully execute on our corporate vision and we're entering a new stage of maturity.

<unk>, our Chief Medical Officer, Dr. Rafael Bejar will discuss why we believe our lead candidate to three nine.

Best in class oral kinase inhibitor designed to treat the disease.

Not just treat a particular target.

And as superior to <unk>.

<unk> for the treatment of AML patients with adverse mutations.

And Lux, which is mechanistically and preclinical remains a well differentiated agent has demonstrated clinical activity in <unk> and AML cancers, plus we continue to make strides with a new formulation with Lux in an effort to achieve greater plasma exposures with lower doses of lots and we've recently highlighted.

Its activity on it.

<unk>, III, and <unk> and a potential application to inflammatory and autoimmune diseases.

Again, Dr. Bexar will deliver the updates on both product candidates.

Before I turn the microphone over to him I want to make a few remarks about 239.

About the upcoming <unk> conference and about our new Chief commercial officer.

Let's begin with two or three night.

Totally yet event to highlight is our recent news that the FDA granted fast track designation to <unk> three nine for the treatment of patients with relapsed or refractory AML, who have flip three mutations.

Three nine previously had received orphan drug designation from the FDA for the treatment of AML.

And the designation of fast track status certainly is welcome news as it clarifies a recognition that two or three nine already demonstrated meaningful clinical benefit to flip <unk> mutated AML patients.

As most of you are aware fast track status acknowledges <unk>.

To fill an unmet need for AML patient populations.

Supports our efforts as we advance it towards a potential Registrational study.

The fast track designation also helps facilitate and potentially expedite the drugs development, which allows us to have early and frequent communication with the FDA. So that questions and issues are resolved more quickly.

Now, let's discuss our plans for the upcoming <unk> conference that is just a few weeks away.

We recently were notified that an abstract we submitted to eat all encompassing preclinical research on to three nine has been accepted for a poster presentation at Indiana.

But just prior to Ehealth, we plan to hold our Kols corporate event during which we plan to present available clinical data from all patients at all dose levels enrolled in our clinical trials for both two or three nine and logs, we will continue to collect PK PD.

Efficacy and pet scan data up until the time of the cole corporate event and such data will not be embargo.

For <unk>, we also plan to update you on the clinical data with our new <unk> formulation, and AML and B cell cancer patients.

Data from patients receiving G. III will continue being collected over the next few weeks and we plan to present the available data at the Kols corporate event.

Regarding to three nine.

Regard that during the Ash conference in December we presented five complete remissions are Crs with the 80 milligram cohort four of which advanced to the potentially curative allogeneic stem cell transplant.

In addition, one patient who was unfit for transplant harbored wall type flit, three and to Holly adverse T. P 53 mutations.

This patient experienced a durable response, including a CR for more than one year.

These data illustrate that to three nine meaningfully and safely extended the life of multiple patients with relapsed or refractory AML that already had been filled by other therapies.

More recently, we reported.

Debt at the 200 at the 120 milligram dose.

One patient had experienced a partial remission or PR and another patient with <unk> and <unk> mutations experienced a complete remission or CR, adding to the Crs from the 80 milligram dose level reported in December .

Consequently, we already have identified two dose levels 80, milligram and 120 milligram.

That payer complete remissions with Tolerability and we now are exploring a higher dose by expanding at the 160 milligram dose level.

Methodically testing different doses with numerous patients during this phase one trial in a disciplined manner, we optimize our chance to select the best doses to maximize safety and to minimize regulatory risks Bob boarding a dose that could exhibit toxicity.

Also I want to be clear that as we approach ehealth, our focus with two or three nine now is to recruit AML patients with a diverse array of mutations in our ongoing phase one trial.

We already have demonstrated crs and multiple patients with <unk> mutated AML and the FDA has recognized that capability by awarding app dosed with fast track designation for <unk> three nine and these patients how's.

However, we are not attempting to focus solely on flit three mutated patients in this trial.

This is a phase one trial designed to explore doses and the range of activity up to three nine.

We also have seen <unk> in patients with wild type <unk>, three and a host of other adverse mutations we want to further our understanding of the full breadth of activity of 239.

