Q4 2021 Kura Oncology Inc Earnings Call
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Operator: Good day and thank you for standing by. Welcome to the Q4 2021 Kura Oncology and Earnings At this time, all participants are in... Later, we will conduct a question and answer session and instructions will follow. If anyone should require assistance during the conference, please press parton0 on your touch screen. And now I'd like to turn the conference over to your hosts, Mr. Pete Spain, Senior Vice President of Investor Research. Thank you, Kristen.
Good day and thank you for standing by welcome to the Q4 2021, Kura Oncology, Inc. Earnings Conference call. At this time, all participants are in listen only mode.
Later, we will conduct a question and answer session and instructions will follow at that time.
Once you require assistance during the conference. Please press Star then zero on your Touchtone telephone.
I would now like to turn the conference or Whats your host Mr. Pete de Spain, Senior Vice President of Investor Relations.
Pete Spain: Good afternoon, and welcome to Kura Oncology's fourth quarter and full year 2021 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. 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.
Thank you Christian good afternoon, and welcome to Cara oncology fourth quarter and full year 2021 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 before.
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 managements judgment as of today and May involve risks and uncertainties that could cause actual results to differ materially from expected results.
Pete Spain: 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.
These refer to <unk> filings with the SEC, 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. Thank you all for joining us this afternoon. Although 2021 was a challenging year in many ways, we at Kura took the opportunity to invest in and optimize our discovery and development programs. We believe we've made significant advances in understanding the diseases we seek to target, as well as in learning how best to use our drug candidates to drive clinical benefit for patients. This past year was also one of deliberate focus on operational execution throughout the organization.
Thank you Pete and thank you all for joining us this afternoon.
Although 2021 was a challenging year in many ways, we incur it took the opportunity to invest in and optimize our discovery and development programs. We believe we've made significant advances in understanding the diseases, we seek to target as well as in learning how best to use our drug candidates to drive clinical benefit for patients. This.
<unk> was also one of deliberate focus on operational execution throughout the organization.
Troy Wilson: Now, building on the tremendous efforts of our team, we approach a number of catalysts in the year ahead with significant momentum, resources, and enthusiasm. Our enthusiasm is supported by resumed enrollment in the Comet 001 Phase 1b expansion cohorts for our newly named menin inhibitor, Zifto-Menib. The first several patients dosed in our Phase 1-2 combination trial of kipifarnib plus alpelasib in head and neck squamous cell carcinoma, an abstract supporting the therapeutic rationale for our next generation farnesyl transferase inhibitor program accepted for presentation at AACR and an expanded leadership team to support and advance our growth and execution.
Now building on the tremendous efforts of our team we approach a number of catalysts in the year ahead with significant momentum resources and enthusiasm.
Our enthusiasm is supported by resumed enrollment in the comment 001 phase <unk> expansion cohorts for our newly named Menin inhibitor lift a minute.
The first several patients dosed in our phase <unk> combination trial of <unk>, plus <unk> in head and neck squamous cell carcinoma.
An abstract supporting the therapeutic rationale for our next generation Farnesol transfer Ace inhibitor program accepted for presentation at ACR and an expanded leadership team to support and advance our growth and execution.
Troy Wilson: By mid-2022, we anticipate having three independent drug development programs to drive value in both solid and liquid tumors with meaningful data catalysts in the next six to 24 months. And as we approach these catalysts from a position of financial strength with an experienced team and organization and more than a half a billion in cash. Now let's take a closer look at the progress within each of our programs, beginning with our menin inhibitor, formerly known as KO539, Zyfta-Menib.
By mid 2022, we anticipate having three independent drug development programs to drive value in both solid and liquid tumors with meaningful data catalysts in the next six months to 24 months.
And as we approach these catalysts from a position of financial strength with an experienced team.
And organization and more than $5 billion in cash.
Now, let's take a closer look at the progress within each of our programs beginning with our Menin inhibitor, formerly known as <unk> $5 39, zipped a minute.
Troy Wilson: Last month, we were pleased to receive FDA authorization to proceed with our COMET-001 trial of ziftomenib in patients with relapsed or refractory AML. The partial clinical hold was lifted following agreement with FDA on an enhanced mitigation strategy for differentiation syndrome. As we've discussed, differentiation syndrome is known to be an on-target effect associated with a number of therapeutic agents, including menin inhibitors, which may induce differentiation of leukemic blasts.
Last month, we were pleased to receive FDA authorization to proceed with our comment zero-zero, one trial of system and had been patients with relapsed or refractory AML. The partial clinical hold was lifted following agreement with FDA on an enhanced mitigation strategy for differentiation syndrome as we've discussed.
<unk> syndrome is known to be an on target effect associated with a number of therapeutic agents, including <unk> inhibitors, which may induce differentiation of leukemic blasts.
