Welcome to the Aptose Biosciences o Incorporated Reports Result for the First Quarter 2022 Conference Call. My name is Darryl and I will be your Operator for today's call. At this time, all participants are in listening-only mode. Later, we will conduct a question-and-answer session.

[Operator Instructions] 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 Aptose Biosciences conference call to discuss financial and operational results for the first quarter ended March 31st, 2022. Earlier today, Aptose issued a press release relating to these financial results. The news release, as well as related SCC filings are accessible on Aptose's website.

Joining me on today's call are Dr. Dr. William G. Rice, Chairman, President and CEO and Dr. 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 Aptose's 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 Aptose's most recent annual report on Form 10-K and SCC and SEDAR filings.

All forward-looking statements made during this call speak only as of the date they are made. Aptose 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 Aptose Biosciences. Dr. Rice..

80 milligram and 120 milligrams that pair complete remissions with tolerability. And we now are exploring a higher dose by expanding at the 160-milligram dose level.

By methodically testing different doses with numerous patients during this Phase I trial in a disciplined manner, we optimize our chance to select the best doses to maximize safety and to minimize regulatory risk by avoiding a dose that could exhibit toxicity.

Also, I want to be clear that as we approach EHA, our focus with 239 now is to recruit AML patients with a diverse array of mutations in our ongoing Phase I trial.

We already have demonstrated CRs in multiple patients with FLT3 -mutated AML and the FDA has recognized that capability by awarding Aptose with fast-track designation for 239 in these patients. However, we are not attempting to focus solely on FLT3-mutated patients in this trial.

This is a Phase 1 trial designed to explore doses and the range of activity of 239. Because we also have seen CRs in patients with wild-type FLT3 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 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 populations 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 investors.

To be clear, our focus is to select genetically defined AML patient populations with unmet medical need that appear to have sensitivities 239 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 I trial already is delivering this information. Second, for these expansion trials, we must identify an efficacious and well-tolerated dose at the selected expansion for go-forward dose.

In fact, the ongoing Phase 1 already has identified at least two go-forward doses that are both safe and efficacious that we can use to explore and optimize in our expansion trials in specific patient populations.

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. 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 239 to date has delivered results that point us in this direction. We plan to speak more about this plan during the KOL corporate event. As an FYI, we plan to announce formerly the KOL corporate event and its logistics later this week, along with the EHA abstract.

Now let me turn to my last subject. With the maturation of the company's products comes to pass building the right team. And so, I'm very pleased that we've recently added a Chief Commercial Officer, Dr. Philippe Ledru, to our executive management team. Philippe comes to Aptose with exceptional pharmaceutical industry experience in the U.S. and Europe.

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 Merck, he also provided commercial leadership on all licensing and M&A activities including the Peloton Therapeutics and ArQule acquisition in 2019. Prior, Dr. Ledru 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.

There, he also was a member of the brand team any he held early commercial development and global marketing responsibilities for several new compounds including the FLT3 inhibitor midostaurin.

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 Druker that has transformed outcomes for patients with chronic myelogenous leukemia.

Prior to fully joining Aptose, our drug 239 lit up on his radar screen of priority agents, and he actually approached us with his interest in joining Aptose to work on the development and commercial strategy for 239. Need I say more about what a timely fit he is for Aptose, and we're delighted to have him join our team. With that, let's have Dr.

Bejar give us a brief commentary on 239 and lux. Raf..

Thanks, Bill. We're in the fortunate position of having two well-differentiated oral kinase inhibitors for the treatment of hematologic malignancies, HM43239 for AML, [Indiscernible] for both AML and B-cell cancers. First, let's talk about 239. Our lead product candidate that already has demonstrated multiple complete remissions or CRs.

239 is a highly effective FLT3 inhibitor, inhibiting both wild type and all other forms of FLT3 tested. In fact, it may be best in class superior to FLT3 inhibiting competitors such as gilteritinib as a single agent and when combined with venetoclax or azacitidine.

It is important to highlight that 239 is more than just an inhibitor of FLT3, as it also inhibits other oncogenic signaling pathways and validated kinase targets, including SYK, mutant forms of CKIT, as well as JAK1 and JAK2 among others to disrupt proliferation and emergence of resistance.

239 inhibits all tested resistance conferring mutant forms of FLT3 including forms with the ITD, TKD activation mood or gatekeeper mutation, as well as the wild-type kinase and a demonstrated inhibition of resistance-conferring growth factor pathways in particular a FLT3 cKIT, JAK/STAT and MAP kinase ERK pathways.