Patients with diverse mutation profiles.

While this may result, in lower and a lower percentage of Crs in the near term in patients with adverse co mutations. We believe this approach should allow us to select the appropriate population to treat and those populations to avoid in future studies as part of our goal to deliver the greatest value to patients physicians and the inverse.

<unk>.

To be clear our focus is to select genetically defined AML patient populations with unmet medical need that appear to have sensitivities to three nine.

And then to initiate fixed dose expansion trials in these patient populations.

The first step is to identify the appropriate patient populations and we believe the ongoing phase one trial already is delivering this information.

So these expansion trials, we must identify an efficacious and well tolerated dose.

Selected expansion or go forward dose in.

In fact, the ongoing phase one already identified at least two go forward doses.

Both safe and efficacious that we can use to explore and optimizing our expansion trials in specific patient populations and.

In the second half of the year, we plan to present, the selected expansion dose along with the safety and efficacy packages to the FDA and request allow us to initiate the expansion trials soon thereafter.

If data from those trials are successfully are sufficiently compelling.

We then would request an accelerated registrational pathway of course. This is the desired path for 239. There is much work ahead of us, but two or three nine to date have delivered results that point us in this direction, we plan to speak more about this plan during the Kols corporate events.

As an FYI, we plan to announce formally the Kols corporate event and its logistics later this week along with the <unk> abstract.

Now, let me turn to my last subject with the maturation of the company's products comes to the task of building the right team.

So I'm very pleased that we recently added a chief commercial officer, Dr. Felipe lead through to our executive management team.

Felipe.

Toast with exceptional pharmaceutical industry experience in the U S and Europe .

At Merck also provided commercial leadership on all licensing and M&A activity, including the peloton therapeutics and <unk> acquisition in 2019 prior.

Prior Dr. <unk> spent a 20 plus year career at Novartis in the U S and France. Most recently a senior director of early commercial strategy focused on oncology products.

He also was a member of the brand team.

He held early commercial development and global marketing responsibilities for several new compounds, including the <unk> three inhibitor modest store.

Earlier at Novartis oncology he.

He helped lead the launches of several oncology products, including the kinase inhibitor Imatinib brand name Gleevec, a landmark drug priority or by Dr. Brian <unk> that has transformed outcomes for patients with chronic myelogenous leukemia.

Practice Felipe joining up dose our drug to three nine lit up on his radar screen of priority agents and he actually approached us with this interest in joining up to us to work on the development and commercial strategy for Q3.

I'll say more about what a timely videos for <unk> and we're delighted to have him join our team.

With that let's have Dr. Bexar it give us a brief commentary on two or three nine and logs breath.

Thanks Bill.

We are in the fortunate position of having two well differentiated oral kinase inhibitors for the treatment of hematologic malignancies, <unk> 39 for AML, except for both AML and B cell cancers.

First let's talk about 2009, our lead product candidate already has demonstrated multiple complete remissions for Crs.

2019, the highly effective <unk> inhibitor.

Wild type and all other forms of with recasting in fact, it may be best in class superior to quickly inhibiting competitors. It just got treating it as a single agent and when combined with genetic wax decided it.

It is important to highlight that 2009 is more than just an inhibitor. Three is it also inhibits other oncogenic signaling pathways and validated targets, including sick.

Informs a C kit as well as GAAP, one Jack to among others can disrupt proliferation and emergence of resistance.

Q3, nine inhibits all tested assistance concurring mutant forms of <unk>, including forms with the ITD TKD activation or gatekeeper mutation as well as the wild type training.

And he demonstrated inhibition of resistance concurrent growth accurate pathways in particular, let's say three six JAK stat and map kinase or erk pathway.

In simpler language 2019 interfere with the rescue pathways that may lead to resistance from treatment with <unk> inhibitors, while avoiding targets that may compromise safety.

As we have reported the kinase inhibitory profile of 2009 already has translated into strong durable and broad anti leukemic activity and a diverse array of relapsed or refractory AML patients with a striking array of highly adverse presentation delivering multiple complete remissions in the phase one trial, thus far.

