Q4 2020 Aptose Biosciences Inc Earnings Call
The conference operator today I would like to welcome everyone to the <unk> Biosciences conference call for the year and and fourth quarter ended December 31st 2020. 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 the question there.
Your line simply press Star followed by the number one on your telephone keypad. If you would like to withdraw your question. Please press the pound key.
As a reminder of this conference call may be recorded I would like to introduce MS. Susan Pedro Pablo. Please go ahead.
Thank you Carmen and good afternoon.
And welcome to the <unk> Biosciences conference call to discuss financial and operational results for the year end and fourth quarter ended December 31st 2020, I am Susan and Petro Paolo of Communications representative for <unk> Biosciences, joining me on the call today are Dr. William G Rice, Chairman, President and CEO, Mr. Gregory Chow.
And the sticky the vice President and Chief Financial Officer, Dr. Jordi morale and goes senior Vice President and Chief Business Officer, and Dr. Rafael Bejar, Senior Vice President and Chief Medical Officer before we proceed I would like to remind everyone that certain statements made during this call will include forward looking statements within the meaning of the U S and Canadian Securities laws.
Forward looking statements reflect apoptosis and current expectations regarding future events that are not guarantees of performance and it is possible that actual results and performance could differ materially from the 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 and apoptosis. The most recent annual report on form 10-K, and the C C and Cedar filings all forward looking statements made during the call speak only as of the date. They are made at total undertakes no obligation to revise or update the statements to reflect the events or circumstances. After the date of this call except as.
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 for the year end and fourth quarter ended December 31 2022.
Today I want to highlight several matters first and want to express and.
<unk> and delivering clinical signals that give us the confidence to begin the natural evolution of epitopes and took the next stage of development.
Toward this vision, we previously recruited Rafael Bay, our M D ph D as our Chief Medical Officer, and now we have recruited additional skill sets to our senior leadership team.
George Melco.
Co Pharm D brings more than 20 years of senior regulatory experienced the App toes as vice President of regulatory Affairs, and Rob Kelley and ph D has been named to the newly established position of Vice President of chemistry manufacturing control or CMC Joy.
George and Rob bring years of demonstrated leadership and they considerably strengthen our.
Our expanding CMC and regulatory functions at a critical time, perhaps dose you can read all about their experience and the press release that we distributed last week suffice to say, we're pleased that we attracted such quality talent to <unk> and we believe they will help us achieve that next level of maturation as a biotech company.
And just as we are welcoming George.
George and Rob to the company, we watched the departure of a dear friend and a business partner with whom I've worked closely for the better part of the last decade.
Most of you are likely aware that today, we announced the resignation of our executive Vice President and Chief Financial Officer, Mr. Greg Chow, who is leaving <unk> to pursue a new opportunity at a pre IPO biopharma.
Over several years, Greg and I worked closely together to grow and transform app dose to a clinical stage company with two unique and exciting product candidates, Greg is respected and beloved by all of us and it has been and honor and a privilege to work side by side with Greg.
This is the appropriate time, and the evolution of <unk> and and grades career for him to make this move.
I'm fully supportive of this career move at this time and we are certain of its continued success going forward I will serve as the chief accounting officer, and Doctor Jodie and Morocco, Our Chief business Officer will assume chief financial officer duties until a permanent CFO is announced.
Well, while I could spend more time, praising these individuals and emphasize.
The company is and how much all of them either have done or will do for <unk>, we now need to move on to discuss other advancements.
First I wish I wish to note our financial status during 2020 as the result of our progress and market conditions, we were able to appreciably strengthen our financial position, which gives us cash runway.
And the first half of 2020 three allows us to accelerate our clinical programs and to significantly expand our drug substance and drug product manufacturing for C. J O six.
Speaking of CGA, it'll six let's address its generic nomenclature.
As you likely saw and our press release today the unit.
I'd states adopted name.
Or use and council recently adopted accepted it and the non proprietary name for CGI to six this is another step and the maturation of the drug and we will use looks after the for all future references, including scientific publications and corporate materials, and we will take the liberty of calling it blocks for short.
Today's call will give you a quick recap as we look back to the highlights of 2020 for each of our clinical programs with a more general status update.
Looking forward as you know, we expect to present updated quantitative data around <unk> and June and around Ash later this year.
And so any updates today will.
And we'll be more qualitative in nature.
And also despite the challenges of Covid presented for so many people and businesses <unk> executed on our three clinical trials two studies with our kinase inhibitor of la acceptance and Lux, one and patients with acute myeloid leukemia, or AML and the other and patients with b cell cancers.
And the third trial with our <unk> inhibitor <unk> three in patients with AML and Mds.
