Aptose Biosciences Inc (APTO) 2015 Q3 法說會逐字稿

Good afternoon. My name is Tricia and I will be your conference operator today. I would like to welcome everyone to the Aptose Biosciences conference call for the third quarter ended September 30, 2015.

At this time, all participants are in a listen-only mode. After the speakers' remarks, there will be a question-and-answer session.

(Operator Instructions).

Thank you. As a reminder, this conference may be recorded.

I would now like to introduce Ms. Karen Bergman. Please go ahead.

Thank you, Tricia. Good afternoon and welcome to the Aptose Biosciences Conference Call to discuss financial and operational results for the quarter ended September 30, 2015.

My name is Karen Bergman with BCC Partners, the investor relations representative for Aptose Biosciences. Joining me on the call today are William G. Rice, Chairman, President and Chief Executive Officer; Mr. Gregory Chow, Senior Vice President and Chief Financial Officer; and Mr. Avanish Vellanki, Senior Vice President and Chief Business 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 those stated expectations. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements 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 prospectus annual report on Form 20-F, and SEC and SEDAR filings. All forward-looking statements made during this call speak only as of the day 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, Karen. I'd like to welcome everyone to our call for the quarter ended September 30, 2015.

On today's call, we'll present the quarterly financials as well as three separate topics related to research and development. These include, first, the press release from this morning regarding our agreement with the Moffitt Cancer Center and Laxai Avanti to create multi-targeting, single agent epigenetic inhibitors which represents our first new program to expand our pipeline behind APTO-253 and to build a fully integrated oncology company.

The second R&D topic is a press release from last week describing data from the OHSU Knight Cancer Institution and Beat AML, describing the ability of APTO-253, or 253 as I'll call it, as a single agent and in combination with other agents to kill AML cells from primary patient samples, which will be presented at next month's ASH meeting.

And the third R&D topic is an update on the 253 Phase 1b clinical trial in patients with AML and other hematologic malignancies. And because 253 represents the core of our business, we will first update you on the 253 Phase 1b clinical trial.

We reported in our last call that the Phase 1b trial with 253 was underway at four clinical sites. As you may recall, this study is an ongoing, open-label, single agent, dose escalating Phase 1b clinical trial in patients with relapsed or refractory hematologic malignancies, including AML and high-risk MDS. The study is designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics responses as well as efficacy of 253 as a single agent.

As a quick background, epigenetic suppression of the Kruppel-like factor 4 or KLF4 gene has been reported in the scientific literature as a key transforming event in AML and high-risk MDS. 253, Aptose's lead drug candidate, is the first in class and the only clinical-stage inducer of the KLF4 tumor suppressor gene. Our trial got off to a slower than hoped pace for several reasons. As previously mentioned, we originally went to the clinical sites and received our IRB approvals for single-arm study in which all types of hema malignancies were incorporated into a single dose escalating arm. After consultation with the FDA, we separated the trial into two arms and then return to the clinical sites for IRB approval of the new study design. This is the right decision because it separated the lymphoma and myeloma patients from AML patients that have very different inclusion and analysis criteria, but it delayed the enrollment by two to three months.

We also mentioned previously that we were surprised to learn that physicians were not placing patients on 253 initially because the drug is not a cytotoxic agent and it's not myelosuppressive. AML patients presented the clinical sites with a very high blast counts and physicians must reduce the blast counts quickly to prevent strokes in other cardiovascular events. The physicians felt compelled to place the patients on myelosuppressive drugs, such as Hydrea, to reduce the blast rather than placing the patients on our drug.

However, the investigators did not reveal this bias for several months to us. When they did, Dr. Druker and Dr. Talpaz made the argument that 253 is more of an analogous to the Gleevec situation in which the drug can selectively kill malignant cells but is not generally myelosuppressive for normal bone marrow. And this is the type of drug that we want to develop for AML patients. Well, this impacted the investigators, and the trial enrollment then proceeded to a much grater pace.

Finally, 253 was evaluated previously in a trial with solid tumor patients. Yet, the current trial involves very sick AML patients and our dose density or the frequency of dosing is twice that of the solid tumor trial. Therefore, we were very deliberate and stringent in our entry criteria to ensure the drug is safe and well tolerated in AML patients. We wanted to do the trial right the first time and take no shortcuts that could undermine the trial or call this to expand cohorts unnecessarily as a waste of time.

