Q2 2023 Aptose Biosciences Inc Earnings Call
Okay.
Okay.
Good afternoon. My name is Gina and I will be your conference operator today I would like to welcome everyone to the uptick Biosciences conference call for the second quarter ended June 30th 'twenty 'twenty thing.
This time all participants are in listen only mode. After the Speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time, what you will need to press star one on your telephone you will then hear an automated message advising you him. If he would like to withdraw your question. Please press star one again thank you.
As a reminder, this conference call maybe recorded I would now.
Like to introduce Ms.
Is that the joke Paulo. Please go ahead.
Thank you Jada good afternoon, and welcome to the Atlas Biosciences conference call to discuss financial and operational results for the second quarter ended June 30 is 22 2023 earlier today I took issued a press release relating to these financial results news release as well as related SEC filings are accessible on <unk> website.
And me on todays call are Dr. William G Rice, Chairman, President and CEO , Dr. Rafael Bejar, Senior Vice President Chief Medical Officer, and Mr. Fletcher Payne 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 U S.
Avian securities laws forward looking statements reflect our current expectations regarding future events. They are not guarantees of performance and it is possible that actual results and performance could differ materially from these stated expectations.
Bob 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 absolutes. Its most recent annual report on Form 10-K, and S E T and theater filings all forward looking statements made during this call speak only as of the date there.
Made atmos 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. We encourage you to refer to today's press release and the 10-Q for additional information and disclosures regarding today's announcement I will now turn the call over to a Doctor writes Chairman President.
And CEO of <unk> Biosciences, Dr Rice.
Thank you Susan I want to welcome everyone to Oracle for the second quarter ended June 32023.
You likely have noticed that we've been relatively quiet since our last call, but there's been a lot going on behind the scenes since our last call in June and today, we're happy to provide some important updates.
I'll also point out that many of the details related to day to todays comments on this call are provided in the accompanying press release and 10-Q that were filed earlier.
I want to begin today with speaking about financing activities earlier. This year, we had the opportunity to raise capital with the financing what I'll refer to as flavor of the day, which would have included extensive warrant coverage and would've been extraordinarily just let me move to our team and to our existing investors at that time, we chose not to execute such a financing, but rather to add.
Activate an at the market or ATM facility.
To establish a committed equity facility neither of which would involve warrants.
As we told our board that we would seek partnership investments.
So today, we're delighted to highlight our most recent news regarding our partner Hanmi pharmaceutical of South Korea.
From whom we license <unk> about a year and a half ago.
Today, we announced that Hanmi committed to purchase at post equity up to a total ownership at $19, 99% over two tranches and up to a limit of $7 million.
Delighted to strengthen our relationship with Hanmi, which reflects the recognition of the growing value of test as you can.
Nick treatment for AML and possibly Mds.
And a significant progress at half doses made with Testbed in its clinical development.
Thank the Hanmi team and in particular, Miss Lim President of pardon me pharmaceutical for her leadership and her commitment to App dose.
Our CFO Mr. Fletcher Payne will provide a more detailed financial update later in our presentation today.
But I want to point out that in addition to the Hanmi investment during the quarter. We did activate an ATM facility and we did enter into a $25 million committed equity facility with Keystone capital.
We're pleased to have secured these financing instruments as promised although to date, we have only used the ATM and committed equity facility to a limited capacity and in situations. When we believe they would not have a material impact on the trading of stock.
In addition to these financing activities. We also continue to pursue and evaluate partnering activities that may provide strategic support for our programs. It's fair to say the interest in our key clinical asset <unk> continues to grow and we continue to engage in productive discussions.
Ultimately, we expect that our global reach will be required to realize the full impact of tests at the patient level and the full commercial value of <unk>. So we continue to take steps with the clinical development plan and with partnering discussions to achieve that global reach for Testbed.
Another highlight of the second quarter was a successful end of phase one meeting with the U S. FDA participate there.
We completed an extensive dose escalation and dose exploration trial, which is in accordance with the guidance of the Fda's project Optimus and we then presented our findings to the FDA.
We were pleased with the outcome of the end of phase one meeting and it dovetails perfectly with our ongoing activate expansion trial in which highly treatment experienced relapsed or refractory AML patients are being dosed with <unk> as a monotherapy.
N P or in combination with banana clocks.
In a few minutes, our chief Medical officer, and resident Kate well, Dr. Raphael Bexar will provide an overview of our recent findings with tests pattern there.
Including takeaway messages from our end of phase one meeting with the FDA.
But before he does so I want to emphasize that we are a data driven as an organization and since the last earnings call. We've been quietly gathering information from published research from our collection of Kols from our internal Kols, Dr. Bexar and from our clinical trials to understand the emerging needs of AML patients, it's essential for us to.
