Q4 2019 Earnings Call
Good afternoon, My name is Gi and I'll be your conference operator today I would like to welcome everyone to the Aptose Biosciences conference call for the fourth quarter and your ended December 31st 2000.
19 at this time all participants are in listen only mode. After the speaker's remarks, there will be a question and answer session. If he would like to ask a question. During this time simply press star followed by the number one our your telephone keypad. If you like to withdraw your question. Please press the pound <unk>. Thank you as a reminder, this conference.
Call may be recorded I would now like to introduce Ms., Susan Pietro Paulo. Please go ahead.
Thank you James Good afternoon, and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the fourth quarter and year ended December 31st 2019, and she's been picked your Palo communications.
For Aptose Biosciences, joining me on the call today are Dr., William G., Rice, Chairman, President and CEO Mr., Gregory Chow Executive Vice President and Chief Financial Officer, Dr., you already Marando Senior Vice President Chief Business Officer, and Dr. Rafael They Hart Senior Vice President Chief Medical Officer before we proceed I would like to remind.
Hi, everyone that certain statements. 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, but are not guarantees of performance and it is possible that actual results in form it's could differ materially from these stated expectations they involve known and unknown.
No risks uncertainties assumptions that may cause actual results performance and achievement to differ materially from those expressed to learn more about these risks and uncertainties. Please read the risk factors set forth in 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 up his 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 the Doctor Rice, Chairman, President and CEO of Aptose Biosciences Dr. rice.
Thank you Susan blocked welcome everyone to our coal.
And your ended December 31st 2019, we're happy to have many new shareholders joining us on the call today.
Have you been with US on this journey through more children torch I'm truly privileged to lead this company well, we painstakingly constructed the foundation for our two hematology compounds Tsujino six and Apto two parts to read.
And now have moved these highly differentiated targeted agents into the clinic.
We along with there's still a group of research collaborators generated a welcome preclinical data that's supported the advancement of these called girls to the clinic.
<unk> 29 team we had two active clinical trials, we expect 2020 to be one of continued execution as we treat.
More patients and continue to generate meaningful clinical data.
Let me begin todays call. We recap highlights from 29 team followed by discussion of the progress of our critical.
During the year, we presented a wealth of preclinical data at the annual meetings with HCR <unk> and ash.
Those.
Patients and the full names of these conferences and the acronym are available on our website.
Clinical highlights, particularly with Cgeight hundred six included data presented by Dr., Brian Drinkers team and a waitress you demonstrating that CJ O six our first in class three BTK inhibitor.
More potent and older such inhibitors.
Including the story shrapnel soon it needs to be the M resort, new and old <unk> and guilt written up against acute myeloid leukemia or email primary patient samples.
Filling preclinical combination studies with phonetic Lux and patient samples demonstrated enhanced cell, killing which suggest the potential future combination strategy.
I know her charting preclinical study how about the exceptional in vivo anti leukemic Hep C. O CG had a six xenograft mouse model.
She jadrosich suppress leukemia growth at all doses tested throughout the 28 day period of dosing.
After dosing was halted tumors treated with the lower doses were seeing group as the same with other.
Other agents however, in the mice treated with a higher dose of 100 mix for keurig borrowing from 11 marks were cheered through day, one twentys and in the 300 make for Cig, Bruce Chan of 11, or 91% or the March will cure.
Retreatment of the I'm sure advice and these two dose groups for an additional 20 days.
Getting on day 88, after the tumors were allowed to grow.
Led to a rapid anti tumor response, resulting insurers have already treated mice through day 120, and the retreated Maui no drug resistance and no toxicities were observed collectively these studies laid the groundwork for delivering cgeight hundred six to email patients that have built.
<unk> three inhibitors, venetoclax, hypomethylating agents and sort of talks.
As well as patients having email with mutations in P 53, brass and already age that are less responsive other therapies.
A reminder, in spite of her extensive efforts to induce talks is due in animal models Tsujino six demonstrated.
A desirable safety profile and all of our preclinical studies to date.
Most recently at Ash in December of 2019, researchers from the MD Anderson Cancer Center presented two posters elucidating CGD don't Sixs mechanism of action in targeting chronic lymphocytic lymphocytic leukemia or CLL cells and its.
Before you back on a brutal resistant mantle cell lymphoma or mcl cells.
Data showed she judo seems to be more <unk>. The current standard of care in primary patient cells of CLL.
Did you don't six also demonstrated superior Intel lymphoma effects compared with the brute exerting potent so.
And.
Inventory effects on a bruton up resistant mcl cells.
Electively. These data from multiple labs demonstrate April six as potent activity against CLL and various non hodgkin's lymphoma cells, including those resistant tour bruton, thereby position us for clinical trial and these b cell cancer patients.
Turning to how.
Did the year for us it's a much anticipated initiation oversee judo six clinical program mid year.
I'll bring you up to date on that clinical program as well as the Upto 253 kind of clinical trial momentarily.
Also during 2019, we considerably strengthened our management team. We've introduced you previously to Dr.
The Bronco, who joined US mid year, a senior Vice President and Chief business Officer in December we announced the appointment or Docker Rumsfeld. They are an internationally recognized position scientists with extensive research and clinical experience in hematology should position of senior Vice President and Chief Medical Officer Importantly in November we also announced to.
Movement of Mr. Victor Victor Mum, Taba Lugo as our vice President of clinical operations. In addition to their outstanding traditional credentials Mr. Dr. Morongo Dr. Bay or Mr. Montalvo, I've already proven to be an integral part of our collaborative culture, we've been very fortunate to attract the interest of such high caliber individuals.
And our field to join the executive team.
As a result with the progress we made throughout 2019, we also were able to appreciably strengthened our financial position enclosed onto offerings during the year, our CFO Mr., Greg will discuss this further momentarily.
I want to provide a clinical update and let's begin with Cgeight hundred six.
Our oral highly potent non covalent inhibitor of the BTK and three dropper clinics is.
Cgeight hundred six for just a little six there's like no other drug commercialized are under development.
As much more than a typical fleets or BTK inhibitor.
Not only inhibits all wild type of mutant forms of BT <unk> three.
Hopefully in simultaneously suppresses multiple oncogenic signaling pathways upon which cancer cells were like for survival and drug resistance.
We consider it all seems to be a mutation agnostic agent selectively targets clusters of related Chinese and suppresses the mutations that occur in email and CLL sales that.
As such cells resistant to other agents.
Question, we sometimes get asked is wouldn't a multi cluster kinase inhibitor.
