Q1 2022 Kura Oncology Inc Earnings Call
Operator: Good day, and welcome to the Kura Oncology first quarter 2022 earnings conference call. Participants will be in listen-only mode.
Good day, and welcome to the care and collagen <unk> first quarter 2022 earnings conference call. All participants will be on Osama Mad shutting their assistance. Please signal conference specialist by pressing the star key followed by zero.
Operator: Should you need assistance, please signal a conference specialist by pressing the star key followed by 0. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then 1 on your telephone keypad.
After today's presentation there'll be an opportunity to ask questions.
Can I ask a question you May press Star then one on your telephone keypad to withdraw your question. Please press Star then two.
Please note. This event is being recorded I would now like to turn the conference over to Mr. Pete Disdain Senior Vice President of Investor Relations. Please go ahead.
Operator: To withdraw your question, please press star then- Please note, this event is being recorded. I would now like to turn the conference over to Mara Goldstein, Senior Vice President of Investor Relations. Great, thank you, Ian. Good afternoon and welcome to Kura Oncology's first quarter 2022 conference call. Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer, and Tom Doyle, our Senior Vice President of Finance and Accounting.
Mara Goldstein: Dr. Stephen Dale, our Chief Medical Officer, is also with us and available to answer questions. Before I turn the call over to Dr. Wilson, I'd like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the SEC or on the Kura Oncology website, for information concerning risk factors that could affect the company. With that, I'll now turn the call over to Troy.
Great. Thank you and good afternoon, and welcome to Curl Oncologists first quarter 2022 conference call. Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer, and Tom Doyle, Our senior Vice President of Finance and accounting Dr. Steven <unk>, Our Chief Medical Officer is also with us and available to answer questions.
Before I turn the call over to Dr. Wilson I would like to remind you that today's call will include forward looking statements based on current expectations such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to <unk> filings with the FCC.
Which are available from the SEC or on the current oncology website for information concerning risk factors that could affect the company with that I'll now turn the call over to Troy.
Troy Wilson: Thank you, Pete, and thank you all for joining us this afternoon. Despite what continues to be a challenging, broader market environment, we continue to operate from a position of strength here at Kura, armed with three independent drug development programs, a strong, experienced team, a well-designed clinical development strategy, and a cash runway through 2024. Now, as we approach a series of important catalysts driven by completion of enrollment in the Phase 1b study of our Menin inhibitor, Ziftaminib, and culminating in top-line data next quarter and a full data presentation in the fourth quarter.
Thank you Pete and thank you all for joining us this afternoon despite what.
It continues to be a challenging broader market environment. We continue to operate from a position of strength here at Kura armed with three independent drug development programs are strong experienced team a well designed clinical development strategy and a cash runway through 2024.
Now as we approach a series of important catalysts driven by completion of enrollment in the phase <unk> study of our Menin inhibitor Ziff demanded and culminating in topline data next quarter and a full data presentation in the fourth quarter.
Troy Wilson: As mentioned, I'm pleased to report we recently completed enrollment of the patients in the Phase 1b portion of COMET-001 required to identify a recommended Phase 2 dose for zyftominib. Recall, the study was designed to enroll two expansion cohorts, 200 mg and 600 mg, with each cohort comprised of patients with NPM1 mutant or KMT2A rearranged, relapsed, and or refractory acute myeloid
As mentioned I am pleased to report, we recently completed enrollment of the patients in the phase <unk> portion of comment 001 required to identify a recommended phase II dose preserved a minute.
Recall the study was designed to enroll two expansion cohorts 200 milligrams and 600 milligrams with each cohort comprised of patients with <unk> mutant <unk> rearranged relapsed or refractory acute myeloid leukemia.
Troy Wilson: The goal of Phase 1B is dose optimization consistent with FDA's guidance around Project Optimist, and the two doses were selected based on the encouraging clinical activity, safety profile, and tolerability demonstrated in the Phase 1A portion of the study. We're now assessing the patients in each expansion cohort for safety and tolerability, pharmacokinetics and exposure, as well as efficacy. We remain on track to identify the recommended phase 2 dose for ziftimenib and to report top-line data from the phase 1b study in the third quarter, with a more complete data set from Comet 001 reserved for presentation at a medical meeting in the fourth quarter.
The goal of the phase <unk> dose optimization, consistent with Fda's guidance around project Optimists and the two doses were selected based on the encouraging clinical activity and safety profile and Tolerability demonstrated in the phase <unk> portion of the study.
We are now assessing the patients in each expansion cohort for safety and Tolerability pharmacokinetics and exposure as well as efficacy.
We remain on track to identify the recommended phase two dose for <unk> and to report top line data from the Phase <unk> study in the third quarter with a more complete data set from comment 001 reserve for presentation at a medical meeting in the fourth quarter.
Troy Wilson: As a reminder, the study protocol gives us flexibility to enroll additional patients in Phase 1b, enabling us to maintain momentum while we transition into a subsequent Phase 2 registration-directed portion of Comet 001. We believe data from all patients treated at the recommended Phase 2 dose will have the potential to contribute to the registrational patient population. Meanwhile, we remain enthusiastic about the encouraging safety profile, tolerability, and clinical activity we are observing in the Phase 1B study, as we continue to add sites in the U.S. and Europe in anticipation of the subsequent Phase 2 portion of Comet 001. We also intend to conduct a comprehensive development strategy that builds upon the potential to register Zyftomeneb as a monotherapy while giving us flexibility to access larger opportunities through combinations and in earlier lines
As a reminder, the study protocol gives us flexibility to enroll additional patients in the phase one b, enabling us to maintain momentum while we transition into a subsequent phase III registration directed portion of comment 001, we believe data from all patients treated at the recommended phase II dose.
We will have potential to contribute to the registrational patient population mean.
Meanwhile, we remain enthusiastic about the encouraging safety profile.
Profile Tolerability and clinical activity, we are observing in the phase <unk> study.
As we continue to add sites in the U S and Europe in anticipation of the subsequent phase II portion of comments there was zero one.
We also intend to conduct a comprehensive development strategy that builds upon the potential to register Ziff de <unk> as a monotherapy, while giving us flexibility to access larger opportunities through combinations and in earlier lines. We look forward to sharing much more regarding our global development strategy for <unk> later this year.
Troy Wilson: We look forward to sharing much more regarding our global development strategy for ZIF-demented later this year following identification of the recommended phase 2 dose. Now, let's turn our attention to our farnesyl transferase inhibitor program. We continue to view farnesyl transferase inhibition as a potentially valuable therapeutic and commercial franchise, one with the potential to deliver multiple opportunities in oncology.
Following identification of the recommended phase two dose.
Now, let's turn our attention to our Farnesol transfer Ace inhibitor programs, we continue to view Farnesol transfer ace inhibition as a potentially valuable therapeutic and commercial franchise, one with potential to deliver multiple opportunities in oncology.
Troy Wilson: One of the first examples of the use of FTIs as a targeted therapy was the demonstration of the potential for tipifarnib to drive durable responses in recurrent and metastatic HRS mutant HNSCC, and our ongoing AMHN registration-directed trial continues in that indication. More recently, we've begun efforts to build upon the initial monotherapy activity of tippee-farnab with two goals. Number one, to drive deeper and more durable responses, and number two, to expand the potential patient population.