Understand what AML patients truly will need in the future and how we best apply testbed nib to those needs.
<unk> benefits from having some of the most respected hematology minds as our investigators on our scientific advisory Board and on our Hematology clinical Advisory Board.
Our Kols include Doctor novel Darva, Dr. Courtney Dinardo, Dr. Michael Andreyev.
Brian <unk>, Dr. Shaw Sacher, Pearl and other hematology focused kols from numerous sites in the U S. Europe , the U K, Australia and other regions.
And our Kols at a recent meeting of our Gaza reward, providing us with insights emerging trends and patient needs that are not yet available through publications glean.
Gleaning from the guidance of these thought leaders, we see several scenarios in which we believe to spend that could improve upon the standard of care for AML patients currently in perfectly being served by therapies.
It's becoming clear that one of the greatest needs is for the superior combination therapies with targeted agents and frontline newly diagnosed AML patients to reduce toxicity to boost response rates and to deliver greater durations of response without relapses.
Doublet therapy, with <unk>, and <unk> lending agents or Hma's can deliver 60% to 70% response rates response rates and frontline unfit patients and there's a desire to move to highly effective and less toxic therapies into more fit patients and move away from intensive chemotherapy.
To effectively treat a breath of frontal frontline AML patients with cocktails of targeted agents.
Cocktails must be even more effective.
Toward that in <unk>.
Triplet therapy of <unk>, and Hma's, coupled with an anti proliferative drugs.
It's been explored recently in frontline AML patients and this triplet cocktail of targeted agents delivered a remarkable near 100% response rate.
While this is encouraging the anti proliferative drugs used in that study or flit three inhibitors. Unfortunately, the flip through inhibitors used in that study were associated with prolonged suppression GTC prolongation and are applicable only to approximately 30% of the AML population those with a mutation in <unk> three.
Canadian triplet therapy is for a superior anti proliferative agent that is once daily it can be taken orally with banana Clark's causes less mellow supplier suppression and avoids Qt prolongation with long term dosing and conserve not only the flit three mutated population, but also the remaining 70% of the AML population with.
And mutated to flip through these.
Please characterize characteristics described to spend it.
And we want to drive test patented through doublet combination studies with <unk> on the way to triplet therapy in frontline AML Dr.
Dr. <unk> is a leader in triplet therapy for AML patients and we will leverage his expertise to apply testbed nib to the triplet therapy approach and our future trials.
Separately, there is a need for superior maintenance therapies that are convenient to take orally that are well tolerated and the non motto suppressive that can protect from relapse and extended disease free survival.
And that can serve AML patients with mutated and wild type <unk> III as well as patients with mutations in <unk>, three Ras NPM, one ml and other adverse genes.
Again, those needs and maintenance therapy precisely correspond with Testbed, new properties properties, and we want to drive to us patented toward maintenance therapy as rapidly as possible, although such an approval would most likely follow initial approvals for doublet and triplet therapies with test pertinent.
While we believe <unk> can be applied effectively to triplet therapy and maintenance therapy in the future, let's talk about the here and now.
I want to underscore the greatest emerging need and that is to effectively treat AML patients who already have failed treatment with <unk>.
The vast majority of U S based AML patients entering clinical trials now have tried and Ben fell by the <unk> at some point.
<unk> is so commonly used its jopling referred to as vitamin D.
Regrettably prior from prior therapy with and failure of Venetic lacks leaves patients with very high risk biology, with broadly resistant mutation patterns and with dismal response rates to salvage therapy and with CR rates in the single digits, whether treated with various monotherapy or drug combinations as salvage third.
Indeed, we see from our App debate expansion trial that the lion's share of patients entering the study have wild type and mutated <unk> three and have failed prior therapy with <unk>. There is a clear medical need.
Remarkably our preliminary data from the <unk> trial in patients treated with the combination of <unk> <unk>.
Panetta clicks or tests, Ben as we referred to it.
Showed the doublet has been well tolerated and that had a significant response rate has been observed in patients who already have felt venetic lax, thereby potentially expanding the pool of patients that may be responsive to <unk> Dr.
Dr. Bexar will provide additional color regarding our preliminary findings with the Testban drug combination, but these data are generating excitement among our team and the investigators as reflected in a very brisk enrollment rate.
During the coming months of August September and October we plan to place as many patients as possible on the test been doublet.
Data to demonstrate the doublet as active in patients who have prior <unk> failure with mutated and <unk> III.
To meet and share preliminary data with bankers analysts investors and potential partners to show, how we can position to sputnik for frontline triplet therapy, and maintenance therapy and to move test and <unk> on a clear path towards success.
Now as for <unk> as we call. It. We currently have continuous dosing ongoing in the clinical setting with the 200 milligram dose of the G. III formulation and we will have more definitive comments about lux and with the G. III formulation in the coming weeks.
