Q2 2022 Aptose Biosciences Inc Earnings Call
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Good day and thank you for standing by welcome to the <unk> Biosciences, Inc. Reports results for the second quarter of 2022.
At this time all participants are in a listen only mode.
The speaker's presentation there'll be a question and answer session to.
Two last quick questions joined that session you will need to press star one on your phone.
Today's conference is being recorded.
Now I'd like to hand, the conscious over to MS. Suzanne Pietro Paolo.
As Pietro Powell. Please go ahead.
Thank you Chris Good afternoon, and welcome to the <unk> Biosciences conference call to discuss financial and operational results for the second quarter ended June 30th 2020 too.
Earlier today after its issued a press release relating to these financial results news release as well as related SEC filings are 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 and Chief Medical Officer, and Mr. Fletcher Payne Senior Vice President and.
<unk> Financial 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 <unk> current expectations regarding future events, but are not guarantees of performance and it is possible that actual results and performance could differ materially.
These stated expectations.
I've known and unknown risks uncertainties and assumptions that may cause actual results performance and achievements 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 at D. C. In Cedar filings all forward looking statements made during this call speak only as of the date they're made.
I've told us undertakes no obligation to revise or update the statements to reflect events or circumstances. After the date of this call except as required by law I will now turn the call over to Dr. Rice, Chairman, President and CEO about Joe's Biosciences, Dr right.
Thank you Susan I want to welcome everyone to our call for the second quarter ended June 32022.
How that test we are developing two distinct clinical stage, where all kinase inhibitors, and we are focusing our cash and human capital.
The activities that can generate the greatest value in the shortest period of time, while building an experienced team and extending our cash runway into 2024.
I also want to emphasize that our trials now we're accruing patients rapidly in fact ahead of anticipated schedules and we've experienced no significant clinical challenges during the past quarter.
Our most advanced drug candidate H M 43 to 394 to three nine as we refer to it as a clinically derisked myeloid kinase inhibitor for the treatment of patients with relapsed or refractory acute myeloid leukemia or AML and to three nine continues to excite us our kols, our clinical investigators and the pace.
Once participating in our clinical trial.
Three nine as a selective kinase inhibitor that suppresses a handful of clinically validated <unk> critical to the survival of AML cells, including the sick kinase all forms of the flit three counties. The JAK, one inject two kinases and the mutant forms of the cacique kit kinase.
By the time, these relapsed or refractory AML patients reach our trial each patient harbors a mix of adverse mutations not just a single mutation and each suffers with disease that is highly resistant to therapy, having already been filled by other lines of therapy, including approved chemotherapy targeted therapies combination therapy invested.
No therapies and hematopoietic stem cell transplant.
These are physically compromised patients or their advanced disease in their prior failed therapies.
It's why it's so impressive that two or three nine has demonstrated its capacity to be powerful enough to deliver complete remissions also referred to as complete responses or Crs.
And a wide range of these heavily disease AML patients.
Yet to three nine as mild enough on the normal cells to be safe and well tolerated physical compromised population.
These impressive clinical responses across the very sick and diverse AML populations that have earned orphan drug designation and fast track status for two or three nine from the FDA.
To date to three nine has delivered complete remissions in AML patients with highly refractory disease, having complex carrier types and adverse mutations and high profile genes, including M. P. M. One M. L. L. I D H T P 53.
Yes.
<unk> D N M T <unk> and others, but with wild type flip III status. It also includes relapsed or refractory AML patients, having mutated flip three that had been failed by prior therapy with approved flip three inhibitors, such as guilt written have been modest store and this is a population in desperate need of new and effective.
PS and a potential population for accelerated approval.
Our ongoing phase <unk> dose escalation and dose exploration trial are treated more than 50 patients to date and near term value is being created by increased awareness of the broad and impressive clinical activity and response rates from this ongoing trial.
S trial already has delivered safety and efficacy data that allowed us to select our doses and are genetically defined patient populations for the next stage of clinical development, which involves dose expansion trials planned to begin in the second half of this year that are designed to confirm activity in specific populations.
And then segue into phase II Registrational studies to support accelerated approval.
The target profile and proven breadth of activity of 239 advocate for this agent to address sizable markets that include several rather than just one Janet typically defined AML populations.
This includes two AML target populations for potential single agent accelerated approval first the flip three mutated patients that have been failed by prior therapy with <unk> inhibitors and second the T. P 53 mutated patients.
On a more traditional development path, we plan for additional AML target populations to expand the market through combination therapy studies and investigator initiated studies, including the broader flip three mutated population.
