Q2 2020 Aptose Biosciences Inc Earnings Call
I'd like to welcome everyone to the Aptose Biosciences conference call for the second quarter ended June Thirtyth, 2029% all participants on in listen only mode. After the speaker's remarks, there will be a question answer session. If you like asked the question. During this time simply press star one of by the number one.
On your telephone keypad, if you like to withdraw your question. Please press the pound.
Thank you as a reminder, this conference call maybe recorded I don't I like to introduce misses in future caller. Please go ahead.
Thank you Victor good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the second quarter ended June Thirtyth 2020, I'm, Susan Pedra Palo Communications representative for Aptose Biosciences, joining me on the call today are Dr., William G., Rice, Chairman, President and CEO Mr. Gregory Chow.
I would executive Vice President and Chief Financial Officer, Dr., you already Morongo Senior Vice President and Chief Business Officer, and Dr. Rafael They Hart Senior Vice President Chief Medical Officer before we proceed I would like to remind everyone that certain statements made during this call will include forward looking statements within the meaning of U.S. and Canadian Securities laws.
Forward looking statements reflect aptoses current expectations regarding future events that are not guarantees or performance and it is possible that actual results in performance could differ materially from these stated expectations. They involve known and unknown risks uncertainties assumptions that may cause actual results performance in achievements to differ materially from those expressed.
To learn more about these risks and uncertainties. Please please read the risk factors set forth in Aptoses. Most recent annual report on form 10-K, and FCC and SEDAR filings. All forward looking statements made during this call speak only as of the date. There made aptose undertakes no obligation to revise or update the statements to reflect events or circumstances. After the date of this call.
Except as required by law I will now turn the call over to Dr. Rice, Chairman, President and CEO of Aptose Biosciences Dr. rice.
Thank you Susan.
Okay welcome everyone to uphold the second quarter ended June Thirtyth 2020.
Separately I do hope that all of you and your loved ones for say from Crazy and I hope that all of you on the east coast in particular or safety, we're going to tropical storm. So please do take care.
I know back afterwards.
Sure Okay sit developing two distinct different classes first we don't see June six which has become a high painful first in class C and to be Teekay Corporation.
Second is okay, two parts to the only known clinical stage major directly targets to Myc oncogene suppresses expression.
Or bring you up to date on both colored glasses. Let me note that we remain firmly bullish on C. June six and we understand the partner importance of successfully executing or clinical plan fragrances and indeed, we are executing on the original plan to first developing them six for patients with chronic lymphocytic leukemia, or she'll, though and other be so.
Good job inhibition BTK lymphocytosis in CLL patients and to be on track to reach higher dose levels and deliver clinical efficacy.
In parallel we sought to identify and appropriate starting dose of bagel six that may be active in patients with acute models, the genius or email.
To obtain a new R&D for the treatment of any meld patients and to demonstrate clinical efficacy in a male patients by your.
Well, we wanted to build a strong balance sheet to support this expanding development plan.
We now built the foundation for success going forward and we believe we can accelerate our pace of clinical development as we entered the second half from 2020 with doses aveo six that should deliver activity in both CLL and NHL patients.
So today I will provide a corporate update and then our CFO Mr., Greg Joe will review our financials after which we will open the call for your questions, but first I'll address our most recent news.
A couple of weeks ago, we announced a public offering of 10.5 million common shares at a price at $5.25 per share raising more than $55 million for the company.
Sure Joe will speak to the particulars of this recent offering but I just wanted to expressed we're pleased to have raised this capital.
And with strong participation from fundamental healthcare investors in a market environment with growing uncertainties.
More than two years of cash runway gives us a strengthened balance sheet and assurance that we have to write resources to press forward with the clinical development CGM six and Upto two part three appropriately.
This includes ability to perform multiple dose escalate in clinical trials to initiate multiple expansion cohorts and to boost the global manufacturer of drug substance drug product to support the expanding clinical activities.
Overall, the recent financing increases the likelihood of success of our molecules the likelihood of delivering effective treatments for patients in our clinical trials and the likelihood of success for our investors.
Now, let's turn to see June six and first discuss our ongoing phase one clinical trial of 8.6 in patients with relapsed or refractory CLL and other b cell malignancies.
