Q4 2021 Aptose Biosciences Inc Earnings Call
Good afternoon.
My name is Jonathan and I will be conference operator today I would like to welcome everyone to the episodes Biosciences conference call for the third quarter Indeed.
Portfolio.
Entered December .
31st 2021 at this time all participants are in a listen only mode. After the Speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this session no need to press star one on your telephone if you'd like to withdraw your question. Please press the pound key.
As a reminder, this conference call is being recorded I would now like to introduce your host for today's program Susan Pietro Polo from please go ahead.
Thank you Jonathan good afternoon, and welcome to the <unk> Biosciences conference call to discuss financial and operational results for the year ended fourth quarter ended December 31st 2021 earlier today up to its issued a press release related to these financial results news release as well as related SEC filings are accessible and after this website joining me.
On today's call are Dr. William G Rice, Chairman, President and CEO , Dr. Yoder, Senior Vice President Chief Financial Officer, and Chief Business Officer, and 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.
Forward looking statements reflect apoptosis current expectations regarding future events, but are not guarantees of performance and 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 S E T and SEDAR filings.
Forward looking statements made during this call speak only as of the date. They are made and 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 Susan.
I'd like to welcome everyone to our call the year end and fourth quarter ended December 31 2021.
In today's call I'll give you a quick recap of highlights for 2021, a status update on our clinical programs.
One of the key milestones we anticipate in 2022.
Remind you posted a clinical stage precision oncology company developing highly differentiated oral kinase inhibitors for the treatment of patients with hematologic malignancies.
You'll find that we are visibly upbeat about our progress and our molecule H M 43 to three and looks at it.
I also want to stress a few actions that illustrate our team's foresight, which positioned the company and our drug candidates for success.
First in 2020, we raised capital to before some fault necessary and last year, even with a strong balance sheet, we began them in chicken as process to focus resources on the value driving programs and to streamline expenses not by cutting corners by carefully evaluating the essential needs of our programs. This was implemented.
Strategically to extend cash runway, but without undermining company capabilities for value.
Right right.
Prioritization and streamlining of our pipeline programs, we now have extended our cash runway into the fourth quarter of 2023, which we believe goes well beyond a series of potential value building updates from our clinical programs and this year and into next year.
Second bullet chatting it are just looks.
More than two years ago, we recognized the potential need for an improved formulation as we move the original formulation through the clinic and demonstrated Lux isn't active molecule. We built our CMC team and initiated development of the <unk> formulation, because we believe such a formulation could improve the opportunity for logs demonstrate greater exposure.
And more responses and to deliver greater value to patients to the company and to shareholders and we now are reevaluating that G III formulation in humans.
Third we initiated a deliberate asset search more than two years ago that led to the licensing of atrium for three two or three night or just two or three <unk> referred to it now two or three nine has moved to the forefront of our pipeline.
As a more advanced derisked asset with proven clinical activity to three nine literally added a well tolerated and effective drug with significant value to our pipeline overnight in two or three nine continues to demonstrate value to patients and to impress us and our clinical investigators.
And fourth before we even took control of the two or three nine clinical trial, we lead efforts to rapidly increase the available clinical supply. We also began to expand the number of clinical sites and to introduce protocol amendment to increase the number of AML patients in the cohort expansions.
This was done to deliver additional responses to select multiple doses that could serve as effective expansion doses as a single agent and in combination with other agents and to identify junot typically enriched AML populations for upcoming expansion trials that could serve as populations for accelerated approvals.
Also want to acknowledge that we recognize our messaging now focus is far more on tier three nine ahead of logs.
The cost to three nine entered AML patients a year ahead of logs and two or three nine already has delivered the safety and efficacy data that place it on a fast track.
We will continue to prioritize the more mature to three nine we continue to believe in Lux and we want to give them the best possible chance to succeed as we assess our new G III formulation.
So big picture, because we are forward looking.
We are in the fortunate position of having two well differentiated oral kinase inhibitors for the treatment of hematologic malignancies, and we will have all the clinical data the patient needs and the maturity of the agents to drive the path forward.
Electively as you know we take a very disciplined approach to how we run our business and our studies and our investment in this approach has begun to bear fruit and place the company in a bullish position in 2022.
Before we go there, let's recap 2021.