We had dirty kinase inhibitor and the answer is no itll six has been shown to target. The primary drivers a b cell malignancies in email, including beat you came to three yet what the precision that avoids known.
Targets, such as tech, T.C.E., Jeff or and or be too, they're often associated with toxicity.
This selectivity is what since April six apart from other hematology drugs on the market or in development and what is contributed much of the excitement surrounding the color.
Regarding the lack of toxicity noted thus far our.
New Chief Medical Officer Dr. Rothfeld. They are recently commented that this is one of the most Holly rigorously tested preclinical compound he has ever seen and it is one thing to say we have not observed toxicity, but it's also important to highlight that weve rigorously tested for toxicity.
And John Joy of 29 team we initiated.
Hosting of 8.6 enter phase one I'd be multicenter open label dose escalation clinical trial in patients with B cell cancers to remind you. The trial is designed to assess the safety tolerability pharmacokinetics, and pharmacodynamic responses and preliminary efficacy or they go six and established a recommended.
Phase two dose because there's a favorable favorable preclinical safety profile. The trial protocol loud for an accelerated dose escalation schedule for only one patient or is required at each of the first two dose of 150 milligrams and 300 milligrams would be ideal.
Yes unexpected side effects necessitated additional testing at.
Those levels as route we reported last quarter, one heavily pre treated patient with CLL was treated successfully with the dose level. One of 150 milligrams be I'd and another relapsed refractory CLL patients treated successfully with dose level two of 300 milligrams to be I'd. The first two cohorts are now.
Complete oral eight ilsix at these doses was well tolerated with no drug related toxicities, including no myelosuppression.
And at the second dose level. There were early indications are pharmacologic activity to demonstrate pharmacologic activity, we performed a plasma inhibitory assay or P.I., I say, which we.
Click plasma from the patients at various times throughout the 28 day cycles, we bring the plasma back to a lab and placed it on indicator sells for six hours and then we set the activation state of key oncogenic pathways, but even in a bloody.
In these studies, we observed complete inhibition of also BTK Faso ERC and.
And fossil sick once the patient reach steady state levels of drug exposures, demonstrating the trough plasma exposure levels are sufficient to potently unsustainably inhibit our key targets and pathways. In addition in this yellow patient at the second dose level, we observed a robust increase in peripheral blood lymphocytes.
For lymphocytosis.
Lastly, described as a response to envision a BTK.
These first two dose levels proof that we had a pharmacologically active agent at these safe dose levels.
And these first two patients we were pleased to observe dose related pharmacokinetic properties such as steady state was reached by the ended the first.
We could dosing and in the CLL patients at the second dose level, we observed a steady state or trough levels to be in the near my promote concentration range. We were thrilled to see that it'll six was absorbed and that the second dose level could approach plasma levels that we believe should deliver benefit to patients so of course.
We were eager to progress to the next dosing cohort.
Since our last call weve been rolled and have been treating three patients at dose level, three which is 450 milligrams be I'd. Further protocol, we will need to successfully complete a 28 day dosing of three patients at the 450 milligram BRD.
Before we can continue to the next does.
I'm happy to report that we expect to finish the 450 milligram cohort with three patients by health day of this week middle of this week.
We hope to see well behaved steady state PK parameters with acceptable variability among patients and see serum exposures.
Ring around the one Mcdermott will range from 450 milligram dose.
I can tell you that no drug related toxicities have emerged to date.
Once collected we will deliver all safety PK and PD data to the court safety Committee will be advising us on next steps with all going well three patients at.
450 milligrams will be followed by sending cohorts with three patients each at 607 5900 milligrams be I'd.
With the intent to select a recommended phase two dose for patients with diesel cancers, including those with relapsed and refractory CLL and non Hodgkin's lymphoma.
It's an MTD are safe and biologically active dose has been selected as a recommended phase two dose up to 100 patients maybe enrolled for treatment in the expansion phase at that dose as of today. We have 18, you as clinical sites opened 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 doctrine.
Now, let's discuss our proposed AOL study with CGM six.
And remind you that April six is the only BTK inhibitor that also obsess just strong split three inhibitory activity is.
Applicable therefore to both lymphoid and myeloid malignancies based on our extensive preclinical work some of which we mentioned recent previously it has always been our intent to treat email patients with NATO six in addition to B cell malignancy patients.
The biomarker analysis of the patients in the current B cell study our.
Adding our preparation for the protocol for the animal study.
And we as as we've discussed in prior calls we plan to seek allowance from the FDA to move either gsix into patient populations that include relapsed or refractory email.
As a reminder, relapsed or refractory AML patients are acutely gill.
And we did not wish to doses patient population with the sub therapeutic dose that likely would not provide better clinical benefit.
Therefore, we chose to initiate the first clinical trial in patients with B cell malignancies, and click the safety PK and PK data from such data, we should be able to identify dose that we.
We believe had the likelihood to deliver therapeutic benefit immediately email patients.
Based on the exposure levels, we observed in the clinical trial with CLL patients compared to the exposure levels that we observed to eradicate the tumors in mice. We believe that we are close to identifying a starting therapeutic dose for MLP.
We need to review the collective safety PK and PD dataset from dose level three.
Again, which is 450 milligrams be I'd before we can make a final determination dose level three can be recommended to the FDA as our starting dose.
Well underway with our clinical protocol preparation for this new trial.
And we expect to be in position to submit an approval of the appropriate documents to the FDIC. During the first half of this year. Our clinical team has identified and it's working closely with top tier academic sites to initiate the new email trough for the intended troll and MLP patients. We plan to focus initially on the relapsed or refractory email.
Population with high unmet medical needs in other words, all email patients that are not receiving benefit from current treatments.
Well the current their targeted therapeutic therapies may initially show clinical benefit.
Significant number of patients rapidly relapse or become refractory to such treatments.
Those are viewed who tuned into our kill well symposium focused on a mill held last month also available on our web cast website.
Appreciated the enthusiasm of our guests panelists about potential April six and email I.
Ill now turn it over to Dr. Bronco.
To briefly recap the key takeaways from the care will.
Thank you Bill we were very pleased with the outcome of the tailings and humble both played a key opinion leaders as presented on behalf of Cgh Ics and those of you attended in person and via webcast. Our guest kill ill emphasize the unmet need in and out between the most common.
Station in and out and the currencies, we inhibitors are not warranted.
They all have limitations that lead resistance and ultimately disease progression.
In the last two liter and those seasonal bounce sleep approval of two between inhibitors I don't store in in combination with chemotherapy in untreated and though.
