Good afternoon. My name is Victor, and I will be your conference operator today. I would like to welcome everyone to the Aptos Biosciences Conference Call for the Second Quarter ended June 30, 2020. At this time, all participants are in listen-only mode. After the speakers' remarks, there will be a question-and-answer session.

[Operator Instructions] As a reminder, this conference call may be recorded. I would now like to introduce Ms. Susan Pietropaolo. 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 30, 2020. I'm Susan Pietropaolo, a Communications Representative 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. Jotin Marango, Senior Vice President and Chief Business Officer; and Dr. Rafael Bejar, Senior Vice President, Chief Medical Officer.

Before we proceed, I would like to remind everyone that certain statements made during this call will include forward-looking statements within the meaning of U.S. and Canadian securities laws.

Forward-looking statements reflect Aptose's current expectations regarding future events that are not guarantees of performance, and it is possible that actual results and performance could differ materially from the stated expectations.

They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievement to differ materially from those expressed. To learn more about these risks and uncertainties please read the Risk Factors set forth in Aptose's most recent annual report on Form 10-K and SEC and SEDAR filings.

All forward-looking statements made during this call speak only as of the date they are 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. I'd like to welcome everyone to our call for the second quarter ended June 30, 2020. Separately, I do hope that all of you and your loved ones are safe from COVID. And I hope that all of you on the East Coast in particular are safely weathering the tropical storm, so please do take care. And now, back to Aptose.

As you're aware, Aptose is developing two distinctive clinical assets. First, we have CG-806, which has become a high-profile, first-in-class FLT3 and the BTK kinase inhibitor, and second APTO-253, the only non-clinical stage agent that directly targets the MYC oncogene and suppresses its expression.

Before I bring you up to date on both clinical assets, let me note that we remember firmly bullish on CG-806, and we understand the primary importance of successfully executing our clinical plan for 806.

And indeed, we are executing on the original plan to first develop 806 for patients with chronic lymphocytic leukemia or CLL and other B-cell malignancies, to observe inhibition of BTK and lymphocytosis in CLL patients, and to be on track to reach higher dose levels and deliver clinical efficacy by year-end.

In parallel, we sought to identify an appropriate starting dose of 806 that may be active in patients with acute myeloid leukemias, or AML, to obtain a new IND for the treatment of AML patients, and to demonstrate clinical efficacy in AML patients by year-end. Plus we wanted to build a strong balance sheet to support this expanding development plan.

We now have built the foundation for success going forward, and we believe we can accelerate our pace of clinical development as we enter the second half of 2020 with doses of 806 that should deliver activity in both CLL and AML patients. So today, will I provide a corporate update, and then our CFO, Mr.

Greg Chow, 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 of $5.25 per share, raising more than $55 million for the Company. Mr.

Chow will speak to the particulars of this recent offering, but I just wanted to express 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 the right resources to press forward with the clinical development of CG-806 and APTO-253 appropriately.

This includes the ability to perform multiple dose escalating clinical trials, to initiate multiple expansion cohorts, and to boost the global manufacturer of drug substance and 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 CG-806 and first discuss our ongoing Phase 1 a/b clinical trial of 806 in patients with relapsed or refractory CLL and other B-cell malignancies.

Since our last call, we presented 806 data at the European Hematology Association, or EHA, meeting, demonstrating that 806 was well tolerated in patients treated with 150 milligrams, 300 milligrams, and 450 milligrams BID over multiple cycles with no drug-related dose limiting toxicities or serious adverse events.

CG-806 treatment led to lymphocytosis in two classic CLL patients, and delivered complete inhibition of phospho BTK and multiple oncogenic survival pathways in all patients receiving the 300-milligram dose or higher, thereby demonstrating molecular and physiologic activity of 806.

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 possible BTK.

Just yesterday, we reviewed the 600-milligram data with our cohort safety review committee, and I'm happy to report that the 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 lower and intermediate dose levels with a minimum number of patients so that we now may focus efforts on the higher dose levels that are more likely to deliver responses.