During 2021 post continued to dose at XO ex escalate in the Lux clinical trials in both acute myeloid leukemia or AML.
In B cell cancer patient populations.
In June we presented data for both programs concurrently with our participation in the European Hematology Association or <unk> of 2021 virtual Congress.
We reported that in the email the first two cohorts delivered encouraging anti leukemic activity and multiple patients, including a heavily pretreated AML patients that experienced a durable and mardi negative.
Complete remission.
And B cell cancers intermediate doses had delivered clear signals of clinical activity, including tumor reductions across different b cell malignancies.
The reversal of disease growth upon intra patient dose escalation and longer times on drug suggested that even aggressive disease may be successfully challenged with higher exposure levels of logs.
Reminiscent of sorry ability properties of the BTG inhibitor of Bruno our original formulation of looks at low solubility.
It's forced us to continue to escalate the dose the dose of logs to seek higher exposures that may demonstrate superior activity.
So it was good timing in parallel that the dose escalation of blocks in patients with B cell malignancies, and AML. We've made significant progress in the development of a next generation, formerly formulation, which we call G III.
We have been working to optimize the looks formulation as I've said for more than two years.
And we announced that in preclinical studies, the new G. III formulation had effectively address the Saudi ability issues of the original <unk> formulation and delivered up to 30 fold greater exposure on a per milligram basis of drug administered.
More about G III and our 2020 update for logs in a few minutes, but now back to Q4 of 2021.
During the fourth quarter of 2021, we delivered additional good news.
In November we entered into an exclusive worldwide license agreement with Hanmi pharmaceutical company to develop and commercialize two to $3 <unk>.
<unk> three nine our new lead molecule is clinically validated the myeloid kind of inhibitor that pose.
<unk> inhibits <unk> operative in the email with adverse mutation profiles.
Including <unk> III sick mutant forms of C kit and JAK kinase.
This kinase inhibitory profile enables to three nine to suppress resistance conferring mutant forms of list three and growth factor pathways, such as the JAK stat on the map kinase pathways that confer resistance to other regions to three nine already has delivered complete remissions in a diversity of relapsed or refractory.
AML patients and an ongoing international phase one two clinical trial and Dr. Bexar, Our Chief Medical Officer will describe to you in a few minutes.
Importantly, 239 delivered meaningful clinical benefit to all responders either through urging them to a stem cell transplant or by providing a durable response over time.
In an oral presentation.
At Ash in December of 2021, Dr novel dollar from the MD Anderson Cancer Center lead investigator for the two or three nine troll delivered the first public release, a promising clinical results from the ongoing clinical trial.
<unk> reported that to three nine demonstrated multiple complete remissions are ours.
In patients with relapsed or refractory AML with Holly adverse mutations, thereby allowing us to identify Juno typically defined AML populations with high unmet medical need for potential accelerated development and to establish it to three nine is strikingly broad activity across patients with diverse genotypic back.
Yes.
During the fourth quarter, we worked closely with Hanmi and principal investigators to ensure a smooth transition of the clinical trial to apoptosis.
To hear more about the 2022 activities for <unk> three nine in a moment.
As you are aware at the end of 2021, we also announced the discontinuation of the clinical development of <unk>.
253.
The decision followed prioritization of the company's other more advanced pipeline candidates and allows us to operate efficiently as we devote our focus and resources towards the development of our kind of inhibitors to three nine and Lux Im.
Collectively we took steps to advance and Derisk, our pipeline to prioritize our most actionable programs to reduce any non essential expenses to accelerate patient enrollment and add clinical sites and to place the company in a position of strength for 2022 that allows for delivery of value driving milestones within.
Our cash runway.
We have a clear vision of our clinical strategy and objectives for the development of $2 three nine months as we continue to execute and advance these clinical programs.
I'm pleased with the rapid progress and the position we've created for <unk> during the first part of 2022 and.
<unk>, we expect 'twenty to 'twenty two to be an important year for 239.
So let's have our chief Medical officer, Dr. Rafael Bejar move directly into the update for 239 breath.
Thank you Bill.
Let's take first amendment to talk about what differentiates <unk> from other kinase inhibitors in our last call. We described the very impressive preclinical profile of 239 superior to go through it and have as a single agent and when combined with <unk> right beside it.