The N P M. One mutated in M. L L rearrangement population.
And the wrong, one D N M T three eight and Ras mutated mixed populations.
Plus the paradoxical powerful efficacy and safety profile of two or three nine supports potential use as the agent of choice for combination therapy and for use in MRV positive maintenance therapy.
And while we and others believe the annual U S market potential may exceed $1 billion.
Leave it to the analysts to calculate their own composite commercial market potential for these genetically defined patient populations of AML patients.
It is gratifying to see the continued progress with additional complete remissions during the first half of this year to see the breadth of complete remissions in patients with Holly adverse mutations or other agents already have failed to.
To see all the newer patients going on study recently and to see how these findings got our path towards registration studies and suggest ample commercial opportunities through multiple AML target populations.
And our Chief Medical Officer, Dr. Bexar will expand on these concepts in a few moments when he provides our clinical overview of 239.
But now let me move on to our second molecule looks at it.
<unk> as we call. It is an oral <unk> inhibitor that inhibits b teekay flit three another important Chinese <unk>.
<unk> in two separate phase <unk> dose escalation trials for the treatment of patients with B cell leukemias, and lymphomas and for patients with AML.
And then anti tumor activity already has been demonstrated with the original formulation and heavily pre treated cancer patients. In fact, we continue to observe signs of clinical activity with the original Lux formulation and recently two relapsed b cell cancer patients still on study at the 900 milligram B I D level habits are 35% or more.
Or tumor volume reductions thus far.
As you know we've also been exploring an improved formulation, which we call G III.
And we've rapidly accrued patients who received one of four different dosage levels of the G. G three formulations.
Which may deliver higher plasma exposure levels with reduced dosages and could lead to dose optimization studies in the coming months and a few moments Dr. Beth <unk>, who will provide further details from the luxe trials.
And now on my final point, but certainly not model East Let me welcome our new Chief Financial Officer, Mr. Fletcher Payne to his first <unk> quarterly call.
He accomplished CFO electric joined our team a month ago and he brings extensive experience in corporate finance strategy and operation specific to the biotech industry.
More recently <unk> served as CFO of sign ups, where we completed several financing transactions and oversaw accounting finance corporate development and legal functions I won't go through his entire background here you can refer to the press release on its announcement, but suffice to say, we're delighted to have him join our executive management team and I've heard congratulation.
For many of you.
I am pleased to introduce Fletcher, who will start today's call by bringing you up to date on our financial status Fletcher.
Okay.
Thanks, Bill and good afternoon, I'm delighted to be working with Atlas team when they help advance 2009, and Lux Im Pizza already met some of you I look forward to working with you.
Let's review the second quarter financials.
As most of you know from following App test, we take a frugal and disciplined approach to cash management and direct our cash to the highest impact activity.
Last quarter, we reported that our cash runway extending into the fourth quarter of 2023.
Continuation of our financial discipline has allowed us to further extend the current cash into 2024 without compromising our assets.
So let's review our cash position. We ended June 32022, with approximately $62 4 million in cash cash equivalents and investments.
It is a decrease of $7 $1 million as compared to March 31 2022.
During the quarter the net loss was approximately $10 6 million.
Translating into approximately <unk> 11 per share loss and down from $13 5 million Ross from the comparable period in 2021.
During the six months ended June 32022, the net loss was approximately $22 million translating into approximately 24 cents per share loss and down from $29 7 million loss from the comparable period in 2021.
As identified in the income statement, we had no revenues during the second quarter of 2022.
Research and development expenses were approximately $7 3 million for the quarter down from $9 8 million. During the same quarter of 2021 research and development for the six month period ended June 32022 were $14 7 million as compared to $18 million for the compare to peers.
A decrease of $3 3 million.
The decrease was due to lower Lux manufacturing costs as a result of the <unk> formulation, which requires less API.
And to lower clinical trial costs.
G&A expenses were $3 $3 million for the quarter down from $3 7 million in the same quarter of 2021.
G&A expenses for the six month period ended June 32022 were $7 4 million.
As compared with $11 $7 million for the comparative period, a decrease of approximately $4 2 million.
The decrease was primarily due to a reduction in stock based compensation during the first half of 2022 relative to 2021.
Before I turn it off to Dr. Bexar preclinical update.
Some of you asked me about the letter from NASDAQ noted the company's closing stock price bid was below the minimum $1 per share for 30 consecutive days.
