Susan Pietropaolo - SMP Communications William Rice - Chairman, President, and CEO Gregory Chow - SVP and CFO.

John Newman - Canaccord Genuity Joseph Pantginis - H.C. Wainwright Jotin Marango - ROTH Capital Partners.

Good afternoon. My name is Amanda and I will be your conference operator today. I would like to welcome everyone to the Aptose Biosciences Conference Call for the First Quarter Ended March 31, 2018. At this time all participants are in a listen-only mode. After the speakers remarks there will a question-and-answer session. [Operator Instructions].

Thank you. And as a reminder, this conference maybe recorded. I would now like to introduce Ms. Susan Pietropaolo. Please go ahead..

Thank you, Amanda. Good afternoon and welcome to the Aptose Biosciences conference call to discuss financial and operational results for the first quarter ended March 31, 2018. I am Susan Pietropaolo, Communications Representative for Aptose Biosciences. Joining me on the call today are Dr. William Rice, Chairman, President and CEO and Mr.

Gregory Chow, Senior Vice President and Chief Financial Officer. Before we proceed I would like to remind everyone that certain statements made during this call will include forward-looking statements within the meaning of the U.S. and Canadian Securities Laws.

Forward-looking statements reflect Aptose's current expectations regarding future events, but are not guarantees of performance and it is possible that actual results and performance could differ materially from these 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 20-F 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. Dr. Rice..

Thank you Susan. I would like to welcome everyone to our call for the quarter ended March 31, 2018. Although our last update call was just a month and a half ago we have much to report.

This includes the exercise of our option to fully capture the license for CG-806, news from the American Association for Cancer Research or AACR Annual Meeting, various initiatives, upcoming milestones, recent publications, anticipated timelines for initiation of clinical trials and R&D submissions.

As you know I'm candid about my expectations but will also remind you that unexpected events either positive or negative can affect our projections. Following these updates our CFO, Mr. Greg Chow will review our quarterly financials and then we will open the call for your questions.

So let's start with our most recent announcement regarding the early exercise of our option from Korea based CrystalGenomics to license CG-806 or 806 as I’ll refer to it. Our pan-FLT3 and BTK kinase inhibitor being developed as an oral agent for the treatment of patients with AML and certain B-cell malignancies.

As mentioned previously we saw the potential of 806 even as a very early stage molecule and we entered into an option agreement that allowed us to vet the molecule before committing ourselves to the obligations of a full license agreement.

We announced the initial option agreement with CrystalGenomics in June of 2016 and the molecule was so early that there was no synthetic route for scale up manufacturing, there were no formal talks data, and the IP estate was viewed as in progress but not definitive. Since that time we've solved the chemical [sense to this][ph] challenges.

We've invested in IP endeavors and had the patent allowed in the U.S. and received notices of allowances in the EU, Japan, and Australia. We unveiled its superior capacity to kill AML and B-cell cancer cells relative to competitor drugs.

We gained a better understanding of its mechanistic activities and we gained confidence in its anti-tumor efficacy in the absence of toxicity. Because of these advancements and an appreciation for the qualities of 806 we made the decision to exercise the option and obtain a full license to 806 and its attendant IP estate.

And that was executed on May 7th or Monday of this week. With the exercising option, Aptose now owns global rights to develop and commercialize 806 for all indications outside of Korea and China, the licensed territory. The exercise triggered a payment of $2 million to CrystalGenomics and we were honored to make that payment.

CrystalGenomics will also receive regulatory and commercial based milestone payments and a royalty on sales in the licensed territory. Now let's discuss our data for 806 disclosed at 2018 AACR Meeting.

At AACR which was held mid April in Chicago Aptose with our research partners had three poster presentations; two on CG-806 and one on APTO-253 but I will focus now on data regarding 806 and its application to AML and then separately for B-cell malignancies.

As a reminder AML is a devastating and heterogeneous cancer of the blood and bone marrow and approximately a third of patients have a mutation referred to as ITD in the FLT3 receptor tyrosine kinase and the FLT3 ITD mutation is the key driver of the disease in these patients.

With these scientific discoveries came the development of the first generation FLT3 inhibitors. Just last year midostaurin became first approved FLT3 inhibitor.