One of the first examples of the use of <unk> as a targeted therapy was demonstration of the potential for <unk> to drive durable responses and recurrent and metastatic <unk> mutant <unk> FCC and our ongoing aim HN registration directed trial continues in that indication.
More recently, we have begun efforts to build upon the initial monotherapy activity of <unk> with two goals.
Number one to drive deeper and more durable responses and number two to expand the potential patient population toward this end we are pursuing the current HN trial to evaluate the combination of <unk> and inhibitor of <unk> kinase Alpha in selected <unk> SCC patient cohorts by combining <unk> and <unk>.
Troy Wilson: Toward this end, we're pursuing the current HN trial to evaluate the combination of tipifarnib and delpelicib, an inhibitor of PI3 kinase alpha, in selected HNSCC patient cohorts. By combining tipifarnib and delpelicib, we believe we can achieve both goals. Our preclinical data suggest the combination has the potential to provide meaningfully better anti-tumor activity relative to inhibiting either target alone.
<unk>, we believe we can achieve both goals.
Our preclinical data suggests the combination has potential to provide meaningfully better antitumor activity relative to inhibiting either target alone and by targeting both <unk> and HRS dis regulated <unk> SCC.
Troy Wilson: And by targeting both PIK3CA and HREF dysregulated HN-SCC, the combination has potential to increase the total addressable population for tipi farnip to as much as 50% of patients with HNSCC. In December, we dosed the first patient in our Phase 1-2 current HN trial of tipifarnib in combination with alpelesib in HN-SCC. The initial cohort includes patients who have PIK3CA
The combination has potential to increase the total addressable population for <unk> to as much as 50% of patients with HSBC.
In December we dosed the first patient in our phase one two current HN trial of <unk> in combination with <unk> in <unk> FCC. The initial cohort includes patients who have pick three CA dependent <unk> FCC screening has commenced an in HRS over expression cohort and we expect to dose the first patient.
Troy Wilson: Screening has commenced in an HRAS overexpression cohort, and we expect to dose the first patient in this cohort by the third quarter. Our goal with the current HN trial is to identify a recommended phase 2 dose schedule for the combination and look for early signs of clinical activity. Our team is making excellent progress, and we look forward to providing an update. Beyond HNSCC, we're beginning to understand that FTIs may represent an ideal combination partner for certain classes of targeted therapy in large solid tumor indications.
In this cohort by the third quarter.
Our goal with the current HN trial is to identify a recommended phase II dose and schedule for the combination and look for early signs of clinical activity. Our team is making excellent progress and we look forward to providing an update.
Beyond <unk>, we are beginning to understand <unk> may represent an ideal combination partner for certain classes of targeted therapy and large solid tumor indications. The first of these emerging combination opportunities was highlighted last month in a late breaking presentation at the American Association for <unk>.
Troy Wilson: The first of these emerging combination opportunities was highlighted last month in a late-breaking presentation at the American Association for Cancer Research annual meeting in New Orleans. The new findings were generated through a collaboration with INSERM, the French National Institute of Health and Medical Research. The presentation featured preclinical data supporting the potential for tipifarnib to prevent the emergence of resistance to osimertinib in EGFR mutant non-small cell lung cancer. Several farnesylated targets were identified that appear to control the ability of lung cancer tumor cells to enter and exit a state that makes them tolerant to osimertinib.
Answer research annual meeting in New Orleans, the new findings were generated through a collaboration with <unk>, The French National Institute of Health and Medical research. The presentation featured preclinical data supporting the potential for <unk> to prevent the emergence of resistance to <unk> nib in Egfr mutant non small cell lung.
Cancer.
Several foreign insulated targets were identified that appear to control the ability of lung cancer tumor cells to enter and exit the state that makes them tolerant <unk> using preclinical in vivo models of Egfr mutated lung tumors co treatment with Tippi foreign a durably prevented relapse to <unk> for up to six months.
Tom Doyle: Using preclinical in vivo models of EGFR mutated lung tumors, co-treatment with tipifarnib durably prevented relapse to osimertinib for up to six months with no evidence of toxicity. Collectively, these data strongly support the potential use of an FTI to prevent or delay the adaptive response to osomertinib. We're preparing to initiate a Phase I study of tipifarnib in combination with osomertinib in treatment-naive, locally-advanced, and or metastatic EGFR-mutated non-small cell lung cancer, and we expect to dose the first patient in that study, which we call the current lung trial, in the third quarter.
With no evidence of toxicity collectively these data strongly support the potential use of an STI to prevent or delay the adaptive response to <unk>.
We're preparing to initiate a phase one study of <unk> in combination with <unk> nib in treatment naive locally advanced <unk> metastatic egfr mutated non small cell lung cancer, and we expect to dose the first patient in that study, which we call. The current lung trial in the third quarter.
Tom Doyle: We intend to perform initial clinical evaluations with Tippi Farnab and Ossa Mertinib while in parallel advancing KO 2806, the lead development candidate in our Next Generation FTI program through IND-enabling studies. We remain on track to submit an IND application for KO 2806 in the fourth quarter. With that, I'll now turn the call over to Tom for a discussion of our financial results. Thank you, Troy.
We intend to perform initial clinical evaluation with typify <unk> nib, while in parallel advancing <unk> thousand 806, the lead development candidate in our next generation FTA program through IND, enabling studies, we remain on track to submit an IND application for <unk> 2008, six in the fourth quarter.
With that I'll now turn the call over to Tom for a discussion of our financial results.
Tom Doyle: And good afternoon, everyone. I'm happy to provide a brief overview of our financial results for the first quarter of 2022. I invite you to review our 10-Q file today for a more detailed discussion. Research and development expenses for the first quarter of 2022 were $20.9 million, compared to $20.3 million for the first quarter of 2021. The increase in R&D expenses was primarily due to the increase in ZIF-dominated clinical trial and personnel costs.
Thank you Troy and good afternoon, everyone I'm happy to provide a brief overview of our financial results for the first quarter 2022.
I invite you to review our 10-Q filed today for a more detailed discussion.
Research and development expenses for the first quarter 2022 were $20 9 million compared to $20 3 million for the first quarter of 2021 the.
The increase in R&D expenses was primarily due to the increase in settlement of clinical trial and personnel cost.
Tom Doyle: General and administrative expenses for the first quarter of 2022 were $11.9 million, compared to $10.6 million for the first quarter of 2021. The increase in G&A expenses was primarily due to an increase in professional fees and non-cash share-based compensation.
General and administrative expenses for the first quarter of 2022, or $11 9 million compared to $10 6 million for the first quarter of 2021.
The increase in G&A expenses was primarily due to the increase in professional fees and noncash share based compensation.