As we move into our higher dose levels in CLL patients and begin to inhibit additional kinase-driven oncogenic pathways, we are hopeful that 806 will begin to deliver formal responses, as patients will remain on higher doses of drug for longer periods of time.

Depending on the clinical activity in specific subgroups in this dose escalation phase, we may enroll patients across expansion studies that may include subpopulations with different genotypic or phenotypic properties. As of today, we 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 detailed malignancy trial and the clinical sites enrolling patients, please visit clinicaltrials.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 event, 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 CG-806 to patients with relapsed or refractory AML. Certainly, one of the most significant events of the second quarter was the FDA's review and allowance of our IND for the initiation of Phase 1 a/b clinical study of 806 in patients with AML, expanding the development of 806 beyond B-cell malignancies.

AML is a cancer of 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 AML, the majority of patients will relapse or remain refractory to current therapies, and there persists a tremendous unmet need for new therapies.

For example, as we look to gilteritinib, a FLT3 inhibitor recently approved in relapsed or refractory AML, the majority of patients who initially respond to treatment will relapse, and ultimately, their two-year survival is no different than untreated patients.

806 is the only BTK inhibitor that also possesses strong FLT3 inhibitory activity, giving a broad therapeutic potential across the hematology spectrum, including both lymphoid and myeloid malignancies. Because of Dr.

Brian Druker's strong preclinical evidence of 806's activity against AML, including demonstration of mutation agnostic and genotype agnostic activity, particularly compared with other FLT3 inhibitors, as well as its ability to safely cure AML in mice, we believe 806 offers hope to the fragile and difficult to treat AML patient population.

Our strategy from the outset was to begin testing 806 in patients with B-cell cancers including CLL, and to dose escalate and seek responses in the CLL patients. Separately, we sought to identify a starting dose of 806 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 BID. Allowing us to start at the 450-milligram dose was a major success for Aptose and for 806.

At this dose in humans, we already have observed steady state plasma levels in the same range as the exposure levels observed in our preclinical work that led to cures of AML in mice and without any observed 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 trials design is the 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 IND solely focused initially on treating AML patients.

We believe that there will be additional opportunities for 806 in patients with model dysplastic syndromes, or MDS, and in combination with venetoclax. We plan initially to treat only patients with AML in this study, and then expand in MDS and into combination with venetoclax as appropriate.

CG-806 is too important of a drug, and we will continue to take this thoughtful and deliberate approach in expanding its value footprint rationally and steadily toward the long term.

So, where do we stand in getting this recently allowed AML clinical trial up and running? Currently, we are advancing the approved AML protocol through institutional review board or IRBs at key clinical sites and scheduling our site initiation visits.

So, while we are working to get our larger AML 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're taking actions to expedite the tedious parts of the trial startup process, and we continue to target the third quarter for enrolling our first AML patient.

We will want to enroll patients having AML cells with the FLT3 ITD mutation, often referred to as FLT3 positive AML, as well as those patients with wild type FLT3, with the hope of demonstrating early clinical responses with the 450-milligram or 600-milligram dose levels. Just a quick aside.

If you have not seen the KOL presentation from February of this year that featured Dr. Aaron Goldberg and Dr. Eytan Stein from the Memorial Sloan Kettering Cancer Center, as well as Dr. Brian Druker of the Oregon Health and Science University, and our Chief Medical Officer, Dr.

Rafael Bejar, it provides a great perspective on the treatment of AML in the age of targeted therapies. It's available on our website in the presentation section. To wrap up on 806, we continue to diligently execute on the plan 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 AML. And we have the resources we need. Finally, we hope to see you in December, as we provide a more robust and detailed update on 806 at a corporate event during ASH.

Now, onto APTO-253, our second clinical candidate and a first-in-class MYC inhibitor, currently in a Phase 1B trial for AML and MDS. As we've mentioned before, the MYC oncogene is a major driver of cancer cell proliferation. In fact, its expression is estimated to be elevated in up to 70% of human cancers.