In simpler language, 239 can interfere with the rescue pathways that may lead to resistance from treatment with FLT3 inhibitors while avoiding targets that may compromise safety.

As we have reported, the kinase inhibitory profile of 239 already has translated into strong, durable, and broad antileukemic activity in a diverse array of relapsed refractory AML patients with the striking array of highly adverse co-mutations, delivering multiple complete remissions in the Phase 1 trial thus far.

I'll remind you; this includes patients with mutations in the TP53, NPM1, RAS, IDH2 genes as well as with wild-type FLT3 and in patients harboring the ITD or tyrosine kinase domain in forms of FLT3. We already have shown 239 as an active and well-tolerated drug at 80 milligrams and a 120 milligrams and we have efficacy paired with tolerability.

An extensive pre -clinical animal model suggests 239 can be paired with other drugs to create drug combinations that are even more effective at treating disease. Now we are exploring the 150-milligram dose in 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 on different sub-populations of AML patients.

Our observations to date illustrate antileukemic activity at multiple dose levels and 239 appears to have the potential to treat FLT3 mutant patients compromising about a third of [Indiscernible] AML, as well as FLT3 wild-type patients, the other two-thirds, both fit and unfit patients, since it has been so well-tolerated at active doses today and the relapsed refractory population, as well as the newly diagnosed frontline AML population.

In addition, we expect that it can be used successfully in combination with other drugs. In the ongoing Phase I trial, designed for extensive dose exploration according to newer FDA guidelines, we are "dotting the Is and crossing the Ts " in exploring all types of AML patients in our dose expansion ops. As Dr.

Rice mentioned, we're not seeking to focus only on FLT3-mutant patients in our current trial. We already have validated 239 is active in FLT3 -mutant patients, even if they previously received other FLT3 inhibitors, such as [Indiscernible]. So we now seek to define a mutation profile susceptible to 239, so we can better treat appropriate patients.

We are seeking to undercover the genetic breadth of AML patients responding to 239 and we're encouraged by what we're seeing. CRs in patients with challenging highly-adverse mutations, growing our list of adverse AML genotypes that appear to respond or are capable of responding to 239.

This includes a recent patient with a CR who revealed 239 can deliver responses in patients harboring abnormalities of the MLL gene, as well as mutation in RUNX1.

We believe this deliberate, thorough approach will help us define the subgroups of AML patients that are likely to respond to 239 and those less likely to respond, thereby 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, that could serve as a go-forward dose to take into expansion trials.

We continue to explore the 160 and 200 milligram dose levels so we may select the optimal expansion dose and select genetically defined AML patient populations to initiate our fixed dose expansion studies with an eye towards accelerated registrational pathways.

Well, we're not providing further details of the patients at this time, we are continuing to collect data over the next few weeks and we plan to disclose it all available data to date at our [Indiscernible] corporate event next month. Okay, now, onto a quick review of luxeptinib.

Just a reminder, lux is the only known clinical agent that potently inhibits both FLT3 and BTK with a precision that avoids known targets that are often associated with toxicities. Pre -clinically, orally administered lux demonstrates potent antitumor activity in animal models of disease.

Clinically, the drug has less far demonstrated clear target engagement of BTK and FLT3 and in antitumor activity including dose and exposure dependent tumor reductions observed in multiple patients. But the original formulation has not absorbed well enough to achieve exposure levels to consistently and effectively treat these aggressive cancers.

And the one CR we did report for lux in a relapsed AML patient, the patient had achieved greater exposures in the drug even at the 450 milligram BID dose level. As we mentioned in our last call, we've made significant progress with our new formulation of lux which we call G3 and which may be able to enable greater exposures across patients.

I'm pleased to report that we have now dosed a G3 at two different dose levels, safely competing dosing three patients at the 50-milligram dose level, and recently escalating the G3 dose to 100 milligrams in our ongoing clinical program.

After patients received a single G3 dose, samples are collected for PK evaluation and then patients go on to the original formulation of lux for the direct comparison. As mentioned in our last call, the PK data on G3 to date are encouraging and we plan to discuss them further at our upcoming KOL corporate event.

We expect the ongoing single dose G3 studies will allow us to define the single dose PK profile and from those data, we can model the continuous dosing PK profile.

If that PK modeling data are sufficiently compelling, we plan to take those data to the FDA and request to transition fully to continuous dosing with the G3 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 G3 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 manufactured to support the trials.

Finally, let me close out the lux review by drawing attention to the recent press release highlighting three publications of lux.