I'll remind you. This includes patients with mutations in the <unk> 53, NPM one racks at each two gene as well as with wild type <unk> three and in patients.

The ITT or tyrosine kinase forms.

We already have shown 2090 is an active and well tolerated drug at 80 milligrams and 120 milligrams or we have efficacy paired with tolerability.

And the extensive preclinical animal model suggests 2009 can be paired with other drugs to create drug combinations that are even more effective in treating disease.

Now we are exploring the 150 milligram dose and an expansion cohort to characterize with therapeutic window to reduce regulatory risk and to ensure we leave no efficacy on the table.

We're often asked about the full breadth of activity of 239 on <unk>.

Sub populations of AML patients our observations to date illustrating anti leukemic activity at multiple dose levels.

<unk> hundred nine appears to have the potential to treat with <unk> mutant patient compromising about a third of novo AML as well as with the wild type patients. The other two thirds.

Both fit and unfit patients since it hit.

And so well tolerated active doses to date.

And the relapse refractory population as well as the newly diagnosed frontline AML population.

Addition, we expect that it can be used successfully in combination with other drugs.

In the ongoing phase one trial design for extensive dose exploration. According to newer FDA guidelines, we are dotting, the i's and crossing the Ts and exploring all types of AML patients in our dose expansion arms as Dr. <unk> mentioned, we're not seeking to focus only on treating patients in our current trial, we already have validated <unk> hundred 90 active patient even.

He previously received <unk> three inhibitors, which is might historically.

So we now see you could define the mutation profile susceptible to three nine so we can better treat an appropriate patient.

We are seeking to undercover.

Breadth of AML patients responding to 2019, we're encouraged by what we're seeing.

<unk> in patients with challenging highly at risk mutations growing our list of adverse ALLL genotypes would appear to respond or are capable of responding to 2009.

This includes the recent patient with the CR reveal 2009 can deliver responsive patients harboring abnormalities with MLG.

Patients in <unk> one.

We believe this deliberate thorough approach will help us define the subgroups of AML patients likely to respond to 2009, and there is less likely to respond by guiding the path forward in our next phase of clinical development.

As we discussed in our last call. We already have identified two well tolerated and active dose of 80 milligrams and 120 milligrams and could serve as the go forward dose to take into expansion trials.

We continue to explore the 160 intuitive milligram dose level. So we missed like the optimal expansion dose and select genetically defined AML patient populations to initiate our fixed dose expansion studies with an eye towards accelerated registrational pathway.

Okay now on to a quick review of accepting it.

Just a reminder, luxury the only known clinical agent that Potently inhibits both swiftly and PTK with the precision that avoids known targets that are often associated with toxicity.

Pre clinically orally administered box demonstrated potent anti tumor activity in animal models of disease clinic.

Clinically the drug thus far demonstrated clear target engagement PDK for the three and anti tumor activity, including dose and exposure dependent tumor reductions observed in multiple patients.

But the original formulation, but not absorbed well enough to achieve exposure levels consistently and effectively treat these aggressive cancers.

In the <unk>, we get a report for Lux relapsed AML patient the patient had achieved greater exposures in the drug even at the 450 milligram dose level.

As we mentioned in our last call. We've made significant progress with our new formulation of <unk>, which we call at G III, and which may be able to enable greater exposures across patients.

Im pleased to report that we have now dosed at G. III at two different dose level safely competing dosing three patients 50 milligram dose level recently escalating the dose to 100 milligrams in our ongoing clinical program.

After patients receive a single <unk> dose samples are collected for PK valuation and then patients go on to the original formulations of <unk>, but the direct comparison.

As mentioned in our last call. The PK data to date are encouraging and we plan to discuss further at our upcoming <unk> corporate events.

We expect the ongoing single dose <unk> III studies will allow us to define the single dose PK profile and trim. Those data we can model that continuous dosing PK profile is.

In addition to potentially delivering higher exposures that any resulting greater responses. We expect the GP formulation may reduce significantly the pill burden the amount of drug acceptance administered patients and thereby the amounts of drug substance and drug product manufacturing to support the trial.

Finally, let me close out the Lex reviewed by drawing attention to the recent press release, highlighting three publications in blocks.