Midostaurin and other kinase inhibitors in development for AML can provide benefit but the benefit can be transient as patients can develop drug resistance because of additional non-ITD mutations and by actions of various kinase driven pathways that can rescue the cells. Thus a great unmedical need still remains in AML.

Our compound 806 is the only known pan-FLT3 inhibitor for AML, meaning it retains picomolar to low nanomolar potency against all forms of FLT3 including the clinically relevant mutant forms of FLT3 that arise in AML patients that are associated with poor prognosis and which rendered the disease resistant to other FLT3 inhibitors.

Moreover even if all forms of FLT3 inhibitors that is insufficient to control AML because other kinase driven pathways emerge to rescue the cells. In AML and other cancers derived from the bone marrow compartment those rescue pathways include FLT3, BTK, Aurora kinase, AKT, AURK, CSF-1R also known as FMS, and PDGFR alpha.

You'll recall from my product presentations that 806 has been deemed a multi cluster kinase inhibitor that potently inhibit certain clusters or related kinases but not other families of kinases.

The clusters inhibited by 806 include one, the BTK cluster which includes BTK, BLK, and ITK; two, the FLT3 cluster which includes FLT3, CSF1R, and PDGFR alpha; three, the track kinase cluster; four, the Aurora kinase cluster, and inhibition of these pathways results in downstream inhibition of the AKT and ERK pathways that are operative in AML and B-cell cancers.

But 806 does not inhibit the TEC, the T.E.C., EGFR, [ERK B1202] [ph] kinase that are responsible for safety and tolerability concerns with certain other kinase inhibitors.

As a potent and superior inhibitor of FLT3 ITD, 806 may become an effective therapy and high risk subset of AML patients and in older AML patients that cannot tolerate any of the cyto toxic agents. There's a great deal of excitement about the development of 806 and that was apparent at our presentations at AACR.

Our first poster at AACR demonstrated the broad activity of 806 against primary bone marrow specimens from patients with various hematologic malignancies. This research was conducted by Brian Druker, Dr. Brian Druker's entire research team including Dr. Steve Kurtz, and Dr. Jeffrey Tyner.

From the nice Cancer Institute at the Oregon Health and Science University or OHSU as part of the beat AML initiative. As you're aware we have performed multiple animal studies that demonstrate a strong anti-cancer efficacy of 806.

However, such xenograph studies use AML cells grown in the laboratory and are not fully representative of malignant cells in patients. So before we take 806 to the clinic we wanted to ask if cancer cells taken directly from the bone marrow of AML patients are sensitive to 806 relative to other FLT3 inhibitors. Dr.

Druker's team at OHSU performed these studies with freshly collected bone marrow samples from 188 AML patients and demonstrated that 806 elicits greater potency against a broader set of AML samples relative to other FLT3 inhibitors including midostaurin, gilteritinib, quizartinib, sorafenib, crenolanib, and dovitinib.

This was especially true in FLT3-ITD positive and FLT3 tyrosine kinase domain mutated cases. Although enhanced activity was also observed in FLT3 wild type samples. Indeed the superior range and potency of 806 are due to its ability to suppress all forms of FLT3 and the multiple rescue pathways in AML as I described earlier.

These data which were provided in scatter plots and heat maps reveal the striking activities of 806 and justified advancement of the molecule to clinical trials for AML patients.

Separate from the AML and FLT3 story, over expression of the BTK enzyme can drive oncogenic signaling, a certain B-cell malignancy such as chronic lymphocytic leukemia or CLL, mantle cell lymphoma or MCL, diffused large B-cell lymphoma or DLBCL, and others.

Therapy of these patients with covalent irreversible BTK inhibitors such as ibrutinib that target the active site existing residue of BTK can be beneficial in many patients.

However treatment with ibrutinib and other BTK inhibitors can be limited by acquired resistance as well as by refractory disease and intolerance challenges which can lead to discontinuation of therapy.

As was done with AML we ask if freshly isolated CLL cells from the bone marrow of CLL patients were sensitive to 806 and we compared head to head against ibrutinib. To remind you ibrutinib is a covalent of BTK inhibitor, FDA approved for CLL and other B-cell malignancies.