Now I will ask Dr. Rafael Bejar, our chief Medical officer to provide a recap of our clinical activities for the acceptance of rap.
Thank you Bill.
During 2020, we completed force dose.
Levels and our phase one trial of looks at the net b cell malignancies, including chronic lymphocytic leukemia, or CLO and non Hodgkin's lymphoma, or NHL, who have failed or intolerant to current therapies. The first presented early clinical data demonstrating favorable on target pharmacologic activity and steady state pharmacokinetics and patients.
Increasing plasma exposure with increase.
<unk> levels with sustained steady state trough level of about two micro molar and the ongoing and cohort five and which patients are receiving 750 milligrams of Lux twice daily.
Progressive evolution of leading indicators of pharmacologic and clinical activity to date, including modest tumor reductions and different tumor types, such as C. O L. S L L and Follicular lymphoma.
And that will accept and and that was well tolerated and patients at 150 milligrams three hundreds of milligrams 450 milligrams and 600 milligrams twice a day over multiple cycles.
You'll recall that during ash in December and earlier. This year you highlighted the follicular lymphoma patients who began to experience reductions and tumor side after escalation of the dose from 400.
And and 50 milligrams and 600 milligrams twice daily.
And that patient continues now and study for more than a year and has been has seen continued reductions over multiple scan.
A portion of these data from the B cell cancer trial are summarized in the corporate presentation on our website and.
And we look forward to presenting subsequent data and details of these findings and others with B cell cancer patients.
Around the European Hematology Association meeting in June.
And I will note that the DHA abstracts were submitted where placeholders based on data we had available at the time of the submission of this past December the posters, we presented DHA will include updated data.
The good news is the dosing of continued with no concerning drug related and safety trends to date, including and the expanded.
Standard 750 milligram dose cohort of.
And the importance, we have not seen consistent or concerning suppression of the bone marrow function as Milo suppression is the dose limiting toxicity for the majority of chemotherapeutic agents.
As a result of the safety and Tolerability to date, we are continuing to treat the newly enrolled patients at the 750 milligram dose level for.
For more specific information.
On the B cell malignancy trial, and the clinical sites that are enrolling patients. Please visit the clinical trials Dot goes.
Now onto a discussion of the application that looks after net and AML.
Except the Navy is the only non clinical agent that Potently inhibits post slippery and B P K, giving it broad therapeutic potential across the spectrum of lymphoid and myeloid.
And hematologic malignancies.
And in October we were grateful that the FDA allowed us to initiate a phase one trial, except nib and patients with AML.
And as I'm sure. Many of you are aware of despite recent advances and the targeted treatment of AML and the majority of patients will relapse of remain refractory to current therapy, including gets written and might've store and in the medical acts and the remainder.
And the tremendous unmet need for new therapies.
And as a reminder, and looks at the net not only inhibits the wild type and beat the farms with three M. P. T K.
And also suppresses other select clusters of kinases that drive oncogenic signaling pathways that are operating in AML, including the flip three P. D. G Fr Alpha CSF, one of our 8-K T Ras Burke.
Stat and sick pathways yet.
Yet it avoids off target activity that might contribute to toxicity without clinical benefit.
The FDA and allowed us to initiate dosing and the AML trial with a 450 milligram twice daily dose based on data from our phase one and a b D cell trial, which showed that the 450 milligram dose level was safe well tolerated.
And <unk> and achieving plasma exposure levels that inhibited fossil fleet three activity, which is a key driver of the AML.
As we've reported we've rapidly enrolled patients on study drug including book AML patients with the split three ITD mutation as well as patients with wild type for the three and found that initial PK data were consistent with exposures observed with the 450 milligram dose level.
CLO and NHL patients.
The trial design is the traditional three plus three dose escalation, but also allows us to enroll more than the minimum three patients at a dose if appropriate, allowing us to explore the safety and activity of Lux and additional AML patients and as we dose escalate.
At the first dose level of 450 milligrams, the I D. We observed ex.
Interest leading to meaningful inhibition of multiple oncogenic driver kinases by plasma inhibitory assay or P. I a assay.
As well as encouraging anti leukemic activity, including a patient with a narrow complete response remains on study after multiple cycles with no apparent safety signals.
After the has completed the 450 milligram B I D dose cohort.
Exposure related to the 600 milligram B I D desk level.
Also I'm happy to report the and the ongoing AML trial, and we continue to find that box was generally well tolerated no toxicity signals of trends to date that we believe would prevent dose escalation and we look forward to reporting to you further on our AML trial around and DHA.
For more information on the AML trial and the clinical sites.
And as I was reading patients please because of clinical trial Gov.