Troy Wilson: The net loss for the first quarter of 2022 was $32.5 million, compared to a net loss of $30.7 million for the first quarter of 2021. This included non-cash share-based compensation expense of $6.7 million, compared to $5.1 million for the same period in 2021. As of March 31, 2022, we had cash, cash equivalents, and short-term investments of $480.1 million compared to $518 million as of December 31, 2021. Based on our current plans, we believe that our cash, cash equivalents, and short-term investments will fund current operations through 2024.
Net loss for the first quarter of 2022 was $32 5 million compared to a net loss of $30 7 million for the first quarter of 2021.
This included noncash share based compensation expense of $6 7 million compared to $5 1 million for the same period in 2021.
As of March 31, 2022, we had cash cash equivalents and short term investments of $480 1 million compared to $518 million as of December 31, 2021.
Based on our current plans, we believe that our cash cash equivalents and short term investments will fund current operations through 2024.
Troy Wilson: With that, I now turn the call back over to Troy. Thank you, Tom. Before we jump into the question and answer session, let me just lay out our anticipated milestones for 2022. For our Mennon inhibitor program, identify the recommended phase two dose of ZIF for Mennon and report top-line data from the phase 1B study in the third quarter; present updated data from Comet 001 at a medical meeting in the fourth quarter.
With that I'll now turn the call back over to Troy.
Troy Wilson: And for our FTI programs, dose the first patient in the HRAS-over-expression cohort of current HN in the third quarter, dose the first patient in the current lung trial in the third quarter, and submit an IND application for KO-2806 in the fourth quarter. With that, Operator, we're now ready for questions, and I'll begin the question and answer session. If you have a question, you may press star then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the button.
Thank you Tom before we jump into the question and answer session. Let me just lay out our anticipated milestones for 2022.
For our Menin inhibitor program identify the recommended phase II dose of Ziff demanded and report topline data from the phase <unk> study in the third quarter.
Present updated data from comment 001 at a medical meeting in the fourth quarter.
And for our FTA programs dose the first patient in the HRS over expression cohort of current HN in the third quarter dosed. The first patient in the current long trial in the third quarter and submit an IND application for <unk> hundred $28 six in the fourth quarter with that operator, we're now ready for questions.
We will now begin the question and answer session.
To ask a question you May press Star then one on your telephone keypad.
If youre using a speakerphone please pick up your handset before pressing the keys.
To withdraw your question. Please press Star then two.
Operator: To withdraw your question, please press star. At this time, we will pause momentarily to assemble our... Our first question comes from Jonathan Chang of SVB. Please go ahead. Hi guys, thanks for taking my questions- Jonathan Chang at SCB Securities now. First question on Zisto Menib.
At this time, we will pause momentarily to assemble our roster.
Troy Wilson: Can you please refresh our memories as to what investors can expect in the top line third quarter data versus the medical meeting presentation in the fourth quarter? Sure, Jonathan. Thanks for the question. So, the focus of the top-line data will really be around the safety, tolerability, and clinical activity at the recommended phase 2 dose, Jonathan, with a particular focus on the CR-CRH rate in the patients that were enrolled in the dose that we've identified as the recommended phase 2 dose. That's what you should look for in the top line.
Our first question comes from Jonathan Chang.
The.
Leerink. Please go ahead.
Hi, guys. Thanks for taking my questions.
Jonathan Chang at FCB Securities.
First question on the stove mandate.
Can you please refresh our memories as to what investors can expect and the top line third quarter data versus the medical meeting presentation in the fourth quarter.
Sure Jonathan Thanks for the question.
The focus of the topline data will really be around the safety tolerability and clinical activity at the recommended phase two dose Jonathan.
Particular focus on the CR cri rate in the patients that.
That were enrolled in the dose that we've identified as the recommended phase II dose. That's what you should look for in the topline.
Troy Wilson: The data that will be reserved for a little bit later in the year at a medical meeting, there you should look for a much more fulsome presentation of the data from the COMET-001 study, and that's where we'll get into, you know, the breakdown between the specific genetic subtypes, more detail around both the safety and tolerability as well as the efficacy, you know, potentially, you know, specific anecd And just a much more comprehensive data set.
In the data for the <unk>.
It'll be reserved for a little bit later in the year at a medical meeting there you should look for a much more fulsome.
The presentation of the data from the comment 001 study and Thats, where we will get into the.
The breakdown between the specific genetic subtypes.
More detail around both the safety and Tolerability as well as the efficacy.
Potentially specific anecdotes around around patients that are interesting and I was just a much more comprehensive dataset. The topline is really intended as we've guided consistently just to communicate that we have identified the recommended phase II dose and to help.
Troy Wilson: The top line is really intended, as we've guided consistently, just to communicate that we've identified the recommended phase 2 dose and to help inform investors that we continue along the path toward what we believe will be the start and ultimately the execution of a successful phase 2.
To help inform investors that we continue along the path toward what we believe will be the start and ultimately the execution of a successful phase II.
Got it thank you.
Troy Wilson: And second question, with enrollment completion in the phase 1b expansion cohorts, can you provide any color on how many patients in the cohorts have the NTM1 mutation versus KMT2A rearrangement? Yeah, it's a good question, Jonathan, and thank you for it. Without getting specific, you know, what I can tell you is we actually see a pretty good balance between the two populations. I'm going to hold off on the specific numbers until we get to the data presentation in the fourth quarter, but suffice it to say, we didn't see any sort of disproportionate enrollment to one genetic subtype or the other.
And second question with enrollment completion in the phase one expansion cohorts can you provide any color on how many patients in the cohorts have NPM, one mutation versus KN <unk> rearrangement.
Troy Wilson: We see a good balance, and that gives us confidence that, as we've said all along, from our perspective, we think there will be one recommended phase two dose to treat both patient populations, and we're seeing, you know, we're seeing what we want to see in both populations. So, you know, hopefully that helps give you a little bit more color on your question. Great. Thank you. Thanks for attending.
Yes, it's a good question, Jonathan and thank you for it.
Without getting specific.
What I can tell you is we actually see a pretty good balance between the two populations.
I'm going to hold off on the specific numbers until we get.
Until we get to the data presentation in the fourth quarter, but.
Suffice it to say, we didn't see it sort of a disproportionate enrollment to one genetic subtype or the other we see good balance and that that gives us confidence that as we've said all along from our perspective, we think there's going to be one recommended phase two dose to treat both patient populations and we are seeing.
We're seeing what we want to see in both populations. So hopefully that helps give you a little bit more color on your question.
Great. Thank you thanks for taking the questions.
Sure. Thank you.
Operator: Sure, thank you. Our next question comes from Peter Lawson of Barclays. Please go ahead. Mr. Lawson, your line is now live. Thanks so much, Troy.
Our next question comes from Peter Lawson with Barclays. Please go ahead.
Mr. Lawson Your line is now live.
Thanks, so much Troy.
Operator: The first question's just around safety, just how much safety data we're seeing, the date and if you've seen any further cases of differentiation syndrome and... How's the money? Yeah, thank you, Peter, for the questions. So given that it's going to be a top line cut of the data, I, you know, we'll probably give some color around safety and tolerability. I can, I can tell you what we've seen thus far.
First question is just around safety, just how much safety data, we'd seen the <unk> update and if you've seen any further cases the differentiation syndrome.