And finally I'm certain you wished to know about upcoming milestones I'll remind you that we may provide updates during earnings calls and medical conferences, but also at anytime we see necessary or consider information as material.
Costing up to upcoming milestones are linked to clinical data I'll ask Dr. Bexar to outline the milestones after he provides a clinical update.
With that.
Let me now hand, it over to Dr. Bejar, our chief Medical officer to go over more detail about the App debate clinical trial or test and AML and to go over our clinical plans and timelines with you. He also will be available to answer questions graph.
Thanks Bill.
Let me start by giving you some background on <unk> patented molecule, which suppresses a handful of kinases that drive several key oncogenic pathways was created as a once daily oral myeloid kinase inhibitor to treat patients with AML.
By targeting all forms of split three kinase Jack one into our SK wanting to and mutant forms, but not wild type farms kit and even cap one and tab one Hispanic and suppresses multiple oncogenic pathways that often lead to disease progression relapse get importantly dependent also maintains a highly favorable safety profile with no personal.
Milo suppression with prolonged dosing.
As Ben has no noteworthy safety profile as a major differentiating factor relative to other AML drugs and as I said before the importance and the superior safety profile cannot be underestimated and that's what our old patient population.
As Dr. <unk> mentioned earlier, we had a successful end of phase II meeting with the FDA for it to Scott after completing an extensive dose escalation and dose exploration trial.
2075 patients we presented our findings to the FDA.
After review of the data and 80 milligram once daily dose is selected as the recommended phase two dose for monotherapy treatment of AML patients with suspected in addition, the FDA confirmed that all available path all development paths for just that it remain open including the single arm accelerated path and that no special TTC or metabolite monitoring studies, we're going to be required.
And by the way the 80 milligram dose level is now being used as monotherapy and in combination with <unk>.
Following completion of the successful dose escalation dose exploration phase one two trial expected in 77 year stretch for AML patients we initiated the.
Phase one two expansion trial with <unk> as a monotherapy or as a doublet therapy in relapsed and refractory AML patients.
I'm happy to talk about what we're seeing in the activate traffic perspective, and where that information is leading us from a clinical development perspective.
As you know in the activate expansion trial, we have two arms a monotherapy cohort in the combination therapy arm, which is patent is being administered with phonetic box.
It is a global trial and our clinical team now has numerous sites up and running across the globe, including sites in U S Korea, Australia.
And in Europe .
During June we provided a very preliminary highlight at the after the expansion trial and we had initiated in the first quarter. This year, we highlighted brisk enrollment and we already had noted anti leukemic activity, including a complete response in our doublet testing in a patient that had already failed, but net of tax treatment.
Enrollment continues to be brisk as we further expand our steady internationally with newly activated sites in Australia, Spain, and additional countries poised to begin enrolling soon.
As of August one 2023, we had enrolled 29 relapsed or refractory AML patients in the activate study.
114 in the test monotherapy arm and 17 in the <unk>.
As of that date seven patients in the monotherapy arm reached efficacy Evaluable stage and there was one response in a patient that previously had been treated with fanatical ask a number of the patients on the monotherapy arm of the progress quickly had failed prior <unk> therapy and were less responsive to test monotherapy.
And we also observed earlier cohorts.
In contrast, Canada for 2017.
On the test then doublet arm had already reached the efficacy evaluable stage, meaning they had received sufficient therapy had undergone appropriate response assessments in the doublet arm.
We're very pleased with our findings in the test and Dev and I want to walk you through some of these preliminary findings now.
Although it may have shown a little bit of my Thunder here and with appropriate cautionary comments. We report today out of our 10 evaluable patients on the test and doublet, thus far we've seen a complete a composite complete response rate where CRC of 50%.
This is defined as the combination of complete remission or complete remission with incomplete hematologic recovery.
Recovery.
Partial hematologic recovery.
And we see our eyes in the study are inclusive morphologic leukemia free state.
These responses were all in a very ill relapsed refractory AML population nine out of 10 Evaluable patients had failed prior <unk> treatment with four of the nine achieving responses.
You have the overall response rate of 44% among patients with prior <unk> failure.
Recent publications and investigator conversations have highlighted that patients who failed <unk> often acquire or expand this cloud they are highly refractory to salvage therapy.
Considering the scarcity of salvage therapies to effectively treat this prior to <unk> daily population and we're excited to see these positive results.
And these data point us towards a registrational trial with our cost then doublet therapy and its growing prior to <unk> daily population that is in desperate need of affective salvage therapies.
Also among the 10 evaluable patients who received the test and Dublin three responses emerge among seven patients with <unk> mutated <unk> III for an overall, 43% response rate.
Patients with unmet <unk> three account for approximately 70% of the AML population yet there were a few treatment options have little in development for this patient population.