Now, we'll move to App to of three to five three.
During 2020, we progressed our clinical trials with after the 253 are somewhat under the radar of <unk> inhibitor being tested in the phase one a b trial in relapsed or refractory AML and Mds patients.
And while we're still determining the.
The correct development pathway for after the 253 remain and treat the its potential.
And as you know they make oncogene is a major driver of cancer cell proliferation, including hematologic cancers, and the development of a safe Nick inhibitor and cancer has alluded research for years and make inhibition remains of interest the pharmaceutical industry.
Interestingly as we May have mentioned to you before.
For the study published in 'twenty, and 'twenty demonstrated that even of transient reduction of make expression sensitize tumors to chemotherapy treatment.
During our Ash review, we reported that we had escalated dosing to the fifth dose level of 150 milligrams per meter squared.
These observations were reported then remain valid today, including continued safety and Tolerability and continued dose related exposure.
Most importantly, we continue to observe Nick repression and indicator of activity would suggest future potential for broad anti cancer activity.
We are pleased by such indicators of activity from book looks up the nib and after the 253 and the safety and Tolerability of both candidates are allowing dose escalation and all three of our ongoing trials.
And we treat more patients and higher doses.
Those are opening additional pharmacokinetic and Pharmacodynamic data that we look forward to providing up the updates at <unk> and ash meetings this year.
I will now turn the call over to Mr. Greg Chow, who will review financial results for the year and fourth quarter Greg.
And thank you Ralph and good afternoon, everyone. We ended December 31, 2020 with approximately one.
Of your generate $22 million and cash cash equivalents and investments.
And third to $133 million of September 32020, and $98 million at December 31, 2019 during the quarter, we use of approximately $10.
$4 million of cash and operating activities, which were attributable to increased activities surrounding.
100, and the nib, and 253 and for general and administrative purposes.
Moving onto the income statement, we had no revenues for the fourth quarter or the year ended December 31 2020.
Research and development expenses were $9 million for the quarter and $29 3 million for the year.
G&A expenses for the quarter were five.
And it looks $8 million for the quarter and $26 5 million for the year.
Our net loss was $14 $7 million for the quarter and $55 $2 million or 67 cents per share for the year.
More detailed information can be found in our findings and Edgar and SEDAR.
Before I turn it over to Bill.
And I wanted to add a couple of things on a personal note I have thoroughly enjoyed my time at out to us over the past eight years I want the especially thankful for the opportunity as well as the board support growth in challenging and good times.
I think there are two occasions when it is considered ideal to leave the company. The first is the August one and when the companies acquired and the teams actually disburse.
And the other one is when the company isn't the best financial and operational condition and has ever been and which is where apoptosis today with three dose escalate and clinical trials and more than two years of cash runway.
And not just saying this for optics.
We remain very confident and both the program's adapters and the growing team under Bill.
And so you're already and.
And <unk> continued leadership.
And I strongly believe it is absolutely the position to execute on the strategy and to deliver on its promise to develop.
Innovative therapies for patients that have failed all currently available drugs.
Thank you everyone a its been pleasure.
Speaking to all of you out there on the.
These calls and with that I'll turn it over to Bill.
Alright, Thank you so much Greg.
I'll remind everyone that on the line. We also have with the Doctor Jodie of Morocco, and Dr. Rafael Bejar as we open the call for questions feel free to pose the question to any of US operator, if you could please introduce the first question.
And at this time I would like to remind everyone that the people like you asked the question. Please press Star then the number one on your telephone keypad, what parts of the guests moment to compile the Q&A roster.
Our first question comes from Tyler Van Buren with Piper Sandler.
Hey, guys.
Good afternoon, and great best of luck and your future endeavor, I guess I have a couple.
I guess the first one is on the.
The C O L. NHL study you mentioned that the Follicular lymphoma patient.
The dose escalate from $4 50 to 600.
<unk> continued to experience reductions on subsequent scans.
So.
Could you help us understand those reductions as it.
And of greater than the debt 27 per cent that we saw Maxwell at ash.
Or in general.
The maximum tumor reduction gone up from that level, maybe even qualitatively can you state that and then the second question is are the.
And the AML a complete response very exciting I'm, assuming it's not that patient at ash that had the reduction down to 10% blast.
<unk> has the since the patient kind of started to trend upwards. After that as I just wanted to confirm that the that is indeed of new patient. Thank you.
Hi, Tyler Thanks for the question. So I'll start on these questions and then I'll ask Dr. Bejar, if he wants to jump in.
Regarding the Follicular lymphoma patient.
And what we have.
<unk> <unk> and we will continue to describe qualitatively for now is that this patient has continued to observe decreases and tumor size of upon serial biopsies or excuse me of zero scans.