Since our last call we presented data on six data at the European Hematology Association or he called me to.
Demonstrating the April six was well tolerated patients treated with 150 milligrams.
300 milligrams and 450 milligrams be I'd over multiple cycles.
No drug related dose limiting toxicities for serious adverse events.
Digital six treatment led to lymphocytosis, two classic CLL patients and delivered.
Complete inhibition of fossil BTK and multiple oncogenic survival pathways in all patients receiving the 300 milligram dose or higher, thereby Jim demonstrating molecular and physiological activity of 8.6.
Based on these data and subsequent data from our 450 milligram dose we continue to dose escalate and since our last call. We successfully completed the fourth dose level of 600 milligrams. This includes another classic CLL patient that also experienced rapid lymphocytosis and inhibition of box will be decay.
Just yesterday, we reviewed the 600 milligram data with our court safety review competing and I'm Happy to report that committee agreed that we should escalate to the fifth dose level of 750 milligrams. So now we are actively screening for three patients at 750 milligrams.
In keeping with our original development plan. This illustrates that we efficiently moved to the low.
Okay.
With a minimum number of patients. So that we now let me focus efforts on the higher dose levels that are more likely to deliver responses.
As we move into our hard dose levels in CLL patients and begin to inhibit additional kinase driven oncogenic pathways.
We are hopeful that April six will begin to deliver formal responses as patients from what I remain on higher doses of drug for longer periods of time.
Depending on the clinical activity in specific grub subgroups in this dose escalation phase we may enroll patients across expansion studies that may include sub populations with different genotypic or phenotypic property.
As of today, we'd have 23, U.S. clinical sites open for screening and enrolling patients for the study with additional sites scheduled to come on board.
For more specific information on the B cell malignancy trial, and the clinical sites enrolling patients. Please visit clinical trials dot Gov.
Also note that we plan to present more data at the higher dose levels. During ash later in the year and we plan to do so in a separate corporate update as much as we did last year that allows us to provide a more extensive clinical data review and enter into deeper discussions with you.
Now, let's discuss the application of Cgeight hundred six to patients with relapsed or refractory email.
Certainly one of the most significant events of the second quarter was the FDA review and allowance of our I. Indeed for the initiation of phase one of the clinical study aveda six in patients with email expanding the development of 8.6 beyond B cell malignancies.
Email as a cancer, the bone marrow and blood with a poor prognosis and an overall five year survival rate of little more than 27%.
Despite recent advances in the targeted treatment of being mill. The majority of patients will overlaps or remain refractory to current therapies and their pursuit persist a tremendous unmet need for new therapies. For example, as we look to guilt written.
Three inhibitor recently approved in relapsed or refractory a male.
The most the majority of patient to a new actually respond to treatment will relapse and ultimately there are two year survival is no different than untreated patients.
It was six is the only BTK inhibitor that also possesses strong three inhibitory activity, giving a broad therapeutic platoon across the hematology spectrum, including both lymphoid and myeloid malignancies.
Cost of Dr., Brian Truecar strong preclinical evidence of 8.6 is activity against a email, including demonstration of mutation agnostic and genotype agnostic activity, particularly compared with other fleet three inhibitors as well as its ability to safe secure email mice. We believe April six offers hope to the fragile in difficult.
To treat AML patient population.
Our strategy from the outset was to begin testing and you'll see in patients with diesel cancers, including CLL and to dose escalate and see responses in the CLL patients.
Separately, we sought to identify starting dose if they don't six that might be therapeutically active in the critically ill relapsed or refractory AML patient population and we've done just that.
Indeed, the FDA has allowed us to initiate this trial in AML patients with our desired starting dose of 450 milligrams be I'd.
Allowing us to start at the 450 milligram dose was a major success for Aptose and for Ito six.
At this dose in humans, we already have observed steady state plasma levels in the same range is the exposure levels observed in our preclinical work that led to cures a billion mill in mice and without any observe toxicities.
Starting at the 450 milligram dose truly gives us an opportunity to begin seeing early anti leukemic activity in these critically ill relapsed or refractory AML patients.