Within the past few weeks, we held a meeting with our Scientific Advisory Board, an exceptional team that includes physicians and scientist, Drs. Brian Druker, Daniel Von Hoff, and Michael Andreeff. At that meeting, we reviewed the real time safety and pharmacokinetic data available to us, and the SAB, the Scientific Advisory Board, was very pleased by what they saw and by the way the trial is being conducted.

We are collecting and processing real time safety and pharmacokinetic data. And thus far, 253 continues to be very safe, and there are no drug-related SAE that derailed the trial from going forward. I want to repeat, at this time, there are no drug-related serious adverse events.

Moreover, the PK parameters demonstrate the expected exposure levels in the patients. We have completed the 20, 40, and 66 mg/m2 dose cohorts, and the PK exposure levels at the 66 mg/m2 dose were beginning to reach the [micromolar]. This is important because the data from the Beat AML initiative, as we will describe in a few minutes, demonstrate that AML cells in the majority of patient samples can be killed by one [micromolar] levels of 253.

We now have escalated to the 100 mg/m2 dose, and we expect to achieve one to two [micromolar] exposure levels of the Cmax and the plasma of these patients. At 100 mg/m2, we believe we now are maybe entering the therapeutic exposure levels. Our ability to continue dose escalation allows us to get more drug on board and we believe increases chances of success.

At this time, we're reporting that the clinical investigators are keen to enroll patients expeditiously and we are adding additional clinical sites, and that the drug is behaving precisely as we expected from safety and PK perspectives. But we have not yet observed meaningful responses because we believe we are just now beginning to enter the therapeutic exposure level. Just like you, we're passionate to test 253 at the higher dose levels and to observe responses, but we are not yet at those levels in which we expect such responses.

While these articulated circumstances that caused us to have a slower enrollment during the initial stages of the 253 clinical trial, we still anticipate completing enrollment during the first half of 2016. With robust safety and PK data for 253 and our full belief in the molecule, we've expanded our clinical operations team and are adding clinical sites. For example, we recruited Mr. Ernest Kitt to head our clinical operations program. Mr. Kitt is the former molecule lead director at Onyx-Amgen for the development of Kyprolis or carfilzomib. We truly have an exceptional clinical team, and I'm confident in our ability to have six or more additional clinical sites up and running by the end of the first quarter of 2016, and that effort is already underway.

We also remind you that 253 is not a cytotoxic agent, and we have seen no evidence of damage to the normal bone marrow in humans. The Phase 1b study is designed to transition to single-agent expansion cohorts in AML and MDS followed by combination studies. The Phase 1b data, of course, will help us to inform our development plans and got our decisions regarding patient population, dosing, timing, cost, potential partners, and other relevant parameters. We, along with our scientific advisory board, are excited about the progress we're now making with 253 while we're learning about its characteristics and its potential to make an impact and the treatment of the AML patient population very much in need of new therapies.

Now, let's turn our attention to ASH. Many of you asked us about next month's ASH or American Society of Hematology Meeting, and what data we will present at that conference. At ASH, being held this year in Orlando, Florida, December 5th through 8th, our collaborators at OHSU Knight Cancer Institute will be presenting pre-clinical data on 253 that are derived from our participation in the Beat AML Initiative with Dr. Brian Druker. The poster presentation entitled, Broad Activity of APTO-253 in AML and Other Hematologic Malignancies Correlates with KLF4 Expression Level. It is scheduled for Saturday, December 5, 2015, from 5.30 to 7.30 p.m.

An initial Aptose abstract was accepted for publication in the ASH online conference materials and will be in the December edition of the Journal of Blood and in ASH in the Journal of Blood abstract archive. The abstract is entitled, Clinical Pharmacokinetics of APTO-253 Support Its Use as a Novel Agent for the Treatment of Relapsed or Refractory Hematologic Malignancies. And the abstract describes the favorable pharmacokinetics and safety profile of 253, which collectively suggest we should be able to reach safe exposure levels sufficient to impact patients with AML.

As you may remember, the Beat AML Initiative, a groundbreaking initiative that was formed in collaboration with the Leukemia & Lymphoma Society and the Knight Cancer Institute, has allowed Aptose working with these leading investigators to evaluate the effect of 253 alone or in combination with other anti-cancer agents and fresh bone marrow isolates from patients with AML, myelodysplastic syndrome or MDS, chronic myeloid leukemia or CML, and chronic lymphocytic leukemia or CLL.