The current standard of care for those conditions and a $5 billion to $8 billion year drug.

And our study presented at AACR, 806 demonstrated direct cell killing and significantly greater potency and range of activity on patient derived CLL samples than ibrutinib and 806 retained potency against the vast majority of CLL samples that were unaffected by ibrutinib.

Furthermore in-vitro studies have shown that 806 kills B-cell malignancy cell lines on average approximately 1000 times more potently than ibrutinib. Again the superior range of potency of 806 are due to the ability to suppress the B-cell signaling and multiple kinase driven rescue pathways that are operative in CLL cells.

These findings also demonstrate another major distinction between 806 and other BTK inhibitors like ibrutinib. Ibrutinib is reported to act primarily through an indirect mechanism that involves inhibition of BTK and bone marrow stromal cells and those cells then promote the migration of CLL cells and the loss of CLL cell viability.

806 also inhibits BTK that will be operative in the stromal cells to indirectly affect CLL cells. But in contrast to ibrutinib 806 also directly kills the CLL cells due to its ability to suppress multiple signaling pathways. Thus 806 must be viewed as more than just a BTK inhibitor for the treatment of CLL and other B-cell malignancies.

To summarize the ex-vivo studies from the OHSU team against patient derived cells, 806 appears superior to other FLT3 and BTK inhibitors and the wealth of data supporting its development in AML and B-cell malignancies continues to grow.

Now let's discuss our second poster in which the Aptose research team demonstrated that FLT3-ITD positive AML cells in those cells 806 induced apoptosis through inhibition of FLT3 signaling and 806 was superior to quizartinib in this pre-clinical study.

Although FLT3-ITD is found in approximately one third of AML patients, most AML patients express wall type FLT3 and a lesser fraction of AML patients have FLT3 housing mutations in the tyrosine kinase domain or the gatekeeper domain.

806 was found to be superior to quizartinib, gilteritinib and crenolanib FLT3 inhibitors against FLT3 wall type AML cells and in cells with non-ITD mutations.

In B-cell malignancies 806 decreased BTK phosphorylation in all malignant B-cell lines tested and inhibited -- the B-cell lines that were tested and inhibited cell proliferation and colony formation 50 to 6000 times more potently than ibrutinib an effect which could not be explained by the exclusive innovation of BTK signaling.

As I indicated just a moment ago it has been emphasized that ibrutinib potently inhibits BTK in the CLL cells. But typically it is not considered to promote direct apoptotic death to those cells. Rather ibrutinib is reported to primarily act on the BTK in the nurse like stromal cells of the bone marrow and lead to indirect killing of the CLL cells.

Like ibrutinib 806 does inhibit BTK that can lead to indirect killing of CLL cells but the 806 also targets additional pathways and lead to direct killing of the CLL cells thereby differentiating 806 from ibrutinib and other BTK inhibitors.

So to wrap up our AACR data with 806, 806 demonstrated the ability to target all wall type of mutant forms of FLT3 and BTK and to inhibit multiple signaling pathways producing potent and direct killing of diverse types of key malignancies driven by different genomic aberrations. And we continue to advance the scientific understanding of 806.

As of pan-FLT3/pan-BTK multi cluster kinase inhibitor that is well tolerated in animal models 806 has demonstrated the ability to kill a broad range of cells through inhibition of multiple oncogenic pathways with potentially greater potency relative to other inhibitors and the ability to overcome resistance to other drugs.

I would also like to quickly mention here that we just recently were notified that an abstract on 806 had been accepted for presentation at European Hematology Association or EHA meeting in Stockholm in June and we look forward to sharing more data at that time.

We are indeed eager to pursue clinical development of 806 and all of these studies have helped us prepare for that. So where are we in the development of CG-806.

First, we crafted a synthetic chemistry pathway that allows us to readily manufacture multi kilogram quantities of 806 with high purity, we selected the formulation for GLP toxicology studies and early human studies to be a markerized [ph] material co-milled with a wedding agent.

We have completed multiple animal efficacy studies, completed dose range finding studies in rodents and dogs, prepared multiple kilos of GLP drugs substance and drug product for IND enabling GLP toxicology studies in rodents and dogs. And we plan to begin GLP toxicology studies during the second quarter of this year.