This myeloid kind of inhibitor is a highly effective for three inhibitor inhibiting both wild type and all other new forms that split to be tested but 239 with more than just inhibitor. Three is it also inhibits other oncogenic signaling pathway, including the downstream sick JAK stat, and Chinese map kinase pathway.
These kinase inhibitory profile of 2009 already has translated into strong anti leukemic activity and a diverse array of AML patients delivering multiple <unk> in the phase one trial, thus far and it has been well tolerated to date, because only mildly he's LDL teams through the completed dose level of 160 milligrams.
I just want to remind you that our phase one two clinical studies the traditional three plus three dose escalation protocol, but the structure allows us to expand out and add additional groups of patients to dose cohort. Most patients have been treated at the 80 milligram dose level at which we already have reported five composite complete remission or crc's, which encompass for unqualified complete.
Remissions and one complete remission with incomplete hematologic recovery.
Cry among a diverse group of refractory AML patients with a series of highly adverse classification.
This includes patients with mutations in the <unk> 53, NPM, one brass 90, HG young patients with wild type clip pretty or in patients harboring the ITT or tyrosine kinase domain farms with three.
As one would hope this includes slipping mutant patients previously treated with approved <unk> inhibitors, just guilt ridden it might've story is there.
As an increasingly common highly treatment refractory subgroup that could serve as a population with unmet medical need ideal for accelerated approval.
Among the patients with <unk> mutations to experience a complete remission and one at Cri, one patient carried flit, three ITD and an <unk> mutation and they achieved a complete remission and two a stem cell transplant.
Second patients carrying <unk> ICD in NPM, one mutation achieved a complete remission and also bring it to a stem cell transplant.
And the third patient Harvard and Carrington kinase domain mutation with <unk> and had failed prior therapy with both might've storing and guilt ridden this patient achieved a complete remission with single agent <unk> three nine also bridge system cell transplant.
And there were two patients with split pretty wild type AML and highly adverse compensation, but also experienced complete responses or complete remission.
One patient with wild type <unk>, three potentially with a highly adverse genotype defined by <unk> 53 mutations in a complex karyotype.
Patients with this mutational background typically do not respond to therapy or relapse quickly after treatment, even if they do well. This patient was considered unfit for stem cell transplant due to age the patient achieved a complete remission on 2019 enjoyed a duration of response that exceeded one year next.
This example speaks to the breadth and durability that two or three that is capable of.
Another patient also with a wealth of three carry the <unk> mutation and after achieving complete remission was also taken a stem cell transplant. In fact, four out of five patients who achieved remission either a CR Cri 80 milligrams were breached allogeneic stem cell transplantation, potentially curative procedure and the one patient with a <unk> mutation I mentioned within the eligible for trans.
Plant experienced a very significant clinical benefit with a durable complete remission I think more than a year.
I'm happy to report that we recently completed enrollment of the 120 milligram dose cohort expansion and very happy to report that from the early data we've observed an additional cri in a patient with relapsed AML while we.
We are not providing further details of the patients at the 120 milligram dose level at this time. These observations illustrates strong anti leukemic activity at multiple dose levels. These data also grow our list of adverse AML genotype that appear to respond to 239.
<unk> patients that carry abnormalities in the MLR gene mutations of BRCA, one and these are important messages to communicated this is a very relapsed refractory population to treat.
We plan to disclose data specifics currently with DHA in June but the key takeaway here is that our treatable patient population appears to be expanding as we identify additional genotypes that are responding to the trial.
And this is going to be important for the future up to three nine.
In this trial are enrollment has been brisk and we are now focused on populating the 160 milligram dose cohort expansion.
Why would we do this instead of simply moving on with our lowest doses demonstrated remissions just because these dose expansions have helped us uncover the genetic breadth of AML patients responding to Covid. We are encouraged by what we're seeing in patients with challenging highly adverse mutations some of which we may require higher doses of 290 to respond in short we want to continue exploring the full potential.
A 239 as we prepare for our next set of clinical trials and make sure that we don't leave any unexplored clinical activity on the table.
Said, we 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 milligram dose. So he may select the optimal expansion dose and select genetically defined AML patient population to initiate fixed dose expansion trials with an eye towards accelerated restaurant.