And gildan business as monotherapy in relapsed or refractory on now.
However, as our guest can you highlighted the collective experience with this drop in child and in the real world. So far suggest that there is still ample room for improvement.
In the ratify phase three study in treatment naive.
Well My does story, which is a broad multi kinase inhibitor like we lived through inhibitor in combination with chemotherapy extended for your survival from 44% to 51% compared to chemo unimportant. However, very modest improvements further studies of Microstar in patients with.
Relapsed or refractory disease, it not observe any meaningful clinical response it.
Meanwhile, looking at Kildair isn't it we just a more potent and more selective inhibitor roughly three in the ads narrow seats, we study in relapsed or refractory disease. The 12 month survival rates for good reason it versus salvage chemo.
<unk> was 37% versus 17% respectively.
Oh, good reason, if responders eventually relapsed and survival rates in both arms equalize by 25 month.
Each time, approximately 90% of the patients had to come to this terrible disease.
In the patients who failed currencies, we inhibitors decel under certain recurrence and diverse mechanisms of resistance, including mutations in fleets me Ras P 53 and others.
These observations highlight the urgent clinical need towards the development of newer generations of kidneys inhibitors.
Nano ideally combining the strength of the old regions, while overcoming the weaknesses.
I guess scale out as well as top and no investigators with whom will continue to interact are all eager to treat the resistant or refractory patients with Ito six.
They are enthusiastic about the.
Agents preclinical and clinical safety and Tolerability profile to date, which suggests an encouraging therapeutic window and combinatorial optionality. Both of these are important considerations, the relapsed or refractory am.
At the same time, the agent eco moeller to Nanomolar potency.
Eight in tandem with its coverage other key oncogenic pathways suggest that it may represent a biologically optimal intervention part of the confidence genetics of relapse or resistant ammo.
Overall, our data to date support the potential of 8.6 to benefit patients that failed other fleets.
We inhibitors and middle class, eight decided dean and even chemo and to treat patients with any wild type Egfr mutant form of three or with mutations in P 63, and rats, IDH NTM line or mixed regulation.
If any of you have questions about how eight to six.
In the and they'll treatment paradigm, you may want to listen to this informative presentation again available on our website with that I will turn it back to bill.
Thank you already.
To wrap up on April six the competitors element radar screen of many on the hematology community as well as many new investors, we look forward to respond reporting.
Our progress on the ongoing phase one a b study.
In patients with CLL and other b cell malignancies, as well as the perspective A.M.L. trial throughout the remainder of this year.
So now just a quick update on the Upto two fivethree, our second clinical candidate and first in class, making Hubert currently in a phase wouldn't be trial.
Patients with AML and Mds.
As many of you know the myc oncogene as a major driver cancer cell proliferation. In fact, its expression is estimated to be elevated or dysregulated and up to 70% of human cancers, including AML and Mds as well the solid tumors.
As we mentioned previously targeting of Nick.
Has been the goal of many researchers over the years, but because myc protein has been an elusive been challenging target mic has been deemed undruggable power to five three does not target the myc protein rather it targets the regulatory multi and the promoter of the Myc gene and suppresses expression of the myc protein and least depletion.
The myc protein levels in cancer cells.
During the Ash meeting in December 2019, preclinical data for two or three confirmed its activity as a mic inhibitor and further define the drugs mechanism box.
Some quick backgrounds in preclinical studies, using 88 mill patient sample sell samples 54%.
You have to food to Fivethree with an IC 50 below one mark.
In addition in a prior phase one trial in patients with advanced solid tumors to factory was found to be well tolerated importantly, with no myelosuppression and showed signs of anti tumor activity.
Her phase one clinical protocol to five please to five.
He is being administered once weekly over 28 day cycle of ascending doses in patients with relapsed or refractory AML or high risk Mds until the maximum tolerated dose has reached the study is designed to then transition as appropriate to single agent expansion cohorts in AML and Mds.
I'm happy to report that.
We're now in the fourth dose cohorts in this trial.
Thus far we've completed the 28 day dosing in the first three dose cohorts the last through the last being three patients on the 66 mics per meter squared dose.
We now have completed the 28 day cycle with one patient at dose level for overseas.
The 100 mics per meter squared two pads or drug products and we now are screening for additional patients in that cohort. The good news is that too far three continues to be well tolerated with no observed malo suppression, we continue to absorb Mick inhibition at all dose levels today, we plan to continue dose escalation too.
Our dose levels that we hope will deliver responses for AML and Mds patients. We also wish to note that no one truly knows what to expect clinically from a mic inhibitor. It may be that we received we observed robust single agent activity at an appropriate dose or it may be more like panetta clocks in AML patients such.
Its effect is modest as a single agent the highly effective in combinations for a mill because it hit the pathway distinct from other agents.
Eager to learn how best to use to fight through and we think all the patients that have received two five htthree and all that positions participating in our clinical trials.
I'll now turn the call over to our objective for.
Vice President and Chief Financial Officer, Mr., Greg, Joe who will review the results for the quarter and year end.
Thank you Bill and good afternoon, everyone. We ended the quarter with approximately $97.6 million in cash cash equivalents investments compared to $15.7 billion at December 31st 2019 at 30.2 million at September.
20 like.
This increase in cash is primarily due to the recent $74.2 million.
Additionally, marketed public offering that we needed to mid December.
During the quarter, we utilized approximately $6.3 million of cash and upgrade activities, which were attributable to increased activity surrounding NATO six and to buy three and also.
General and administrative purposes moving onto the income statement, we had no revenues for the fourth quarter.
The year ended December 31st Tween, 19 research and development expenses were $5.3 million for the quarter and 16.8 million for the year gene expenses were for the quarter with $2.6 billion for the quarter and 10 million for the year.
Our net loss was 7.7 million for the quarter, and 26.3 million or 52 cents per share for the year.
One last item to note during the quarter includes the filing of a $200 billion shelf registration statement in late December that was subsequently declared effective in early January this shelf replaces the previous one that was exhausted for the recent.
Especially marketed public offering.
Or detailed information can be found in our filings on Edgar and SEDAR.
Before I turn the call back to Bill and open up for Q1 day, we want to mentioned a few things about how coded 19 may affect our progress in our operations with regards to manufacturing of our drug candidates and learning for past experiences we had.
What's the supplier that source building blocks to lines that you put the apiay and the clinical drug products of data six to five htthree at this point, we do not see any delays or and are inconsistent communication with our manufacturing partners and suppliers with regards to the clinical trials. Our team is in constant contact with each of them.