One of those papers was related to inflammation, autoimmune disease, and provided novel insights into the mechanisms by which lux interferes with the NLRP3 inflammasome and endotoxin -induced inflammatory signaling pathways, along with its protective effects against inflammation-induced toxicity in [Indiscernible] models.

The ability of luxeptinib to inhibit inflammatory pathways at concentrations which are well tolerated in patients makes it a potential clinical candidate for the treatment of inflammatory and autoimmune diseases, as well as inflammation of associated resistance in cancer. We are very pleased with the progress in our lux and 239 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 visit clinicaltrials.gov. For now, I'll turn it back to you, Dr. Rice, to review the financials. Will..

Thank you, Raf. We take a disciplined approach to our cash 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 2023. So let's review our cash position.

We ended March 31st, 2022 with approximately $69.5 million in cash, cash equivalents and investments. During the quarter, the net loss was approximately $11.5 million translating into approximately $0.12 per share. As providing 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 decreases primarily due to reduction in stock-based compensation during the first quarter of 2022 relative to 2021. With that, we will turn to the Q&A session. So Operator, if you would please, introduce the first question..

[Operator Instructions]. And our first question comes from Greg Renza. Go ahead, Greg..

Yes, hey. Good afternoon, Bill and team, and congrats on the progress and thanks for taking my question. Bill, just to come to the 239 strategy, certainly your mention of looking at those diverse mutation profiles.

I'm just curious if you could just touch on the inputs involved there, how we should think about it really steadying the molecule up for success. Looking at the commercial inputs and maybe weaving in if you could just fully presence in 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 end results. Thank you so much..

Thanks, Greg, that's an extensive question. So I'll begin and then I'll ask Dr. Bejar also to jump in. So it's clear that what we've been asked, is this a FLT3 inhibitor? And we say, well, of course it is, it does inhibit FLT3 and inhibits all forms of FLT3 that have been tested very well.

And so, we feel confident we can move into patients that have FLT3 mutations including those with a variety of mutations and including those who have already been failed by other FLT3 inhibitors such as alloSCT and gilteritinib. So that positions at well as a FLT3 inhibitor to be very competitive.

But this molecule goes well beyond that because of its ability to inhibit SYK or Jak1, JAK2, the mutant forms of cKIT and allows it then to inhibit those key pathways, those rescue pathways that can compensate for. Let's say you inhibit FLT3 but these other pathways then can rescue the sales while the drug is able also to suppress those pathways.

So we've already seen that we have patients that are wild-type in their FLT3 have a variety of adverse mutations and we've actually seen CRs in such a group of patients there.

But we want to understand kind of the full breath of activity, we want all mutations are going to be covered by this drug? Now, we've said that a patient who had a TP53 mutation responded to the drug.

That does not mean our drug directly inhibits the TP53, it just means that we're able to cover enough of the pathways to be able to kill those cells, the patient responded. So our task right now is to fully understand the breadth of activity against all these different types of mutations as best we possibly can.

Which means in our current Phase 1 trial, we're really now trying to focus on getting as many of those diverse mutations as we can. As Dr. Bejar mentioned, just recently, we had a patient with a CR that had the MLL mutations as well as the RUNX1.

Well, that brought on a new group of co-mutations that are adverse in a patient, so we want to get as many of those as we can.

Now, it's likely we'll 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 guide 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 to move forward. And we hope we actually have maybe three doses that can be used in those expansion cohorts. So at this point, let me turn it over to Dr. Bejar and he can speak more about this and the patients..

Sure. Just -- I would add that you can learn a lot from patients in the clinical study, not only do you know enough which mutations. Well, improved free that you'll learn a lot about the molecular basis of the disease and how their drug is affecting that.

So when patients getting started on a study, we understand what you're generally mutations are at baseline. And then if a patient responds and then relapses, we can understand what mutations might have controlled resistance or if a patient with particular mutations never respond, we understand that those might be primary resistance mutations.

So these are the kinds of things that we have to learn from these patients beyond whether or not they respond but what factors are actually driving that response or lack thereof. And we can then use to identify patient populations that we might wanna go after in a more narrow or focused sense.

And as we've talked about before, obviously the FLT3 population is going to be targeted for this drug as patients that have unfortunately adverse disease, straight into relapse and are not cured by available therapies as the shortest stem cell transplant.

So we will be focusing on that patient population but there are others out there that may drive great benefits and allow us to in these Phase 1 trial alone just to mark who they are and we might focus on.

Just to add to that, you see drugs out there being developed for patients with NPM1 mutations, TP53, various other pathways. And we want to see how many of these other pathways and targets we can cover with this module, so that's our plan. Thank you, Greg. I hope that answered your question..