Registrational pathway.
So now, let's recap key messages for two or three night to summarize it in early dose level, two three noncash and broad activity across several major AML genotype.
<unk> hundred nine represents a genotype agnostic profile, we've identified several genotypes with high unmet clinical need that we believe can leverage we can leverage for accelerated development and marketing approvals with an intent to later expand the label to additional genotype.
A potential minimum therapeutically effective dose has already been identified to take into expansion trials.
Because of the favorable safety profile to date, we are exploring higher doses dose expansion across a diverse set of AML patients will allow us to select the optimal expansion dose.
Based on the strong signals already seen to date as well as the new lessons from later cohorts and expansions. We are planning registration directed development for 239.
Ongoing studies of <unk> hundred 39, as a single agent, particularly difficult to treat genetically enrich sub populations for a single agent expansion trials this year.
In addition to our single agent studies, we are planning combination studies that would allow to three nine to complement existing therapies and moving to earlier lines of treatment.
Okay now onto a quick review of locks up to that just as a reminder, lexington only non clinical agents that potently inhibits both with three and PTK with the precision that avoids known targets that are often associated with toxicities, giving a broad therapeutic potential across the spectrum of lymphoid and myeloid hematologic malignancies in.
In both of our Phase <unk> studies <unk> has been generally well tolerated dose levels of $4 5600, 750, and 900 milligrams B I D over multiple cycles and is currently being dose at 900 milligrams PID in both studies.
Target engagement at the Teekay and put three and anti tumor activity, including dose in exposure dependent timber reductions had been observed in multiple patients collectively between the studies, including patients with Follicular lymphoma diffuse large b cell lymphoma CLO in AML.
In preclinical studies of AML Lux triggered profoundly proptosis and demonstrated in vivo tumor eradication.
To push the dose of <unk> in order to reach the exposures that would demonstrate this kind of activity in patients.
New better absorbed formulation of MX G. III may help deliver on that promise as he mentioned that the intuitive. This call preclinical studies <unk> three has been shown in depending on the species dose to deliver from 10 to 30 fold greater exposures that drives many original formulation.
Please to report that with strong execution from our team we have started administering a single dose.
50 milligrams of <unk> in ongoing clinical program.
After patients received a single dose samples are collected for PK valuation. They go onto the original formulation of Lux for direct comparison at this time, there going into the 900 milligram PID cohorts of the original formulation, where we can collect additional safety and efficacy data from these patients.
A preliminary look at the PK data available to date suggest that G. III delivers rapid absorption with improved exposure on a per milligram administered basis as compared to the original <unk> formulation.
Very preliminarily. These data are encouraging we plan to continue evaluation of <unk> three in a sufficient number of patients to determine if Q3 is truly a superior formulation of blocks for our patients.
We do have G. G III will reduce significantly the pill burden and the amount of drug substance administered to patients and this could be a meaningful step for the advancement of <unk> through the clinic as always new formulation work and translation from preclinical models to the clinic comes with many uncertainties and risks and there is no guarantee of success for this reason, we are being diligent and not rush to narrow enrollment.
Valuation of patients dosed with G suite, we plan to share more details on our experienced in Q3 in the clinic second quarter.
We are pleased by the progress across our clinical programs and that the safety and Tolerability of our drug candidates to three nine and Lux have allowed continued dose escalation in the ongoing trials.
As we treat more patients at higher doses, we are generating additional pharmacokinetic and pharmacodynamic data and we look forward to providing further updates for more information on all of our ongoing clinical trials and clinical sites are recruiting patients. Please visit clinical trials Gov.
Now I'll turn it back to Dr. Rice Bill.
Thanks, Brett.
Before we speak to the financials, let's take a quick look at our upcoming anticipated milestones for 239. We currently are dosing at the 160 milligram dose cohort expansion, which is enrolling well and we expect to glean further data and a greater number of patients, which will help us determine a go forward dose for expansion trials.
As Doctor Bexar mentioned 80 milligram and 112 mm 120 milligram doses already conserving this capacity and we want to understand that the 160 milligram dose also good service expansion.
And we plan to communicate the selection of our optimal expansion dose to you soon.
Soon we also plan to communicate our selection of genetically enriched AML populations for the expansion trials and registration paths.