To remind you we're halfway through the second quarter of this year so those studies are planned again imminently. In addition we received Orphan Drug Designation for 806 in patients with AML and we plan to seek such designation for other indications as data emerged to support those indications.

We're still on track to submit the IND this year and then expect to initiate first in human Phase 1 studies soon thereafter. To remind you we plan to initiate a trial that includes AML patients and a second trial that includes patients with various B-cell malignancies.

Me and our colleagues are most eager to drive 806 into the clinic and we will keep you abreast of the timelines as the year progresses. So now let's turn to APTO-253. Aptose's small molecule inhibitor of c-Myc oncogene expression.

The c-Myc oncogene regulates cell growth in apoptosis and is over expressed in hema cancers including AML as well as other cancers and it has been notoriously difficult to inhibit c-Myc expression.

Because c-Myc is a key target in many malignancies our research suggests that 253 may have a broad cancer application across many end malignancies and certain solid tumor indications. Some of that research was just presented recently in a poster at AACR.

For that poster we explored the mechanism of action of 253 and demonstrated heightened sensitivity of sensitivity of BRCA1 or BRCA2 mutated cancer cells to 253. The research team found that 253 stabilizes certain quadruplex DNA structures.

One such quadruplex multi is found in the promoter region of the Myc gene and stabilizing that structure with 253 can suppress transcription of the Myc gene leading to Myc depletion in the cells and induction of programmed cell death.

Such quadruplexes are also found in [indiscernible] replication force and stabilizing those structures can trigger the DNA damage response in certain cancer cells. As far as the DNA damage response by a drug can lead to a synthetic lethal situation in cells that have faulty DNA repair studies and functions.

Indeed we found that cancer cells with BRCA1 or BRCA2 mutations and impaired DNA repair functions were highly sensitive to 253. Although 253 acts by different mechanisms they exhibit synthetic lethality comparable to olaparib.

The FDA approved JAK inhibitor that acts against cancers in people with hereditary BRCA1 or BRCA2 mutation including some ovarian, breast, and prostate cancers. These findings reveal potential new solid tumor indications and partnering opportunities for 253.

Hopefully we can leverage these findings but we must remember that AML cells exhibit a particular sensitivity to 253 and Aptose must maintain a focus for now on development of 253 for patients with AML.

I also wish to mention that we recently published two articles via online publication in an AACR journal, Molecular Cancer Therapeutics in which we provide details of the mechanism by action of 253 that causes Myc inhibition and the mechanism that leads to synthetic lethality in cancer cells with DNA repair deficiencies.

In addition to advancements and our scientific understanding of 253 we've made progress -- significant progress with 253 development. You will recall that 253 was placed on clinical hold for a solubility related CMC matter.

Since then we have optimized the drug substance manufacturing, optimized the formulation, optimized the drug product manufacturing process, and have successfully manufactured multiple prototype and engineering batches of drug product.

During the first quarter of this year we successfully manufactured a new GMP clinical supply of drug product and we have been performing stability, sterility, and more fusion studies as well as animal bridging studies in order to demonstrate the fitness of the drug product for clinical usage.

These studies have been completed and passed through required tests and we now are on track to submit those findings to the FDA and hear a response back from the FDA during this second quarter. Remember that 253 has Orphan Drug Designation in AML.

If the FDA accepts our complete response and has either no minor or few questions then we hope to have the clinical hold lifted during this quarter and then pushed to reinitiate dosing of AML patients with 253 in a Phase 1B trial soon thereafter. With 253 we do have an open Phase 1b trial in patients with AML or myelodysplastic syndromes, MDS.

And we expect a dozen or more clinical sites to participate for both the dose escalation and expansion phases of the trial. A couple of these sites have secured early RFB approvals and if the CMC based clinical hold is lifted they plan to begin screening patients immediately.

So we're hopeful of restarting the 253 clinical trial soon and the physicians are eager to test a Myc inhibitor for the treatment of AML patients. So for our last order of business before I turn it over to Mr. Chow for our financials I'm very pleased that recently we welcome Ms Caroline Loewy to the Aptose Board of Directors. Ms.