The research being presented at ASH highlights 253 data that we generated through the Beat AML Initiative and spearheaded by the OHSU Knight Cancer Institute researcher, Jeffrey Tyner, PhD, an assistant professor in the Department of Cell Development & Cancer Biology in the OHSU School of Medicine. Using a range of doses from low nanomolar to 10 micromolar, the researchers observed very meaningful trends. The ASH abstract just published online last week described the ability of 253 to kill AML cells in a majority of patient samples with a trend toward correlation with baseline KLF4 expression level. Moreover, the data demonstrate how 253, an inducer of the transcription factor KLF4, demonstrated enhanced killing ability of AML cells in patient samples when combined with two other emerging targeted therapies, the BET bromodomain inhibitor JQ1 and the FLT3 inhibitor quizartinib.

The team evaluated specimens from 177 patients with a variety of hematologic malignancy diagnoses. The highest frequency of 253 sensitivity occurred among AML patient samples with 54% of samples exhibiting an IC50 of less than 1 [micromolar]. At this cutoff, 35% of CLL samples and 12% of MDS/MPN samples were sensitive to 253. These data demonstrate that 253 is effective at killing tumor cells from a majority of AML primary patient samples and also is active in CLL. Moreover, the expression level of KLF4 may be a predictive marker for 253 efficacy in the clinic.

Separately, the majority of cases tested with a combination of 253 and the JQ1 bromodomain inhibitor showed the combination IC50 to be at least two-fold lower from the IC50 of either agent alone. [Distractingly], this enhanced efficacy of 253 with JQ1 was observed across all hematologic malignancies tested. In contrast, the combination of 253 and the quizartinib FLT3 inhibitor demonstrated enhancement of sensitivity that was confined to AML. These data actually make sense because FLT3 is generally restricted as a target to AMl while bromodomains represent targets across many types of malignancies.

Importantly, 253 combined well with the BRD and FLT3 inhibitors to kill hema malignancy cells from primacy patient samples. These results support KLF4 silencing as an important and frequent operator in AML, and suggest that KLF4, the KLF4-inducing capacity of 253 is responsible for the effective killing of tumor cells from a majority of AML cases. The data also demonstrated activity of 253 against other hematologic malignancies, in particular, CLL. They suggest that the expression level of KLF4 may be one component of a biomarker for prediction of 253 efficacy and a more global gene expression signature analysis is underway.

Finally, these data have identified prominent interactions of 253 with the BET bromodomain inhibitor JQ1, as well as an AML restricted interactions of 253 with the FLT3 inhibitor quizartinib, suggesting these class of drugs can serve as preferred combination partners for 253. Recall that at last year's ASH meeting, we presented data that demonstrated 253's robust safety profile and potent activity as a single agent and administrating combination with a chemotherapeutic drug azacitidine; notably, combination therapy led to enhanced antitumor activity versus either agent alone. So the potential use of 253 in combination therapies present a compelling opportunity for us in one that we continue to investigate.

Again, this new data from OHSU and Beat AML are from human bone marrow isolates of actual patients with hematologic malignancies not from cell line. These data have given us exceptionally important insights about 253 that are supportive of our current clinical strategy and also inform our future development plans. We look forward to sharing more of these data with you at ASH. So please be sure to stop by our poster presentations.

Let me now ask our Chief Business Officer, Mr. Avanish Vellanki, to walk you through today's business development announcement. Avanish?

Thank you, Bill, and good afternoon, everyone. As Dr. Rice mentioned in the comments about the Beat AML data, we believe that the strong efficacy of APTO-253 in combination with the bromodomain inhibitor or BRD inhibitor JQ1. We'd like to share today that Aptose has significant interest in bromodomain inhibition, not just as a means to possibly combine with APTO-253 but a stand-alone, single-agent programs for our pipeline.

While BRD inhibitors are not new, we believe inhibitors that are selective for BRD 4 and potent across multiple synergistic targets are in fact new. Specifically, we see a multi-targeting epigenetic strategy as required to do two things -- one, lead to sustain inhibition of proto-oncogene transcription, oncogene such as c-Myc; and two, facilitate oncogenic protein degradation. This strategy, we believe, would be more impactful in targeting the bromodomain family alone.

Therefore, this morning, we announced two transactions to begin building the Aptose pipeline with these multi-targeting epigenetic inhibitors. First, we have entered into an agreement for an exciting group of molecules from the Moffitt Cancer Center. As part of the Moffitt collaboration, Aptose will receive exclusive global rights to a family of highly potent, small molecule, multi-targeting inhibitors that target BRD 4 and certain other kinases. The enzymatic potency against these targets are currently in the low nanomolar range but would be optimized further by Aptose for the appropriate interplay of activity against the targets.