We expect to initiate those fixed dose expansion trials and these enriched populations during the second half of this year.
Guarding data release, we are planning a top line readout of data for presentation concurrent with the EAA meeting in June and we plan to reserve full clinical dataset datasets for presentation concurrent with ash and the fourth quarter.
For <unk>, we will keep you posted on the clinical trials in B cell cancers, and AML and our observations with the new G III formulation.
Expect updates around scientific meetings similar to what we've done in the past as well as banking conferences and earnings calls.
Now I will turn the call over to Dr. <unk>, Our Chief Financial Officer, and Chief Business Officer. So he May review our financial results.
Thank you Bill and good afternoon, everyone.
We ended December 31, 2021, with approximately $79 1 million in cash cash equivalents and investments, which we expect to support operations of the company into the second half of 2023.
During the quarter, we utilized approximately $16 million of cash in operating activities, which were attributable to increased activities surrounding <unk>, two phase III general and administrative purposes as well as the in licensing of <unk> 2009.
Moving on to the income statement, we had no revenues for the fourth quarter of the year ended December 31 2021.
Research and development expenses were $22 million for the quarter and $46 million for the year.
G&A expenses were $4 1 million for the quarter and $19 5 million for the year.
Our net loss was $24 $3 million or 27 cents per share for the quarter and $65.4 million or <unk> 73 per share for the more detailed.
This information can be found in our filings on Edgar and SEDAR.
I'll now turn the call back over to Dr. Rice COO Bill.
Thanks Jody.
As we open the call for questions. Please feel free to pose a question to any of US operator, if you could please introduce the first question.
Certainly our first question comes from the line of Ted Pent off from Piper Sandler Your question. Please.
Great. Thank you.
Good afternoon.
So I had a quick question with respect to the new Cri that you discussed with 239.
That deepening response of the prior PR or was that a numerous farnborough.
Hi, Thanks for coming on the question no that was an entirely new patient.
Alright.
Dr. Bexar would you like to add to that please.
Nothing much more to add yes, it was different patients and the patient that was previously reported as having PR.
Great. Thank you and then can you give us a sense with respect to the update that DHA will it be more on the 81, Bonnie will we get any one key data yet thank you.
Well clearly we will present all the data we have at the Ada in the 120 milligram expansions and we hope to have the 160 fully enrolled but no guarantees.
But.
I think you noted we tend to be very disciplined on this we we provide as much information as we can once we've completed enrollment on a cohort. So we've done that in the dose escalation from 20 milligrams up to 160 milligrams provided information there once we have completed enrollment.
And then when we had completed the 80 milligrams. We gave you the information there, but not on the 120, but now we've completed the 120, we're beginning to release information as the data are emerging from that 120, and we hope to have that 160 milligram dose cohort of the expansion completed by then.
Again, no guarantees on that because there's a it's not that far away and we have a number of patients to go but hopefully we'll be able to give you more information on the 160.
Alright I appreciate it.
Thank you.
Thank you. Our next question comes from the line of Gregory <unk> from RBC capital markets. Your question. Please.
Hi, there being one for Greg. Thank you for taking our questions and congrats on the progress.
Maybe first on Q3 Nines wondering could you please provide.
Some color around the profile of that patient with BRL 120 may cohort, maybe just general qualitative color and how that compares with the rest of the cohort shall we expect more patients to have a similar profile. Thank you.
So what information that we are providing at this point as we spoke about it allowed us to understand there are a few more of the genetic alterations that this drug can target.
We mentioned the MLR in one or the other.
The other genotypes.
And we've talked a bit about the cri.
Cook time to make sure that.
The patient had achieved the cri, we waited to get that confirmed and then you always hope to see will that deepen how will that change over time, but at this point, we're not providing any additional information at this time. We've confirmed these data at this point in time.
We hope it all continues well with this patient and others, but these are some of the early data that are beginning to emerge from the 120 milligram.
Can I ask if Dr Bexar or Dr. Rhonda <unk> want to add to that.
I would just reemphasize the point you made though.
We do take the time to confirm that a patient is truly intermission before declaring it and that usually means waiting additional cycle repeating a bone marrow biopsy and we do always look at the generic genetics of the patient's disease and as you mentioned many of these patients have very adverse permutations.