And how is the management strategy going with us.
Troy Wilson: ZIFT Amended appears to have, you know, a very encouraging safety and tolerability profile. Now, we have to address the second part of your question. Really, the one thing of note is that we have continued to see differentiation syndrome, but as we discussed on prior calls, we now have what we believe to be a very robust and enhanced mitigation strategy, and it seems to have given the investigators the toolkit that they need to manage it. And to that end, you know, neither we nor the investigators run away from differentiation syndrome. On the contrary, if you see it, it's usually an indication of clinical activity.
Yes, Thank you Peter for the questions.
So the given that it's going to be a top line cut of the data.
We'll probably give some color around the safety and Tolerability.
I can tell you what we've seen thus far ziff demand appears to be.
Have a very encouraging safety and tolerability profile.
The second part of your question.
It really the one thing of note is we have continued to see differentiation syndrome, but as we discussed on.
Fire calls, we now have what we believe to be a very robust and enhanced mitigation strategy and it seems to have given the investigators the toolkit that they need to manage it and.
Troy Wilson: The key is whether you can manage it effectively and keep the patient safe. And at this point, I can tell you the enhanced mitigation strategy appears to be, you know, doing exactly what it was designed to do. We'll have a, you know, we'll probably have some very, you know, high-level color around it in the top-line release with much more data to follow. But, you know, there shouldn't be any surprises, it should be very consistent with what we've said all along. Thank you. I may have missed this, I apologize, but the current... Head Neck Trial. When did we see the first kind of readout?
And to that end.
Neither we nor the investigators runaway from differentiation syndrome to the contrary if you see it it's usually an indicated an indication of clinical activity. The key is if can you manage it effectively and can you keep their patients safe and at this point I can tell you the enhanced mitigation strategy appears to be.
Doing exactly what it was designed to do we will have.
We'll probably have some very high level color around it in the topline released with much more data to follow but there shouldnt.
It should be very consistent with what we've said all along.
Got you. Thank you I may have missed this I apologize, but the.
The current.
Head neck trial, when do we see the first killer.
Readouts of that.
Troy Wilson: Yeah, you didn't miss it, Peter. We were a little bit vague, but let me answer your question. So, this trial is intended to determine a recommended Phase II dose and schedule for the combination. It's a Bayesian design that allows us to adjust the levels of both of the two drugs, tipifarnib and dalpelicib.
Yes, you Didnt Miss it Peter.
We were a little bit vague, but let me answer your question. So this trial is intended to determine the recommended phase two dose and schedule for the combination. It's a Bayesian design that allows us to to adjust the levels of both of the two drugs to be foreign <unk>.
Troy Wilson: The primary focus is safety and tolerability, but we are looking for clinical activity. I think at this point, Peter, in my prepared remarks, I commented that the trial is going well, and we are encouraged. There may be an opportunity, I hope there will be an opportunity in the not too distant future to share some more data with you, but we haven't given any specific guidance around what that data would be or the venue.
The primary focus is safety and Tolerability, but we are looking for clinical activity I think at this point Peter.
Troy Wilson: Once we have it, we'll be sure to share it with you and others on the call. Great, thanks. Thank you, Peter. Our next question comes from Tiago Foss.
In the prepared remarks I commented that.
The trial is going well and we are encouraged.
There may be an opportunity I hope there'll be an opportunity in the not too distant future to share some more data with you, but we haven't put a specific.
We haven't put any specific guidance around what that data would be or the venue. Once we have it we'll be sure to share it with you and others on the call Greg.
Great. Thank you so much.
Sure. Thank you Peter.
Our next question comes from Thiago <unk> of Credit Suisse. Please go ahead.
Operator: Please go ahead. Hi guys, it's Jonathan on for Tiago. Thanks for taking our question. So we already know a lot about the differentiation between ZIF-dominib and the main competitor you're frequently compared to, but there are now several other menin inhibitor trials being run in. So with that in mind, it looks like you're likely ahead of those, but from what you've seen from those trials so far, is there anything you could say about the relative differentiation between those programs or anything pre-clinical or even from the standpoint of trials?
Hi, guys, it's Jonathan on for Thiago, Thanks for taking my question.
So we already know a lot about the differentiation differentiation between.
Permanent and main competitor frequently compared to but theyre naphtha or other than an inhibitor trials run in so with that in mind. It looks like Youre likely ahead of those but from what you've seen from those trials. So far is there anything you can say about the relative differentiation between those programs or anything pre clinically or even from the standpoint of trials.
Thanks.
Operator: Yeah, Jonathan, thanks for the thanks for the question. You know, I'm going to defer on addressing, you know, our competitors. I'll let them speak to their data and their designs, and I'll maybe highlight something I think that a year ago was perhaps viewed as a negative, and now I view very much as a positive, and that is the Phase 1B design that we've just completed enrollment in. You know, at the time, the concern was, oh, you've lost time. You know, why is the FDA making you do this? This was very early in the dawn of Project Optimist.
Yes, Jonathan Thanks for the thanks for the question.
I'm going to defer on addressing our competitors I'll, let them speak to their data and their designs.
And I'll, maybe highlight something I think that a year ago was perhaps viewed as a negative and now I view very much as a positive and that is the phase <unk> design that we've just for which we've just completed enrollment.
At the time the concern was that you've lost time why is the FDA, making you do this this was very early in the in the Dawn of project Optimists, what its provided US is a significant amount of experience at two different doses, one of which will be our recommended phase II dose. So as we now look to transition.
Troy Wilson: What it's provided us is a significant amount of experience at two different doses, one of which will be our recommended Phase 2 dose. So as we now look to transition from Phase 1B to Phase 2, I think we have a very solid understanding of the safety, the tolerability, the PK, the exposure, and the efficacy at, ultimately, what will be our recommended Phase 2 dose. That perhaps wasn't fully appreciated by everyone at the time, but what it means is you're going to get a very full picture at the RP2D in Q3, and it should give everyone much more confidence that those parameters are going to follow through, not only through the medical meeting presentation in Q4, but on into Phase 2. That's probably the most significant difference, Jonathan, that we've seen between what we're doing and others, and I think it positions Very helpful.
From phase one beta phase II I think we have a very solid understanding of the safety tolerability, the PK exposure and the efficacy and ultimately what will be the recommended phase II dose.
That perhaps wasn't fully appreciated by everyone at the time, but what it means is you're going to get a very full picture at the <unk> in Q3, and it should give everyone much more confidence that that that that that those parameters are going to follow through not only through.
<unk> medical meeting presentation in Q4, but on into the phase II.
That's probably the most significant difference Jonathan that we've seen between what we're doing and others.
And I think it positions if <unk>.
Competitively relative to the others drugs in the landscape.
Very helpful. Thank you.
Sure.
Troy Wilson: Thank you. Sure. Our next question comes from Roger Song of Jefferies, please. Good. Thank you for taking the question. Maybe, Troy, could you just comment on...
Our next question comes from Roger song of Jefferies. Please go ahead.
Great. Thank you for taking the question maybe Troy can you just comment.