Importantly, Aptose now may access Moffitt's intellectual property around specific chemical modifications. These modifications enable potent BRD inhibition on top of the kinase inhibitor backbone. The [IP6] further enhances the flexibility for Aptose to develop innovative clinical candidates. Therefore, we are exceptionally pleased to be working with Moffitt in the arena of epigenetic multi-target single agent inhibitors.

Second, we have announced that we have forged a partnership with Laxai Avanti Life Sciences, or LALS, a medicinal chemistry organization that brings expertise required to create and optimize new multi-targeting epigenetic inhibitors. Under our agreement with LALS, we will discover and develop new candidates based on bromodomain inhibition and others. LALS would be responsible for [hit] identification and optimization, and Aptose will select candidates to bring to the clinic. Aptose will own all global rights new candidates generated under the collaboration including all intellectual property.

We expect to generate multiple clinical candidates from these partnerships with the first lead candidates emerging in late 2016. While these two collaborations are earlier stage and one of the first transactions, we are announcing we are far from done. Please stay tuned over the next several months for additional pipeline expansion activities along with updates from a previously discussed combination studies of APTO-253 with other investigational agents.

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

Thank you, Avanish, and good afternoon, everyone. As a reminder, effective July 17 of last year, the company changed its fiscal year from May 31st to December 31st. Now, as a result, the period that we are reporting today is for the three months ended September 30, 2015, and we'll compare to the four months ended September 30, 2014. In addition, our reporting currency is in Canadian dollars.

And now, turning to our financial results for the fourth quarter ended -- I mean for the third quarter ended September 30, which I will refer to as a quarter starting with our cash balance.

We ended the quarter with CAD23.4 million in cash, cash equivalents, and investments compared to CAD25.2 million at the end of the prior quarter on June 30, 2015. During the quarter, we utilized approximately CAD2.6 million of our cash in our operating activities compared with CAD3.9 million during the four months ended September 30, 2014. And we also received proceeds of CAD40,000 related to stock option and warrant exercises. We currently believe the capital we have on hand is sufficient to fund our research and development, and operations into early 2017.

Moving to the income statement. We had no revenues in the three months ended September 30, 2015, or in the four months ended September 30, 2014. Research and development expenses were CAD1.7 million for the quarter compared to CAD1.3 million for the four months ended September 30, 2014. This increase is due to the initiation of the Phase 1b dose escalation trial this year as well as formulation studies and research while supporting the ongoing clinical trial.

General and administrative expenses for the quarter were CAD2.2 million compared to CAD3 million for the four months ended September 30, 2014. The decrease over the prior year is attributable to a four-month reporting period in the prior year compared with the three months reporting period in the current year.

We reported net interest income of CAD48,000 and a foreign exchange gain of CAD661,000 for the quarter compared to net interest income with CAD124,000 and a foreign exchange loss of CAD12,000 for the four months ended September 30, 2014. Finally, our net loss for the quarter was CAD3.3 million with CAD0.27 cents per share compared to a loss of CAD4.2 million over or CAD0.36 cents per share in the four months ended September 30, 2014.

I will now turn the call back over to Dr. Rice. Bill?

Thank you, Greg. I'd like to open the call for questions. Operator, if you could, please introduce the first question.

(Operator Instructions) And our first question comes from the line of Chris Marai with Oppenheimer. Your line is now open.

Hi. Good afternoon, guys. Thanks for taking my question, and congratulations on all the activities at Aptose. The data you presented at the ASH Abstracts was quite encouraging. I was wondering if you could just -- those are patient samples on -- that this drug was previously also, actually inpatients? Just how many patients have you previously treated with APTO-253? And maybe could you help us understand any potential side effect profile that you'd seen there. Thanks.

Hi, Chris. Well, we agreed that the data from the abstract, ASH Abstracts, were encouraging. In terms of the previous study, those were solid tumor patients in a previous Phase 1 clinical trial and there were approximately 35 patients or so that were treated with various doses of 253. A couple of the points here -- one is the drug was found to be very safe, very well tolerated, and there were some hints of efficacy, particularly in a patient with lung, particular type of lung cancer.