They included mutations like <unk>, one and <unk> 63 in anticipation in particular, as we announced today a patient had an abnormality that may allow us allow PTT, which is a very adverse finding in both Mds and AML.
Yes. Thank you, yes, what's interesting as many drugs that will go through clinical development tends to narrow the patient populations that you believe you can treat but in this case it continues to expand and that's an important.
Important message here.
As we begin to treat more and more patients it looks like the potential treatable patient population is continuing to expand so that's good news for us and thank you for the call today.
Great. Thank you.
Our next question comes from the line of Joe P entities from H C. Wainwright Your question. Please.
Hey, guys. Good afternoon, thanks for taking the question.
Wanted to focus on screening and enrollment question regarding Lux So first.
If I heard you guys correctly, you're currently enrolling the 900 milligram B I D arm.
For both studies and I guess I would ask it this way.
Have you seen any inflection or change of the slope or what have you regarding being able to identify patients and what I'm getting at and hopefully it's not too convoluted is.
Is it potentially any harder to find patients for that arm of the study because you are looking to get them on the G. Three arm of the study and doctors might be waiting to be on G. III for example.
Yeah. Thanks, Joe a couple of ways to respond to that first of all it is heavy PK sampling very quick one so.
The way the study is designed and we've talked about this so the first dose that we gave so a patient they get a single capsule of 50 milligrams of <unk> III.
And then we do PK sampling over the next 72 hours. So that we can fully understand the pharmacokinetic profile and it is dense PK assembling, especially during the first 24 hours and then after 72 hours, we give them a single dose of the current dose of the original formulation of <unk> and at this point, that's 900 milligrams.
We followed the PK over the next 24 hours again PK sampling did sampling and then they go on the <unk>.
I'd dosing about 100 milligrams. So not every patient wants to undergo that Jens PK sampling, but I think it's going to make it easier from this point forward now that we have data that we can present to the to the site and actually show them that.
What we're seeing is very encouraging.
What we wanted to accomplish with this new formulation is that we get rapid emulsify patient in the stomach and rapid absorption and we clearly could see that and so we're very happy with what we saw there again, it's one patient we're happy with what we saw but we can't take it too far.
Encouraging, but we still have a ways to go to fully understand.
The dose dependency of this new G III formulation.
But the clinical sites now I think are going to be more enthused and they are bringing forward patients for this new G. III they definitely are.
Got it that's helpful. Bill. Thank you alright, thanks, Joe appreciate the question.
Thank you. Our next question comes from the line of Matt Biegler from Oppenheimer. Your question. Please.
Hey, guys.
Thanks for taking my question.
Just had a big kind of a big picture question here on <unk>.
Our current thinking for the market opportunity for Q3 nine outside of three well you just mentioned.
Ending which is obviously a good thing that we don't very often with drug development.
I know, we've got responses now in PM one.
I think you mentioned there was a new one ml. So I'm just kind of curious where you think.
The biggest opportunity is some of these obviously are indications where there are other drugs in development for that have all flash on promise. So I'm just kind of curious what your thoughts are on the largest unmet need in AML.
Sure. Thanks, Matt.
This drug does inhibit flip through it actually inhibits split three exceptionally well to wall type and the mutant forms, but we were not interested in just getting another <unk> three inhibitor to be quite candid and we've been told hold me to it.
What made this drug interesting is the fact that yes. It doesn't inhibit the flip three and then it also inhibits very effectively certain of these other targets and then we're able to follow these pathways in the sale.
And these are the pathways that.
So it's kind of like whack, a mole you might dog down three but one of these other pathways, whether it's the Ras AK T map kinase. All these different various pathways can emerge rescue the the sales or it might be the mcl, one and bcl two metabolism. All of these so to fill as many ways to get around the drug.
And we clearly could see this drug was inhibiting many of these pathways simultaneously and making it difficult to get around the drug.
Yes, we do see activity in patients would have to flip through mutations, but also in the wall type.
And as patients get treated with more and more drugs over the years youre going to find more and more different mutation profiles and more patients that are refractory.
And resistant to the drugs, so our eyes are to into the future.
Looking to see what types of patients are going to emerge in the next two to three years, what are the patient needs there and what are the mutations and these are very adverse co mutations that were seeing in their patients and this is where we see this drug.