The trial design is to traditional three plus three dose escalation and the protocol allows us to enroll more than the minimum of three patients at each dose level if appropriate.
I just want to mention here that we purposely kept this R&D solely focused initially on treating patients. We believe that there will be additional opportunities for eagle six in patients with model just plastics interims for Mds and income combination with Venetoclax.
We pellet plant initially to treat only patients with email in this study and then expand in Mds and into combination with Venetoclax as appropriate.
Cgeight hundred six is two important of a drug and we will continue to take this thoughtful and deliberate approach and expanding its value footprint rationally and steadily towards the long term.
So where do we stand and getting has recently allowed email clinical trial up and running.
Currently we are advancing the approved email protocol through institutional review boards or IR be a clean key clinical sites and scheduling our site initiation visits.
So while we're working to get our larger email clinical sites on board such as the Memorial Sloan Kettering Cancer Center and others at the same high caliber.
We also are focusing on faster activation sites, including specialty regional cancer centers.
We are taking actions to expedite the tedious parts of the trial startup process and we continue to target the third quarter for enrolling our first milk Asia.
We will want to enroll patients having AML cells with uplift three ITD mutation often referred to a split three positive email as well as those patients with wild type two or three.
I hope of demonstrating early clinical responses with a 454 600 milligram dose levels.
Just a quick aside if you have not seen the colwill presentation from February of this year that featured Dr. errand Goldberg Dr. eight on starting from the more memorial Sloan Kettering Cancer Center, as well as Dr., Brian Drucker, Oregon, Health and Science University, and our Chief Medical Officer, Dr. Rockdale Blackhawk. It provides a great perspective on the treatment of.
You know in the age of target there.
It's available on our with web sites in the presentation section.
To wrap up on April six we continued to diligently execute on the plane. We originally crafted and we now have set the stage to move forward at an accelerating pace and with unreserved optimism, we're moving into higher doses with the right patients in both CLL and soon email and we have the resources we need.
Finally, we hope to see you in December as we provide a more robust and and detailed update on April six at a corporate event during ash.
Now on to Apto, two Fivethree, our second clinical candidate and a first in class Mic inhibitor currently in a phase one be trial for AML and Mds.
As we've mentioned before the Myc oncogene is a major driver of cancer show uplift duration. In fact, its expression is estimated to be in elevated and up to 70% of human cancers.
As the mic inhibitor to five three may have a broader anti cancer application among a host of hematologic malignancies and solid tumor indications, but as you know our initial development focus is on email and Mds.
Mic inhibition has been an elusive clinical target and pharmaceutical development. So we've been gratified to observe evidence of mic inhibition in this trial at all dose levels evaluated today.
Just as a reminder for phase one clinical protocol.
253 being administered once weekly.
Over a 28 day cycle at ascending doses in patients with relapsed or refractory email or high risk Mds until the maximum tolerated dose is reached the study is designed to then transition as appropriate to single agent expansion cohorts and email and Mds.
Since our last call. We've completed the 28 day dosing and three patients on the 100 milligram per meter squared dose, which is dose level for on Friday of last week, we held our cohort seek to review committee that allowed us to proceed to dose level five.
Because too far three continues to be well tolerated at these higher dose levels and still with no models Christian we amended the protocol to allow us to accelerate the dosing schedule.
So we currently are screening patients who will be treated with a dose of 150 150 milligrams per meter squared, which is a 50% over increase over that of dose level for and also have identified a patient to begin dosing in this cohort.
We're still learning about this drug at higher doses, we hope to see sustained mic inhibition and clinical responses.
I'll now turn the call over to our executive Vice President and Chief Financial Officer, Mr., Greg, Joe who will review results for the quarter Greg.
Thank you Bill and good afternoon, everyone, let's start with the details of our recent offering and then we'll review the quarter on July Twentyth, we closed on the previously announced underwritten public offering of 10.5 million common shares.
Public offering price of 525 per share raising 55.1 to 5 million to date and netting approximately 51.5 million. The underwriters have been granting a 30 day option to purchase up to an additional 1.5 75 million common shares the offering under the same terms as bill mentioned, the offering gives us a healthy balance sheets and cash runway.
In 2023.