Active stock <unk> stock continues to trade uninterrupted since many of you know the company has 180 days to regain compliance with NASDAQ minimum bid price requirement.
Is that considered these matters closed when the stock closes at or above $1 for a minimum of 10 consecutive business days and anytime during the 180 day period.
If the company does not regain compliance within that 180 day period, we still may be eligible to receive an additional 180 day period.
Our.
<unk> to drive a higher strike stock price levels is to increase awareness of the tier three nine asset and its clinical data.
And to advance both <unk> and Lex programs through key clinical achievements.
We believe it's too early to contemplate implementing any other specific actions to address this topic.
With that let's have Dr. Barra gave us a brief commentary on 2009 and Lux Ross.
Thanks, Roger it's great to have you onboard.
Amtrust has two very distinct well differentiated oral kinase inhibitors for the treatment of hematologic malignancies, <unk> 39 for AML and an exceptional for both AML and B cell cancers.
Let's start with Q3 nine our lead asset, which is a clinically validated myeloid kinase inhibitor that in our ongoing phase one two clinical trial has already safely delivered complete remissions for AML patients with a multiplicity of address mutations.
While excuse me your line is much more than if it three inhibitor. It doesn't inhibit all forms of <unk> III. So let's look at it in the context of competitors with <unk> inhibitors in preclinical studies <unk> hundred nine consistently demonstrated superior anti tumor activity.
<unk> three inhibitor currently used to treat AML patients with <unk> mutations.
I'll leave that to three nine may be best in class superior as a single agent and when combined with <unk> decided in.
While we have begun to better understand the breadth of activity of 2009 and clear clinical pathway for development has evolved to two nine is positioned to be a superior competitor <unk> three inhibitor because of its kinase inhibitory profile and its ability to kill AML cells resistant to competitive with <unk> inhibitors by interfering with the rescue pathways that lead to that resistance at the same time.
<unk> nine avoids targets that may compromise safety.
During the second quarter, the FDA granted fast track designation to <unk> 39 for the treatment of patients with relapsed or refractory acute myeloid leukemia with with <unk>. Three mutation. It is previously received orphan drug designation from the FDA for treatment of acute myeloid leukemia in 2018.
In this patient population patients who already have been failed to adequately three inhibitors.
Current analysis show that we have achieved a response rate of 43% among patients treated with 80 milligrams or greater most of these responses emerged at the 80 milligram dose level the dosage at which we have treated 20 patients more.
More recently, we placed additional patients on the 120 and 160 milligram dose levels.
Although they are early in their course of treatment, we will watch the responses in these patients at the higher dose levels. In addition, we've begun treating patients at the 40 milligram dose I want to identify the lower limit of doses that can deliver responses.
While this 43% response rate number will evolve as we dosed additional patients demonstrates important activity in a patient population with tremendous unmet medical need.
To give you some context on the significance of this response rate those of you who participated in our Kols event in June .
Dr novel, daughter, and Dr. Brian Jonas investigators in our trial as well as many others say that it is very challenging to get a complete remission with a single agent in relapsed refractory AML patient population, it's not accommodate that and that the even response rates in the teens and twenties can be extremely meaningful.
This highlights how important it is to compare apples to apples when comparing response rates to other agents from other studies.
Fact, Dr. Deborah pointed to go through it in the gold standard of care is having an initial single agent CR rate in the relapsed refractory AML patients at about 15%, even though most had not been previously treated with <unk> three inhibitors, such as <unk> 90 response rate in our even more highly relapsed population is quite impressive.
One explanation for this activity is at two three times more than a <unk> inhibitor and has the potential to serve as a multi drug therapy in one tablet that can currently suppressing multiple proliferation and resistance confirm pathways in AML.
The second EBITA JAK <unk> inhibitor mutated C kit inhibitor and indeed, it's likely to be the additional inhibitory activities that contributed to the significant response rate in patients that have had prior <unk> treatment.
But as I want to highlight about the responding patients is the diversity of mutations in patients that we've had in the study with complete responses to include patients that have had for three mutations.
The TD and <unk> and those that had been previously treated with other tyrosine kinase inhibitors that target for three including Might've story and orchestrating them.
But importantly, we've seen complete remissions in patients that have very adverse mutations and the split three mutated group.
These included mutations in Ras K, Ras and <unk> 11, as well as mutations in <unk> and MLR PTT. Some of these mutations are typically associated with resistance to tyrosine kinase inhibitors and they continue to be sensitive to 239.
Importantly, we've also seen activity in patients who do not carry it through mutation.