The ability of <unk> to treat patients with <unk> mutated for three significantly extends the market potential for this drug and this is an important differentiating feature anticipated.
In addition, while they refused with <unk> mutated patients in the test and debit trial to date, we observe responses in two of the three evaluable patients for an overall response rate, 67%, albeit small numbers one of the responders harbored the <unk> ITD mutation and the other hardware to mutation with tyrosine kinase domain again, highlighting the broad activity of this drug.
Against mutant forms of the three.
Thus far we have treated one evaluable patients in the doublet trial with a highly adverse mutation in the <unk> and we observed a response in this patient.
With very small numbers the numbers are trending in the right direction.
All of these patients have a great unmet medical need and as we have mentioned before the ability to rescue these patients may allow us a quicker and clear path to registration and EBIT monotherapy trial might.
Another differentiator is.
Suspending its favorable safety and Tolerability profile, even in the test and double it to date.
It may well prove to be an ideal therapeutic to combined with genetic lacks a noteworthy drug that can have its own side effects that could limit its prolonged use.
I mentioned in our last call that the <unk> represents an attractive treatment option for patients and their physicians, leading them to enroll earlier in the course of treatment and increasing the likelihood of achieving a meaningful clinical benefit as a result enrollment has been brisk. During the first half of 2023 and this continues with rapid enrollment we have become more heavily focused on accrual of patients where it has been.
Dublin Sir.
Factors drove the decision to focus more heavily on the Tesla in Dublin.
We know that test is very high has a highly favorable safety profile and its convenient as a once daily tablet.
And second does that have combined synergistically in preclinical in vivo models of AML and.
In addition in vitro drug resistant infection studies indicate that no drug resistance creates synthetic with Valerie Hermann <unk> and ourselves supporting the idea of anticipated as an ideal drug partner for combination therapy.
Anymore, the advisors and advising boards see a rapidly emerging need in AML patients treated with <unk> because once they stay on this drug they become highly refractive refractory to salvage therapy.
Our testing doublet data are still maturing, but they suggest that <unk> can deliver meaningful responses and its very difficult to treat prior venetic lock exposed AML population.
Because if that Nick has shown activity against a broad range of an L highly edgar expectation, including patients with <unk> mutated solid three mutations with <unk> mutated <unk> 53, mutated Ras mutated NOL.
We believe that test and other cancer in this broad population after failure of <unk> again, both in <unk> mutated and <unk> mutated patients.
This highlights the breadth of activity illustrating test is much more than a <unk> three inhibitor.
Data from the test end of our guidance towards the test been randomized Registrational trial in patients with second line or third line AML with private <unk> failure with exhausted. They were approved therapeutic options if any are available.
This trial may be powertrain early assessment to deliver an accelerated approval, while being continued for a full approval upon maturity of the data.
It served the needs of a significant AML population you would provide potential partners with data to build the commercial model is recognizing the value and it's the type of trial was recommended by Dr. <unk> and our clinical Advisory Board.
In addition collection of data with the test and tablet can provide immediate understanding to apply this debt as part of a test than HMA triplet study in frontline AML patients.
We know the paradigm for treating AML is quickly shifting towards a doublet and triplet combination therapies as our lead investigator Dr. <unk> and his team at MD Anderson have recently published achieving great success in combination therapies limited only by some of the additional toxicity that are brought into the mix.
By each of these agents.
Just noticed that in the strong safety profile.
HMA tablet as an addition to create a triplet that can be applied broadly to AML patients with mutated or mutated with three not nearly the 30% at carrier for <unk> mutation, a diagnosis and it can be done without the addition of cardiac toxicity and call. It minus depression that can be caused by competing agents.
So now let's briefly talk about just that did at monotherapy.
During our recently completed dose escalation dose expansion phase one two trial instead of as a monotherapy head delivered multiple responses across four dose levels with no DLT mutational diverse in difficult to treat relapsed refractory AML population.
<unk> with respect to monotherapy data emerging from our dose escalation and exploration trial as well as from our after the trial to date includes the patient with the CRC.
It's a lot about the single agent activity of Testbed Nib. It is clearly active across a broad range of annual genotype, including Dr. <unk> mutated <unk> mutated disease and even in the presence of other adverse mutations such as those in the Ras pathway in at <unk> 53.
We've also learned it later line activity and activity in patients previously treated with <unk> is less impressive as one might expect for any therapy.
Since our study began more and more AML patients are being treated with <unk> in the frontline and in first or second salvage setting off label, even when other approved therapies are available. Therefore, we will focus our ongoing efforts in AML on the combination of <unk>, where we have already seen clear activity, even infinera <unk> pretreated patients.
As we proceed through the second half of 2023, we plan to test us that in patients with Mds as I never ran out patients that aren't you said it was three and MTS like genetic features have responded well to dispatch it.