Let's now turn to the quarterly results, we ended the quarter with approximately $83 million in cash cash equivalents and investments approximately $90 million at March 30, Onest at this year.
During the quarter, we utilized approximately $7.2 million of cash nothing activities, which were attributable to activity surrounding T. Five three and native six as long as DNA purposes.
Based on corporate based on current operations cash on hand at June 30, plus the net proceeds from the recent offering.
This provides the company the sufficient resource to fund all planned company operations.
Including research development into Q1 2023.
Moving onto the income statement, we had no revenues for the quarter research and development expenses were $6.9 million for the quarter and attributable to 8.6 into phase three clinical trial costs manufacturing the drug product for clinical trials, including continuing development on improving GMP formulations to both data six in 253 and personal.
Cost for head count supporting clinical trials and manufacturing activities and research studies.
And finally, our net loss for the quarter was $15.8 million.21 per share or excluding the onetime items $8.1 million or 11 cents per share more detailed information can be stein, our findings on Edgar and SEDAR with that I will turn it back to Dr. nice Phil.
Thank you, Greg I'll remind everyone that on the line. We also have with those Dr. Goody Morongo, our chief business Officer, Dr. off they'll be hurt our chief Medical officer as we open the call for questions. Please feel free to pose questions to any of us.
Operator, if you could please introduce the first question.
As a reminder, ladies and gentleman asked a question you any press star one on your telephone.
It will join question just press the pound key.
My first question will come through I know I live and billing.
Piper Sandler.
We began.
Hey, guys.
Good afternoon, and congratulations on all the progress said a couple questions with respect to it was six.
So I guess, you mentioned that you completed dose level for and that you're the one CLL patients who also achieved lymphocytosis.
Is that the same patient that you guys referred to eat Hawk and if so.
If you're able to clarify that.
Is there an update that you can provide on that patient and then the second question is with respect to the.
New higher dose cohorts with dose level is there I know that you guys are screening patients to enrol is there enough time to enroll those patients and potentially allow them to generate responses prior to the ash data update.
All right Hey, Tony Thanks for coming on so thanks for the the complements on the progress.
For the first question.
Yeah, we have mentioned and additional CLL patient that came on the 600 milligram dose that's dose of before that was a separate patient that also.
Underwent lymphocytosis. So it was immediate lymphocytosis inhibition also be T.K.. So we're going to speak in terms of trends today, rather than a particular detailed on patients, but thus far we've had patients at 300 and at 600 milligram dose levels.
These are the classic CLL patients that entered the trial with some level of lymphocytosis. Those are the ones that you have an active BTK inhibitor that you would expect to see each fruit lymphocytosis induced and we have so in all three classic CLL patients that have come into our study weve seen drug really leading drug.
Related inhibition of BTK and lymphocytosis.
Now with regard to dose level five to 750 milligram.
We planned we we just have allowance to move into that dose level as of yesterday. So we are screening for patients immediately. So the question is will we have time to get the patients on study and it usually takes at least.
Two months, if you're fortunate to see.
Caustic our formal response in these patients what I can tell you is we're trying to focus on CLL patients at the higher dose level as best we can we've been form the sites that we do.
Particular up CLL patients, we want to get them on 750 as quickly as we can and we hope that we will see responses. So we're very hopeful that we can get them on there we can get them enrolled get them dosing and then we'll scan them. After after effectively two months okay.
So what cash cycle.
Our two most yes did that answer your question.
Yeah, that's very helpful color, especially because your quote noted the goal of delivering responses, specifically and CLL patients. So appreciate you take questions. Thank you. Thank you. Thanks.
Thank you. Our next question comes line of Gregory Renzo from RBC you may begin.
Hey, Bill and team. Thank you for taking my question and congrats on.
On the progress here cruciate it.
Deal, maybe just a building off of talent sounds question Im just curious if you could perhaps some expectation certainly focused sport for year end and.
The event that you will do to potentially happening in.
In December just curious if he could help frame those expectations a.
A little bit unresponsive on patient counts, perhaps but then also how youre just closure plans could potentially a volumes certainly keeping to kind of the bi annual disclosures on data, but just curious if there any prospects for peace.
Providing any efficacy update prior Q.
Our plan. Thank you.