The three wild type patients in particular when patients that had a very adverse genotype a T. P 53 mutation along with highly complex cytogenetics and a very prolonged remission as.
As Brian commented, our Kols events, I can't remember ever seeing a patient get to a CR with a single agent with a T. P 53 mutations.
Other patients with wild type <unk> three that experienced complete remissions by 2009 had mutations at age two and Ras and various mutations in chromatin and splicing factors.
Again, this reinforces that principle that 2009 is more than a <unk> three inhibitor and likely can treat the patient populations identified earlier by Dr. Rice.
Now, let's talk briefly about the safety of 2009 since our last update we have not had any drug related serious severe adverse events no drug related deaths.
Not observed any dose limiting effects that have affected other tyrosine kinase inhibitors in particular, we've not seen adverse events related to elevated creatinine kinase.
We've not seen adverse events related to Qt prolongation, and we've not seen actually no relationship between the change in Q T C and tests.
Importantly, we've not had any dose limiting toxicities up to and through the 160 milligram dose level, while we do have one dose limiting toxicity of muscle weakness at the 200 milligram dose level. It was not due to muscle breakdown otherwise known as Rhabdomyolysis.
We believe we've identified a safe therapeutic range with a broad therapeutic window spanning the dose of $81 20, and 160 milligrams, which is the doses that we would take forward in our expansion study planned to begin in the second half of this year.
Selected 120 milligrams as their primary single agent expansion dose of 80 milligrams and 160 milligrams is bracketing doses that we can adjust to in order to refine our dose selection if necessary.
We plan to explore this dose in <unk> mutant patients who have been found by prior for <unk> inhibitors and supported by a fast track designation and significant response rate to date. These patients have a great unmet medical need and no approved off the shelf options.
Diluted your rescue these patients and perhaps send them to transplants, we have now done that.
Would allow us a quicker path to registration.
We also include relapsed refractory AML patients with <unk> mutated with three other adverse mutations in genes such as T. P 53.
For safety and activity in these patients with 2009 treatment, both as a single agent and in combination with venetic wax.
<unk> meaningful activity in other prognostic lead research groups that could lead to other options for accelerated approval.
While we better define the single agent activity of 2009, we will simultaneously explore treatment in combination with inadequate. This will help us understand how best to use 2009 as a treatment partner in earlier lines of therapy.
We will be conducting these expansion trials starting the second half of this year and throughout 2023, leading two registrational trials anticipated to begin as soon as we collect sufficient data in these subpopulations that could trigger an accelerated development path.
These clinical plans are outlined in our July corporate presentation available on the website.
Okay.
Now onto a quick review of Lux Jester.
Just a reminder, <unk> is the only known clinical agents that Potently inhibits both split three and PTK with the precision that avoids known targets that are often associated with toxicities.
It is being tested in a phase one trial in patients with relapsed or refractory b cell malignancies, who have failed or were intolerant to standard therapies and in a separate phase one trial in patients with relapsed or refractory AML or high risk Myelodysplastic syndrome.
Clinically the drug into thus far demonstrated clear target engagement and PTK handset degree.
As well as important anti tumor activity in both AML and various b cell malignancies. However, using the original formulation. It has not been absorbed well enough to achieve levels of consistently and effectively treat these aggressive cancers.
We have mentioned prior we've made significant progress with our new formulation of <unk>, which we call G. III that may enable greater exposures across patients.
As an example on a per milligram basis, the two hour time point.
Milligrams at G. III developed approximately 200 times the exposure rich relative to 150 milligram dose of <unk>, one and a comparator patient.
I'm pleased to report that we have dosed G. III at four different dose levels safely completing dosing of <unk>, three and 13 patients up to the 200 milligram dose level.
After patients receive a single G. III dose samples are collected for PK evaluation and then patients go on to the original formulation of <unk> for a direct comparison.
Modeling the expected PK exposures in the T. Three if administered continuously.
Ongoing and will inform the protocol amendments necessary to continuous G III dosing for all patients.
If the modeling data are compelling we plan to submit the data in our new dosing plan to the FDA likely later in this year with a plan to transition our clinical trials away from that she went formulation towards continuous dosing and dose escalation of the <unk> formulation.
Represents a significant action began its transition to <unk> formulation may allow us to deliver higher plasma exposure levels and reduced doses to patients with hematologic malignancies.
In addition to potentially delivering higher exposures that may result in greater responses. We expect the <unk> formulation may reduce significantly the pill burden the amount of drug substance administered to patients and thereby the amount and cost of drug substance and drug product manufacturer to support the trials.