One of the speakers as related to inflammation autoimmune disease novel.

Notable insights into the mechanisms by which less than your peers with the <unk> III plant is up and endotoxin induced inflammatory signaling pathways, along with its protective effects against inflammation induced toxicity in murine models.

The ability to inhibit inflammatory pathways concentrations, which are well tolerated patients makes it a potential clinical candidate for the treatment of inflammatory and autoimmune diseases as well as inflammation associated with assistance in cancer.

We're very pleased with the progress in our <unk> and <unk> clinical programs, we remain steadfast in our discipline to reduce regulatory risk and we look forward to providing further updates to you next month.

For more information on all of our ongoing clinical trials and clinical sites that are recruiting patients. Please do the clinical trial that got it.

Now I'll turn it back to you Dr. <unk> to review the financials Bill.

Thank you Rob.

We take a disciplined approach to our cost management to ensure cash is deployed to the high impact agents and studies and as we reported last quarter, our cash runway extended well into the fourth quarter of 2020 through so let's review our cash position.

We ended March 31, 2022, with approximately $69 $5 million in cash cash equivalents and investments during.

During the quarter the net loss was approximately $11 5 million.

Translating into approximately <unk> 12 per share.

Provided in the income statement, we had no revenues for the first quarter of 2022.

Research and development expenses were approximately $7 4 million for the quarter down from $8 2 million during the same quarter of 2021.

We will turn to the Q&A session. So operator, if you would please introduce the first question.

If anyone has a question you can press zero one on your Touchtone phone. Once again, if you have a question zero one on your Touchtone phone and our first question comes from Greg <unk> go ahead Greg.

Yes, Hey, good afternoon, Bill and team and congrats on the progress and thanks for taking my question.

Just to come.

Come to the tier three nine strategy certainly your mention of looking at those diverse mutation profiles I'm. Just curious if you could just touch on the inputs involved here, how we should think about really setting the molecule up for success looking at the commercial inputs and maybe.

We think and if you could just believes presence and determining that path forward and then lastly, just how it pertains to the timing and even if I add the patients that you are alluding to with respect to getting the results. Thank you so much.

Thanks, Greg.

That's an expansive question. So I'll begin and then I'll ask Dr. Bejar also to jump in so it's clear that we've been asked is it the flip <unk> inhibitor and we say well of course. It is it doesn't inhibit split three inhibits all forms of flip three better been tested very well.

So we feel confident we can move into patients that have put three mutations, including those with a variety of mutations and including those who have already been filled by other <unk> inhibitors, such as auto sorting deal.

So that positions it well as a <unk> inhibitor to be very competitive.

But this molecule goes well beyond that.

Because of its ability to inhibit sick the JAK one jet to the mutant forms of C kit.

And allows it then too.

To inhibit those key pathways those rescue pathways that can compensate for let's say you inhibit flint flit three but these other pathways that can rescue the sale while the drug is able to also to suppress those pathways. So we've already seen that we have patients that are wild type in their fleet three.

A variety of adverse mutations and we've actually seen Crs and such a group of patients there, but we wanted to understand kind of the full breadth of activity. What all mutations are going to be covered by this drug.

We've said that a patient who had a <unk> three mutation responding to the drug that does not mean, our drug directly inhibits the <unk> 53. It just means that we're able to cover enough of the pathways to be able to kill those sales. The patient responded so our task right now is different.

To fully understand the breadth of activity against all of these different types of mutations at best we possibly can which means in our current phase one trial, we're really now trying to focus on getting as many of those drugs versus mutations as we can as Dr. <unk> mentioned just recently.

A patient with the CR had the MLR <unk> mutations as well as the <unk>, one well that brought on a new.

Group of co co mutations that are adverse.

A patient so we want to get as many of those we can now.

It's likely we will have a lower percentage of for sponsors and these types of patients, but that's important for us to see now because we want to know which ones will respond which ones will not respond that then guide our our expansion trials going into the future. So we're collecting the data on these patients we want to be able to write that up get it to the FDA.

Identify the we'll call it the expansion dose that we're going to select and move forward.