As a MYC inhibitor, 253 may have a broader impact cancer application among a host of hematologic malignancies and solid tumor indications. But as you know, our initial development focus is on AML and MDS. MYC inhibition has been an elusive clinical target in pharmaceutical development.

So, we've been gratified to observe evidence of MYC inhibition in this trial at all dose levels evaluated to date. Just as a reminder, per our Phase 1 clinical protocol, 253 is being administered once weekly over a 28-day cycle at ascending doses in patients with relapsed or refractory AML 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 in AML and MDS. Since our last call we have completed the 28-day dosing in three patients on the 100-milligram per meter squared dose, which is dose level four.

On Friday of last week, we held our cohort safe to review committee that allowed us to proceed to dose level five. Because 243 continues to be well tolerated at these higher dose levels, and still with no mild suppression, we have admitted 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 milligrams per meter squared, which is a 50% increase over that dose level four, 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 MYC inhibition and clinical responses.

I will now turn the call over to our Executive Vice President and Chief Financial Officer, Mr. Greg Chow, 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 20, we closed on a previously announced underwritten public offering of 10.5 million common shares at the public offering price of $5.25 per share, raising $55.125 million to date, and netting approximately $51.5 million.

The underwriters have been granted a 30-day option to purchase up to an additional $1.575 million common shares in the offering under the same terms. As Bill mentioned, the offering gives us a healthy balance sheet and cash runway into 2023. Let's now turn to the quarterly results.

We ended the quarter with approximately $83 million in cash and cash equivalents, and investments come to approximately $90 million at March 31 of this year. During the quarter, we utilized approximately $7.2 million of cash in operating activities, which were attributable to activities surrounding 253 and 806, as well as G&A purposes.

Based on current operations, cash on hand at June 30 plus the net proceeds from the recent offering, this provides the Company with sufficient resources to fund all planned company operations, including research and development into Q1 of 2023. Moving onto the income statement, we have no revenues for the quarter.

Research and development expenses were $6.9 million for the quarter and attributable to 806 and 253 clinical trial costs, manufacturing of drug product for our clinical trials, including continuing development on improving GMP formulations for both 806 and 253, and personal costs for headcount supporting clinical trials and manufacturing activities and research studies.

G&A expenses for the quarter were $9 million, of which $6.8 million is related to one-time stock-based compensation. And finally, our net loss for the quarter was $13.8 million, or $0.21 per share, or excluding the one-time items, $8.1 million, or $0.11 per share. More detailed information can be found in our filings on EDGAR in SEDAR.

With that, I will turn it back to Dr. Rice.

Bill?.

Thank you, Greg. I'll remind everyone that on the line, we also have with us Dr. Jotin Marango, our Chief Business Officer; and Dr. Rafael Bejar, Chief Medical Officer. As we open the call for questions, please feel free to post questions to any of us. Operator, if you could, please introduce the first question..

[Operator Instructions] Our first question will come from line of Tyler van Buren from Piper Sandler. You may begin..

Hey, guys. Good afternoon, and congratulations on all the progress. I had a couple of questions with respect to 806. So, I guess you mentioned that you completed dose level four and that you had the one CLL patient who also achieve lymphocytosis.

Is that the same patient that you guys referred to at EHA? 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, the fifth dose level, is there -- I know that you guys are screening patients to enroll.

Is there enough time to enroll those patients and potentially allow them to generate responses prior to the ASH data update?.

Hey, Tom. Thanks for coming on. So, thanks for the compliments on the progress. For the first question, we have mentioned an additional CLL patient that came on the 600-milligram dose. That's dose level four. That was a separate patient that also underwent lymphocytosis, so it was immediate lymphocytosis and inhibition, also BTK.

So, we're going to speak in terms of trends today, rather than particular details on patients. But thus far we've had patients at 300 and at 600 milligram dose levels. These are the classic CLL patients that enter the trial with some lymphocytosis.