We are pleased with the progress in our lucks and tier three nine clinical programs and we look forward to keeping you updated.
For more information on all of our ongoing clinical trials and clinical sites that are recruiting patients. Please visit clinical trials dot Gov. So now please let me turn it back to you Dr. <unk>.
Thanks Ralph.
Ralph mentioned the Kols event that we held in June and if you have not yet heard the <unk>.
<unk> of these respected leaders and hematology you really should do so.
Access to webs webcast or transcript on our website.
As we open the calls for questions. Please.
Please feel free to pose a question to any of us and operator, if you could please introduce the first question.
Yes Doctor.
As a reminder to ask a question you'll need to press star one one on your phone. Please standby, while we compile the Q&A roster.
Okay.
One moment please.
Our first question will come from Matthew Biegler with Oppenheimer. Your line is open.
Oh, Hey, guys. Thanks for taking my questions Congrats on the progress.
Maybe just start off with one for our Doctor Bay are on two nine to three nine I think you may have kind of alluded to that in terms of its multi kinase potential, but something that struck us as.
Is unique in the patients that got responses, where the depth of response as well.
Secondly, it looks like a more complete remission CR with incomplete count recovery.
Like CRP our cri.
How do you guys go about explaining that.
Brad you may be on mute Sir.
No I heard.
Starting with delayed Matt. Thanks for the question I think that the response is extremely important I think patients who have a CR and.
Are they like to do better slightly.
Better.
Bob.
It demonstrates that the drug is not overly myeloid suppressive, if you want to be able to treat patients for a long time, having a drug that severely miles suppressive can be limiting because as patients may still require transfusions or other things. So the ability to achieve an unqualified CR I think is an important milestone and it's also when it is recognized as the FDA has a potential.
Very good marker for overall survival.
Approvable.
Accelerated approval studies. So we were happy to see that in patients who were on the drug for a substantial amount of time, they actually had maturation of the responses. If they didn't have a complete response at the beginning they saw evolution to see our overtime.
And we think that that's going to be very key.
You may be familiar with this disease state called <unk>.
Morphologic leukemia free state, which is really just clearance of glass without any count recovery and the outcomes Unfortunately with that.
Seat with that type of response, if that's the only responsive patients have isn't quite as good seeing this more complete response I think is an important factor I'm glad you keyed in on.
Gotcha Okay.
That's good explanation.
Maybe just a quick one on walks then and the reformulation that G III.
I'll hop back in the queue, but do we know yet what a restart of the NHL trial.
Look like have you decided you are going to also be concomitantly and taking it forward in AML as you did before specifically going to be a b cell asset going forward.
Do you think youre going to need to redo that traditional three plus three dose escalation or might you be able to get away with some sort of accelerated titration.
Going forward. Thanks.
Okay.
So Brad.
I'll take this one.
So we haven't made any final decisions yet until we get all of the full data set on the G. III pharmacokinetics those data are coming in we're presenting them to the PK modeling.
Modeling specialist we hope then in the coming weeks or next couple of months to be able to get data back to guide us as to which direction, we may or may not be able to go should we be able to use your once or twice daily dosing continuous dosing and hopefully be able to achieve that four to five micro motor level, if the modeling suggest that.
We will try to move it forward and we will look at all the Ah patient.
Patient data at that time, whether its a b sales for AML.
But on the other hand, if it doesn't show that we will have we have to make different decisions as how we would want to move forward.
But the plan is to then if it does look like we should be able to achieve those dose levels. We would request the FDA again allow us to take it one at a higher dose level.
Likely just under the exposures that we would that we are currently achieving with the <unk> one the original formulation and try to <unk>.
Implement continuous dosing there, but again at a at.
That exposure level, just below where we are now ensure that we see safety and then continue to dose escalate. So we would not see.
The necessity to start over so that would be our plan, but again all of that requires that.
Thoughts from the FDA.
Okay I hope that answered your question Thanks, Matt.
Absolutely thank God.
Thank you.
One moment please for the next question.
And our next question is shall come from Lee <unk> of Cantor. Your line is open.
Hey, guys. Thanks for taking my question.
First one on <unk>.
Nine ongoing trial I'm wondering if you can give us an upgrade on.
On the follow up with right now.
Sure.
One <unk> one conclude allow.
I'll now turn the lesson that overall long haul.
Okay.
That will start in the protocol, so I wonder with landmark group for all of that will go down.
But were put out.
Just wondering wenger.