But you also asked about the side effects. The dose-limiting toxicity was at, I believe, 389 mg/m2; at which, there was a hypersensitivity and a hypotension. So there were two SAE at the highest dose, hypotension, low blood pressure, and hypersensitivity. It was believed that both of those were related to the solvent of the drug in which the drug is [stabilized] (inaudible).

There was also another SAE at a lower dose that was -- I believe it was hypokalemia. But that was -- we believe that was a red herring because many of the patients, as we look back, have altered electrolytes. So there was no true compelling data showing the drug was related to cause that.

Does that answer your question?

Yes. Absolutely. No, that's very helpful. Thanks. And then maybe just to follow up on some of the business developments that you've conducted. Obviously, the BRD inhibitors are quite exciting. You noted that yours is a BRD in kinase inhibitor. Did I catch that correct? It has a [dual look]. Can you elaborate on that further?

Yes. Perhaps, Avanish would like to talk about this one since you inked the deals.

Thanks, Bill, and hello, Chris. So you're right. So it's a BRD inhibitor, specific for BRD4, and it does hit other targets and those other targets are multiple. We're not disclosing necessarily what those other targets are. But the reason for the interest in the deals were that these are the targets are very rational and they're highly synergistic with the bromodomain inhibition. So we like that combination. It's a combination in a single-molecule, which we think [assuming we get a high ED] opportunity for achieving those patient remissions.

Okay.

Let me add just a bit to that. So do you mind if I add just a bit? (Multiple speakers) --

^ Okay.

All right. I'm Bill and I'm an old mechanism guy. So if you look back at many of the kinase inhibitors over the years, they've had, some of them had better activity than others. And if you look closely, some of those actually have structures that allow them to lay into the binding domain of bromodomains. And a couple of publications have come out on this.

So we felt that those very compelling to design from the outside not just to rely on serendipity of a kinase that also hits a bromodomain. We wanted to, first, take a set of high potent bromodomain inhibitors with novel medicinal chemistry around them and then design into those molecules specific kinase inhibitory activity. And the technologies from the Moffitt Cancer Center have allowed us to get an entry into that field.

Again, as Avanish said, we haven't disclosed exactly which kinases we're going after, but we know exactly what we're going after now, and it will be a single agent that is a multi-targeting drug. We think that's very important especially since the bromodomain inhibitors it's known that you can develop resistance around those. We want to be able to hit some of these other key pathways with the kinase inhibitory portion of the molecule and hopefully minimize the resistance development to the bromodomain inhibitory activity. So there.

Absolutely. Thanks. That's really helpful actually. Thanks. And then just with respect to the BRD 4 inhibition, I mean, you have traditionally been noted to be quite active in AML models. I would assume that you guys are looking to combine this with APTO-253 in AML. Are there any other indications that you're potentially looking at? Thanks.

Yes, I'll add a bit to that and then I'll ask Avanish to also jump in again. So if you look throughout the literature, there are clearly publications showing that the bromodomains are operative in AML, especially BRD 4, and typically binding domain one is what much of literature talks about. So you want to make sure that you're able to design a molecule that selectively targets the binding domains that you want. And it is clear that a bromodomain inhibitor will be synergistic in combination with 253 because now we have already shown that through the Beat AML Initiative inpatient samples. So we did want -- I mean we were already interested in the bromodomain as a new target, but the fact that we can also combine with our lead molecule is a real plus for that.

Avanish, would you like to add to that?

Yes. One additional point. So, Chris, the major point I would make on this issue is that we're no longer limited to just AML or other closely-related heme malignancy. I think one of the reasons we're very compelled by bromodomain inhibitors and bromodomain inhibition as a strategy is it opens up a variety of potential indications including many of the solid tumor applications that we may want to pursue down the road. The data in the industry support applications in glioma, in lung cancer, in colorectal cancer, and various others as you're certainly familiar with. So we like the opportunity to be able to go after a variety of options based upon the profile of the molecule that we developed.

Yes. Right now, we're focused in the hematologic malignancies because there's a tremendous need for those patients. Also, it's a faster path in clinical proof of concept. But we want to have molecules as we bring them into the future that can be directed against multiple heme malignancies and then expand out the label and opportunities into the solid tumors.

Excellent. I guess one final one. When do we see first human data for that BRD inhibitor? And then I will let the other guys ask some questions. Thanks, guys, and congratulations.