All right Hey, Greg Thanks for coming on a couple of good questions. So let's talk about the expectations for later this year, particularly at Ash. So we're looking effectively at year end. So right now we just entered August.
We will get as many patients on quickly as we can at the 750 milligram dose. The good news is we're able to get into our higher dose levels, where we believe that we can start seeing responses. We have reason to believe that.
The drug is is active we're seeing submissions mechanist physiological activities. Even at 600 milligrams. We started seeing some differences that makes us believe that we should start seeing something as we get into these higher dose levels, particularly at the 750 milligrams level, but in reality, it's the weeks.
Second three patients.
As we move into the is into dose level five to 750 milligrams. So how are we going to get more patients on it well we have a an amendment from FDA thats, allowing us now to begin backfilling.
So I think it's our chief Medical Officer earlier, Dave was talking about its almost backfilling is almost like a mini expansion, while you're doing the dose escalation. So yes, we're going to patients 750, we hope the majority of those are CLL patients and that we hoped in by the time that we reach Ashley or in this year.
That will be able to deliver responses in parallel will also be trying to backfill patients at the 600 milligram level and then when 750 is shown to be say if it is then we'll move those patients 600 up to 750 I should also say we have couple of patients in a seven at 450 now they are going.
To be moved up to 600, so we're increasing the ability or increasing the likelihood of have.
Hinsley demonstrating responses at Ash later this year.
So the second part of the and I'll ask Dr. Bahar, if he wants to add to that just a moment, but second part of your question was disclosures is there anything possibly between now and ash between these mid years, what I would say as I wouldn't expect anything for us to be disclosing anything between now and the reason is.
As we've just gotten into the 750 milligram dose the higher dose levels, we need time to get the patients on to give them time to response and then hopefully we'll see something by December and Ash.
Separately, we're also going to try to get to am mill patients up and on the trial as I've said, we still continue to target getting the first patient enrolled in the third quarter of this year. If we can do that can we get a couple of patients on the 450 milligram dose level get them through by the time to get to Ash in may.
We have some patients on the 600 milligram dose level that gives us the opportunity to help responses can email during this period and again I'll remind you email, it's an acute leukemia and typically you're able to to view what happens in these patients much more quickly with CLL. It takes typically at least.
Two cycles before you see anything but it can take anywhere from two cycles up to a year.
Two months of two year, whereas an email you would expect to start seeing something reduction in blast first month, and then possibly a response by the second or third month, and I'm going to ask Dr. Bihari, if he would like to add anything to that in terms of what to expect in patients.
I think that was a great answer John I think.
After that perfectly.
Okay.
Just putting on the patients now seven having that ability to backfill will get us more opportunity.
The response.
At these levels.
And we're definitely push to do that.
The previous statements that AML.
He is that have very different response kinetics and that we should know.
Center than we might for that T cell malignancy that take much longer to demonstrate responses.
Yes, so the irony is there even though we started the b cell malignancy trial earlier it takes those patients longer to show responses and it may be that even the ml might show responses earlier, even though we're starting it later, but we are starting at a dose that we believe can show activity. So.
I hope that answers your questions.
If not let us here has it your has gone Patrick Thank you and actually hit the also answer my follow up question, which was around the back selling.
Thank you to confirm so would we presumably given that Pete.
The fifth guess cohort just recently cleared it say trusted to anticipate that there could be additional 600 make patients that since added prior to that clearance.
Right.
Not that are added prior to it because we had.
Leach.
Sorry, we have a lot of background. So in reality. The 600 milligrams you have to get three patients and show the FDA, our core show excuse not to CSRC, but you have three patients that have completed safely that cohorts. You can then move up to 750. Only then can you start backfilling on the 600, so right now were.
Going to try to both get patients on the 750 immediately and the 600 as quickly as we can.
Cash for taking the question.
Thank you.
And our next question comes the line John Newman from Canaccord, you may begin.
Hi, guys.
Thank you for taking my questions and good progress here on both the agents in clinical trials. So just a question for.
For Bill Bill you mentioned.
That seems like there was an additional patient at the 600 milligram dose where.
You saw some signs of them for psychosis, which is great.