Loewy is an accomplished and respected executive leader in our industry. Many of you know her from her past CFO positions at both public and private biotechnology companies and her years as a senior biotechnology analyst at Morgan Stanley and Prudential.

We know that Caroline will bring keen insight and add another dimension to our Board and we very much look forward to working with her. Ms. Loewy's appointment brings the number of Aptose Board Members to seven. So it's been a busy month and a half and we look forward to more important milestones during 2018. We will certainly keep you posted.

I will now turn the call over to our Chief Financial Officer, Mr. Greg Chow who will review our results for the quarter. Greg. .

Thank you Bill and good afternoon everyone. We ended the quarter with 16.2 million in cash and cash equivalents and investments compared to 11.4 million at December 31, 2017. During the quarter we utilized approximately 4.1 million of cash in our operating activities compared with 2.7 million for the first quarter of 2017.

As disclosed in our press release, just beginning of the year we have raised $15 million from the committed At The Market [ph] facility with Aspire Capital. 8.9 million was during the quarter and 6.1 million was subsequent to the quarter. This has extended our cash flow well into the second half of 2019.

Moving on to the income statement we had no revenues for the quarter. Research and development expenses were $3.2 million compared to $1.7 million for the same period in 2017.

This increase is primarily due to the CG-806 development activities including dose range finding studies and the manufacture of drug substance to be used in the GLP animal toxicity studies and increase expenditures on the APTO-253 program including the manufacture GMP drug supply and related stability and testing for return to the clinic.

General and administrative expenses for the quarter were $3.7 million compared to $1.6 million for first quarter in 2017.

This increase was primarily due to increased professional fees related to the filing of $100 million shelf registration statement and implementation of the $30 million ATM, At The Market facility that we previously announced as well as annual stock compensation expense that was awarded in the first quarter.

Finally our net loss for the quarter was $6.8 million or $0.23 per share compared to 3.3 million or $0.19 per share for the first quarter in 2017. I will now turn the call back over to Dr. Rice. Bill. .

Thank you Greg. I would now like to open the call for questions. Operator if you could please introduce the first question. .

Thank you. Our first question comes from the line of John Newman of Canaccord. Your line is open. .

Hey guys, good afternoon. Thanks for taking my questions. Just a couple here, the first one for Bill is, Bill the bone marrow data that you showed at AACR was quite interesting.

I just wondered, why we don't see this more often from other companies, it seems like we're all very familiar with looking at cell lines but these type of data seem more representative, I am just wondering if you hear -- if you have any sense as to why other people don't do it? And I also wondered if you could give us just a general sense as to what we might see at EHA just sort of broadly speaking? And then just had one question for Greg which is, do you have any warrants or debt at the capital structure at this time? Thanks.

.

Thanks John, appreciate you calling in. So, why don’t I let Greg answer first and then I will address the other two questions. .

Yeah, thanks John for the question. No actually our cap structure is very clean. The only security we have outstanding is common stock. We don't have any warrants, preferred stock, or any debt outstanding. .

Well, that was an meaty question. Alright so you also asked about the use of bone marrow samples with that we have shown with -- actually we did it with 253 and now we've done it with 806, why aren’t others doing it, a couple of reasons. First of all it’s extraordinarily difficult to get this number of patient samples.

We worked closely, we had to set up a relationship with Dr. Brian Druker's laboratory, the Knight Cancer Institute, Leukemia Lymphoma Society, Beat AML Initiative. So it took a relationship with all of these organizations to pull this together.

Then at the Knight Cancer Center they collect these fresh bone marrow samples and then they have to be evaluated immediately. You can't freeze them away. It's technically very difficult. They've published on this procedure.

Recently they had a paper in TNAS and I believe they have another paper coming out in Nature very soon that will describe what they found and how they do this. But first of all it’s extraordinarily difficult to do these studies and to ensure integrity of the samples.

Secondly, it's very expensive and third, it's difficult to get the patients to agree to collect these samples. We felt it was of primary importance to do this because you know my background as a mechanism guy and it's one thing to test cell lines and even to put those in animal models but all of that is really a PK system until you get into humans.