And we hope we actually have maybe three doses that can be used in those expansion cohorts and so.

So at this point, let me turn it over to Dr. Bejar, if he can speak more about this in the patients.

Sure.

You can learn a lot from patients in the clinical study not only.

Which mutations.

Well.

<unk> learned a lot about the molecular basis of the disease and how their drug is affecting that so when patients get started on the study.

Staying with the genomic mutations are at baseline and then if a patient responds and then relapses. We can understand what mutations went out control resistance or patients with particular mutations never responded we understand that this might be primary resistance mutations. So these are the kinds of things that we hope to learn from these patients beyond whether or not they respond what factors are actually driving that response or lack thereof.

You can then use to identify patient populations that we might want to go after in a more narrow or focus that and as we've talked about before obviously looks like a mutant population is going to be a targeted this drug.

Patients that have unfortunately adverse disease relapse and are not cured by available therapies out there sort of stem cell transplant. So we will be focusing on that patient population, but there are others out there that may derive great benefit and allow us to.

One trial will allow us to more whom they arent, where we might focus on.

Okay.

Yes, just to add to that you know you see drugs out there being developed for patients with <unk> mutations <unk> 53.

Various other pathways and we wanted to see how many of these other pathways and targets. We can cover with this molecule. So that's our plan. Thank.

Thank you Greg I hope that answer your question.

Sure Doug. Thank you very much guys and looking forward to the updates in a few weeks.

Thanks for being here.

And our next question comes from.

Matt Biegler from Oppenheimer go ahead, Matt.

Hey, guys. Thanks for the question, maybe I can squeeze you in first.

Just maybe a sense for how many patients we should expect for 293 ehow relative to what we saw at ash.

Number one and then I do want to make.

One about acceptance outside of Eric I appreciate the preclinical data that you guys.

<unk> shared with US a couple of weeks ago.

I guess given its strong tolerability so far.

B cell.

Planetary suckers are obviously you need a good therapeutic window is there.

It's something that you're actively considering.

It's something that you would only pursue with a partner.

Thanks, Matt straight to your horse again rigs.

Regarding how many patients we're going to have since December .

I don't have a good handle on exactly how many maybe Dr. <unk> can give you a sense in a second so let me just flipped into your second question looks outside of cancer.

Clear that some of these PTK inhibitors <unk> inhibitors are being developed for inflammation and so because of the kinases that looks inhibits we began to look at these.

And look at the pathways all the way from the cell surface of all the way down through.

Say three to four levels within the within the.

Signaling pathways and it really pointing to the fact that we should have activity in the animal models. We then initiated a series of animal models in which we were using originally the original formulation and we're delivering it orally and we started seeing activity and now we're trying to move forward with our new formulation in animal.

Models and expand out on these these.

Inflammation and autoimmune diseases.

It is also important as you said in a disease like this youre going to be dosing for long term in these patients. So you want to have a drug that's well tolerated well. We know that luck is very well tolerated and it appears as though lower doses could have an effect on these inflammation and autoimmune diseases lower dose.

Is that are required to kill these very aggressive malignant cells. So yes. We are pursuing this we are we've kept it pretty quiet up until now because we wanted to make sure. We have animal data, we're now extending that into additional animal models and then we'll see where it takes us but again as always we will follow the data.

So I'll flip it back to Dr. Bexar, if he wants to talk about the <unk>.

<unk> between Ash in Bihar, and then also if he wants to add anything else to the Love's and inflammation.

Sure. Thanks, Paul so.

I'll remind you that at ash the data cut for that was quite a bit before the actual ash meeting itself. So I think at ash.

And it wasn't even at the total picture of how many patients were on site even at that time.

After that meeting has seen the trial and has accrued additional patient.

Reported already that we had completed 120 milligram dose expansion, we're now exploring 160 milligrams.

So youll see all of that all the patients that are filling out the 120 and good data that we have to date on the 116.

But I don't have a good number on the exact number of patients out there so Matt sorry about that.

It may well change between now and then as well it will yes it.

Changes daily.

Anything else you wanted to say about.

Inflammation.

I think it's exciting there is inflammation.