Operator: So far. Regulatory Interaction. So have you discussed with the FDA your RP2D plan and when you will, Chimidou, once you do, will that be up, top line data in 3Q versus the full data in 4Q. Yeah, Roger, so I want to be careful here on specifics. We interact with the agency regularly across all of our programs.
So far.
The regulatory interaction so.
Discussing with the FDA about your option to the plan.
In that way.
Well discuss the pivotal.
You will be after the topline data in <unk> versus the full data <unk> or maybe later.
Yeah, Roger so so I want to be careful here on specifics, we interact with the agency.
Regularly across all of our programs.
Troy Wilson: You know, we work very much in partnership with the agency, and we've found them to be very, very productive partners. I don't want to speak to the specifics, just given the timing and some of the sensitivities. Suffice it to say, you know, today is significant in that we've completed enrollment of the 24 patients needed to support the Phase 1B. We are, you know, in the process of collecting and analyzing that data ultimately to identify the recommended Phase 2 dose, and then that's going to require a package that needs to be submitted to the FDA. That hasn't happened to me yet.
We're very much work in partnership with the agency and we found them to be very very productive partners.
I don't want to speak to the specifics just given the timing and some of the sensitivities suffice.
Suffice it to say today, it's significant in that we've completed enrollment of the of the 24 patients needed to to support the phase <unk> B. We do we are in the process of Av.
Collecting and analyzing that data ultimately to identify the recommended phase two dose and then that's going to require.
Our package that needs to be submitted to the FDA that hasnt happened yet.
Troy Wilson: That is, you know, but the team knows exactly what it needs to do, and it's very much focused on that. I don't want to be a lot more specific as to the timing, just out of respect for the agency and for their process, but I will tell you, I think the team is not only doing everything they need to do, but, I hope it is clear, is executing with the diligence and the urgency that's needed for this program to really be competitive. Yeah, I think last time the room was...
That is.
The team is the team knows exactly what it needs to do and it's very much focused on that I don't want to be a lot more specific as to the timing.
Just out of respect for the agency and for their process, but I will tell you I think the team is is not only doing everything they need to do but but I hope is clear is executing with the diligence and the urgency that's needed for this program to really to really be.
To be competitive.
Got it yes, I think last time, we remove the clinical hold.
Great.
Operator: Okay, got it. So maybe just another question from us is, so forth to the, Thank you for joining us today for the COMBO trial. Can you just remind us where you are with the monotherapy, the pivotal study, and also if the COMBO data looks good, and how you're going to strategize this COMBO versus monotherapy? Thank you.
Wow.
Okay got it so maybe just.
Another question from.
So for the PPE.
This combo trial.
Just remind us where are you add that monotherapy the pivotal study and also.
The combo data looks good how are you going to strategize.
Combo versus mono therapy moving forward.
Thank you right, yes, Roger Thanks for the question and Roger Let me just pick up on something that you said because I can't resist if you don't mind.
Troy Wilson: Right. Yeah, Roger, thanks for the question. And Roger, let me just pick up on something that you said, because I can't resist, if you don't mind.
Troy Wilson: You know, it wasn't that long ago that the clinical hold was lifted, and at the time, shortly thereafter, we said we were seeing high interest and high engagement among the investigators in the AML community for Zift Amenib. I hope now that we've come back exactly on schedule with the cohorts enrolled and enrollment ongoing, that that underscores what we said back then. There is a very high level of interest and engagement in this compound and in this class within the AML community, so just wanted to round out the answer to that.
It wasn't that long ago that the clinical hold was lifted and at the time. Shortly thereafter, we said we were seeing high interest and high engagement among the investigators in the AML community preserved amended I hope now that we've come back exactly on schedule with the cohorts enrolled and enrollment ongoing.
That that underscores what we said back then.
There is a very high level of interest and engagement in this compound in and in this class in the AML community. So just wanted to just wanted to round out the answer to that on your <unk> question, Yes, we find ourselves at an interesting point so enrollment in aim which is the monotherapy registration directed.
Troy Wilson: On your FTI question, yeah, we find ourselves at an interesting point. So enrollment in AIM, which is the Monotherapy Registration-Directed Study for Tipi Farnabe and Ahretz-Meaton Head and Neck, is continuing. We know the drug is active. You know, you've seen the data from the Phase II RUN-HN trial. We continue to see monotherapy activity. The challenges that we've faced are that the patients coming to that study have typically gone through both platinum and I.O., and as a result, you know, a large majority of them are just not sufficiently fit to go on to a study. It sort of is what it is, that, you know, the team is working very hard to execute against that, but that's the reality of that patient population. Current really addresses that in three different ways.
Study for Tiptree foreign <unk> in <unk> mutant head and neck enrollment is continuing.
We know the drug is active when you've seen the data from the phase II run HN, we continue to see monotherapy activity. The challenges that we faced is that the patients coming to that study has typically coursed through both platinum and Io and as a result.
A large majority of them are just not sufficiently fit to go onto the study.
Sort of is what it is that the team is working very hard to to execute against that but thats. The reality of that patient population current really addresses that in three different ways. The first is by by combining El Pollo <unk> you open up the potential popular.
Troy Wilson: The first is, by combining Alpalisib and Tipi, you open up the potential population from, you know, 4 to 8 percent, which is the Ahretz monotherapy, to as much as 50 percent when you look at Ahretz dysregulated and PIK3CA dysregulated populations, so nearly a tenfold difference in the potential patient population. The second, of course, is by providing additional biomarkers, you're giving physicians As we said in the prepared remarks, the Ahretz overexpression cohort is open and in screening. We, of course, have patients who are being screened for both PIK3CA mutations and amplifications. That helps just open the funnel up, if you will.
<unk> from.
4% to 8%, which is the <unk> monotherapy to as much as 50%. When you look at HRS dis regulated and pick <unk> CA dysregulation populations. So nearly a tenfold difference in the potential patient population. The second of course is by providing additional biomarkers youre, giving physicians more reasons to do screening.
You heard us say in the prepared remarks, the H Ras overexpression cohort is opened and in screening. We of course have patients who are being screened for both pick three CA mutations and amplifications that helps just open the funnel up if you will and then the final point is the <unk>.
Troy Wilson: And then the final point is, the preclinical data suggests that, you know, there's really a strong potential for drug-drug synergy with this combination in these genetically selected populations in head and neck. We see synergistic activity that's greater than what you could do with either drug as a monotherapy. Obviously, if you can offer patients better efficacy with acceptable safety and tolerability, that's a win. It's a very good question, how do you integrate those two development streams, AIM on the one hand, and CURRENT on the other?
Preclinical data suggests that there is really a strong potential for drug drug synergy with this combination in these genetically selected populations in head and neck, we see synergistic activity, that's greater than either what you could do with either drug as a monotherapy. Obviously, if you can offer patients better efficacy with.
Acceptable safety and Tolerability Thats a win it's a very good question. How do you how do you integrate those two development streams aim on the one hand current on the other and.