And so we are very happy with what we're seeing with that patient and we will provide the absolute quantitative data at the heart.
And the screen of moment, Dr. Bejar may want to add to that.
Regarding the AML patient.
You're correct. The complete response was observed in a and a completely separate AML patient because as you said.
You indicated that debt earlier patient the sort of dramatic reductions from 93 down to 10% and adverse.
Our blood blast of those.
The blast did begin to rise because they had persistent clones of debt exposure level.
And that patient did go off of our study. This is a completely different patient and again, we're very happy with what we've seen Dr. Bexar did you want to add anything to that.
I think that's an accurate assessment of those two patients.
Great. Thanks for taking the questions.
Right.
Our next question comes from Gregory <unk> with RBC capital markets.
Hey, Bill and team congratulations on all of the progress and Greg and I wish you all of the best and your future endeavors and thanks for taking my questions guys.
Perfect.
Bill just to follow up and certainly respecting the the qualitative approach to characterizing what your findings are today and I'm just curious on the AML and.
Or that you are disclosing today of just curious if you could perhaps maybe provide some context around how it fits in your expectations of of the activities.
And you are seeing and namely on this this dose level, perhaps on the the speed at which.
It occurred and how perhaps that actually translates to the.
Two of the dose upward and the activity that youre expecting to see from those as well and then build it out just yet.
The next door.
The last question here and perhaps if you could have the ability to just set some of those expectations on what type of quantitative data and do you think could be teed up for under armour.
Mid year disclosure, perhaps that Eddie and book the AML trial as far as patient Sam as well as on the B cell trial. Thank you very much for taking the question.
I was just the.
Thanks, Gregg that was quite the question of very clever.
Okay. So in terms of the expectations of what we've seen at the 450 milligram dose and the email let.
And let's step back and time Youll recall that we initiated studies with <unk> in patients with the B cell malignancies because.
So these patients are not quite of sick, we were starting at a lower dose levels. We wanted to continue to dose escalate and also because we expected the drug to be safe and we expected it would take higher concentrations exposure levels to truly see responses in the the b cell malignancy patients and that's somewhat borne out and we're starting to see that at.
We filtered and 750 milligram dose level.
You'll also recall that as we went through that trial.
We watched at each dose what we felt would be the appropriate dose and then the transition over the email we chose 450 milligrams because of as Dr. <unk> said, we and the assay we inhibited the <unk>.
600, the other pathways and it was safe well tolerated and we felt as though that was the lowest dose that could show clinical activity and AML patients. So we transitioned in the $4 50, and we've been telling everybody all of the longer. We believed this drug is active so these data.
And it today truly show debt.
This drug is in the active drug and so we show that we've proven that even at the 450 milligram dose level, our starting dose level, we have seen of CR.
Now that will not be the case for every patient at the 450 milligram dose level because some patients will require.
Three of additional exposures they'll have various other pathways that are operative and so as we continue to dose escalate, we hope to see additional responses in the clinic, but the big news is that this patient. They continue on study they've had no safety signals as we've seen and.
And we've seen the CR and we'll leave it at debt for the quantitative data.
On this patient.
In terms of when we get to midyear we.
We plan on providing all available data on all patients at every dose level at that time.
Both of the <unk>.
Clinical status.
And.
And in fact, all available data on the patients that have been sourced verified.
Required at the Bexar did you want to add to that or Dr. Morocco.
Yeah, I'll just reiterate what you said bill.
The goal of the disclosure today is to highlight the activity of the drug and as we gather more information will make a more complete picture of that we'll.
And set out of DHA.
Thank you.
The Dr <unk> have anything to add to that one.
No well said.
Thank you and nothing to add thank you alright, thanks, so much Greg.
Thank you and kill.
Our next question comes from Alethia Young with Cantor Fitzgerald.
To date.
Hi, This is Emily on for Alethia, and thanks for taking our question.
And then about the patient.
And that you previously set of assets had a case of hypertension and there was possibly related to the study drug are there any updates on the patient and do you still believe that that was kind of a one of case and then.
Maybe could you, possibly the Scott your next of all of that development plan and kind of.
And getting towards the rest of the phase one data. Thank you.
Alright, so thank you and maybe I'll I'll address those so we feel as though we've put to bed the patient debt that was on the b cell malignancy.
And all of it the 750 milligram B I D dose level. This is a patient that we observed greed for hypertension and they had only been on the drug I think they had completed four days.
So at that time that is quite a remarkable finding and so it raises your antenna is there something wrong. So what.
See true then is take your time go back review of the data when we've done that we realized this patient had been on multiple cycles prior cycles of Ibrutinib, which can lead to.