Those are the ones that if you have an active BTK inhibitor that you would expect to see Ibrutinib lymphocytosis induced and we have. So in all three classic CLL patients that have come into our study, we've seen drug-related inhibition of BTK and lymphocytosis.

Now with regards to dose Level 5, the 750 milligrams we planned 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? It usually takes at least two months if you're fortunate to see a classic or 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 informed the site that we do want to, in particular, have CLL patients. We want to get them on 750 as quickly as we can and we hope that we will see responses. So we are very hopeful that we can get them on there. We can get them enrolled, get them dosing, and then we'll scan them after effectively two months.

[Technical Difficulty] Did that answer your question?.

Yes, that's very helpful color, especially because your quote noted the goal of delivering responses specifically in CLL patients. So appreciate you taking the questions. Thank you..

Our next question will come from the line of Gregory Renza from RBC. You may begin..

How are you doing team? Thank you for taking my question and congrats on the progress here. I really appreciate it. Bill, maybe just building off of Tyler's question and just curious if you could perhaps tee up some of those expectations, certainly in focus for year-end and the event that you will do to potentially having in December.

I'm just curious if you could help frame those expectations a little bit unresponsive on patient counts, perhaps, but then also how your disclosure plans could potentially evolve.

Certainly keeping to kind of the BI annual disclosures on data, but just curious if there are any prospects for providing any advocacy updates prior to on that December plan. Thank you..

Hey, Greg, thanks for coming on. A couple of good questions. So let's talk about the expectations for later this year, particularly of 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 active. We're seeing, as I mentioned mechanistic and physiologic activities.

Even at 600 milligrams, we started seeing some differences that make us believe that we should start seeing something as we get into these higher dose levels, particularly at the 750 milligram level. But in reality, we expect it three patients as we move into dose Level 5 to 750 milligrams.

So how are we going to get more patients on it? Well, we have a an amendment from the FDA that's allowing us now to begin backfilling. So I think it's our chief medical officer earlier today was talking about it. Backfilling is almost like a mini expansion while you're doing the dose escalation. So Yes, we'll do patients on the 750.

We hope the majority of those are CLL patients and then we hope then by the time that we reach ASH later in this year, that we'll be able to deliver responses. In parallel, we'll also be trying to backfill patients at the 600 milligram level. And then when 750 is shown to be safe, if it is, then we'll move those patients at 600 up to 750.

I should also say we have a couple of patients in at 450 now. They're going to be moved up to 600. So we're increasing the ability or increasing the likelihood of having potentially demonstrating responses at ASH later this year. So the second part of that and I'll ask Dr. Bejar, if you want to add to that in just a moment.

But the second part of your question was disclosures. Is there anything possibly between now and ASH between these mid years? What I would say is, I wouldn't expect for us to be disclosing anything between now and then.

The reason is, we've just gotten into the 750 milligram dose, the higher dose levels, we need time to get the patients on and give them time to respond and then hopefully we'll see something by December in ASH. But separately, we're also going to try to get the AML patients up and on the trial.

As I said, we still continue to target getting the first patient enrolled in the third quarter of this year.

If we can do that, and we get a couple of patients on the 450 milligram dose level, get them through by the time we get to ASH and maybe have some patients on the 600-milligram dose level, then that gives us the opportunity to have responses in AML during this period.

Again, I'll remind you AML is an acute leukemia and typically you're able 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 up to a year, whereas in AML, you would expect to start seeing something reduction in blast the first month, and then possibly a response of a second or third month. I'm going to ask Dr.

Bejar if he would like to add anything to that in terms of what to expect in patients..

I think that was a great answer, but I think that he has said it perfectly that just putting on the patients now at 750 having that ability to backfill will give us more opportunity to see responses at these levels. We're going to definitely push to do that. I agree with your statement about AML.