Troy Wilson: And you know, Stephen and the development and regulatory teams at CURRA are very much engaged in that right now. I don't have a lot more to tell you, but it is very much top of mind, and we'll share additional updates as we have them. You can tell we're quite encouraged by the progress that the team is making on CURRENT, and we'll share more progress as we have it. Great. Thanks for that.
Steven and the development and regulatory teams at <unk> are very much engaged in that right now I don't have a lot more to tell you, but it is it is very much top of mind and we'll share additional updates as we have them where you can tell we're quite encouraged by the progress that the team is making on current and <unk>.
I'll share more progress as we have it.
Great. Thanks for the comprehensive comments.
Thank you.
Sure. Thank you.
Operator: Sure. Thank you. The next question comes from Ren Benjamin of CHAMP Securities. Hey, good afternoon, guys. Thanks for taking the questions. Maybe just starting off with just a minute, Troy, when we're, I think in the past we talked about.
Our next question comes from Ren Benjamin of JMP Securities Go ahead.
Hey, good afternoon, guys. Thanks for taking the questions.
Maybe just starting off with Humana.
Froylan.
I think in the past we've talked about the potential combination studies and other clocks was one of the potential partners. There were some others I'm just kind of curious as you continue to progress through both preclinical and clinical development.
Troy Wilson: Combination Studies, Veneta Clax was one of the potential partners. There were some others, too. I'm just kind of curious, as you continue to progress through both preclinical and clinical development, have there been any kind of changes to your thoughts? Are you still looking for what are the top two Combination Studies that you'd like to get started on, and when do you think that? Yeah, Ren, thanks for the question. There's a lot, a lot sort of packed in there. Let me see if I can, if I can unpack it.
Is there been any kind of changes to your to your thoughts or are you still looking what are the top call. It top two combination studies that you'd like to get started and when do you think that might get started.
Yes, Ren Thanks for the question Theres, a lot lot sort of packed in there let me see if I can if I can unpack it.
Troy Wilson: Combinations are of high interest to us. Ultimately, that's probably going to be the best use for men and inhibitors if you want to serve the most patients and provide the greatest unmet need. I think there's a very, continue to believe there's a very strong case to be made for the monotherapy registration, but AML will be a disease, and the treatment paradigm will be one of combinations. The predicate for any of those combinations, of course, is identification of a recommended phase two dose so that you know where to start. With the combo, we are, you know, we are moving toward that goal with all due speed. We've just, you know, we've now completed enrollment.
Combinations are of high interest to us.
Ultimately, that's probably going to be the highest best use fermented inhibitors. If you want to serve the most patients and provide the greatest unmet need.
I think theres, a very continue to believe there's a very strong case to be made for the monotherapy registration, but AML will be a disease of the treatment.
Paradigm will be one of combinations.
The predicate to any of those combinations if courses identification of a recommended phase II dose. So that you know where to start with the combo.
We are we are.
Moving toward that goal with all due speed. We've just we've now completed enrollment.
Troy Wilson: And we're looking forward to giving the top line data next quarter. There are a lot of activities, Ren, going on in the background to support the combination studies, both in the frontline and in earlier lines of therapy. We haven't said a lot yet about timing because, again, we want to be respectful of interactions with the agency, but I can assure you that those activities are going on very actively in the background. And we'll say more when it's appropriate and, you know, the studies. The studies are underway. In terms of prioritizing them, I mean, you put your finger on at least a couple of them.
And we're looking forward to giving the top line data next quarter. There are a lot of activities rent going on in the background on to support the combination studies, both in the frontline and in earlier lines of therapy.
We haven't set a lot yet about timing because again, we want to be respectful of of interactions with the agency, but I can assure you that those activities are going on very actively in the background and we'll say more when it's appropriate.
The studies the studies are underway in terms of prioritizing them I mean, you put your finger on at least a couple of them Vanadic clocks continues to be a very attractive combination partner. There is strong evidence for potential synergy between <unk> and <unk>.
Troy Wilson: Venetoclax continues to be a very attractive combination partner. There is strong evidence for potential synergy between Venetoclax and Ziftaminib. You know, there are some suggestions clinically that that synergy may carry over into patients. Obviously, you know, we have, that's not a substitute for running a study, but I think there's a very strong rationale to do that. The other, of course, is FLT3.
There are some suggestions clinically.
That synergy may carryover into patients.
Honestly, we have that is not a substitute for running a study, but I think theres a very strong rationale to do that the other of course is split three.
Troy Wilson: FLT3 is, you know, a very large patient population. When we unveil our development strategy, I think you'll find it's a continuation of what we've done well. It's effective.
<unk>.
Very large patient population.
When we unveil our development strategy I think youll find its a continuation of what we've done well it's efficient.
Troy Wilson: It's meant to be comprehensive. It targets both patients in the two genetic subtypes, as well as look for expansion opportunities outside of those genetic subtypes. And, you know, I'm looking forward to sharing it with you probably a little later in the year as we get closer to the medical meeting. So, hopefully, that gives you some color and much more to share, I think, you know, in the second half, which we're very close to, very quickly approaching. Got it. That's just perfect.
<unk> meant to be comprehensive it's meant to target both patients in the two genetic subtypes as well as looking for expansion opportunities outside of those genetic subtypes.
And.
Im looking we're looking forward to sharing it with you probably a little later in the year as we get closer to the medical meeting. So hopefully that gives you some color and much more to share I think.
In here.
Here in the second half is which we're very close very quickly approaching.
Troy Wilson: Maybe just switching gears, too, for Tippi, the first with the current, you know, head and neck study in combination. You know, you're going to be starting enrollment of the H-RAS over... So outside of it being a target, are there any other rationales that have been bypassed?
Got it alright.
That's perfect.
Maybe just switching gears to <unk>.
First with the current head and neck study in combination.
Youre going to be starting enrolment of the HRS over expression cohort.
So outside of it being a target for <unk> is there is there any other rationale is that a bypass mechanism for for patients who get exposed to <unk> alpha or are they kind of patients.
Troy Wilson: For patients who, you know, get exposed to PI2K-alpha, or are they the kind of patient, is it a patient population that has a much worse, much worse prognostic, you know, factors? How should we be viewing this overexpression code? Yeah, so it's a really good question, you know, it's a great question, Ren, and you have two questions in there, and I'm just going to tease them apart and answer each of them. So, there are at least two populations in that current trial that relate to farnesylated targets. And I'll just draw everybody's attention to it.
A patient population that has a much worse much worse prognostic.
Factors, how should we be viewing this over expression cohort.
Yeah, So it's a really good.
It's a great question, Ryan and you have two questions in there and I'm, just going to tease them apart and answer each of them. So so there are.
There are at least two populations in that current trial that relate to two to foreigners related targets and I'll just draw everybody's attention. We updated our corporate presentation. This afternoon in connection with this call and there is a very nice graphic that shows the both.
Troy Wilson: We updated our corporate presentation this afternoon in connection with this call. And there's a very nice graphic that shows both the relevance of TIPI-Farnab to HRAS overexpression, where HRAS is the farnesylated target, and then a second major mechanism, which is REB farnesylation. So, Ren, in your question, you mentioned bypass resistance.