Additions and clinical sites. Unfortunately for the patient population that we are addressing these treatments are not elected and thus we do not receive any delays and the treatment of the patients currently on study or the enrollment of patients moving forward.
I'll now turn the call back over to talk to us.
Thank you.
I'd now like to open the call for questions. Operator, if you could please introduce the first question.
At this time I would like to welcome I would like to remind everyone that if he would like to ask a question. Please press Star then the number one our your telephone keypad well pause for just a moment to compile the culinary roster.
Your first.
First question comes from the line up Tyler Van Buren from Piper Sandler Your line is now open.
Thanks, Good evening and congratulations on all the progress during the quarter I guess my first question is related to the second patient for 300 Med D dose cohort you guys reported on the ash.
Was hoping you could provide an update regarding the two observations.
Increasing lymphocytosis has anything changed there have you seen lymphocyte count to come back down like I understand that everyone behaves differently.
So maybe that Didnt occur and then the second part is.
They also both your nodal disease, and you mentioned that theres potential signs of decrease in eight of the night lesions or that there were signs decrease so has there been anymore.
Decrease absurd there.
Oh, Hi, Charles This is bill so all first answer and then I'll open it up to Dr. Barry Harvey.
He also wants to add anything too. So we had mentioned I guess it was in January that that second patient or the one of 300 milligrams be I'd, we actually took them off study.
This patient came on with extensive bone marrow involvement.
When we put them on the drug they immediately had.
Autos is which was caused by inhibition of BTK, indicating that it's pharmacologically active.
This patient also when they entered the trial they had platelets will they had neutropenia as well as thrombocytopenia their platelets were literally.
Right at a great for when they entered the trial.
So.
As we continued to dose them overtime, we did not see any worsening of the platelets, but we also didn't see any benefit over time, but what we did see is the patient tolerated drug very well the the lymphocytosis continued.
But since it was only the the second dose level and we.
We assume that was not an optimal dose level, we decided to take the patient off of our drug and allow them to go on a full dose of a.
Currently approved therapy and hopes that they might actually do better.
Anecdotally now what we can say as they have been placed on a nother another drug.
That is an approved drug at the full dose level and effectively what they're seeing is the exact same thing in the patient that we saw on our drug at what we assumed was a an early dose level. So the good news is our drug was was working in that patient, but we're trying to be very cautious because that's a sick patient and and.
We were just hoping that when they went onto another drug they might be able to get additional benefit but it looks like it was just as good as that hours was just as good as the full dose with the currently approved drugs. So do you want to add anything to that Dr. before.
Great. Thanks, I think we learned drug is well tolerated are important.
Despite having of highly compromise bone marrow, we didn't see any additional Milo Texas.
Yeah. So we also might a good remember in that one and that patient we collected the plasma love plasma from the patient.
And perform that P. I see and once we reach steady state, which was by the end of the first week we had.
The inhibited fossil be decay paulsboro sick, that's also as wide Kay and fossil work. So we know we were at a pharmacologically active dose, but we assume that since it was actually one of our lower doses that that patient might actually get additional benefit from a full dose of another drug.
But apparently that's not the case and they.
They actually do quite well on out.
So I hope that answers your question right.
Yeah, that's helpful and yes. It does the final the second question with respect to the imminent cohort safety review.
I guess you know clearly safety is a major focus but is there anything.
Specific.
Equally that needs to be seen on PK PD to be able to move forward other than just clean safety and have you guys already screen patients for the next cohort. The most recent cohort was obviously.
Enrolled very quickly.
All right again, all began here so what we want to measure.
Her in these patients first of all is safety, we've we've watched carefully for safety, we've seen no signals of any drug related adverse events in these in any of these patients today, secondly, pharmacokinetics and all of the the prior dose cohorts cohort one or two there was only one patient in each and so you.
Don't know how well behaved your pharmacokinetics will be in this third cohort, we actually have three patients have flipped worth of data out through at least 28 days.
And what we want to see as the is that the pharmacokinetics are well behaved that the coefficient of variability is minimal so that we.
Actually predict what the patients are going to get a we're starting to get some of the PK data, but we actually don't have all of these samples from all the patients yet.
So that the second part is the PK, we want to see it in I'll call. It the circa one marker molder range and also see that it's minimal variability.
Also in these patients we absolutely want to see the Pharmacodynamic markers are active are responding to the drug again, we take the plasma from all of these patients would bring it back to the lab and we want to look and see our we inhibiting the false will be decay, the sick ERC and the major pathways.
It's also important not only to show that its active in these patients with CLL and various lymphomas.
We want to see that were also inhibiting flipped three in those patients. So we have an indicator cell line.
We'll be looking at inhibition of split three and that will tell us whether or not we have.
Sufficient droke levels to inhibit flipped three and that will also guidance as to whether or not we have a dose that we believe we can recommend to the FDA. So.
Dose cohort three is a very important dose level to us.
Safe, Yes pharmacokinetics. This is the first time, we've got three patients.
And we want to hopefully.
We see a minimal variability and then pharmacodynamics that show is active in the B cell cancer patients and also hopefully it will show us that we can directed toward the ml studies.
Anything else you wanted to add just answer the last part of your question. We are directing sites that sort of screening patients assuming that we won't see any issues.
Fortunately.
Great.
It's very helpful. Thanks for taking the questions.
Thank you.
Thank you. Our next question comes from the line of Gregory Ransom from RBC Capital. Your line is open.
Hey, guys. Thanks for taking my question and congratulations on all the progress.
<unk>.
Got it just wanted to return a bit too on the commentary on coming I can I appreciate that prepared remarks, but just curious if you had any additional thought or detail on the situation involving with respect certainly to the clinical trials, but also with potential regulatory interface thing that you foresee.
Coming up and how your.
During.
There was potential interactions as well as just general stakeholder interactions that as you convene the.
The key stakeholders in order to to move this and the annual trial forward. Thank you.
All right, Oh, Hi, Greg Thanks for the questions questions.
So.
We've been.
During this very closely as has every company out there. The first thing we wanted to assure everyone is that we we don't see any effects of this on the manufacturing of our molecules.
We've been very careful not to be dependent on any particular site around the planet our manufacturing to date has all been.
Performed in the U.S. of our starting materials are available through multiple suppliers.
And so at least right now we do not see any risk to the manufacturer of <unk> or the drug products. So that's the first concern that we always have because many companies will be dependent upon.