That's because that has a very different response kinetics, and we should know sooner than we might further be something that needs to take much longer to demonstrate responses..

The irony is there even though we started the B cell malignancy trial earlier, it takes those patients longer to show responses. It may be that even AML 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, Greg, I hope that answers your questions..

It sure has, Bill. Thank you. Actually it also answered my follow up question which was around the backfilling.

Just to confirm, so would we presumably, given that the fifth dose cohort has recently cleared, is it safe for us to anticipate that there could be additional 600 mig patients that have since added prior to that clearance?.

Not that are added prior to it because we had to delete -- sorry, we have a lot of background. So in reality, the 600 milligrams, you have to get three patients and show the FDA -- show excuse me, not the FDA, the CSRC that you have three patients that have completed safely that cohort.

You can then move up to 750, only then can you start backfilling on the 600. Right now we're going to try to both get patients on the 750 immediately and the 600 as quickly as we can..

Thanks for taking the question..

Our next question will come from the line of John Newman from Canaccord. You may begin..

Hi, guys. Thank you for taking my questions and good progress here on both of the agents and clinical trials. So it's a question for Bill. Bill, you mentioned that seems like there was an additional patient at the 600 milligram dose where you saw some signs of lymphocytosis, 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 wondering if you can tell us anything maybe broadly speaking if there were other markers that you noticed that seemed to confirm that there may be some activity there..

Hey, John, thanks for coming on and asking the question. One thing I can confirm is that the lymphocytosis in the inhibition of BTK in the patients, it is due to the drug, because we actually had an instance where we're able to dose reduce and then take it right back up.

When we dose reduced, we actually saw the lymphocytosis decrease, so it is clearly a drug-related event. As for the other markers, I'm not able to address that perhaps Dr. Bejar can provide a little bit more information on that. But again, I don't want to get into too many specifics of any patient until we get later in the year. Dr.

Bejar, was there anything else that you wanted to add to that?.

Yes, I would just say 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'd recommend these but we don't know the answer to your question..

No problem. Just had one quick follow up question, if I may. That is just in terms of the type of AML patients that you're looking to enroll. I know that when you're dealing with the AML population, it's always a challenge, almost regardless of the agent, because you're dealing with patients that are very frail and fragile.

Are there things that you're able to do in terms of your selection criteria, just to give yourself sort of a reasonable chance to be able to answer the question if your drug is active rather than fighting a very frail state of 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 the trial at a dose level that we think should be active. So that's the first thing that we're doing to give the drug the best opportunity to show responses.

Secondly, one of the most highlighting feature of this drug in terms of AML is the fact that we believe that can be developed for FLT3 positive as well as FLT3 ball type patients. So again, about a third of the patients have the mutated FLT3, two thirds of the patients do not.

They have wild type FLT3 so we want to be able to treat those patients with the wild type FLT3. However, it is generally accepted that the patients with the ITD mutation of FLT3 positive patients would tend to be more sensitive to a FLT3 inhibitor; that's been shown with gilteritinib because aren't [ph] some of the other molecules.

So we absolutely want to get FLT3 positive patients on this trial as soon as possible. They are likely the, I'll use the phrase low hanging fruit that would most likely get us responses earlier. Again, starting at a dose that we think is going to be pharmacologically active in these patients, it gives us a great opportunity to show responses.

Again, that's where we are and we hope that we're able to get to both FLT3 positive as well as the wild type on but again, most likely showing the FLT3 positive patients will 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.

But thanks, john, for your questions..

Sure. Thank you, guys..

Our next question comes from the line of Matt Biegler from Oppenheimer. You may begin..

Hey, guys, thanks for taking my questions. Great to hear from you. Can you shed any light Bill, on how the exposures are tracking in the 600 meg cohort? Obviously, these were too premature for the EHA data set.

But maybe high level, can you comment on whether we're still seeing a linear increase that we saw between 150 and 450 doses?.