Particularly treatment with suspected monotherapy as well as in combination with <unk>.
We will have a lot more in Mds in our next earnings call.
The data, which has been collected to date have guided us to specific populations that may allow accelerated approval in the near term, but the spending of safety profile with its productivity and make it the ideal candidate for combination therapy in the frontline addressing a much larger market and that's ultimately what we're working towards while we currently do not have the resources to pursue all of these development and commercialization paths participated.
We will collect data to help select trials that will provide the fastest accrual clearer signals and earliest approvals.
The most interesting it would be of great interest and most potential partners.
Having said that as Dr. <unk> mentioned earlier, we are in discussions with a number of potential partners because it's been it looks like a large biotech large pharma drug.
Beyond our capacity as a small biotech to fully exploit its capabilities and market potential there.
Before we may adjust our patient accruals to meet the needs of App to meet the need that regulatory agencies and to meet the needs of potential partners.
So to summarize our clinical plans does that NIM, because it's proven breadth of activity and superior safety profile ultimately may address the most sizable markets in AML, we are developing and as such first.
The emerging data are guiding us to a registrational trial.
Trial for accelerated approval with the test then double it and to target AML patients, who have failed <unk> therapy, a population with great unmet medical need.
The data from this trial will inform additional registrational trials for a triplet combinations in frontline therapies and finally for use in the maintenance therapy setting as well.
So let me sum up.
Because after the it is an open label trial, we will report data when available at appropriate forums.
As we discussed in our last call we plan to present, an expanded clinical dataset, particularly from the test and doublet arm at the European School of Hematology meeting, our Esa in October and even more data than to be updated at the ash meeting in December .
In November during our earnings call, we will provide additional interim updates and then in December around the Ash annual meeting we plan to present more mature clinical data.
Got it.
Also during the fourth quarter of this year, we expect to provide additional color around our registrational plans with this data.
As Bill mentioned earlier, we may release material findings at anytime during these conferences, earning calls so we have a lot to look forward to in the coming months stay tuned now.
I'd like to turn the call over to our CFO , what youre paying for an update on our financial status.
Thanks, Rob good afternoon, I'd like to start by noting that in addition to our comments in this call additional information may be found in today's press release, and the 10-Q filed with the SEC.
As Phil mentioned during the quarter, we entered into a $25 million committed equity facility with Keystone capital, which provides access to the right to sell and issue up to $25 million of its common shares over 24 months to Houston.
Additionally.
We have.
The $7 million binding term sheet that we signed with Hanmi pharmaceutical, which will help <unk> continue to invest in our clinical programs. We are grateful for the support of Hanmi in Keystone for their confidence in <unk>.
The Hanmi term sheet outlines an investment of up to $7 million or $19, 99% ownership interest in <unk> in two tranches, we anticipate the first tranche of $3 million will be closed by the end of August the second tranche of up to $4 million or a maximum of $19 99% ownership.
Our meeting certain to substantive milestones, which are expected to be achieved by year end. The use of the proceeds were used to fund the <unk> program.
Investment is also conditioned on customary closing conditions and meeting their requirements and approvals of the TSS nasdaq's.
Now lets review the second quarter 2023 financials, we continue our disciplined financial management of our operations and prioritization of our investments in the clinical program. We ended the second quarter of 2023 was approximately $23 $3 million in cash cash equivalents and investments.
A decrease of $12 4 million as compared to March 31 2023.
$102 million increase in our cash burn as it related to spending on the activate study to set the net clinical materials, a decrease in our accounts payable and partially offset by certain liabilities.
On a cumulative basis through June 30 of 2020. The company has raised a total of $1 2 million of gross proceeds from the <unk> two and.
And 'twenty two ATM facility.
Based on current operations.
The company expects a cash on hand, our available capital will provide the company with sufficient resources to fund planned company operations, including research and development through March of 2024.
During the quarter. The net loss was approximately $14 1 million translating into a $2 27 a share per.
Per share loss compared to $10 million $610 6 million dollar loss from the same period in 2022, I will note all references to share prices and numbers of shares per share.
And presented in reflection of the one for 15 reverse stock split completed on June six 2023.
As identified in the income statement, we had no revenues during the first six months of 2023.
Research and development expenses were approximately $10 6 million for the quarter compared to $7 3 million during the same quarter of 2022.
Program costs for certain net were $8 1 million for the three months ended June 32023, compared to $2 3 million for the three months ended June 32022.
The higher programming costs, which is something that in the current period represent the enrollment of patients in our activate clinical trial, our clinical materials healthy volunteer trial and.
Other related expenses.
The program costs.
<unk> were 706000 for the three months ended June 32023, and.