Especially China for manufacturer some of the starting materials I think we're in really good shape. There. So we don't we're not seeing any.
Any near term impact on the manufacturing.
In terms of the clinical trials or regulatory interface I'll, let a doctor be hard.
Address that and just.
The second but you also mentioned the interface with investors. So we also already know that a number of conferences have either been canceled or delayed we know that many of the investment firms for around the country in the world are not necessarily welcoming people into their office and so we're we're having to take it a bit of a different tactics.
Here and have much many more the virtual interactions, but we do plan on providing updates even if some of these major conferences are delayed or canceled we plan on getting the data out one way or enough.
Another to you as well as the the various investors out there so reps do you want to.
Yes, the clinical and Registrational.
To date, we haven't seen any direct impact on our clinical operations. However, I think that will likely change in the near future. We know that many academic institutions. The restricting both travel out of this institution and restricting the never been through that can come in several of them have recommended a remote monitoring strategy for example and were.
Very flexible and able to accommodate that if needed. So we can continue.
Carry out the clinical trial sites, we could oversight other things that are less predictable in the near future. Our weather institutions are going to redirect resources for tackling cobot 19, if that are an outbreak.
The large and they may be.
Less resources available clinical trials, and whether patients might have restricted mobility and ability to commit handle those things as they happen.
It's something that we're monitoring very closely so far but none of our sites have been directly affected.
Thank you Rob.
And thank you group.
Thank you and just one more if if I mean that's out.
Very helpful. Just just turning to the two tapping the full potential of Alveda fixing certainly spoken about and I really.
Establishing the do opportunity with CLL, and and and and I will be selling and now I'm just curious to what extent should we think about youre yeah.
Your appetite for leaning into the aim outside of that I've had a six this potential and certainly respecting the sequencing and the thoughtfulness that you're taking I'm aware of what the trials that as their laid out as these mature how do you think about them both opportunities and certainly out leaning into the equation. Thank you very much.
Okay Great question.
So clearly we have we were aggressive on the the CLL. The B cell malignancies. We went there first we're going to continue there we want to demonstrate that this drug is active in those patients, but I also want to to indicate we are being very aggressive and going toward the a mill we want to get there as soon as possible, but we also one of the.
We don't want to make any unforced errors and for and be certain that we execute appropriately we need to demonstrate that we're selecting the right dose to go into those patients such that we hope we see activity benefit in the patients immediately at the first <unk> dose level that we go into we can't.
[music].
We can't say.
Absolutely will happen, but that's our hope once we go into those patients.
We we clearly want to go into the patients and the data support going into the patients who have failed the other drugs Ralph can speak about this week at our at our Calwell event, we mentioned that there are number of new.
Patients that occur in response to treatment of patients with phonetic clocks with guilt written debit Friday or the other molecules patients with Pete Pfifty three mutations various split three mutations Ras mutations and Ito six maintains activity against those various forms of the bars. So we hope that.
We're able to treat the patients who have failed many of the other drugs.
But yes, we we see a tremendous opportunity in a ml and I think the that was echoed by all the investigators that are looking at the drug BRAF did you want to add to that I just reemphasize the idea that we see preclinical activity not just three mean AML.
There's a good rationale for actually including relapsed refractory patients don't carry that the mutation.
Because we see activity against other mutations that are relevant ml, putting unwrap even patients.
So we're excited to offer this opportunity individual see.
Yeah.
And at some point, we do hope.
We have activity also in India as population, there too and Ralph has a background in Mds, we hope to be able to take advantage of that.
Did that answer your question, Greg Yes fair. Thank you very much guys. Appreciate it. Thank you.
Thank you. Your next question comes from the line of John Newman from Canaccord Your.
Your line is an hour fan.
Hey, guys. Thanks for taking my question.
Bill I just wondered if you could talk a little bit about Oh.
The way that.
Responses tend to evolve.
And he alone and the reason I'm asking the question because I think.
Sometimes investors will.
Look at other companies studies for different agent.
No.
Or they will.
Just sort of question.
When they should start to see responses I'm just wondering if you could walk through the way.
These responses and feel attended develop.
And also just type of imaging.
The U.S.
In order to confirm that thanks.
Hey, John Thanks for your question.
Oh, so as it says CLL is it's a chronic disease. So it's very different from a itself, which is an acute disease.
And we also have to break it into two different populations of patients who are already failures or patients who have just.
A recent diagnosis versus the patients who are deep relapsed refractory patients. So I think a experience has taught us, especially with what the arc you'll compound.
That overtime.
They did develop.
Responses once you get to the higher dose levels of the drugs. If you have a multi targeting kinase inhibitor. Once you get to the higher dose levels and you're actually hitting multiple kind a multiple pathways. Then you begin to see responses in those deep.
Locks refractory patients, but it takes time and it takes longer than the patients who are just recently diagnosed.
So again.
Looking back at the example, our tool so some of the during the day He hall.
Conference last year, and the middle of 29 team.
They they showed a number of responses.
That were earlier on and they said they were expecting throughout the rest of the year. The remainder of 2019 that wants to patients were on the higher dose levels that those responses with deepened and they will get additional responses overtime and that is exactly what happened, but again everyone had this.
Sit and wait and watch to give these are the CLL and b cell malignancy patients, especially the relapsed refractory time to respond we all wish they would respond quickly, but they don't I don't know of any relapsed refractory patient also the has seen a complete response there all partial response and Nate.
Todd.
How do you measure that responds well of course, you can look at lymphocytosis in some CLL patients, but you don't see that it all up, especially if it's more of an SLF Asia rather than seal, though so you have to perform the imaging and you're looking at the be at various lymph nodes spleen.
Indicator lesions, but you only.
You evaluate those every two cycles. So you only take the measurement every two months and typically you don't expect to see much. The first several months and so you don't see we've talked with responses early on and it's a it's much much takes much longer I think arc. You'll also noted that they had a fully bigger lymphoma patients that it took approximately a year to see.
Actual response.
So that's what you tend to expect and that's why we're providing guidance towards the later in the year with our drug this year.
Once we get into our higher dose levels, we have the second half the year for the patients to the on the drugs and give them more time to respond that's why we're not expecting to be able to present responses.
Sure, but look for it hopefully towards the end of year.
Mills are different story, it's an acute disease once we get into an effective dose and that might be the first second third dose that we're into there. The second half. The are you would expect to start seeing response, there BRAF again would you like to add to that I think that's spot on just emphasize the variability between.
Even with the same diagnosis.