The relevance of <unk> overexpression, where <unk> is the farthest related target and then a second major mechanism, which is rab foreign installation so.
Ran in your question you mentioned a bypass resistance that's exactly what you see with <unk> kinase inhibitors. Once you inhibit the Oncoprotein oftentimes Youll see Upregulation of tour, which is the next note down.
Troy Wilson: That's exactly what you see with PI3 kinase inhibitors. Once you inhibit the oncoprotein, oftentimes you'll see upregulation at TOR, which is the next node down. You know, personally, I worked on this 12 or 13 years ago in the context of TOR kinase inhibitors and PI3 kinase alpha. But that is one of the principal resistance mechanisms, and TIPI-Farnab silences that. It deletes the farnesyl group from REB and potentially blocks that bypass resistance.
Personally I worked on this 12 or 13 years ago in the context of Tor kinase inhibitors in pediatric kinase alpha but that is one of the principal resistance mechanisms and typically foreign of silence is that it delete the farnell Farnell Farnesol group off of Rev and potentially blocks that bypass resistance. So.
Troy Wilson: So that's why we think there's a strong rationale for the HRAS overexpressors, where you're just removing RAS, which is a bad actor for a lot of reasons, even if it's not mutated. And then in the PIK3CA populations, you're directly addressing TOR through REB. And again, I would direct everyone, if you're interested, to the graphics in our corporate presentation. But for those reasons, Ren, we think it's a very strong rationale for combination.
That's why we think there's a strong rationale in the HRS over expresses where youre, just removing RASK, which is a bad actor for a lot of reasons, even if it's not mutated and then in the <unk> III CA populations you are directly addressing tour through Rep, and again I would direct everyone. If you're interested.
To the graphics in our corporate presentation, but for those reasons Ren.
We think.
We think it is a very strong rationale for combination.
The.
Troy Wilson: The team's doing a terrific job, and we look forward to sharing results with you in the future. And then my final question is just about the current lung trial. I really like the clinical work that was highlighted at ACR. Can you talk a little bit about the mechanism of... You know, how might it actually prevent resistant mutations? kind of the goals of the study and what might be a kind of go, no go, www.curriculum.com on our side. Right? Yeah, a great question, Ren.
The team is doing a terrific job and we look forward to sharing our results with you in the future.
Sure.
My final question is just the current lung trial really like the preclinical work that was highlighted at ACR can you talk a little bit to the mechanism of action.
How how might it actually prevent resistant mutations.
Kind of the goals of the study and what might be kind of go no go.
The decision matrix mate.
Tricks that that you might be looking at would it be.
Progression free survival, mainly or would you be looking at things like overall response rate primarily.
Troy Wilson: And again, I sound like a broken record here, but I would direct everyone to our revised corporate presentation that's available on our website. There are three or four slides now that speak to current lung and that, you know, really distill it down to its essence. So, Ren, let's just quickly, you know, jog through your questions.
Yes, great question rent and again at Sao.
Like a broken record here, but.
I would direct everyone to our revised corporate presentation. That's available on our website. There are three or four slides now in there that speak to current lung and that really distill it down to its essence. So ran let's just quickly jog through your questions. The mechanism of action is it is it is now.
Troy Wilson: The mechanism of action is it is now well understood that there are a subpopulation of cells that are drug-tolerant. For example, when you treat lung tumors, EGFR mutant lung tumors with osomertinib, a small fraction of those tumors are so-called drug-tolerant cells. The reason those cells are drug-tolerant is they actually rewire their cellular architecture. They actually de-differentiate, and they become DTC cells, drug-tolerant cells. The process by which they enter that drug-tolerant state depends on a farnesylated protein. Similarly, the process by which they exit that state depends on a farnesylated protein. If you block the entrance and exit, essentially, you've barred the door.
Well understood that there are a sub population of cells that are drug tolerance cells. When you treat lung tumors egfr mutant lung tumors with <unk> nib.
A small fraction of those tumors are so called drug tolerance cells. The reason those cells are drug tolerance is they actually rewire their cellular architecture.
They actually dedifferentiate and they become DTC cells drug tolerance cells, the process by which they enter that drug tolerance state depends on a foreign insulated protein the process by which they exit that state depends on a foreign isolated protein if you block the entry and exit essentially barred the door.
Troy Wilson: Now, you don't allow those cells to enter their DCTTC state, and they then become susceptible. They eventually die off under pressure from osomertinib. It is those DTC cells, Ren, to your next question, that are believed to seed the molecular origins of adaptive resistance.
Now you don't allow those cells to enter their DC TTC state and they then become susceptible. They eventually die off under pressure for most of them are nip. It is those DTC sales ran to your next question that are believed to seed.
The molecular origins of adaptive resistance in that drug tolerance state. They can sit there essentially and cook and find a way around dose <unk> nib. So you don't allow the cells to ever get there and the consequence of that and again I'll point you to this.
Troy Wilson: In that drug-tolerant state, they can sit there essentially and cook and find a way around osomertinib. So, you don't allow the cells to ever get there. And the consequence of that, and again, I'll point you to the cartoon and then the data on the next slide in the corporate presentation, in the case of osomertinib alone, eventually, you see tumor relapse. You get little seeds of resistance. They grow out, and boom, the tumor comes back.
The cartoon and then the data on the next slide in our corporate presentation in the case of <unk> alone. Eventually you see the tumor relapse you get little seeds of resistance, they grow out and boom. The tumor comes back in the case, when you're double where you are adding <unk> to the smart nib, you see an extended <unk>.
Troy Wilson: In the case where you're adding tipifarnib to osomertinib, you see an extended delay in that resistance. In some cases, you know, a prevention, nearly a complete prevention. These are preclinical data. The third part of your question, Ren, what are you looking for? What are we looking for in the current lung? You're looking, of course, at safety and tolerability.
<unk> on that resistance in some cases, a prevention nearly a complete prevention. These are preclinical data.
The third part of your question around what are you looking for what are we looking for in current lung Youre looking of course at safety and Tolerability you need to establish a recommended phase II dose for the combination and then PFS as the primary endpoint, but we're going to be looking at a number of endpoints along the way given the given the high <unk>.
Troy Wilson: You need to establish a recommended phase two dose for the combination, and then PFS is the primary endpoint, but we're going to be looking at a number of endpoints along the way. Given the high activity of osomertinib as a monotherapy, you'd have to have a pretty significant trial for a difference in response rate.
<unk> as a monotherapy.
You'd have to have a pretty significant trial.
Troy Wilson: But if the clinical data recapitulates what we see preclinically, you'll see it in PFS, and the trial is designed to look for just that. And if we see that, obviously, you know, that's a big deal because you could keep patients on osomertinib then for that much longer and really provide them with a high quality of life. And this is, you know, just a final comment I'll make, Ren. This is what you'll see. Alpellisib and tipi are the first examples.
For our difference in response rate, but if the clinical data recapitulates, what we see pre clinically youll see it in PFS and the trial is designed to look for just that and if we see that obviously, that's a big deal because you could keep patients on <unk> than that much longer and really.