New onset of of hypertension. We also know that this patient actually began new onset hypertension before.
You have to never went on 806.
Upon screening and that was what two weeks before the everyone on our drug they developed great one hypertension and that was nuance. It the day that they began on our drug that morning, They had great to answer it. So it had already progressed before they ever even received our drug.
For the US later they were already of grade 342 further days there of groups for.
So they already had the new onset and the gross of hypertension the.
The other two factors is that we went back and we looked at the exposure levels and this patient.
We're not even convinced that they were taking truly all of the drug.
Two days of the exposure levels in the plasma their drug was at least six fold less than all the other patients on the trial at that stage you know even at the three or four day dose at that time point and the trial. So the had very little drug and their system. We also then reviewed all cases all patients of either hypertension.
And hypotension and any cardiovascular event, we found no correlation of drug exposure with any of those so and I'll review, we understand the part of the physicians at that time said it was positive related but we don't believe that it's truly related to our drug and we have seen no such trends and Cynthia.
So in a moment all of that Doctor.
Drove the company wants to add to that and then I think you asked about the next development milestones that we are present.
So again the next major release of data will be at <unk> in June we plan to provide data on again all of the patients all of the data available on the AML trial at all dose levels and the same will be.
The true for the B cell malignancy trial, and so that will include the 750 milligram dose of them. Dr. Bexar did you want to add anything to that.
I would just reiterate the point that you made about the exposure and the short duration of treatment and.
The the preexisting hypertension altogether.
It made us look hard to see if there were any other.
And just like that and looking at all of our other patients in both of the AML and B cell malignancy trial, we have not seen any association with change of blood pressure, even in patients who come into our study with the history of hypertension. So I'm very comfortable that this is that this is a one off as you described it and your question that this is not a true recurrent safety signal and.
And that.
We are glad that we took the time.
Of the right into <unk>.
And as that carefully to understand that better.
But that's a really good point, we did take the time everybody I know everyone wanted us to get patients back on immediately but we took the time to make sure we understood. It and that gave the clinicians on the trial much greater comfort I'll also ask Dr. Morocco, if he wanted to add any any any comments.
Time, starting the next development plans going forward.
Yes, Thank you Dale and thank you for the question.
I'll I'll Echo some of the thought that Bill mentioned and RAF described previously our studies right now.
All of the dose escalation and they are designed to really test broadly and then you've seen the enrollment.
Comments were criteria, we are taking all comers.
So it's really the partners to try to test different types of patients different types of genotype.
As we go through and the dose escalation and keep a diverse group out there that we are testing for efficacy and safety because thats. The only way that we are going to try to understand.
And the value of the drug going forward.
And once we have got upfront from the from a diverse group alright that will show us not only how the best position the Nexium cohorts bofa.
The expansion of our phase II, but is also going to get our hands on the on the breadth of the value of here and Thats really the strategy of that.
And the following right now and this is something we've mentioned in the past Andrew.
I just want to add one thing to that so just to remind everyone of these are deep relapsed refractory patients and these patients have aes and Smes all the time, it's very difficult for often for the physicians to really tease that out as the drug related is it not is it related to a prior drug that they had.
And so anytime that happens we have to step back and make certain that we understand what's going on and then also maintained fidelity to our protocol if the protocols as well okay that happened. So you must referred to it as the DLT New most expense we will abide by the protocol and we will then take advantage of that to get more patients on that dose level.
And gain more data so I'll leave it at debt and I. Thank you for the question.
Operator.
Thank you next question comes from John Newman with Canaccord.
Hi, guys. Thanks for taking my question and congrats on the progress here exciting to see more evidence of activity.
<unk>.
Just had a couple of questions. The first one is not sure if you can comment on.
The number of cycles.
And Ah patient had before they saw the CR or if you can't comment exactly if you can tell us whether it was this small number of large number and also just curious across all of the patients.
<unk>, but you've treated.
With CCA to fix for AML have you generally seen glass reductions.
And most of them and then the last question is.
Do you expect to have marrow samples for all of the AML patients.
And going forward and and also perhaps.
And as they see the data at the HMA. Thanks.
Alright, and John will give you a little something so it was greater than one cycle and the patient continues on study now safely.
All of the quantitative data on the patient will be presented at the hub.
In terms of blast reductions again of such a diversity of patients.
So when we.
We will provide all of the data on all of the patients at E. R. But we've noted with several patients we have seen blast reductions but.
I'm not going to go into all of the the quantitative data around each patient we presented a bit of data on two patients thus far and we will do the the others at <unk> both for this dose.