It's great if it works in animals that means the drug gets distributed around but it doesn't tell you really that you're going to kill the cell that are in a patient because they are different than what's in cell lines.

So this is kind of the bridge between what you do in the lab and what you hope to see in the clinic and this cost us a bit of money but it really showed that our drug is superior in terms of its range and potency than all the other molecules.

Also we had no fear of testing our drug head to head against all the FLT3 inhibitors and the AML samples and head-to-head against ibrutinib. And the data really revealed for us the stark difference between our molecule and ibrutinib because we're a direct killer of the CLL cells whereas ibrutinib is not.

So that gives you a sense of why it hasn't been done. It's difficult but we were committed to doing this and I think it has set us apart. You also asked what we expect to see at EHA and that's going to be in June in Stockholm. This again is going to include work that's coming out of Dr. Druker's laboratory with more samples.

We have actually tested now -- I had mentioned a few minutes ago we had tested 188 AML patients, 95 CLL patient bone marrow samples. In total we have I think over 600 patients with all the various types of pain malignancies and we've compared head to head against other drugs.

So you're going to see some of that data -- those data in scatter plots, heat maps and you'll also see a bit more of the X-ray crystallography studies where we're showing our drug binding distinctly or differentially to the BTK and some of the kinases that's different from some of the other drugs. So that's a broad sense of what you're going to see.

So thanks for the questions John. .

Okay, thank you..

Thank you, our next question is from the line of Joe Pantginis of H.C. Wainwright. Your line is open. .

Hey guys, good afternoon, and thanks for taking the question. Great news on licensing 806 in a full capacity.

More of a curious question with regard to you exercising the option, do you have any views that there might have been some others circling the wagons ahead of the June deadline for the drug?.

On that one the answer really is no because we had the option agreement, it was exclusive and all we had to do was exercise the option by a certain time.

The reason we decided to go in early is because we wanted to send the signal to CrystalGenomics, to the Street, everyone that we believe in this compound, we're committed to it, we made the payment and as I said we were proud to do so.

Now in terms of other companies that might be circling they might be circling for other reasons but not to get that license from CrystalGenomics.

Did that answer your question?.

That's helpful. It certainly does Bill, thank you.

And then just to follow up with regard to the patient sample data and thank you for all the details you just provided, I guess I would ask additionally can you provide any sort of physician reactions either at AACR or since AACR with regard to the quality of that data but specifically also the ability of those data to translate to the clinic since these are direct patients samples?.

Yeah, first of all thanks for calling in, Joe we appreciate it. But yeah, the response to those data what I can tell you is those of us who have seen the data came out of Dr. Druker's lab. When Dr. Druker sees it, when Dr. Michael Andrea sees it. These are people who work with us and they are heme-onc docs.

They're literally shocked at the data to tell you the truth, shocked at how well and how potent 806 is against such a broad swathe of these patients samples. And again when you compare the sensitivity versus the other drugs it was striking.

We also had a number of different people come by the posters and literally stand there and just stare at the data trying to absorb it.

Many of the physicians that are involved in clinical trials either with our drug in the near future or they are just better involved with a variety of other clinical trials with other drugs, they too were shocked by the data. We all hope it translates into effective treatment of these patients in the clinic.

But what has come up today is no one ever has really performed these studies, so how well does it translate into the clinic I can't tell you definitively but I can tell you that those cells are directly from the cancer patients whereas the cells that you grow in the lab are not.

So we feel great about the data, we believe it will translate, we just need to get this drug into the clinic as soon as possible so that we can start treating patients and hopefully see responses. So that's our greatest effort. So thanks for the questions Joe, appreciate it. .

You bet, thanks a lot. .

[Operator Instructions]. The next question comes from the line Jotin Marango of ROTH Capital. Your line is open..

Hi team, congrats on locking in 806. I think it's a great molecule. I have two questions just about the general FLT3 field. So we now know that our cells have filed gilteritinib and relapsed these. And then a few days ago as you told Daiichi [ph] has just announced their intent to file.

I suppose their hand was forced by Astelus [ph] but neither one has shown us data.