I'm just wondering if you happen to notice.
Any of the other changes that can go along with the response for example.
If you saw an increase in platelets hemoglobin if lymphocytes.
Decreased in the bone marrow just wonder if you can tell us anything.
To be broadly speaking if there were other markers stats.
You'll notice that seem to.
Confirmed that there may be some activity there.
Hi, John Thanks for coming on in asking the question.
So one thing I can confirm is it the lymphocytosis inhibition to the.
And the inhibition of BTK and the patients. It is due to the drug because we actually had an instance, we're able to dose reduce and then take it right back up and when we dose reduced we actually saw to lymphocytosis decrease so it is clearly a drug related event.
As for the other markers.
I'm not able to address that perhaps a doctor Bay Harkin provide a little bit more information on that but again I don't want to get into too many specifics of many patients until we get later in the year.
Dr. By Heart was there anything else that you wanted to add to that.
Yet we just had the simple answer is that this last patient that you're referring to has just recently finished cycle. One so we haven't actually done any of the additional studies that you reckon. Please ask that we I don't know the EPS if your question.
Okay fair enough problem. Thank you.
The other one quick.
Yes, yes, yes, just had one quick follow up question, if I may and that is.
Just in terms of the type of AML patients that you're looking turn role I know that.
When you're dealing with email population, it's always a challenge almost regardless of the agent.
Because you're dealing with patients that are very frail and fragile.
There are things that you're able to do in terms if your selection criteria.
Just to.
You know give yourself sort of a reasonable chance to.
To be able to answer the question if your drug is active rather than sort of fighting.
Very frail stated disease.
Well we are on the same page with you on that one so the first and most important thing. We did is we're starting this the trial at a dose level that we think should be active so that that's the first thing that we're doing to give the drug the best opportunity to show responses.
Secondly, one of the.
Most.
How about in feature of this drug in terms of email is the fact that we believe that can be developed for flit three positive as well as that three Baltic patients. So again about a third of the patients have the mutated flip three two thirds of the patients do not they have wall type three so we want to be able to treat those patients.
With the wild type three.
However.
It is generally accepted the patient that the patients with the ITD mutation. The flip three positive patients would tend to be more sensitive to a clip three inhibitor. That's been shown with guilt written it was aren't at some of the other molecules. So we absolutely want to get flipped three positive patients.
On this trial as soon as possible they are likely the I'll use to freeze low hanging fruit that would most likely get us responses earlier and again starting at a dose that we think is going to be pharmacologically active in these patients that gives us a great opportunity just show responses.
And.
And again, that's where we are and we hope that we're able to get to both flit three positive as well as the wild type on but again, most likely showing the flip three positive patients.
We show activity earlier, most likely and then it may take some of the higher doses to show activity in the wild type, we won't know till we get the patients on.
Thanks, John for your question.
Sure. Thank you guys.
Right.
And our next question will come from line and that dealer from Oppenheimer you may begin.
Hey, guys. Thanks for taking my questions. Greg here for me on can you shed any light bill on how the exposures are tracking and 600 Neg cohort. Obviously these were too premature for the how dataset, but.
Maybe I level can you on on whether we're still seeing kind of the linear increase that we saw between 100, picky and 400 and it.
Does this.
Yes.
So.
When we.
Recently, we have one patient on the 150 dose levels one patient on the 300 and then we had three patients on for 50 and then for patients on 600. So when you only have one patient per dose level. You really mean, you can draw a straight line between two points, but.
It's really meaningless so what it appears as though is the 150 milligrams. It it starts coming up over 24 hours begins to plateau and it looks like that second patient at 300 milligrams. It looks like that was more of the outlier. Because then as you go to the next dose level and you have.
Three patients.
It comes in about the same as the dose level too and then when you go to the fourth dose level 600, what you can see is another increase so what we are seeing as we increased the dose level. The initial uptake is more rapid higher levels over the first 24 hours. So we're able to.
More of a dose related.
Exposure level during the first 24 hours now and then they began to plateau off as we go forward, but it's not necessarily linear yet.
We had one station to lower dose levels.
But we're definitely getting.