And for the next dose level. That's another thing I did want to emphasize here is the CSR C met.
And it was unanimous to move up to the 600 milligram dose level unanimously and we're already enrolling enrolled.
Enrolled patients on that dose level in terms of marrow samples that comes down to the clinical sites, we always try to get multiple a series.
Most of of bone marrow biopsies from patients throughout there.
Throughout the the treatment, perhaps all of that.
The Doctor Bexar address that a bit further the Maryland.
Yes, so to answer your question about the bone marrow samples, we are collecting them both at screening and then longitudinally during the course of the study.
Great. Thank you.
And all of the data and then we have we've presented ehealth. Thank you. Thanks, John I appreciate the question.
True.
Our next question comes from Matt Biegler with Oppenheimer.
Hey, Congrats guys Greg.
2% and Hugo but weight of leawood.
And you maybe just clarify for us what exactly and marrow complete responses.
Would that be considered the complete response with incomplete recovery or the W. H O criteria.
And also if I can try to squeeze and landmark.
And on the patient and can you tell us if this was the wasn't.
ITD or of wild type patients.
Alright.
So this was a true CR we include and Merrill when Theyre, just because we knew people would ask well are you getting reductions and peripheral blood or you're getting really truly getting reductions and the marrow. So we included debt term amount.
Marrow complete response.
And that was it.
In terms of the the.
The status of the patient we have not disclosed that will we will provide all of that data also at the at perhaps.
Perhaps Dr Bejar wanted to possibly add to that.
Yeah, that's exactly the same point that you made though and I think merits here. It can be confusing you know who the real and the.
Sorry, when they ask you about the.
European response criteria.
This patient had a CR and it shouldnt be qualified as meera on it.
Got it thank you and thanks, Matt for the questions here and help.
And just to clarify thank you.
Yes.
Our next question comes from Matthew.
And you Cross with Alliance Global partners.
Yes.
Hi, guys. Thanks for taking a couple of questions from me and yes. The same for me first off best wishes to Greg on his next adventure as he will be missed.
So I guess is the phase one for <unk> Luxe continues and I had kind of a two part question and then a quick follow.
First off was.
And now we're starting to see some evidence of kind of the single agent response activity at least in AML.
And I'm curious what degree of of single agent activity, you feel like you need to see before beginning combinations and and either trial of <unk>.
And certainly the direction that debt.
<unk> is the focus.
Because of already and I'll, probably inevitably go and the second part of that question was do you expect to fit and.
And we'll continue to enroll higher dose cohorts.
Beyond the 900 milligram B I D.
Escalate until considerable talks or DLT.
Before combined.
Combining again for both of the B cell and AML trials, and then ill hop back.
Yeah.
Alright, thanks for calling it a couple of quick couple of questions. There are the single dose response and the email. So we have seen net one it's important for us to show as many single agent as part of responses that we can and AML. We also want to understand what are the subpopulations of AML that are most sensitive to this.
First of all of that can then help got our clinical trials going forward expansions and the subsequent studies. There thereafter in terms of combinations of course, we will perform combination studies the FDA wants to see that big pharma wants to see debt, we will do that.
But it was absolutely important for us to the first demonstrate single agent activity to prove the.
Drug and the active because if we start talking about combos before them and everybody thinks Oh well your drug is not accurate. So we will pursue combination studies I'm not going to give you. The exact timeline of that we were and I'm going to talk to you about the the drugs were going to we will combined with we already have plans for that.
But we'll talk about the timing and the the combination drugs.
<unk> is a little bit later.
In terms of enrolling patients, possibly all of them beyond the 900 milligrams again, we said and the B cell malignancy trial, we're at 700 and pitch milligrams of <unk> currently we hope to show that and.
And patients that is safe thus far it has been but we have to complete.
The full cycle of <unk>.
Patients that are of valuable if that is true we will move up to the 900 milligram because.
We have seen a significant increase and exposure level between the 650 milligram no between the 600 and the 750 milligram dose level.
Now when we introduced the 900 milligram dose level, assuming we do.
Do we will look at the pharmacokinetics, if once again, we see a significant increase and the exposure levels and its well tolerated then we would possibly expand beyond the 900 milligrams, but if youre starting to plateau or if you're starting to see any dose limiting toxicity than you would probably cap it off at the 900 or the.
750, I'll ask Dr. Bexar, if he would like to add anything to that regarding both the combos and the 900 milligram.
And again I think you summarized it nicely so for the the exposure levels and Thats. The key point that we need to see what we what we see and patients at 900 milligrams if the.
The exposure is don't seem to the declining.
And where it wouldn't make sense to just try to push the dose much beyond that especially if we're running into any toxicity issues and.