Hi, Matt. Originally, we have one patient on the 150 dose level, one patient on the 300, and then we had three patients on 450, and then four patients on the 600. So when you only have one patient per dose level, 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 starts coming up over 24 hours then begins to plateau. It looks like that second patient 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 two and then when you go to the fourth dose level 600, what you can see is another increase. So what we are seeing is as we increase the dose level, the initial uptake is more rapid higher levels over that first 24 hours.

So we're able to see more of a dose-related exposure level during that first 24 hours now, and then they begin to plateau off as we go forward.

But it's not necessarily linear yet because we only had one patient at the two lower dose levels, but we're definitely getting meaningful exposure there at the 600 milligrams and we're starting to see some effects that are giving us confidence that we're really having a physiologic effect.

It looks like it's more so than at the 450, which again, is gratifying and so we expect even more at the 750. So I would not call it linear. But we are seeing now more of dose-related effects as we get more patients on, but it's also an oral drug, and you're giving it to patients of different sizes.

So there will always be differences in the exposure from patient to patient, even at the same dose level..

Right. I understand. Okay, that's good to hear. I just want to be completely clear on cohort four in terms of the patients and what we had and so we know from that one was classical CLL, one was Richter's transformed.

Can you just confirm what type of the third patient has the one [Technical Difficulty] the EHA cut-off? Was that the patient with lymphocytosis you were referring earlier?.

So one patient that was on the 600 milligrams, that one clearly had the lymphocytosis and the inhibition of BTK we showed that. And then we have another patient that's gone on to 600 milligrams. That's a classic CLL patient and they've also demonstrated the lymphocytosis. That's the patient who just completed the 28-day dosing recently.

So it's clear we're able to induce the lymphocytosis, as well as the inhibition of BTK as we get in these higher doses, to inhibit the other pathways that kind of strengthen pathways. And now as we get hopefully, these patients stay on a little bit longer as we go forward and both the 600 and the 750 and it gives us opportunity to then see responses.

So perhaps Dr. Bejar might have something to add to that about the two CLL patients at 600 without details.

Right. So we had one CLL patient at the beginning of the cohort, and then we had the most recent patient complete the cohort so two perfect CLL patients with pre-existing lymphocytosis were in this cohort..

Got it. Congrats on the progress, guys, thanks for taking my questions..

[Operator Instructions] Our next question will come from Naureen Quibria from Maxim, you may begin..

Hi, thanks for taking my question. I guess the first one for me would be on the 253 program. It's been running under the radar.

Will you have any clinical updates shared at this year's ASH and what kind of data would we be likely to see if so?.

We do plan on presenting data at ASH, but you're right, most people it's flying under the radar screen so we're not getting any questions about it.

But as we mentioned, COVID was somewhat of a setback because that's an IV administered drug but once the clinical sides became accustomed to dealing with it, they were able to then start getting more patients on.

We completed Cohort 4 100 mix per meter squared, we're clearly seeing an increase in the PK exposure there now, getting into the range that we had hoped we will get into; that's both the parent drug as well as the [indiscernible].

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 ASH.

And then, we're also now recruiting patients for Cohort 5 that seems to be going well, we're getting -- we're actually getting quite a favorable response in terms of patients coming on 253 now, and we should be able to present data from Cohort 5 at ASH.

Again, we'll be looking at the various biomarkers, the MYC expression and the PBMCs at different times throughout the different 28-day periods, 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 we're able to get PK coverage over a greater number of days.

Again, it's once weekly dosing; so if we can get start getting coverage over 3, 5, 7 days, and maintain suppression of Nic [ph], that gives us the opportunity then to start seeing responses.

So it helps to be able to show that as we're beginning to increase the doses, we're extending the time where you can measure adequate levels of drug in the plasma and hope to be able to see responses in the future..

Great, thanks. And then in terms of the CG-806 study in AML that you're about to start.

You mentioned that you're going to have both FLT3 wild-type and mutated patients but if I recall from your KOL talk back in February, there was mentioned that 806 may also be active in the context of RAF mutations that may confer proliferative capacity in AML patients.