It appears in several different places, where I think <unk> had an opportunity to address it and one is obviously in the areas, where youre talking about b cell inflammatory disorders.

And the inflammation is actually a factor in other conditions, we briefly mentioned.

Cancer therapies inflammation as a driver of that and even in disorders like quantum that of polices inflammation plays a role.

I'd be interested to explore all the potential applications of <unk> in that context.

Alright, guys Thats exciting stuff.

Thank you Matt.

And our next question comes from Lee <unk> from Cantor Fitzgerald go ahead Lee.

Hey, guys. Thanks for taking my questions I guess first on the one <unk> Nick.

Can you comment a little bit more on what you saw from the efficacy point of view.

For many patients do you have.

<unk> right now.

So it seems like 239.

<unk>.

Rod activity, So I guess, what Africa, the rationale that you have.

I guess for you to open.

Expansion cohorts that particular patient population. Thank you.

Interesting question.

So clearly we've seen and we've reported.

<unk> efficacy and well tolerated status at both 80 milligrams in at 120 milligrams and based on that then we moved up to the expansion of the $160. We have not released yet the number of patients at the 160 and as Dr. Bejar that changes daily it takes several months.

To get a patient on.

To get them identified washed out of their prior drugs get them on study and then hopefully over time, you'll see responses merge you confirm those until that process takes months and so what we'll do is between now and <unk>. We will collect all the data that we have available we will present that all the numbers of patients to the types of patients.

It's known about their disease mutations.

And where we have work.

In terms of the broad activity.

You are right its more than just a <unk> three inhibitor.

And in terms of the threshold for selecting patient populations, you really wanted to see single agent Crs in these patients.

For instance, we found one patient we had one patient that had a <unk> three mutation wild type III.

Dr. Bejar would you like to jump in on that too.

Yes, one thing I would add there is I think that the context of the population really matters and so in terms of what your threshold for success should be and those patients really have no. Other alternative therapies in the very short pregnancy.

For example, patients who were previously treated with tyrosine kinase inhibitors for example.

I don't have any additional options threshold for success. There is a lot lower than say, perhaps in the patient population earlier in therapy, perhaps second line or even first line, where you want to see greater activity.

And a bit on who we're talking about but some of those patients. We identified are truly the worst of the worst in terms of prognostic risks television.

Flex carrier type patients patients, who have been sales by minus door and go through it and it is the only approved FDA approved therapies.

Those patient populations will have quite a low bar for success and hopefully that will be able to meet and exceed that.

Okay, great. Thank you.

Thank you Lee.

And our next question comes from Matthew Cross from Alliance Global Partners Go ahead, Matt.

Okay.

Hey, guys. Good afternoon, thanks for taking a couple of questions from me.

One kind of a follow up related to this continued discussion about.

The broader market for for 2009, I guess trying to interpret the fast track designation grants.

Just kind of wanted to clarify I guess to the century what to say.

What data the FDA was able to see in order to.

<unk> received an order to base that decision on if that's anything that we haven't seen but we'll let ehealth. If it was kind of as of ash just to get understanding of what theyre looking at.

And what other potential subgroups that may have responded that they had seen.

When granting that and I guess kind of on a related point just thinking about the potential regulatory paths would you expect it sounded like you might consider the idea.

Pursuing a couple of different specific mutation groups would you kind of expect to rollout a few different possible fast tracks or at what point can let's just be kind of a broader.

Discussion of a relapsed refractory AML population with particular patients that you focus on clinical trials from a regulatory standpoint.

Okay.

Well I'll try to filter through the so thanks, Matt for the question in terms of the broad market. So you were asking the first about the fast track what David we have so we've disclosed essentially all of the data.

Regarding we have many patients at the 80, and then that the 120 milligram that had crs as well as the PR that came in.

Those were flip three mutated and especially those that had failed the motto store and the guilt ridden them. So we're talking about Crs at very well tolerated doses. So we applied toward the faster I can then the FDA provided that to us in terms of the breadth of activity.

No.

We'd love to be able to move this forward for yes, flit three mutated, but also patients who are flip through Walter Dr. Bejar mentioned could flit three mutation that's about one third of the population so you'd like to be able to target. The other two thirds is many of those as we can.