And as far as the combinations go I think that that is the direction that AML is headed as of.
And as a field and I think it would make sense to do that but it'll be very important to understand the safety of the drug and the single agent and before we start combining with other agents that have known toxicity.
Right.
Mining any of the wrap up of Matt. It sounds like you had one additional question yeah. Thanks, Bill and wrap up on both of those fronts. Just a quick follow up with just whether we can get some kind of again, maybe qualitative update I know the focus or certainly some of the big exciting news around AML, but pressing a little bit more on the B cell study. It was curious if we could get a little bit of and update on whether efforts to enroll CLO.
Thank you patients, which I guess, we're now kind of of focus going forward at these higher dose levels, if that had been and began to bear some fruit with the.
The workspace, one and whether you're seeing that have any kind of material impact on the trials enrollment rate is the kind of the threat of flying for for.
Of that particular CLS cell type.
So it's actually a very good question so.
Hello, and 750 milligram dose level and it appears to be well tolerated Brewers and were achieving the PK levels that we expect and we want to continue to dose escalate through that level. So we want to get patients on they have to be reasonable patients that we believe can actually complete the 28 day cycle.
So we.
We're just going to.
Focused exclusively on CLO patients, we will continue to enroll CLO of patients, but we all know that they are becoming a bit more rare. They are staying on other drugs and a little bit longer now, but they are failing so as those patients fail and we just heard this from one of our investigators recently.
Our non theyre excited about putting some of the patient patients on our drug the have felt some of those other experimental drugs that you mentioned that I will not name.
So what we need to do is continue to dose escalate and we will include CLO, but we've also seen activity now in Follicular lymphoma patients. So there are so many lymphoma pay.
And the types of diseases within lymphoma that you'll need new medications. So we plan to continue to place those patients on study lift for activity. There and then hopefully we can show broad activity and lymphomas, and then likely in ore and and then try to pursue this patient population of spelling all other drugs.
<unk> and the CLO population debt.
Once they failed the other drugs they need of new drug that can inhibit the teekay wall type and mutant form of <unk>, but a lot of other pathways to we believe we can serve that population, but again it takes a lot of drug and you have to hit quite a few pathways. So that is why we need to continue to dose.
Since late for that Cielo population and they will come along but it will be slow with the CLO and then also focus and parallel on the the lymphoma patients. So it's like driving if you start down one lane and the the traffic stops you don't sit there and whine and cry you change lanes and move on and so we will continue.
Escalate with CLI is the best we can and will move into the other lines and try to get the the lymphoma patients on there to Dr. Bexar any addition to that.
I would echo what you said earlier that one of our goals of the study is to really understand the breadth and the activity of the drug and we don't want to limit yourselves to any one indication at this moment. So we'll take the opportunity to address all commerce.
And in the line and move more quickly, but that's the escalation and get to that point, where we can expand.
Much more succinctly and eloquently said thank you.
Great and then and thank you to you both for helping our kind of let me know how you guys are gonna be navigating traffic going forward on these trials.
And for letting me squeeze in another way of appreciate it alright. Thanks.
And as we can.
Our next question comes from Sumit Roy Vagelos table.
Hi, everyone and congrats.
Congratulations on the.
Building validating data and I have a lot and my best wishes for Greg all of them.
And David it's good to see the the deep and mechanistic.
The bulk of this coming to fruition with traffic and want the plenty.
Activity of.
The question is because you have such a broad targeting range with lots of them.
Do you what worries you the most key hematological recovery out of your training this matter of enthusiastic Merrill He's got a current.
And whats the kind of range you couldnt get comfortable where you can.
You've seen.
That's not the big concern.
And and other is whats the strategy.
Who enrolled a little already of line cushion would you have to wait until you can combine it with the eval.
Cash flow from kind of each and are you you can see the investigators be able to bring and at least third line patients rather than the retail propane.
This is line.
Yes.
Alright, thanks for the question.
So all interests and a couple of ways and then I'll turn it over the Doctor Bay hard to talk about the.
The second question. There. So you talked about what do we want to see what the the duration and the length of of activity again AML patients.
To hope to get them to of CR.
A significant amount of.
The milestone.
And we hope that this drug and hit multiple pathways and provide real assistance to these patients but in AML.
You are never certain about what the future is going to bring in AML and so if we can clearly.
<unk> single agent activity try to get as much benefit to these patients as possible get the to get the <unk>. Then there are additional avenues, you might be able to get them to of transplant you might and this also set you then up for the the combination trials going forward, but and so I don't want to get into the exact timeline that you would be requiring and an AML patient.
Clearly the and the B cell malignancy patients you would expect to see a longer duration of.