Provide them with a high quality high high quality of life and this is just the final comment I'll make Ren this is what youll see our palisade and typically is the first example, Oc <unk> second I hope Youll see a third and then fourth we're using this concept of precision medicine now to go after much larger patient.
Troy Wilson: OC tipi is the second. I hope you'll see a third and then a fourth. We're using this concept of precision medicine now to go after much larger patient populations but using all of the, you know, this real strength of precision medicine. And, you know, I think it's going to be an exciting few years as we see whether the clinical data recapitulates the very strong preclinical data. We're cautiously optimistic and look forward to sharing updates with you in the future. I hope I've answered all the different parts of your question. You definitely have. Thank you very much for unpacking it so nicely. Have a... Sure.
<unk>, but using all of the.
The real strengths of precision medicine and.
I think it's going to be an exciting several years coming up as we as we see that whether these clinical data recapitulates. The very strong preclinical data, we're cautiously optimistic and look forward to sharing updates with you in the future I Hope I hope I've answered all the various parts of your question.
You definitely have thank you very much for unpacking, it sort of nicely I forget them.
Sure. Thanks Brent.
Operator: Thanks, Ren. And just as a last reminder, if you have a question, please press star. Thank you for your time. Our next question will go to............... Eva Privitera of Cologne. Please go ahead.
So for us or monitor if you have a question. Please press Star then one.
At this time, our next question will come from <unk>.
Perfect.
John Please go ahead.
Operator: Hi, thanks for taking our questions and congratulations. So you mentioned earlier that you've seen additional cases of DS. I just wanted to follow up on the details. What was the severity and at what levels?
Hi, Thanks for taking our questions.
Congrats on completing the <unk>.
So you mentioned earlier that you've seen additional cases.
Yes.
Just wanted to follow up on that.
<unk>.
This is there already and at what dose.
Troy Wilson: So, thanks, Eva, for the question. Starting with dose, there doesn't, at least in our experience, between the two phase 1B cohorts, there doesn't appear to be a dose dependence. The, you know, differentiation syndrome is, it appears, just to take a step back. One expects to see differentiation with this mechanism. The extent and the severity of differentiation syndrome appear to be more patient-specific, maybe related to tumor burden, you know, maybe more common among KMT2A.
Yes, so thanks, Steve for the question.
Starting with dose there doesn't at least in our experience.
Between the two phase <unk> cohorts, there doesn't appear to be a dose dependence.
The differentiation syndrome is.
Just to take a step back.
One expects to see differentiation with this mechanism.
The extent and the severity of differentiation syndrome appears to be more patient specific maybe related to tumor burden.
Maybe more comment among Kmt two way.
We have such a small number it's hard to draw really any any definitive conclusions, but the.
Troy Wilson: You know, we have such a small number, it's hard to draw really any definitive conclusions, but the, you know, our experience has been with the enhanced mitigation strategy; physicians have the toolkit that they need to be able to manage the differentiation syndrome. And, ultimately, our experience, Eva, has been that, again, if you're seeing differentiation and differentiation syndrome, that's usually a marker of clinical activity. And so, what we've found with the investigators now is that they're leaning into that, they're making sure that they can get the patients through it, and they have the, you know, and we've talked about it in the past, and I can, I'm happy to summarize it again if it's helpful, but we have a very thorough and expert enhanced mitigation strategy to give them the tools that they need.
Our experience has been with the enhanced mitigation strategy that physicians have the tool kit that they need to be able to manage the differentiation syndrome and ultimately our experience Eva has been.
Again, if you are seeing differentiation and differentiation syndrome, that's usually a marker of clinical activity and so what we found with the investigators now is that they are leaning into that they are making sure that they can get the patients through it and they have the and we've talked about in the past and I can I'm happy to summarize it again, if it's helpful. But we.
Have a very thorough and expert mitigate enhanced mitigation strategy to give them the tools that they need so it's it's something to watch out for with this mechanism of action, but it isn't really we think going to be any part of the determination of whether 200 milligrams or 600 milligrams.
Troy Wilson: So, it's something to watch out for with this mechanism of action, but it isn't really, we think, going to be any part of the determination of whether 200 milligrams or 600 milligrams is the recommended phase to use. And just one other point to confirm: the top-line data and nomination of the RP2D will be disclosed together at the same time? Yes.
Is the recommended phase II dose.
Thank you that's helpful and just one other point to confirm.
The topline data and nomination of ERP TD will that be disclosed together.
At the same time.
Yes, yes.
Troy Wilson: Yeah, okay. And can we expect any P-K, P-D, or any additional data along with the, you know, our P-P-D disclosure? I don't know that we'll get into PKPD, Eva, because we want to make sure we protect the sanctity of the data set for the eventual presentation at a medical meeting. Suffice it to say, you know, all of the data will line up in support of the ultimate recommended phase two dose.
Okay, and can we expect any PK PD or any additional data along with.
RPT get closure to support the rationale.
I don't know that we'll get into PK PD, either because we want to make sure. We protect the sanctity of the dataset for the eventual presentation at a medical meeting suffice it to say all of the data will lineup in support of the ultimate recommended phase II dose I think the thing that will matter is again.
Troy Wilson: I think the thing that will matter is, again, you know, does the safety and tolerability continue, and I can tell you now it does, and are you seeing a level of clinical efficacy that gives you confidence in a successful phase two, and what are the elements of that? This is going to be top-line data.
Is this does the safety and Tolerability continue and I can tell you now it does and are you seeing a level of clinical efficacy that gives you confidence in a successful phase III and.
And what are the elements of that this is this is going to be topline data, it's probably they're probably going to be questions.
Troy Wilson: It's probably, you know, there are probably going to be questions and, you know, I think it will be a very fulsome presentation at the medical meeting in Q4 where we'll be able to get into things more like exposure and the kind of questions you're – the kinds of questions that you're getting to. Got it. Thank you so much. Thank you. This concludes our question and answer session. At this time, I would now like to turn the conference back over to Mr.
No.
It'll it'll I think it'll be a very fulsome presentation at the medical meeting in Q4 were more we'll be able to get into things more like exposure and the kind of the kind of question. Your the kinds of questions that you are getting to.
Got it thank you so much.
Okay.
Thank you.
This concludes our question and answer session. At this time I will now turn the conference back over to Mr. Troy Wilson for any closing remarks.
Troy Wilson: Troy Wilson for any closing remarks. Thank you, Operator, and thank you all once again for joining our call today. We'll be participating in the Cowan Oncology Innovation Summit, the Jeffries Health Care Conference, and the JMP Life Sciences Conference next month, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Tom, or me. Thank you again, and have a good evening, everyone. The conference is now concluded. Thank you for attending today's presentation. BF-WATCH TV 2021
Thank you operator, and thank you all once again for joining our call today, we will be participating in the Cowen oncology innovation summit, the Jefferies Healthcare conference and the JMP Life Sciences Conference next month, and we look forward to seeing many of you there in the meantime, if you have any additional questions. Please feel free to contact Pete Tom.
Or me.
Thank you again and have a good evening everyone.
Yeah.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
[music].
Yeah.