And decreased by approximately $1 7 million compared to $2 4 million for the three months ended June 32022, primarily due to lower manufacturing costs. As a result of the current G III formulation, requiring less API and prior formulation.
G&A expenses were $3 9 million for the quarter compared to $3 3 million from the same quarter of 2022.
The increase was primary due to increased salaries expense and higher professional fees.
As of August 10, 2023, after <unk> had $6 million 519, 201 common shares outstanding.
Now, let's turn it back to Dr. Rice.
Thank you Fletcher.
Now we will open the call for questions and please feel free to pose a question to any of US operator, if you could please introduce the questions.
At this time I would like to remind everyone that if you would like to ask a question.
You will need to press star one on your telephone.
Well, then maybe message advising lay your hands if you would like to withdraw your question. Please press star one again.
While we compile the Q&A.
Your first question comes from Edward <unk> of Piper Sandler.
Yeah.
Great. Thank you again.
Thanks for taking my question and looking forward to more data later this year.
When it comes to the recent pardon me.
Investment I'm, sorry couldn't quite hear what you said about this.
The second tranche was $4 million. The first purchased $3 million is there a specific <unk>.
Number fair factor with your servers.
Okay. Thanks, very much for the call so.
Proposed term sheet does anticipate selling common stock in the first tranche of $3 million. The structure that has been proposed in the binding term sheet is.
It is made up by to look back features looking at different averages over two different time periods.
And including a slight premium on top of that more details will be provided when we closed the first tranche of that.
So as we move forward.
In October .
Occur in August of this year August sorry, Bob.
The $4 million tranche up to $19, 99%.
<unk> is also anticipated to be some form of equity.
Including common stock.
We also have the flexibility and negotiate a structure that would be acceptable to both parties.
If we reach the $19 99%.
And want to invest above that level.
And the two tranches of Michigan, just so there is flexibility in that fourth tranche.
And it's anticipated that potentially the company will have additional issuances between now and that timeframe and so its uncertain at the exact price point of those shares.
Thank you very much.
Yes, Thanks, Tim.
Thank you.
Next question.
Okay.
The next question comes from Matthew Biegler with Oppenheimer.
Please go ahead.
Hey, guys. Thanks for the update here.
On the combo.
You have any literature on either like a delayed another clock response or re sensitization re sensitization to vanilla costs I guess.
And how confident are we that.
What was driving the activity of the combination which looks really encouraging.
Ralph would you like to take that one and then I can jump in at par. Furthermore, sure yeah, Matt. Thanks for that question. It's a good question.
I think if you look back at the monotherapy trials of <unk> in the relapsed refractory setting even patients that were naive to <unk>. The response rate really werent very impressive.
The singles.
Therapy than aircraft studies, even increase the dose up to 800 milligrams twice, what we give in combination with the standard.
Very modest response rates in very short duration of response. So I don't think there have been <unk> by itself is doing a heck of a lot. However, it may be the case that with a different partner switching from HMA that spend at <unk>.
Kindles the sensitivity to a an aircraft that is one possible interpretation for the activity that we're seeing.
And by targeting a different mechanism.
Action in the combination that we're using compared to what the patient had been exposed to before so we don't believe that it is <unk>.
By itself, that's really doing something here, we do we do believe that it's something that's in combination with many of these patients are coming right off of HMA that Pryor and many patients and had it a long time before and then add other therapies in between when we think about our Registrational trial, we are going to be focused more on a former setting.
Come directly from that prior therapy to our study.
Okay.
Thanks, Rob.
So Matt you may recall that when <unk> was originally being.
Tested in AML it was clear that it didnt have good single agent activity.
And then when you get to the relapsed refractory patient population, it's even less effective as a monotherapy and we hear that from all the kols.
There are very few publications on this but it's clear that the venetic clinics alone in this population.
It's just not very effective at all so we're thrilled to see that when we combine it.
With her spend that we're seeing good response rates.
Matt for being there.
Yes, good contact.
Thank you one moment for our next question.
Your next question comes from Lee <unk> of Cantor Fitzgerald. Please go ahead.
Okay. Thank you for taking our questions and congrats on that.
Uh huh.
A couple for the black.
Can you just remind us when does the RFP benchmark.
Is for patients who are claiming credit with without a quack.
I think you mentioned single J, just wanted to come from that.
The second note what is the C.
Our SCR etch rates 40 10 patients.
Correct.
I had difficulty hearing so perhaps you can though I heard I heard the question.
Yes.
That's a good question. So what is the benchmark for patients who have failed HMA band.
And different settings, and there are a couple of different publications that have come out recently that then identify the.
Poor response rate that these patients have accurate failure of an <unk>.
In one study it was below 10% and that steady at 12% I think on average.
We are see rate, which include Cri is probably on the order of 8% to 12%.