Keep in mind that data update.
Okay. So I have to admit I couldnt understand all of the the verbiage. There. It was it was a bit muted so I'll apologize for that.
So perhaps you can paraphrase quickly.
Yes sure.
From a follow up all.
How long is a follow up.
To higher doses.
Right now and also you mentioned that enrollment has increased since June so I just wonder was it just driven by the data that you put out.
And then is whether you're guiding to the next data update.
Alright, so I can start on those.
So the length of follow up so.
What I did mentioned is we literally had a kind of a wave of patients coming on the study into.
And to the 120 to 160 milligram level now as Dr. Berger also mentioned, we're beginning at the 40 milligram level. So we can explore lower there.
Many of these patients have just been on the trial for a short amount of time.
So they are early in their treatment.
So we don't really have any data that we can present on those patients right now as soon as we do we will come out and provide those we're going to have a number of opportunities whether it be banking conferences earnings calls or conferences over the next couple of months. So we definitely want to be able to get that information out to you as those data emerge.
Now in terms of.
Patient accrual why did it increase we believed a lot of it was based on when we presented the K O L event.
To have these.
These luminaries in the field, describing how disease. These patients are they failed everything may come on and they get a single molecule and the patients get a complete remission out of that.
Especially when they talked about a GBP <unk> three mutated patients you just don't see that.
We believe that that impacted not only.
Investors analysts, but also the investigators as well as patients that are seeing that so we've seen a lot of excitement from the investigators on our clinical trials as well as the patients when they start seeing the.
The Crs come about.
Really wanted to be on these drugs, perhaps Dr. Bejar can add to that.
And you're on mute.
Sure.
It seems he has various sorry I made it back.
We can say I totally agree I think that the investigators have been very engaged with the study and very engaged with the data that we've been producing about responders. We're also expanding the number of sites that we're putting on the steady in anticipation of expanding too.
Greater number of slots in additional patients. So we're helping enrollment in both by getting greater engagement by getting greater numbers of sites that are going to be on board.
Thank you Brian .
Okay great.
The second question is why since like your Laurie the Lord knows what in AG.
Wonder Lake.
Maybe you can comment a little bit on the rationale there was that driven by any discussion with FDA.
Or maybe potential combination consideration sir.
Dr. Bernhard can answer this.
Yes, that's an excellent question. So it was not something that was directly driven by the FDA its something thats driven in part by recent guidance at the FDA has put out where it really does demand the companies do a better job of dose exploration entering phase one studies.
We had an accelerated dose escalation process, we only had a single patient on at 40 milligrams and that patient had an exposure that looked a lot like the exposure that we saw at the average of the 80 milligram cohort. So we're left with quest.
Question of how different is <unk> 40 versus <unk> 80 in terms of patient exposure and might we need to explore that more fully in order to better justify the doses, we're carrying forward into our expansion.
Since we have a period of time here between the opening of these expansion studies and the ongoing study we will continue to explore the doses. We figured we would take that time to put a few patients on at 40 milligrams to better understand the TK, there and perhaps the activity that we see just to ensure that we're actually.
Fully exploring this dose levels at the FDA might come back and asked us to redo later, when it might cost us more time.
But a great point, there was no direct interaction or a question from the FDA on that its just trying to follow the guidance and the.
Of that particularly that they've given other companies too recently.
Thank you so much thank you Lee.
Thank you.
Next question please.
Our next question comes from Edward <unk> of Piper Sandler Your line is open.
Great. Thank you very much for taking my questions I have a couple too just to kind of clarify so firstly with respect to the 43%.
On slide you are discussing.
That may or is that what you presented.
Then on June 2nd because I'm trying to figure out what the denominator is.
Okay.
So Deutsche Bank or do you want to take that from the seven patients.
So I'm not sure. He can hear again, so that is related to a seven seven patients that we had there were flip three mutated and who had failed previous flip <unk> inhibitors and there were three patients that had some level of response to <unk> one is a PR.
And that's those are the data that have derived that response rate. We've been asked repeatedly to provide the numbers and so we've done that okay.
Okay.
Thank you.
Okay, four Crs and the two cri and the one PR so really.
The three out of seven.
<unk>.
Great.
Yes.
Yes.
So the second question I missed what Ross was saying.
Breaking up just a little bit about escalating to 200, Meg is that still ongoing or no.
A follow up on the last question will you be selling more of the dose exploration data later this year recognizing that the new expansion cohorts won't be generating data yet.
So I can take the second part of Dr. But how did you want to address the first part.