Meaningful exposure there to 600 milligrams and we're starting to see some effects that are giving us confidence that that were really having a physiologic effect and it looks like it's more so than at the 450, which again is gratifying and so we expect even more to sevenfifty. So I would not call it linear but we are seeing.
Now more dose related effects as we get more patients on but it's also an oral drug and you're giving it to patients a different sizes. So there will always be.
Differences in the exposure from patient to patient even at the same dose up.
Right right understood. Okay. That's good to hear on I, just want to be completely clear on cohort for in terms of the patient than what.
We hadn't so we know from.
Got one was classical CLL, one with pictures transformed can can you just confirm what type or that the third patient had the one sold.
Hi cut off was that the pace.
Ms plus I tested burbs, referring earlier.
So one patient asked was on the six 600 milligrams that one clearly had the lymphocytosis.
In the inhibition of BT Cave, we show debt and then we have another patient that's going on to 600 milligrams. That's a classic CLL patient and they also demonstrated the lymphocytosis patient who just completed the.
The 20 day dosing recently, so it's clear we're able to induce lymphocytosis as well as the inhibition to be T.K. as we get into these higher doses do inhibit the other.
Pathways that kind of extra pathways.
And now as we get hopefully these patients stay on a little bit longer as we go forward and both the 600 750 and it gives us opportunity.
Responses, so perhaps dr. bihari.
Might have something to add to that about the two CLL patients at 600.
Without details.
Right. So we we had one CLL patients getting a cohort in than we had the most recent patient complete the cohort to see a classic CLL patients with pre existing them because I toast as we're in this cohort.
Great Hi.
Congrats on the progress guys. Thanks for taking my questions. Thanks.
Thank you as a reminder, asked the question.
There will be star one.
And our next question will come from China now renamed Korea from Nexsan you may begin.
Hi, Thanks for taking my question I guess the first one for me would be on the to slide three program. Yeah, it's been running sort of under the radar what do you have any clinical update shared at this year's asking what kind of data would we be likely to see if so.
Okay. Thanks, Yes, we do plan on presenting data at ash, but you're right. Most people its flying under the radar screen. So we're not getting many questions, but but as we mentioned.
Coping with somewhat of a setback because that's an ivy administered drug but.
Once the clinical sites became accustomed to dealing with it they are able to then start getting more patients on we completed cohort for 100 mics per meter squared.
We're clearly seeing an increase in the.
In the PK exposure there now getting into the range that we had hoped we will get into that's both at the parent drug as well as the Arnett up we don't have all the data from that cohort yet, but we would plan to present data from all four cohorts. This year at at Ash and then we're also now recruiting patients.
For cohort volume that seems to be going well, we're getting we're actually getting quite a favorable response in terms of patients coming on to five three now and we should be able to present data from cohort by.
Ash again, we'll be looking at the various biomarkers the mic expression in the Pbmcs at different times throughout the.
The different.
20 day periods of the different cycles, as well as PK safety Tolerability and.
We hope that as we go into the next dose level, the higher doses that were able to get Piquet coverage.
Over greater number of days again, it's once weekly dosing. So if we can get started getting coverage over 357 days and maintain suppression of Nick that gives us the opportunity there to start seeing responses. So we hope to be able to show that as we're beginning to increase the doses were extending the time, where you can measure.
Sure adequate levels of drug in the plasma and hope to be able to see responses in future.
Great. Thanks, and then in terms of the CV to fix study now that you're about to start you mentioned that you know you're going to have both for three well pad and mutated patients, but you know I if I recall from your K, a well talk back in February there was mentioned that.
Hey don't take May also be active in the context of RASK mutations that may confer political proliferative capacity and are not patients and that these BRAF mutations may make patients was just into the flip three inhibitor.
So I'm just wondering are you going to actually pest patients that have selected for the study.
They also have BRAF mutations and will that information off a bit ultimately be you know shared with the public when the data to release.
So we absolutely want to get patients on there. So I can't promise there will be on coat, the first or second cohort, but we absolutely want to get patients on there.
Phil guilt written lived that have these rest mutations.
That or.
It's not just Ross. So there are number different mutations that give resistance to guilt written so you've got the gatekeeper mutation three get the kras mutation some of the P. 50, threes. So yes, we do want to get those patients on we want to make sure that we get them genotype and that we understand the sensitivity there.