Not to mention the CR rate, which unfortunately isn't always broken out in these studies. So we're encouraged by the activity that we've seen in our study to date.
As you'll also note that in several of the studies that have combined <unk> with our agents responses. Initially began will be calling complete responses are with incomplete hematologic recovery and mature over time. So our data right now or are not quite as mature we've only been at this for a couple of months now with the combination.
No.
We will tell you that we have responses, but some of those responses can be maturing further so.
We're giving the CRC right at the moment and we'll give you more detail as the trial develops.
Okay.
The next question is I know, it's early but can you comment.
From a.
Durability.
Yes. It is early I think it's hard to talk about what the overall durability is I would say that we do have patients that have remained for many cycles and have patients that are continue to be ongoing. So we don't think that this is an instance of people having a response and then two weeks later coming our study, we've certainly seen more durability than that.
Ultimately, we will have to see how durable these responses end up being but we're hopeful that.
Patients are tolerating treatment, while we will be able to stay on for a long time.
Okay.
And are any of these patients who achieved CR the went on to transplant.
And current product call you allow patients to get back on the drug after transplant.
Yes, it's still early so no data to reported that stem cell transplant, but as you have had many patients on the monotherapy portion of the debt that we did in the dose escalation exploration go on to transplant.
We now do include the ability for patients to resume dosing after transplant if they meet certain criteria that can be in remission for example, and not have any.
Ongoing toxicity from the transplant, there might interfere with or treatment, but if they meet those criteria it would be able to resume dosing with <unk> as a single agent after stem cell transplantation.
Okay. Thank you very much.
Thank you one moment for your next question.
The next question comes from Joseph <unk> of H C. Wainwright.
Hi, This is Sarah on for Joe I was wondering if you can maybe frame expectations for.
Psh in October I know, it's kind of early but maybe could you speak to what kind of data readouts, we could expect thank you.
So let me take this one initially.
So initially what we're presenting today with what we had planned on presenting at the ESA two in October .
So we're actually putting this information and data out early.
It is because we made the decision earlier this year to begin putting patients on the doublet much earlier than we had anticipated.
Just everything pointed toward the doublet. So we tried to began trying to drive patients on as quickly as possible has been really brisk.
And so the data that we're presenting now was originally what we had planned on presenting at <unk>.
<unk> said that we continue to put patients.
Dr Bejar mentioned a moment ago.
Some of the patients that are currently at now we're hoping to see those patients mature overtime. You said very often when you first put them on the doublet, especially with <unk> you don't get the full count recovery of the normal blood counts initially and it takes a bit of time for them to recover up so we'll be watching for that in addition, we're putting additional patient.
So on now and over the next couple of months. So our primary data cut will be sometime in September .
For the for the final presentation of data at the end of October and El <unk>, but we also provide the preliminary data that were collecting during September and the early part of October . So it will be more mature data than where we are now, but it's still going to be.
From dataset.
Okay. Thank you fair enough. Thank you.
Thank you Ron Let me turn next question.
Your next question comes from Sumit Roy of Jones trading. Please go ahead.
Hi, everyone. Congratulations on the progress on the solid.
Data from the Vantiv <unk> combination arm.
Could you give us.
A little bit color on.
Of the five responders like how many were in.
Complete blood recovery Cri bone marrow Crs.
And what were their baseline.
Glass Carin Claire.
Okay.
So if I can take this initially and then you can jump in so.
Actually we have at this point we have once you are a couple of CR is I believe once ERP.
We don't have any prs or MLR.
LFS. So it's all of a CR type that's why we call it the composite CR.
In terms of the entry blast counts I can't recall all of those for the patients the.
Physicians have characterize these as complete remissions, we will continue to collect all the data with these patients.
The entry percentage blast in the bone marrow.
The recovery of the normal cells in the blood. We will also have to get additional information on the mutation status of all the patients. So we'll get some information like that from the clinic initially, but we have to go back and make sure we source verify everything and do a deeper dive on the mutation. So we pulled I understand these patients can be hard to do.
Yes, yes, I just wanted to correct. One thing that you said in our study the response criteria that are being used to add.
Started the study when it was initially initiated by Hanmi.
Ill go back to <unk> 2003, so in that case MLS Essent Cri or are lumped together. So the responses that we have don't mentioned MLR, specifically because MFS is part of Cri. So there are some patients that clearance of blast without count recovery, yet, but many patients remain on study. So I don't know what will happen to those pages.
They could certainly evolve it to have improved counts in our more mature response, but we'll have to wait to see I think to answer <unk> question I think by the time, we get TSH will have more of that information and then we'll be able to answer. These questions about what has happened to these patients what kind of response that they've had.
It makes sense.
If anybody already underway in transplantation or <unk>.
<unk> being undergone stem cell transplantation.
Second is.