Mentioned, the expanding potential for the population to be treated beyond the flip three as you mentioned the the MLA all in all the various types of uniform. So we're very happy with what we're seeing and I'm going to ask Dr. Bexar to say that a bit more eloquently.
I'm not sure it's possible to be more elegant and your bill but.
I'm going to build up pointing your point that you just made it that that there are multiple for <unk> three inhibitors out there and they all have slightly different patterns of kinase activity and I think it's important that kinase inhibitor do target some of the common mechanisms of resistance that can emerge.
And for drugs that only target. The ITD. For example mutations include three itself and the tyrosine kinase domain mutation are examples of that and Fortunately 2009, great activity against both the ITD advertising kind of estimation.
Domain mutation. So if we're shutting off that particular pathway, but I also think that you would have the ability to target patients that have been previously treated with approved agents or other <unk> inhibitors out there just because it does have a slightly different kinase profile.
And I think that particular pattern sick, Jack and mutant forms of kit.
Great targets to hit while also sparing those tiny so that might cause more toxicity. If they were to be inhibited too strong. So I think we have.
Just the same patient populations that are treated by other agents, but we have a patient population that have become refractory to those agents that we might have activity again in that population really great unmet medical need that I think will allow us an opportunity to get on it sooner than if we had to go more traditional frontline route or something.
Right.
Yeah, that's a very important point, let me just build on that very quickly because as we look to go and we would hope to move this drug forward toward rapid approvals the.
Weighted approval, but that means you have to identify the patients with high unmet medical need we've already done that we already see several populations that have that high unmet medical need and we hope to be able to drive those forward toward the accelerated approval pathways.
But since we also see activity in the third wall type and other populations do you want to be testing the drug in those patients in parallel so that you can begin to expand the label out later so those are our plans with two 3 million and hope that answered your question.
Yes that makes sense, maybe if I could just.
Squeeze in a quick follow up I apologize if I missed this but can you confirm if the new complete responder at 123, Newton or were they flipped through wild type.
We haven't released that information yet so we'll have to we'll have to go back and take a look at what we're going to release all that information is coming up soon.
But either way what it does it proves this drug is active at multiple dose levels and expands out the population so either way, we're thrilled with what we've seen.
Thanks, Ben Unfortunately.
Thank you. Our next question comes from the line of Sumit really from Jones Research. Your question. Please.
Hi, Congratulations from me too.
Yes.
Trying to understand what would be.
And the future most of the patients. That's all <unk> are progressing into stem cell transplantation. So you think this is going to be the paradigm, where DLR off about two to three months and patients become transplant eligible and David's going to.
Transplantation is that how you are looking at team needs to lesser factor is taking.
Great.
Yes. Please.
I can jump in here.
Youre absolutely right that we have seen a pattern of that and this is actually an issue even for might've store and ratified trial, where many of the patients are going in the stem cell transplantation more than they would have predicted and in part it speaks to the activity of the drug that allows the patient to get into a state where a transplant becomes a feasible option. So.
As a clinician I am thrilled to see that I think that if we could offer our patients.
Security procedure to treat such a terrible disease that we should be doing that so I'm encouraged by that activity I think it's a positive. However, not every patient will have that as an option. So either transplant isn't they don't have a donor or that are already in a condition, where transplant makes sense for them. We do want to have patients that have durable responses to these oral agents really.
We improved the quality of life and the duration of life.
We did have the one patient who are ineligible for stem cell transplant.
Profile that you would have predicted had very early relapse risk.
And that patient was on a single daily oral agent for over a year with relapsed refractory <unk> in.
So you need more patients and more experience to really understand what the duration of response is likely to be but I was very encouraged by seeing that activity, there and I've never upset by now and we get a patient to transplant in two or three cycles.
Joe It's a great point, so yes, we want to see if the drug is durable in the patients that are ineligible for transplant, but really what we're looking for is survival here. So anything that we can do to enhance the survival of these patients that's our mission.
So in terms of confirmatory trial do you think.
The survival, which would include now the transplantation.
Coming to effect all of it it could get accelerated approval based on response rate Aro commodity negative status are pushed in transplantation, and then always would be looked at as a confirmatory trial.
How do you envision.