There are eligible for response and accounts for example, others may not be than they already have attacked blood counts I will then have primaries.
Maybe more splenomegaly. So there are criteria that we follow but the timing of that.
That does not immediate I can take months, even in our study we're really looking after every other cycle.
And every patient is almost a freestanding experiment theyre all so different and it's on a patient population basis.
Right.
Well.
Yes, just one additional question, which is I know that yourself as well as investors are sort of eager.
Moving to an.
No, but obviously.
Yes, it takes time to.
Security I Indian could study up and running and those types of things.
Could you remind us again, what types of things you are looking for in order to determine.
That you have a dose.
Can't E B cell building the study that you feel would be.
Active for close to active and ammo.
But it's a good question. So we're looking at the totality of the data related to safety pharmacokinetics and.
A quick responses.
So in terms of the safety, we want us to be able to show that it's a clean dose level and so far as cohort three has been completely clean and we hope that the additional ones into the future will be too.
In terms of pharmacokinetics, we say that we wanted to be and we call. It circa one mark remote.
Around that dose level, our exposure level why do we see that well, it's because if you look at the animal studies in which we have seen complete tumor elimination cures and animals without any toxicity.
We see that range of anywhere from week to this 8.9 macro moeller in the animal studies and that gives us.
Complete responses and the animals. So once we're getting into that range in humans, we think that should be a therapeutically active range and so we're getting into that range, where even beginning to get into that range with dose level too and we hope dose level three.
Also is maintained.
In that circa one makeable doesn't have to be over but in that range and then the third one is the PD.
I would suspect that the FDA would would expect us to demonstrate that.
The exposure levels in the patients.
Can inhibit split three activity.
So how do we do that again, we collect the plasma from the patients over the other 28 day cycles take it back in the lab and put it on the indicator sales.
So the indicator sales that I've been talking about thus far it's one particular cell line and we've been showing you data with BG K sick and ERC well that same cell line we.
Measure sit three we have not disclosed what we've seen a split three and patient dose levels wanting to but we are going to be showing that in dose level three hopefully that'll be at the Hawk, we'll have that but we'll also have to present such data to the FDA and if we hit all of those criteria.
Then that gives us confidence we should be able to go into the AMC or recommend that we go into the email patients then FDA has to look at our proposal as to agree to it.
We hope they agreed to with it'll have to a and then for ml. We also have orphan drug designation. So it should be a 30 day turnaround and so.
So that's why we're hoping to get into the patients as quickly as we can but we have to have the totality of data anything else anyone wants to add.
No I think that covered most of it okay great. Thank you.
All right.
Thank you. Your next question comes from the line of Matthew Crawford from Joan.
Training your line is now open.
Hey, guys. Thanks.
Because in a couple of questions companies here.
So recently presented Klinedinst selling that that's two to six appears to have better activity against unrest and then other put three inhibitors and that's certainly appears significant.
I mean to the dressing this pattern.
So what three into this.
Because of six and have a number of upstream sterne targets the feed into Ras.
I was wondering pseudo six is indirects control of risks.
Suppresses well I'm, just curious obviously want to talk about.
It would explain why.
A FERC in that Craig.
And maybe what that means from a from a safety.
Standpoint, as a kind of consistent.
Market for kind of some of it it with this profile.
Alright, well Matt.
Set of dirt on that one so I guess I'll just jump in with you.
So when we look at the.
The kind on scan.
And the kidney says that we inhibit the various clusters of kinase as we've always talked about the flip three cluster as well as the PDGF are often see us if one or that are also in the flip three we've talked about the track kinase is the BTK SARC finances.
We also have pointed over to the right size, that's kind of the map kinase.
There are some some kinase that are over in that as cheap what are called the S. T E cluster that our inhibited that a little bit higher concentration, sometimes but those are meaningful. So anytime you have a patient who has the the rest mutations you want to be able to have hit some of the <unk>.
I wanted to both upstream as well as downstream so upstream of the rest would be split threecs, if when our PDGF, our alpha as well as BTK sick lip Sark, we hit all those.
And then downstream of the grass you also have the map kinase is.
And we hit some of those so we believe.
That's why we maintain activity even in the presence of the of the rest mutations now our drug does not directly inhibit Ras, but we retain activity even in the presence of breast mutations. The same is true for P. 53, we've been able to maintain activity even in the presence of P 53.
And some of the other so wrap how about anything to add.
No thats exactly.
Okay.
Okay all right.
Great that's very helpful and transfer and Golden rule anything out there.
And then the second one I had was perfect trajectory for for 2.3, it sounds like meaningful data could come from Institute.
Six program that you continent, maybe more so I would ask.
It seems like three enrollment.
Okay.
Well in parallel and.
I was hoping to get the latest somebody would expect a person Anderson results from this colonel in conjunction with those for greater success, you don't ask order pace on Christmas covers a bit based on their design parameters or other factors.
Yes.
So the guidance that we're providing regarding to fivethree as well as we begin to get up into these higher dose levels get more patients on and hopefully be able to freedom for longer term throughout the second half of the year, we hope to begin to see responses and those patients. So we hope to see something by ash and to be able to present the data here again, we we.
I don't know what you expect from a well tolerated mic inhibitor, we don't know for going to get single agent activity or if it's better for combination more like phonetic clocks and they mill, we mentioned that earlier.
But at least you know we have the drug product we have the patients we've completed one patient on dose level for we've now right. We're a.
Are you waiting to more patients to bring on now hopefully we'll get those on soon and continued to dose escalate.
And we've always said that we hope to get a proof of concept with this drug as and IB agent and then hopefully in the future. If we can get to know what we've delivered a form this drug works and still continuing on that.
Path and the fact that we were able to raise sufficient levels of capital in December it's really allowed us to accelerate some people's oral discovery studies.
Great.
Obviously looking forward to this or not but none of this and actually plays out the clinic longer term and number four.
Turning to US for me. Thanks, guys. Thank you bye thanks.
Thank you. Your next question comes from the line of Jason Mccarthy from Maxim Group. Your line is now open.
Hi, this is going on for Jason.
So I just want to piggyback on the math question I was asking earlier.
Could you remind us about incidental last mutations in and now and aside from that so with that you've demonstrated with either take.
Its activity in unrest.
Patrons and both have you done any animal model working well.
Great solidify that you've seen.
All right in terms of the incident the incentive in rats has not been really highlighted in the past its more emerging now the patients are being treated with a variety of different molecules of Annette o'clock. Some of the flow through inhibitors. Some of the others. So it's beginning to emerge.