In the wild type population Thats pretty encouraging two out of three showing composite CR any plan on somehow focusing more on enrolling these wild type patient, it's going to be as the publishing distribution will be occupation issue. Let me let me correct you had.
Two out of three responders in this with the mutant population and where efficacy evaluable.
We've had.
Three out of seven responders indeed.
Indeed.
On mutated supported nine I'm, sorry, blanking on the numbers a little bit here, but.
Two out of three where the <unk> mutant population.
Okay.
My apologies.
But.
And do you have any color on how many patients undergoing stem cell transplant and I missed the last part when you were mentioning about the Mds program are you going to partner out that part of it are.
For the bandwidth issue or what are you talking about.
So it's really too early to discuss transplant in this patient population because even if a patient were intended to go to transplant from the outset. It would take a couple of months to get there and honestly the sites don't necessarily share their plans for the patients with us in real time, we learned about it often.
As patients are coming off study to go on transplant in the past are now going in transplant and taking a pause in dosing. So we'll have more on that Esa, which is the Mds pilot that we discussed we want we're going to do that ourselves and it is included as a subpopulation within the activate study where we can explore the activity in this broader patient indication.
Also for a quick correction so for flip three wild type patients who are three of 743% CRC rate.
$3 seven and the flip <unk> Wild type was two or three.
Say that again.
Im sorry, Im sorry, flip three mutated was two of three <unk>.
Flip three wild excuse me flip three wall type was three seven.
And flip through perfect. It was two or three yes.
Clears my perfect Alright.
Apologies for starting up the confusion, but thank you again for taking the questions and congratulations thank you.
Thank you our next question.
Your next question comes from Gregory <unk> of RBC capital markets. Please go ahead.
Hi, Bill and team, it's a niche on for Greg Congrats on the quarter and thanks for taking my questions. Just a couple for me as we start to think about the competitive landscape and the recent approval of flit three inhibitor from Daiichi, which have met safety bars from regulators. How are you thinking about safety buyers going forward precedent and messaging on the differential safety profile.
To spurt nib and I have a quick follow up.
Rob do you want to take that one.
Sure all right now we're happy to see that create craze. Finally achieved a response rate in an indication that got approved I think it is important addition to the aren't material.
So <unk> got approved in combination with chemotherapy in the frontline setting.
Treating a broader set of patients that were treated in the early might've Stern trials. However, they do have a rems system I think largely because of the concern about TTC prolongation.
We are fortunate not to have that as a toxicity with respect we really haven't seen qt prolongation of something thats related to the drug.
Some of the other potential potential issues that plagued other kinase inhibitors, so as far as how it's going to affect us I don't think it will necessarily I think that the quiz and just about every very different drugs and we would hope that we could be able to treat patients who received <unk> in the frontline we've already.
Seeing activity both in <unk> treated patients. So we expect that that would be the case. So we welcome it to the to the landscape and I don't think its going to change our approach in relapsed refractory where liquidity is not approved.
Great. Thanks that makes sense and lastly, just a quick one what should investors expect around the coming doublet data package in October at Esa and what are your objectives with the data disclosure I appreciate the time and congrats again on the progress.
Alright. Thanks, So we've covered this a bit a few minutes ago.
In terms of what's going to be expected that Esa it's going to be.
A continued maturation of the data that we currently have with patients that are currently on trial to watch these patients to see if the mature towards more mature Crs.
And recovery of the normal bone marrow. So we'll watch these patients that are currently on trial. We're also putting in additional patients on trial and we'll be following those over the next couple of months, but as I mentioned the current data that we're presenting now is what we're expecting to presented yes H. So we're way ahead of the game already or your presentation of the data because we.
Began treating patients earlier this year than.
Than expected with the doublet.
Okay.
Alright, great. Thanks, so much I appreciate it.
Thank you.
Again, if you would like to ask a question. Please press star one on your <unk>.
Perfect.
And I'm currently showing no further questions I will now turn the call back over to Dr. <unk> for closing.
Well. Thank you for joining us. This afternoon 2023, thus far has been a year of clinical and strategic advances for our posts and we thank our employees, our investigators and our patients for their help in this important work our clinical team has been key in getting after the trial up and running so efficiently with multiple global clinical sites on board and so I want to recognize.
Size them for their execution.
We appreciate the support of our shareholders, who have been with us through the clinical development timelines and the analyst who recognize the potential of a drug that has shown such broad activity in difficult to treat AML patients get maintains a superior safety profile. We look forward to keep you updated on our progress and finally I'll remind you that we will be in New York to participate in Investor.
Conferences during September and perhaps we can see you there with that I want to thank you and have a good evening.
Thank you ladies and gentlemen that concludes today's conference you may now all disconnect and have a wonderful day.
Okay.
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Yeah.
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