And that these RAF mutations may make patients resistant to the FLT3 inhibitor, gilteritinib.

So I was just wondering, are you going to actually test patients that are selected for this study, whether they also have RAF mutations? And will that information ultimately be shared with the public when the data is released?.

So we absolutely want to get patients on there.

So, I can't promise they'll be on the first or second cohort, but we absolutely want to get patients on there that have failed gilteritinib, that have these RAS mutations, that are -- it's not just RAS, so there are a number of different mutations that give resistance to gilteritinib; so you've got the gatekeeper mutation in FLT3, you got the RAS mutation in some of the P53s.

So yes, we do want to get those patients on, we want to make sure that we get them genotyped, and that we understand the sensitivity there; and -- especially in the context of the particular mutations, and we will share that with the public.

That's one of the exciting things about this drug, we think it has the potential to treat those patients whereas others don't.

But that's also one of the reasons 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 the patients and look at the clones.

And that also have patients who may have failed gilteritinib; so all of those are in the works. So, good question. Thank you..

Got it. And just one last for me. So, on the same drug, but CG-806 as a BTK player, shall we say. AstraZeneca and some of the larger companies are testing their BTKs in COVID 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 COVID? And how they may have performed on CG-806? I know it's not exactly a direct correlation, but I was curious if you have any anecdotal stories or evidence..

So we don't -- we are not aware of any of the patients on our study that acquired COVID and of any responses. But if you're asking us is there potential for a drug like this midst COVID; there is a potential because if you're talking about the NLRP3 inflammasome complex, and how it utilizes the cleaved caspase-1, releases R1 data, RO18 [ph].

Yes, we can measure those certain activities, we know how well our molecule would act there; so it is possible that the drug could be used in either this or inflammatory processes in the future. But at this point in time, we have to remain focused on the AML 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, we'll do those studies on the side, and we'll collaborate with groups; but we have to remain focused at this time..

Sure, of course. Thank you. That's it for me..

Okay. So let me ask if Dr. Marango wanted to add anything to that. I know he is on the line..

No. No, thank you, Bill. Bill captured it quite fully. Thank you..

Thank you. And we have a follow-up question from John Newman from Canaccord. You may begin..

Thanks for taking the follow-up.

So Bill, I'm just curious, with patients that have shown evidence of lymphocytosis on CG-806; 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 round two here. So in terms of those patients, those are the classic CLL patients. I can tell you, they are so heavily pre-treated with all different types of drugs; I'm going to ask Dr. Bejar if he can give a bit of context as to the background in terms of what these patients may have seen.

But again, they're all different. So a little bit of context..

Sure. I think you're exactly right. Though these patients are very heavily pre-treated, many of them having received prior chemotherapy as well as other targeted agents and immunotherapy. The mass majority of the patients have received a prior BTK inhibitor for some duration and either been refractory or already have that drug.

But as well as many other therapies, so it's not just [indiscernible]..

Thank you..

Yes. I think the remarkable part is, these patients are so relapsed refractory, they failed so many different lines of therapy. It means the cells -- they do depend upon BTK for activity, but they also depend on all these other kinase-driven pathways.

So that's why it's so important for these deep relapsed refractory patients to receive a drug that can inhibit multiple pathways because we don't believe that merely inhibiting BTK is going to be sufficient in 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 like this. Hope that answers..

Great. Thank you..

Thank you, John..

Thank you. And I'm currently showing no further questions. I will now turn the call back over to Dr. Rice for closing remarks..

Well, I want to thank everyone for joining us today. It's been an exciting time for us with our two key assets in the clinic, 806 and 253, progressing now into the higher dose levels, and we remain committed to delivering for our patients and our shareholders.

I want to especially thank our clinical development team, our investigators, our clinical operations teams, the patients for helping us in this mission, and we appreciate your support and we look forward to keeping you 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 all disconnect and have a wonderful day..