Those will be conversations we will have with the agency.
FDA, but Dr. Bexar would you like to address that one.
Yes, I would say for those populations with great unmet medical need.
There is precedence for getting approval based on surrogate endpoints short of overall survival and we are paying special attention to those endpoints with the FDA considers important in that regard and so the patient populations that might fit that need.
And I think down the road ultimately.
Confirmatory trial will have to improve overall survival in this patient population.
That has a fairly short OS I mean, even in the patients that were treated in the Apple trial.
Unfortunately those patients.
Improved their overall survival, but it wasn't a cure for them either so we certainly have a lot of patients that we can help here.
Yes.
Good news is we're not asking a question is this an active drug we see there is activity there were actually now talking about what are the endpoints for <unk>.
For getting approval. So that just tells you how far we've come very quickly with this growth.
Thank you for attending.
Congratulations again and looking forward to Ehow.
Thank you.
Thanks, Matt.
Thank you we have time for one further question. Our final question for today comes from the line of Matthew Cross from allegiance Global Partners. Your question. Please.
Hey, guys. Good afternoon, and congrats on the new CR for two or three nine for me as well.
For the sake of time I will skip a housekeeping questions now I'll just add to the kind of a two parter on unlocks.
You know bill you'd you'd commented on kind of PK sampling for the G. Three moving into Q1.
In the current study of blocks.
Was curious and I don't know if this is kind of two part question is something that you can answer now or something that you can guide towards what we may see midyear.
I was curious if in that PK sampling you've seen so far any kind of equivalency or near there in terms of exposure when patients are moving from the 50 milligram <unk> three to the 900 milligram Q1 and kind of related to that.
While you're exploring the PK for for Q3 and that is I assume kind of the focus right now do you envision kind of pausing Lux Q1, and keeping at that 900 milligram dose. So you kind of explored what's going on with G. III or would you expect to continue to dose escalate in Q1 at the same time. Thanks.
Well, the earth or a few questions in there.
Because we're speaking about limited data with G. III I'll be cautious what I can say again is we did see that rapid rise of the absorption that we have never seen with the <unk>. So it was clearly being.
Being solubilized, well being absorbed well.
Again, we were comparing a 50 milligram dose of <unk>, one to 900 milligrams 18 fold more of the cheap one.
And.
We were very happy with the exposure that we saw there with that one dose.
And even up to 72 hours and we could see that there was some drug left in the system again.
Limited data.
So we don't know if that's going to continue.
But yeah, we were pleased with the profile that we saw and now we need to understand whether or not we get into your exposures are going continue to dose escalate. So were enthused with what we saw but we just don't know.
Going forward those patients.
Currently.
Dosing the G. One collecting the data and then they get 900 milligrams. So the patient that we patients when vision into the future are going to be into the near future going to be treated with the 900 milligrams of <unk> one on a b I D dose thereafter that allows us to collect a great deal of additional data at 900 milligrams PID, that's actually a lot of <unk>.
118 grams a day.
And then compare that to the G III exposure levels.
And then hopefully as the year goes on here, we'll have enough patients to be able to do the PK modeling and tell us whether or not we can truly go towards continuous dosing that gives us the exposures that we believe and then hopefully transition over to G. III only.
But that.
That depends on the data we're hopeful but the data will guide us in that direction and we will continue to provide the data as much as we can as we go forward.
Did that answer your questions about.
Understood Yes. It does for now Bill I'll look forward to so a few more answers middle of the year, but still keep it going thanks looking forward to showing you the graphs alright. Thanks Pat.
Thank you. This does conclude the question and answer session of today's program I'd like to hand, the program back to Dr. William Rice for any further remarks.
I'll keep this short I just want to thank everyone for joining us. This afternoon, we believe that both <unk> and <unk> are really remarkable assets that will bring significant value to <unk> and to our shareholders. We want to thank our employees for their dedication commitment to the company as well as the patients we serve.
Really proud to be part of this team and grateful for the effort.
We're also grateful for all of our shareholders and our clinical investigators and we do look forward to updating you more on our existing pipeline and exciting pipeline in the coming days. So thank you everyone have a wonderful evening.
Thank you ladies and gentlemen that concludes today's conference you may all disconnect and have a wonderful day.
[music].