Of the benefit so perhaps I can turn that back over to Dr. Bexar and he can add to your questions.
Yes no.
Nothing really data, which you just mentioned the I think that that's accurate debt for AML patients and we hope to see.
Good responses, but it will be certainly different and it will then and the visa study I think we have the advantage of doing the studies in parallel so we can learn not only about the activity of the drug but we can also learn about its safety and different context. So you asked specifically about concerns, including myeloid suppression and so on and by being able the test patients who have relatively normal marrow function.
That may have a lymphoma or otherwise, we get a sense of that and I'll.
We haven't seen any any concerning signals. There. So I think that we have the potential for being safe without being overly myeloid suppressive with CJ <unk>.
And then to your question about being able to move into earlier lines of therapy.
That is of Great point and of course, we would very much like to do that.
<unk>.
Patient and at the.
The patient interest come first and so where they need to exhaust all of those therapies that are likely to to demonstrate benefit but given the diversity of the AML and the different populations that get it not everyone has the same options available to them obviously older unfit patients.
And have for example, and approved regimen that contains the play <unk>.
And if they're not receiving induction chemotherapy and the frontline so whether they do that on steady or not the.
There really is nothing approved for them and that setting so that might be and opportunity to bring a drug like looks at net closer.
The closer to front line, but I think that the direction of that ammo and is moving easing combination. So I think your assumption there.
But are likely correct debt to do so it'll have to be in combination with other agents.
And we would not have identified net dose before we went toward the end.
Alright, thank you so much and congratulations again.
Got it.
Thank you and we have time for one more question.
Question from Jason Mccarthy.
There is with Maxim group.
Hey, everyone. It's day upon the line for Jason Thanks for taking my question. So as you mentioned on the net.
The presentation the mechanism of action of <unk> of six lines itself to a wide range of indications so with that in mind I was just wondering if you are currently looking at and add any other hematology.
Khartoum trick malignancies to pursue and the near future.
So yes, we are.
So what we tried to do is base it on hard science and one is we understand the targets that are hit by this molecule. We tried it and identify which pathways are impacted by those kinases.
And what diseases, and then begin to explore those both first preclinical and clinically. So yes, we are doing that and we will continue and it's really great to see that this molecule in the clinic is now still being well tolerated with getting to the single agent activity that helps us think how do we expand so we always have.
And I'll.
And here about how we give the drug is now giving us confidence to move to that next stage and that's part of what you're seeing is now that you start seeing single agent activity. You have all of these plans you can now begin to implement them. So that's a little bit of a long winded.
Path, but the doctor Bexar want to add anything to that.
I think the only other consideration as.
<unk> talked of different genotypes, and the myeloid malignancy universe may have different sensitivities to of drug. So I think we're doing the right thing by exploring AML first.
The the area with greatest need and perhaps the greatest sensitivity and.
And as we get the higher dose levels and are able to explore other indications that might be a more appropriate time to consider the.
Thanks.
Thanks for the additional color.
Thanks, Dave and before we hang up I would like to say one additional thing I think most everybody out there they know how close Greg and I have been working through this company for a long time and I heard from a couple of people very quickly and it's as if they wanted me to be upset they were they were shocked that I.
Hi, guys lot of upset but I'm not I'm, so happy for Greg I'm proud of them.
We will continue to interact and this is a metaphor that he's going to hate, but I have kids my oldest daughter when she went off to college I knew I wouldn't see her every day get to talk to every day I knew I would miss are deeply I guess what I've.
I was not sure now so proud of her I got to see what she was going to do and our next phase Gregg is going into his next phase and he's going to go into the company I think that and can deliver ipos.
And and I'm, so happy for him and I just wanted everybody to hear that.
So our company will not.
Got the tight we'll be fine Greg will be fine and I just had to say that thank you.
And we and no further questions and look here.
Yeah.
Alright, well since the notes are further questions I'll just thank everyone for joining the session. This.
Afternoon of 2020 was quite a year focused on advancing our two and I'll call them, well tolerated and hematology compounds and the clinic. We're pleased that we're now beginning to see meaningful clinical activity and we greatly appreciate and I mean is all of our employees I hope they're listening today and.
Investigators on the clinical trials, but most of all of its the patients.
<unk> I mean, these patients take a risk to come on of these clinical trials that continue to help US advance. This important work. We also thank our shareholders and analysts for your support and staying with US we look forward to keeping you apprised of our progress. Thank you everyone have a wonderful evening with that bye.
Bye bye.
And thank you ladies and gentlemen, this concludes.
At the conference you may all disconnect and have a wonderful day.
Okay.
Yeah.
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Good day.
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Uh huh.
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