Guilt written nibs some of the off leave some of the patients their.
Hoping in rest mutations so again, what we're doing is as or not we but collectively the field as we began to dose patients with different drugs new types of drugs different targeted agents rexy bribing the tumors for different mutations and this cat faced with a variety of other molecules in rest.
These are beginning to emerge so I don't think at the high incidence at this point and perhaps Ralph note, we will know the number.
But those are emerging and it's clear that the investigators for identifying those patients other identifying them as clear failures.
In terms of our work how did how did we look at this we.
We actually took samples from over 200 email patients this was Brian group.
So its primary islands' AML patients treated with our drug eight associates and got an IC 50 for self kill them and our drug was very effective there, but we also had the entire genetic profile of those.
One samples as well as gene expression profile, and we were able to go back and look at wildfire versus kras mutant patients and effectively there was a slight increase in IC 50 in the rest mutate you did mutated sales, but just slightly higher and it looks like those exposure levels required.
Hard to killed the rest mutant fills it looks like will lease we hope we can achieve that in patients and so we should be able to treat those breast meat patient for us when we look at the same thing with other draw other drugs.
Doesn't look like they can achieve levels that can inhibit rescue so a rep.
The rest rep or would you like to add to that to enrich is found in the no AML Austin actually and favorable risk, but it's about 5% to 10% isn't going to meet repay Mel.
As bill pointed out it really it impacts and rent.
Is that emerge after therapy, there often that consistent.
The dress.
Like split three inhibitor and Connecticut. So these are.
The patients that are selected for that or weren't able to expand in this setting a therapy and are therefore.
Had activity again in the relapse refractory setting well isn't the upfront that John it may be that these patients so after being treated with multiple types of therapy.
They have a background not only with threats, but they have other mutations that are occurring and then wrap on top of that and then the other drugs just can't handle.
That.
Constellation mutations.
Would you like to add anything to this.
Yes. So thank you for the question just as rat pointed out the rock in the frontline.
Thank you.
Relative low percentage of incident, however, the real problem with Brad into we lap Theres still patients who failed treatment. For example, if any of the net of that now the data. There is there any preliminary because we're just starting to see real work.
And collecting smelt apart from those.
Small cohorts of patients with relapsed following seems to be therapy for example.
We estimate that the rate of grass mute is.
Now the quarter to a third so that is a fairly high incidence again these are very small.
What it shows further east that some of these rat munis, where it needs to begin with.
Our regional mutation and that some of them are no limitation, so the selling finding ways to get around it the era and so that becomes exceptionally important.
In the.
Looking at Cgh extend the potential for treating all indications that are rising ask a failure.
That's good point, so at baseline into noble and Alvin and Restitutions present, typically a flip free mutation is not tend to be exclusive at first patient, but in the switching patients. When they developed resistant disease. Then you have a crown both with review and the M.
And.
That's the evidence that mechanism.
So one of one or two loss notes here, so we want to be able to test.
It will stick with us a genic cells that have wall type and just the only other changes in rest of we're looking to do those studies with the Doctor group or hopefully into the near future. We're trying to identify the fills that are osteogenic.
Such changes in terms of an animal model, we have not tested that in an animal.
We do not have such an animal model available we can look for them, but hopefully we'll actually have human data later on this year and that'll be much more impact.
Did that answer your question, sorry, Oh, yes, more than half okay that was very good.
[laughter].
No.
Yes that is great.
And just one follow up in terms of Peter Thanks, achieving any now.
You mentioned on the coming into a optionality within Dod and you've shown pretty impressive.
We'll work with data from another question and outpatient vessel.
You know.
The program you know, we know that inadequate that conditional approval any amount in combination with agent Neovacs banking 20 team. Thanks.
I guess, a few days again, you probably read that.
Hey, John technically down one of the confirmatory study, which could potentially jeopardized position in AML venetoclax that is.
Are you considering other strategies outside of.
Potential combination with Fernanda cracks have you done study with eight or are they chemo engine.
Yeah. If there are couple of answers there first of all in terms of our studies with Venetoclax. The data were very impressive whether it was with the MLP and we did all of our combination studies with patient samples patient rise samples.
Well CLL Mds CLL, so we saw very nice activity.
Nation activity in all of those sales.
Venetoclax is an impressive mall molecule, but hey, a mill, particularly a single agent. It did not have impressive activity, but in combination. It does have activity and there's there's a move to move that.
More toward front line and.
That likely will happen into the future, but it's not going to be perfect in every patient population.
But the net of Clecs is going to be used in email I think broadly and we want to be able to show that we have activity. There. The other reason we want to look at the net effect is because it's also use and the b cell malignancy and.
And so our drug.
Much like phonetic flex is active across both my load and limb. So that's another reason to look at combinations with adequate but yes, we have tested in combination with a variety of other molecules.
Hypomethylating agents, we actually tried those and in patient samples to Hypomethylating agents such as the.
They have no effect as a single agent and so we couldn't get an answer as to whether or not we have.
A good combined component combinability data with the Hypomethylating agent in patient samples, but we have tested with a variety of other agents and it performs very well in combination with other types of agent.
There's anyone wants to add anything to that.
I would say that one of the advantages of having a drug that has those to know toxicities that you're able to combine with other agents readily than you might you add toxicities that combination.
You look at the treatment paradigm that involved in multiple myeloma, where we've gone from single agent activity. The now commented for up there.
I think that is the future AML, that's where we're headed going forward as combinations of phonetically Hypomethylating agents. These are low hanging fruit as obvious wants to go. After there are many other combinations are going to be very intriguing, including combination biologic.
Targeted agents into the future rather.
Hopefully that answers thank you.
Yes, thats it from me. Thank you that's helpful.
Thank you again, if you would like to ask a question. Please press Star then number one on your telephone keypad.
Your next question comes from the line of Matt You handler from Oppenheimer. Your line is now open.
Hey, guys. Thanks for squeezing on.
First quickly just wondering if you could tell us if any of the three patients enrolled in the 450 make cohort were non CLL patients.
So I appreciate that protocol does allow other NHL type.
First of all thanks for squeezing out there.
We know it's been busy day for you to what I can tell you is yes, we have had patients other than CLL, we do want to look at those patients, especially as we begin to get into our dose levels here.
So some CLL and not some non CLL, we have not disclosed what they are.
But we're thrilled to get some of those.
Other patient types and they're also.
If you remember at the lower two doses, we really wanted to get CLL patients. So we could see if theres a pharmacodynamic effect.