Well, thanks. Actually, a lot of work went into selecting those molecules in the path forward. What we've outlined is that based on the molecules that we've been able to license in as well as the intent to optimize them further, we hope that we can bring forward a clinical candidate by the end of next year. We always hope for earlier, but we're setting time line for the end of next year. And then you have to run it through the difficult pre-clinical development. So it's not an immediate molecule in the clinic. It is -- I would point out this is not something that's designed to replace 253 because this is well into the future. We hope this will be complementary to 253 as it continues to move forward.

Thanks, Chris, for calling in.

Thank you. (Operator Instructions).

Our next question comes from the line of John Newman with Canaccord Genuity. Your line is now open.

Hi. Thanks for taking my question. I apologize if this was addressed during the call. I joined a little bit late. Can you give us a sense as to where we might see data from the ongoing Phase 1 study for the APTO-253, which I believe is mainly focused on AML?

Yes. Hi, John. It's -- this is Bill. Yes. One of the things we talked about is that we are collecting real-time safety in the PK data on every patient. And literally, by the time the patient has completed the first cycle, we already have all their PK and safety data completed. So I believe we can turn around very soon and present some of the data. Perhaps, Greg, you can join me on this. I think we can present some of the data from the safety and PK on to the clinical site -- I mean on to our Web site very soon.

Yes.

And then I assume you're also asking about efficacy data.

Yes.

Again, we're just now entering into the 100 mg/m2 zone, which we believe is entering the therapeutic realm, the therapeutic exposure realm. So we hope over just the next couple of [whole] cohorts, we'll be able to provide you with some efficacy data. Again, of course, Phase 1, as we always say are designed for safety and PK, and selecting that Phase 2 dose. But of course, we hope to be able to achieve the efficacy data in the next couple of cohorts. So stay tuned.

And what I would say is that as soon as we have any material findings from the trial, whether it's positive or negative, we're going to present that to you guys and get it out as soon as we can. You guys have been very supportive and you deserve to have such data come out as soon as possible.

Okay. Great. And then, how does the collaboration that you have for the bromodomain inhibitors -- how do think that compares to some of the other molecules out there, such as the Oncoethix molecule that Merck picked up just broadly speaking?

Avanish?

Hi, John. That's a great question. So I think one of the things we are most compelled about by the profile of the molecules we've seen is not just the fact that we're hitting multiple targets and the positive implications of that. And Bill alluded to the fact that potentially diminished chances of resistance, enhanced efficacy, et cetera. But when we look at the enzymatic potency of many of the bromodomain inhibitors out there, we see a couple of things. We see pan BRD inhibitors, not highly selective BRD 4 inhibitors. We do believe hitting BRD 4 exclusively is of paramount importance here to alleviate some of the talks and issues with the class.

And the other issue is relative potency. We think they're getting to the low nanomolar range is absolutely critical and many of the bromodomain inhibitors that are being investigated are not that potent. So we see both those characteristics from these groups of molecules that we've just collaborating with Moffitt with now and we're excited about further optimizing for the clinic.

Okay.

Well, let me add just a little bit to that. We actually looked at a variety of bromodomain inhibitors, some of them internally. We've been working with the Beat AML Initiative. And what we tend to see is that as if we begin to dose them up, especially in the animals, we just start running into -- by the time we start to see efficacy, you're also [skating] on the edge of toxicity. So we're too passive to try to reduce that toxic effect. One is, as Avanish said, to have a molecule that selectively targets the BRD 4, and in particular, one of the binding domains.

And then secondly is within the same molecule hit another pathway that's critical to the cells. And we've done drug combinations studies, what we're seeing is we actually have a much better effect at lower doses and lower concentrations, so it enhances the activity of the bromodomain inhibitor without necessarily increasing the toxicity. So that is the reason we're going after a multi-targeting, single agent molecule for the bromodomain inhibitors. And thanks for calling in.

Thanks.

All right.

Thank you.

Thank you. I would now like to pass the call back to Dr. Rice for any concluding comments.

All right, everyone. Well, thank you for joining us today. Aptose, we feel that we forge a strong scientific and clinical foundation for which we're building a specialized oncology company, and we look forward to sharing further updates on our clinical and business development progress with you. We're excited about the opportunity for 253 to advance treatment options in hematologic malignancies. And as always, we thank our employees for their hard work, our shareholders for their continued support as well as all of the investors and analysts that have come on to the call here today.

So note our recent webcast and presentations can be found on our Web site at www.aptose.com. And I want to thank you again and have a good evening, everyone. Operator?

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the call. You may all disconnect. Everyone, have a wonderful evening.