Sure. The first part about reaching the 200 milligrams, yes, yes, I missed it.
So we have treated patients at the 200 milligram dose level.
Desktop, where we did encounter dose limiting toxicity.
And we've instead focused on the lower dose levels and the dose exploration. We do have the ability to go back and further explore the 200 milligram dose level if needed.
Having seen activity at two and a half.
Chinese lower dose levels and 300, we felt that.
There may not be any advantaged to exploring that higher dose level.
And instead, we can focus our efforts on the exploration and then moving on to the expansion.
Could you disclose that DLC.
Did I, what I'm sorry.
Yes, close what the DLC one sorry.
Yes, the DLT was.
Described as muscle weakness, both upper and lower limb weakness.
And I added the qualifier there that it wasn't muscle breakdown it wasn't.
Rhabdomyolysis, instead and had a phenotype that looked more like myasthenia gravis, where.
There is less.
Neurotransmission.
Gotcha, alright, thanks very much.
Thanks Robert.
Thanks.
The data from the partner.
Yes, so I can take that one.
So from the patients that have been placed on recently again. They are early in their disease. So are early in their treatment.
So as those data begin to evolve we will present that throughout the remainder of this year and then we do plan to continue placing patient on there, possibly additional $121 60, and 40 and as we go through the second half of this year, we do plan on presenting those additional data throughout the throughout the year. So.
So we're not going up and then we do not plan on waiting until the end of the year. If that's your question.
Okay, Perfect and then one last one just with respect to the.
<unk>.
Expansion arms that you showed on the bed.
Our one slips are immune to flip through wild type how many patients are you anticipating in those single agent group.
Groups and then how many do you envision.
Dosing with the data Cox. Thank you so much.
Dr Bejar.
Yes, I can take that so we are.
Just submitting a an amendment now.
Well get feedback from the FDA from but we're proposing to treat.
On.
Smaller numbers of patients in each subset so even though we have an ominous for three mutant where one subgroup will be for <unk> mutant patients that have received prior fleet three inhibitor therapy. So.
So that would be a subset then it will be for <unk> patients that may have not received prior fleet. Three therapy, then it will be a subgroup in the single agent arm net will have.
<unk> mutation and one that well.
Right.
It will be.
A handful of patients in each of these cohorts that will add up to a pretty substantial number roughly speaking the ratio of patients in the single agent arm compared to the patients in the combination arm will be about two to one so it'll be twice as many patients in the single agent arm.
Alright, Okay excellent. Thank you so much thanks Ted.
Yes.
Thank you.
One moment. Please our next question.
Our next question is will come from Selman ROI of Jones trading your line is open.
Hi, everyone and thank you for taking the question.
Could you explain us how the.
Patients by getting assigned to the <unk>.
Both of them.
Or the <unk>.
In other words do you foresee any bias towards possibly.
Lower disease burden patients getting into 40.
Milligram dose cohort.
Any color would be appreciated.
Dr. <unk> do you want to address that yes.
I can take that one of the other advantages of looking at 40 milligrams is that we will have some patients in the combination arm, where we will have to pull back the dose to begin with anyway.
So we'll have a little bit better understanding of the dose levels that bracket that so that will be one potential option I'm not sure that we are going to necessarily base. It on.
<unk> burden that the patients have.
But it could matter on where they are in the course of their treatment. So we mentioned the possibility of treating patients and other contacts besides relapse refractory disease, perhaps both earlier lines of therapy in combination, but also perhaps in the maintenance setting where the dose may not necessarily need to be the same so having a better understanding of 40 office understand what we can achieve at lower dose levels if needed.
But you don't expect our investigators to put more frail patients or patients with higher mutational burden to go towards this lower dose cohort just to get a peak.
PK PD or you don't see any bias that alright.
But you are saying no I don't necessarily anticipate that I think when they see that the patients are appropriate for the study in general.
To put them on I don't have anything necessarily.
Biasing the choice of patient based on the test side, what's available to them at the time.
And we Havent seen additional toxicities associated with the higher levels between <unk> and the $160.
Hi, Thank you I guess, that's where I'm taking the question is.
I guess, the the natural progression.
Cost of treatment would be if patients turning to CRD with getting too.
Hematopoietic stem cell transplantation.
So that would sort of update the durability of respond coming directly just from 2009 have you discussed with the SEC.
With the FDA like how primary endpoint would potentially look like our debt for a later time you would bring up.
CR.