And pharmacologic effect, particularly look at the lymphocytosis as well as the collecting the cells in a peripheral blood and looking for the changes, but now that we're getting into some of the.
Higher doses, even if it's our third dose levels still work, we believe we're getting our doses we want to be one again looking at the patients that have these other diseases too.
Got it that's not alone.
And then maybe.
A broader question on positioning in CLL.
It kind of sounds like right now you're thinking of made US X has a past yet for like really all relapse and refractory patients. So I'm just curious if you're still planning on expansion cohorts targeting like maybe more targeted population like he freight one asset richters transformation or is this strategy.
Now really centered on kind of in all comers approach.
Well the the study is designed to allow us to look at a variety of different types of sub populations of CLL as well as the other.
Lymphomas.
Particularly patients who are relapsed or refractory or felt a variety of other.
Molecules, we think that there could be our sweet spot and which we could show activity were other drugs might not show activity and still be well tolerated of if we see particular.
Patient populations, such as you mentioned Richters for example, or a deal bcl or an aggressive lymphoma.
We see activity in those patients so we definitely.
I would want to go after a.
An expansion in such patients you look at.
Flicker lymphoma, there's really no good standard therapy, there and so that's a that's a low hanging population that we'd want to go after.
But ultimately if we're able to hit multiple kinase is much like one of our.
Your drugs.
But we also are very well tolerated we hope over time, we began to move up toward the first line more.
Toward the the earlier lines, because that way, you're still hitting BTK, the wild type and the mute forms of be dk you'd be able to hit multiple pathways.
And then still be well.
The tolerated so.
Yes, initially we're going after the relapsed refractory patients in particular for her and hopefully some of these other very difficult to treat populations and then over time moving up toward the toward the frontline would you like gentleman like to add anything.
Yes, Hi, Matt. Thank you for the question we.
The CLL landscape and we have discussed this together in the past is in constant flux.
Now more than ever in fact, the therapy are shifting around however, we are pretty confident that there is still plenty of clinical and commercial opportunity in CLL within CLL and without even getting into other b cell malignancy, it's already on now.
Yes.
We continue to receive very encouraging eat that and enthusiasm or some of the top CLL academic try it out there.
Which are all interested to join our study and in the end in terms of development path or where the agent would fit in the treatment paradigm. We will just follow the dot that we see.
Later this year. So we have seen then we'll see a pragmatic about how.
That said.
We are very confident in the value of this age even at this stage, where we are at right now because if we just take a step back here and look at it very impartially, we are developing an agent with a clean safety records to date.
We indications that have unmet clinical need and then importantly, with validated target and I cannot stress enough how important differentiating did last point in hematology today engaging multiple validated targets.
Thanks for the question.
Yes, just to emphasize that just a bit more we are bullish on this molecule.
Both in the B cell malignancies, and ml, we're thrilled with where we are in the clinical trials.
But what our focus now is we have we have cash in the bank we have our drug in the clinic, we need to just perform.
You know to execute well and not making unforced errors and hopefully then the responses will emerge as we go.
Into the higher dose looks.
Great makes fun congrats guys on the progress.
Thanks.
Thank you. Your next question comes from the line of Joseph 10, Janey from H.C. Wainwright. Your line is now open.
Hi, guys. This is this kind of fulfilling from Atlanta to show.
Two questions on my so the first one do you expect that to repeated doses to any be P.T.K. levels, we see simultaneously potentially less capacity.
And the cycle what is the consequence would you anticipate that we'd need to same patient potential does is a jeff that may be required in order.
What she the broker tiny seem to be sure. Thanks.
All right.
Oh, I'm trying to determine how best to answer that we.
Even at our second dose club.
Able to inhibit multiple companies. So we're able to inhibit BTK and we saw complete inhibition. So when we take the plasma from the.
And put it on the cells, we can completely inhibit fossil BTK. We also saw complete inhibition of fossil sick at the again that as widely.
And I believe also PDGF our alpha we also have the data on that we just havent spoken about three yet we've done studies, there and we're doing going.
To be doing them and coasts dose cohort three but yes, we believe that even at the doses were already at we're able to inhibit multiple kinase pathway. Both the driver kind of mix as well as many of these rescue pathways that we've described but again.
Hi, or we can go in dose levels and higher levels of exposure that we can get in safely we're going to be able to get more and more of these cases in these pathways and we'll have better activity in patients. That's why we want to continue to dose escalate as long as we're getting more and more drug yet, but doing so safely it has.
Many of those oncogenic pathways as we can that gives us greater applicability to a broader.
Group of cancers, as well as hopefully deeper activity in patients and also preventing rapid emergence of drug resistant.
Did that answer it offer I'm not sure if that actuary.
Entered the second part and.
The second part was like you know what if yeah, what do you need more like dosing adjustments.
Two you know chief.
Broke kinase inhibition.
You mean, a different dose level in a.
Oh patient versus an email.
Correct or we deemed the same patient during like the evolution of CUDC.
Interesting question typically you will try to take your drug to the highest.
Dose level that you can get into patients safely and you would.
Treat patients with that typically don't try to yields at a lower dose level and then increase later because that just allows for the selection of drug Brazil. So you want to hit a cancer patient or even in infectious disease as hard as you can initial try to kill the sales without giving at a a pathway to escape.
Hi.
Okay and my last question so for after three how many sites currently screenings and how many additional one about too. Thanks.
Let's see is that eight or nine I'm looking so it's eight.
Eight clinical sites that are currently screening.
And was that your question.
Yeah, Hi, you are you going to like more sites.
When do you.
Yes, yes more additional.
Yes, there are additional sites pending we're just making sure that we have everything in place.
But you know early on you don't have that many.
Patients to put on his study and so you want to make sure you don't have too many sites because then people get frustrated they're not getting patients on so now that we're getting and begin to getting into the higher dose levels, we hope to be able to put on more patients and get more sites.
Good question all right. Thank you so much thanks for taking my question.
Right.
Thank you and I'm currently showing no further questions I will now turn the call back over to Dr. rice for closing remarks.
Okay, well. Thank you for joining us this afternoon exceptionally proud of our organization employees the top notch investigators and importantly, the patients who participated in advancing our important work after year of.
Performance, we have two well tolerated hematology compounds in the clinic, we greatly appreciate the support of our new and pasture holders and research analysts and we look forward to keeping you apprised of our progress. Thank you have a wonderful leaving.
Thank you ladies and gentlemen that concludes today's conference you may all disconnect.
Have a wonderful day.
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