So how do you think about positioning 806 now initially since we now have midostaurin and chemo frontline and then we see quizartinib and gilteritinib fighting it out in relapse disease, would you move towards the unfit patients or what thoughts are you having at this point?.

Well first of all midostaurin we were actually happy to see that approved. I do not believe it's going to continue for long term to provide support for individual patients. I believe we all continue to see failures, a variety of different mutations that arise in other pathways.

But at least hopefully it'll be a bridge for some patients survival until other drugs come along. Now as you mentioned the gilteritinib and quizartinib we're actually thrilled to see those also move forwards are seeking approval.

I think they're much more focused on the FLT3 population in particular quizartinib you're looking at the FLT3 ITD population there and it's going to be in combination with other drugs. The gilteritinib I think are also focusing much more heavily on the FLT3-ITD populations.

So there's a tremendous medical need there, those patients do not typically last as long, the prognosis is poor for the FLT3-ITD. So we hope that these patients can respond to these other drugs, we hope that they can stay on drugs long enough for AL6 to come along.

So we'll let them battle it out for the FLT3-ITD population in the near-term and then by the time we get out there and we see where our patients are responding. But again one of the populations you mentioned that is of keen interest to us is the maybe the older populations, the ones that cannot necessarily tolerate many of the other drugs.

Our drugs so far has been so well tolerated we think that would be a great group of patients to go after. And I know you mentioned that in the past and we definitely wanted to look at those patients as quickly as possible. So did that answer sufficiently..

Definitely and Bill you just touched on the concept of midostaurin resistant which is interesting, I wonder if we are able to draw a parallel there to the case of ibrutinib and I know that one of them covalent and the other one is not but this is oncology.

So, in CLL ibrutinib resistance at least defines a base population for new BTK inhibitors and 806 is one of them too, Now is there such a thing yet in AML, our patients who are coming out with midostaurin resistance, have you been able to quantify this phenomenon yet..

Yeah, a number of studies were presented AACR, many studies -- excuse me, not AACR at ASH.

So what has been found is that yes, you are getting mutations that are arising in the FLT3 that can generate resistance to the midostaurin but you're also getting a number of mutations showing up in other pathways and again that's what I'm talking about this guacamole.

You may get FLT3 but if you don't get enough of these other pathways then you lose your suppressive effect. And that's effectively what they are seeing with midostaurin. So on one side of the spectrum is it is a dirty kinase inhibitor, we all know that.

So it acts against FLT3 and ultimately FLT3-ITD would fail but the fact that it's dirty doesn't allow it to have some effect on the other, the other pathways that will pop up. The problem is it's dose limiting for its toxicity. So you cannot maintain sufficiently high concentrations to continue pressure on the cells.

And so you're getting failure for a variety of reasons and from a variety of pathways. I know with ibrutinib you're seeing somewhat of the same thing. Yes, you have got the C481S that's coming up in patients. But what is so interesting is it's not necessarily by the resistance to those cells.

So the CLL cells that had the C481S mutation are then sending out signals in the bone marrow that protect the CLL cells that have the wall type BTK. And suppressing them from having a response to BTK -- excuse me, to ibrutinib.

So the point here is these cells it's effectively evolution in vivo and these cells are trying to find a way to survive and get around any drug. And if you don't hit these cells on a number of pathways simultaneously they will escape and that's why I believe our drug in essence it is a multi drug cocktail in one molecule.

But we're going to ultimately going to have to put it in combination with other drugs. Well, you got me on a long winded tear there didn’t you. .

Great, thank you Bill. .

Thank you Jotin..

Thank you and at this time I am showing no further questions. I would like to turn the conference back over to Dr. William Rice, Chairman, President, and Chief Executive Officer for the closing remarks. .

Alright. Everyone thank you for joining us today. We thank you for your continued support and interest in Aptose and we thank our employees for the quality of work and dedication. We're excited about the opportunity to advance to advance potential treatment options for hema malignancies and we look forward to reporting back to you.

Please note that our recent webcast and presentations including the posters presented today can be found on our website at www.aptose.com. We want to thank you again and have a good evening and operator would you please conclude the conference call. .

Ladies and gentlemen this does conclude today's program. Everybody have a great day..