Also fit and unfit.

As a well tolerated drug so we would hope to be able to include the administration of this drug in patients who are unfit for chemotherapy.

That's a little bit of a longer path, but that's something we'd like to do and also reluct refractory and then moving it up toward the first line. If you have a drug that truly is well tolerated get crs. So those are the paths that wed like to take the data are pointing to that but we will follow the data and it will tell us the page.

Populations to go after and you mentioned the regulatory path again, it will depend entirely upon the data that we're seeing as we go into these expansion trials. Currently we believe that the <unk> three mutated is a path and in particular, if you can identify those patients and have a reasonable response rate in patients who have failed modest warning guilty of Britain.

And even in those who havent been pretreated with that we have the fast track broadly in flip through mutated not just the ones who have failed those drugs.

If we're able to see enough patients that are flit, three wild type, but yet.

<unk> able to treat these patients with these other adverse mutations we're able to identify subgroups. There is Dr. Bejar was mentioning we would want to pull those in possibly get fast track, but again, we will need additional data. That's why we're doing all of these patients in this current phase one get it.

Much data is we can just say what to go after and what not to go. After you don't want to waste your money and weight patients going after the wrong mutation profile identify the ones that work take the day to take to the FDA.

What else did I Miss.

No that was well put.

Makes it exactly at this point that.

Three of the fast track.

Very obvious choice since we have multiple patients with responses in that group and they are genetically identified subgroup, you'll take more patients that are not meeting to identify the genetically.

Susceptible subgroups, but that would be another path forward once we do have that data.

Got it thanks, guys I appreciate you kind of gaming out the possible scenarios for me.

And then I guess, just one clarification on the <unk> worked with locks.

Notice that you were elevating I guess are beginning to look at patients with 100 milligram <unk>.

Just wanted to kind of understand whether those patients would still be transitioning to the 600 milligram <unk> after and which I think is basically equivalent to the 15 milligram.

From what we have.

We have gathered so far about the kind of PK equivalency.

So just wanted to understand the plan there and why the kind of doubling of dosage for the next step given the potency.

Okay.

So we haven't really talked about equivalency, yet in terms of the <unk> three versus <unk>. One we used you want as a comparison, but we're putting patients on whatever dose, which one is appropriate for the dose level that they are being treated on so we're not necessarily selecting it based on the G. III dose. The reason to look at multiple doses of G. III is to make sure that we have disproportionality there as we increase the dose we're also seeing greater.

Measures to get a better understanding of how that's going to work and that's going to help us in doing the modeling that's going to be required to understand with multiple doses of GP would look like in the clinic. So we will continue to vary the dose of the G. III based on the data that we see it we could go higher than 100, you could pull back if we needed to so.

Youll see that theres more than one dose that's going to go into beating that model that will then use to justify G. III continuous dose down the road.

Yeah, that's a good point that you mentioned.

Fixed dose here.

So for instance at 50 milligrams, so we're going to get three or four or five patients. There because some of these may be 110 kilos or you may have a smaller 50 kilo person. So you want to make sure you have a good sense what the exposure is going to be in these patients at a fixed dose of 50 move on up to 100 were at 100, we're going to collect as many patients here is we can very quickly and then.

Hopefully if its safe, we'll move up to another dose and then Dr. Bejar said then do that modeling. So you can get the continuous dosing if all goes well and then the dose escalation. So that's the plan.

Understood. Thanks, again look forward to talking to you guys in a few weeks at the corporate update.

Yes, Thanks, Andrew.

We have no more questions at this time I would like to turn it back to Dr. Rice for closing comments.

Well, let's wrap it up I want to thank everybody for joining us this afternoon.

We're advancing through a very interesting stage of development of the company and none of this would be possible, though without the dedication of our employees our investigators and importantly, most importantly, the patients are helping advance our very important work, we thank our shareholders and our analysts for your continued support and we look forward to keeping you all apprised of our progress.

And have a good evening.

And thank you ladies and gentlemen. This concludes today's conference. Thank you for participating you may now disconnect.

Q1 2022 Aptose Biosciences Inc Earnings Call

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