Sponsor it could be a prolonged coins or would have to be a media noise because most patients who were going to see I would be pushed into <unk>.
Right.
Yes.
We have seen a lot of stem cell transplants in our patient population that I don't know that's not always necessarily the case I mean, we have a bias in our early sites for large academic medical centers, where they have a tremendous transplant experience and capability I don't know that as we expanded to more and more sites that the majority of CR patients will go to transplant necessarily many of them might be older and not necessarily.
Eligible for transplant themselves.
But that said I think the FDA, absolutely recognizes that getting a patient, especially with relapsed refractory disease into a transplant is a laudable clinical goal and is considered a win from from a clinical standpoint.
So while they do require for accelerated approval the patients not only achieve permission, but that they have a durable or meaningful remission.
<unk>.
The FDA will work with companies to.
To help counter patients who may have had a short time on drug before they go to transplant and consider the combination of the drug in the transplant okay.
Part of the therapy and a recent example of that was <unk> in frontline study, where many of the patients went to transplant.
The entire arc of their exposure, including the transplant process is counted in the in the assessment there.
Thank you again for taking the questions. Thank you Sherman.
Thank you.
And again to ask a question you will need to press star one one on your phone.
One moment for our next question.
Yes.
And we have a question from Joshua <unk> of Canaccord Genuity. Your line is open.
Mr. <unk> your line may be needed.
Okay.
Yes, sorry.
Yes, Sir Yes, Hi. This is this is actually John Newman from Canaccord.
Just had a follow up question on the.
Expansion cohorts for $2 59.
I think I heard you say that you'll be looking at.
80 milligrams and 120 milligrams not sure if you'd be looking at a higher dose for the.
<unk> three mutated patients as well as key P 53 mutated patients.
And then I also wondered if the approach in terms of stem cell transplant. After a complete response would be any.
Different for those cohorts, if you would just <unk>.
To leave that up to the investigators or if you would perhaps.
Patients that will be less likely to be eligible for transplant and just curious as to how youre thinking about that.
Yes, both.
Both good questions.
So just to clarify the single agent dose that we're going to carry forward and expansion is 120 milligrams to start with.
We have the ability to move that dose and in fact will include the ability to intra patient dose escalation, meaning if a patient isn't getting an appropriate response at 120 milligrams. They have the ability to move up assuming that they tolerate a battery Chilean milligram dose as well.
We have the 80 milligram dose available to us of course, if there is toxicity in the patient needs to drop the dose for whatever reason or if we see.
With more experience that that should be the appropriate starting dose will be able to make that adjustment.
As far as trying to specifically recruit patients that arent eligible for transplant study is open to patients.
Or of any age really over 18.
Including patients that are unlikely to be good candidates for transplant. So if we do see a CR in those patient populations that we would assume that patients will be transplanted.
We don't have any efforts specifically to enrich for those patients to better understand duration I think that we will leave it open and leave it up to the investigators as to who they put on the study.
But I don't think that you're specifically taking patients that are necessarily eligible for transplant.
Do you also want to mention about the dose that you would.
We plan to select for the combination studies with <unk>.
Yes, so as I mentioned before for the combination study, we're purposely planning to pull back the dose to one dose level below the 120 milligram.
The 80 milligram dose level in order to start with the combination of <unk> and that gives us a safety margin there just to understand the interaction between the two drugs and perhaps any.
We see that they might have together that we wouldn't have expected.
It gives us a little bit more.
A safety margin, we will have the ability to adjust that as well if need be both up and down and again, having more experienced at 41 help us understand what we might expect if we went to a lower dose.
Sure.
Great. Thanks.
Thanks, John .
Thank you.
Sure.
And that will end, our Q&A session I would now like to turn the conference back to Dr. Rice for closing remarks.
Hello, everyone. Thank you for joining us. This afternoon, although we have still have a great deal of work ahead of us regret if I buy the enthusiasm we've seen in the patients and the investigators resulting in what I called earlier wave of recent patient accruals onto our trials and we're particularly pleased with the progress for two three non clinical program that momentum.
And when we look ahead to what promises to be a really exciting time for our post. This year. However, we want to thank our clinical team our investigators our patients for their help in this important work with I appreciate the support of our shareholders and analysts and we look forward to keep you updated on our progress and we want to tell everyone. Thank you so much for.
Being here today and have a wonderful evening. Thank you operator.
Go ahead Sir.
This concludes today's conference call. Thank you all for participating you may now disconnect and have a pleasant day.
The conference will begin shortly to raise Johan during Q&A, you can dial star one one.
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