It sure does. 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..

Oh, hey guys. Thanks for the question. Maybe I can squeeze two in. First, just maybe a sense for how many new patients we should expect for 293 at EHA relative to what we saw at ASH. That's number one. And then I do want to just sneak in one about luxeptinib's use outside of cancer.

I appreciate the preclinical data that you guys shared with us a couple weeks ago. I guess, given its strong tolerability so far as -- B-cell inflammatory disorders are obviously, you need a good therapeutic window. Is this something that you're actively considering or is it something that you would only pursue with a partner? Thanks..

Thanks, Matt. It's great 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. Bejar can give you a sense in a second. So let me just flip it into your second question. lux, outside of cancer.

It's clear that some of these BTK inhibitors, SYK inhibitors are being developed for inflammation. And so, because of the kinases that lux inhibits, we began to look at these inflammation and autoimmune types of diseases and the kinases that are hid 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, all the way down through say three to four levels within the signaling pathways.

And it really pointed to the fact that we should have activity in the animal models. And we then initiated a series of animal models in which we were using originally the original formulation, and we were 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 inflammation and autoimmune diseases. It's also important, as you said, in a disease like this, you're going to be dosing for long-term in these patients. So you want to have a drug that's well tolerated.

We -- well, we know that lux is very well tolerated and it appears as though lower doses could have an effect on these inflammation and autoimmune diseases. Lower doses that are required to kill these very aggressive malignant cells. So, yes, we are pursuing this.

We are -- we 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 -- we'll see where it takes us. But again, as always, we will follow the data. So I'll flip it back to Dr.

Bejar, if he wants to talk about the patients between ASH and EHA and then also if he wants to add anything else to the lux and inflammation..

Sure. Thanks, Will. So I'll remind you that ASH, the data cut for that was quite a bit before the actual ASH meeting itself. So I think with ASH, it wasn't even a total picture of how many patients run spend even at that time. So after that meeting, we have assumed the trial and have recruit additional patients.

We've reported already that we had completed the 120-milligram dose expansion and we're now exploring a 160 milligrams. So you'll see all of that, all the patients that are filling out the 120 and the data that we have to date on the 160..

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

And it may well change between now and then as well..

It will, yes. It changes daily.

Anything else you want to say about the inflammation?.

I think it's exciting because inflammation isn't -- it appears in several different places where I think lux has an opportunity to address it. And one is obviously in the areas where you're talking about B-cell inflammatory disorders.

But inflammation's actually a factor in other conditions and we've briefly mentioned resistance in cancer therapies, inflammation's a driver of that. And even in disorders like quantum medical issues, inflammation plays a role. We'd be interested to explore all the potential applications of lux in that context..

Thanks guys. That's exciting stuff..

Thank you, Matt..

And our next question comes from Li Watsek from Cantor Fitzgerald. Go ahead, Li..

Hey, guys. Thanks for taking my question. First, on the 160 mg dose, can you comment a little bit more on what you saw from the efficacy point of view, and how many patients do you have at this dose right now? And also, it seems like 239 has pretty broad activities.

So what efficacy threshold do you have for you to open, perhaps, a expansion cohort in that particular patient population? Thank you..

Interesting question. So clearly, we've seen and we've reported both efficacy and well-tolerated status at both 80 milligrams and at 120 milligrams. And based on that, then we moved up to the expansion at 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 see responses merge, you confirm those. And so that process takes months. And so, what we'll do is between now and EHA, we will collect all the data that we have available.

We'll present that, all the numbers of patients, the types of patients, everything that's known about their disease, the mutations, and where we have with them.

In terms of the broad activity, you are right, it's more than just a FLT3 inhibitor and in terms of the threshold for selecting patient populations, you really want to see single agent CRs in these patients.

For instance, we found one patient -- we have one patient that had a TP53 mutation, wild-type FLT3, if we got several of those patients and we saw responses, that is a meaningful group that we can move forward. But right now, the one that we're absolutely confident in is the FLT3 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 couple of different mutations. Dr.

Bejar, would you like to jump in on that too?.

Yeah, the one thing I would add there is, I think that the context of the population really matters as to in terms of what your threshold for success should be in those patients that really have no other alternative therapies and the very short prognosis.

For example, patients who have been previously treated with [Indiscernible] and kinase inhibitors, for example, that don't have any additional option. Threshold for successor is a lot lower than say, perhaps in a patient population earlier in therapy, perhaps second-line or even first-line where you want to see greater activity.