Especially in the context of the particular mutations and we will share that with the public that's one of exciting things about this drug we think it has potential to treat those patients, whereas others don't.
But that's also one of the reasons, where we're going too far we're going to specific institutions cancer centers that have the capability to perform those analyses on the patients and understand the genotype the underlying genetic background that are able to follow that genotype going forward as we begin to treat patients and look at the clones.
And that also have patients who may have filled guilt written them. So all of those are in the works. So good question. Thank you.
Got it and just one last from me so.
On the same drag, but you know.
CB eight opex as a BTK shall we say you know after then again some of the larger companies are testing they'd be teekays and covert patients and I know that you don't have any plans to do that but I was just wondering have you had any anecdotal evidence of any of your patients actually getting cove, it and how they may have performed.
On Seattle effects I know, it's not exactly a direct correlation but I was curious if you have any anecdotal stories are evidence.
So we don't we're not aware of any of the patients on our study that.
The acquired cobot and of any responses, but if you're asking us is there potential for a drug like this.
Mr. Cope with there is the potential because if you're talking about the initial RP three and plan Masone complex and how it utilizes the.
Cleat cast a swan releases, all $1 billion team.
Yes, we can measure those certain activities, we know how well our molecule would act there. So it is possible that drug could be used in either this for inflammatory processes in the future.
But at this point in time, we have to remain focused on a mill and the CLL. We have our hands are full with those and we don't want to lose focus.
If something can emerge from this as a separate indication in the future will do those companies on excuse me will do those studies on the side and will collaborate with groups, but we have to remain focused at this time.
Hi, Chris. Thank you that's it from me.
So let me ask if a doctor morongo wanted to add anything to that.
An always on no no. Thank you Bill Bill captured it quite quite fully thinking.
Right.
Thank you and we have a follow up question from John Newman from Canaccord may begin.
Thanks for taking the follow up.
So bill Im just curious.
For the patients that have shown evidence of lymphocytosis on Cgeight hundred six just trying to recall wondering if you can talk to us about whether those patients had.
All had previous exposure to other BTK inhibitors and also if you happen to know.
What the mutational status might be for those patients. Thanks.
All right. So you came back around for around two here.
So in terms of those patients those are the classic CLL patients I can tell you. They are Ics, so heavily pretreated with all different types of drugs I'm going to ask dr. be harder if he can give me a bit of context as to the background in terms of what these patients may have seen but again, there all different so little bit of context.
Sure I think you're exactly right, though are very heavily pretreated many of them, having as the prior chemotherapy as well as other targeted agent and immunotherapy.
The vast majority of the patients have received prior BTK inhibitor.
For some duration and either been.
Refractory for all of that drug.
But as well as many other therapies. So it's not not just that.
Yeah, I think the remarkable part is these patients are so relapsed refractory. They felt so many different lines of therapy. It means the sales they do depend upon BTK productivity, but they also depend on all these other.
Kind of these driven pathways. So that's why it's so important for these deep relapse refractory patients to receive a drug that can inhibit multiple pathways. Because we don't believe that merely inhibiting b teekay is gonna be sufficient these deep relapsed refractory patients I think we've seen that from some of the other drugs out there.
And so we're hopeful that in these patients as we get to the higher doses and we're seeing these multiple pathways affected we're hoping we're going to see responses in them because they desperately need a drug.
Hope that answers great. Thank you.
Thank you John.
Thank you.
And I'm currently showing no further questions I'll now I will now turn the call back over to Dr. rice for closing remarks.
Right.
Well I want to thank everyone for joining us today, it's it due to an exciting time for us with our two key assets and the clinical six in two fivethree progressing now into the higher dose levels and we remain to remain committed to delivering for our patients and our shareholders. One of the especially think our clinical development team or investigators are.
When cooperations team the patients for helping us in this mission and we appreciate your support and we look forward to keeping updated on our progress in particular later this year at Ash, hopefully, we'll be able to give a very detailed update and we want to say, thank you and have a wonderful evening bye bye.
Thank you ladies and gentlemen that concludes today's conference you may now disconnect and have a wonderful day.
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