So it'll depend 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 risk, TP53 mutant complex karyotype patients, patients who have been failed by [Indiscernible] and gilteritinib as their only approved -- FDA -approved therapies.

Those patient populations will have quite a low bar for success and hopefully 239 will be able to meet and exceed that..

Okay. Great. Thank you..

Thank you, Li.,.

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

Hey guys, good afternoon and 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 239, I guess trying to interpret the fast-track designation grants.

Just kind of wanted to clarify, I guess, to the extent you're able to say, what data the FDA was able to see in order to -- or receive in order to base that decision on if that's anything that we haven't seen but we'll at EHA, if it was kind of as of ASH, just to get understanding of what they're looking at and what other potential subgroups that may have responded that they had seen when granting that? And I guess on a related point, just thinking about the potential regulatory pass, would you expect it? It sounded like though you might consider the idea of pursuing a couple of different specific mutation groups.

Would you expect to roll up a few different possible fast tracks or at what point can this just be kind of a broader discussion of a relapsed refractory AML population with particular patients that you focus on in clinical trials from a regulatory standpoint?.

Well, I'll try to filter through these. Thanks, Matt, for the question. In terms of the broad market. So you were asking first about the fast track, what data we have. So we've disclosed essentially all the data regarding -- we had many patients at the 80 and then at the 120 milligram that had CRs as well as a PR that came in.

A number of those were FLT3 -mutated, and especially those that had failed the [Indiscernible] and the gilteritinib. And we're talking about CRs at very well-tolerated doses, so we applied for the fast track and 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, FLT3 -mutated, but also patients who are FLT3 wild type. As Dr. Bejar mentioned, the FLT3 -mutated, that's about one third of the population, so you'd like to be able to target that other two-thirds, as 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. Now that's a little bit of a longer path, but that's something we'd like to do.

And also relapsed refractory, and then moving it up toward the first line if you have a drug that truly is well-tolerated and gets CRs. So those are the paths that we would 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 trials.

Currently, we believe that the FLT3 mutated is a path and in particular, if you can identify those patients and have a reasonable response rate and patients who have failed midostaurin and gilteritinib and even in those who haven't been pre -treated with that, we have the fast track that broadly can flip through mutated, not just the ones who have failed those drugs.

If we're able to see enough patients that are FLT3 wild-type but yet are able to treat these patients with these other adverse mutations, we're able to identify subgroups there as Dr. Bejar was mentioning, we'd want to pull those in, possibly get fast tracked.

But again, we'll need additional data, that's why we're doing all these patients in this current Phase 1 to get as much data as we can to 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 data, take to the FDA. Dr.

Bejar, what else did I miss?.

No, that was well put. I was going to make exactly those points that for FLT3 to fast-track, it was very obvious choice since we have multiple patients with responses in that group and they're a genetically identified subgroup.

They'll take more patients that are not FLT3 meeting to identify the genetically susceptible subgroups but that would be another path forward once we do have that data..

Thanks, guys. I appreciate you gaming out the possible scenarios for me. And then I guess just one clarification on the G3 work with lux, noticed that you were elevating, I guess or beginning to look at patients with a 100 milligram G3 lux.

Just wanted to kind of understand whether those patients would still be transitioning to 600 milligram G1 lux after and which I think is basically equivalent to the 50 milligram from what we have gathered so far about the PK equivalency.

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

Yeah. I can,.

Okay, please..

So we haven't really talked about equivalency yet in terms of G3 versus G1, we use G1 as a comparison, but we're putting patients on whatever dose of G1 is appropriate for the dose level that they are being treated on. So we're not necessarily selecting a based on the G3 dose.

The reason to look at multiple doses of G3 is to make sure that we have dose proportionality there, that as we increase the dose, we're also seeing greater exposures and to get a better understanding of how it's going to work.

And that's going to help us in doing the modeling which is going to be required to understand what multiple doses [Indiscernible] with the clinic. So we will continue to vary the dose of G3 based on the date of as we see it, we can go higher than a 100. We could pull back if we needed to.

So you'll see that there is more than one dose that's going to go into feeding that model that we'll then used to justify G3 as continuous dose down the road..

Yeah. That's a good point. So you mentioned the fixed dose here. So for instance, at 50 milligrams, we won't get three, four, five patients there because some of these maybe 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 a 100. We're at a 100, we're going to collect as many patients here as 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 of thoughts..

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

Yeah. Thanks, Matt..

Thanks, Matt..

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

All right. 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 who 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.

Thank you and have a good evening..

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