Troy Wilson: Highlights of our enhanced mitigation strategy include heightened awareness, increased monitoring, and recommendations for aggressive intervention, all to ensure physicians are fully informed and prepared to address future events should they occur. I'm very proud of our team for working so diligently with FDA and our site investigators over the holidays to resolve this issue, which speaks to our focus on operational execution. Screening for new patients began in earnest, and we're pleased to report that patient enrollment in the Phase 1b expansion cohorts has resumed.
Highlights of our enhanced mitigation strategy include heightened awareness increased monitoring and recommendations for aggressive intervention all to ensure physicians are fully informed and prepared to address future events should they occur.
I am very proud of our team for working so diligently with FDA and our site investigators over the holidays to resolve this issue, which speaks to our focus on operational execution.
Screening for new patients began in earnest and we're pleased to report that patient enrollment in the phase <unk> expansion cohorts has resumed.
Troy Wilson: While we're excited to recruit new patients to our Phase 1B study, it's important to remember that patients already enrolled were eligible to remain on study during the partial clinical hold. And we continue to be encouraged by the safety and tolerability profile, as well as the clinical activity we're seeing with Zyfta Menis.
While we are excited to recruit new patients to our phase <unk> study, it's important to remember that patients already enrolled were eligible to remain on study during the partial clinical hold and we continue to be encouraged by the safety and tolerability profile as well as the clinical activity, we're seeing with zipped a minute.
Troy Wilson: Looking forward, we expect to complete enrollment of 24 patients in the Phase 1b study by the second quarter, after which we will assess the patients in each cohort for safety and tolerability, pharmacokinetics and exposure, as well as efficacy. Our goal is to identify the recommended Phase 2 dose and report top-line data from the Phase 1b by the third quarter with updated data from Comet-001 reserved for a medical meeting in the fourth quarter.
Looking forward, we expect to complete enrollment of 24 patients in the phase <unk> study by the second quarter after which we will assess the patients in each cohort for safety and Tolerability pharmacokinetics and exposure as well as efficacy. Our goal is to identify the recommended phase II dose and report topline.
Data from the phase <unk> by the third quarter with updated data from Comet Zero-zero, One reserve for a medical meeting in the fourth quarter.
Troy Wilson: Once we've identified the recommended Phase 2 dose, we plan to continue enrolling up to an additional 18 patients in the selected cohort of the Phase 1b study, enabling us to maintain momentum while we transition into the Phase 2 portion of Comet-001. We believe data from all patients treated at the recommended phase 2 dose will have potential to contribute to the registrational patient population. Meanwhile, we continue to add sites in the United States and Europe in anticipation of the subsequent Phase II portion of Comet 001.
Once we've identified the recommended phase II dose we plan to continue enrolling up to an additional 18 patients in the selected cohort of the phase <unk> study, enabling us to maintain momentum while we transition into the phase II portion of comments there was zero one.
We believe data from all patients treated at the recommended phase II dose will have potential to contribute to the registrational patient population. Meanwhile, we continue to add sites in the United States and Europe and anticipation of the subsequent phase III portion of comments there was there a one.
Troy Wilson: We're also designing a comprehensive development strategy that builds on the potential to register ziftimenib as a monotherapy while giving us flexibility to access larger opportunities, including earlier lines of therapy in combination more quickly. We expect to have much more to say regarding our global development strategy for ziftimenib later this year. Now let's turn our attention to our farnesyltransferase inhibitor program. We continue to view farnesyl transferase inhibition as a potentially valuable therapeutic and commercial franchise, one with potential to deliver multiple opportunities in oncology.
We're also designing a comprehensive development strategy that builds on the potential to register Ziff to <unk> as a monotherapy, while giving us flexibility to access larger opportunities, including earlier lines of therapy in combination more quickly we expect to have much more to say regarding our global development.
<unk> <unk> later this year.
Now, let's turn our attention to our Farnesol transports 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: Our most advanced effort is focused on patients with HRS mutant head and neck squamous cell carcinomas, or HNSCC, through our ongoing AMHN registration-directed trial of tippy farnesyl monotherapy. In addition, a growing body of preclinical and clinical data support the development of tipifarnib in combination regimens directed at larger genetic subsets. Among these potential combinations, we've prioritized the combination of tipifarnib and an inhibitor of PI3 kinase alpha. Our preclinical data suggest that HRAFs and PI3-kinase alpha are codependent oncogenes in HNSCC and that combining tipifarnib with a PI3-kinase alpha inhibitor has potential to provide meaningfully better anti-tumor activity relative to inhibiting either target alone.
Our most advanced effort is focused on patients with <unk> mutant head and neck squamous cell carcinomas or <unk> FCC through our ongoing aim HN registration directed trial of <unk> as a monotherapy.
Troy Wilson: Furthermore, we believe this combination has potential to increase the total addressable population for tipefarnab to as much as 50% of patients with HNSCC. Last year, we announced a clinical collaboration with Novartis to evaluate the combination of tipifarnib and the PI3 kinase alpha inhibitor alpelicib in patients with HNSCC. Alpelicib is approved to treat patients with PIK3CA mutant breast cancer, and it has demonstrated encouraging evidence of clinical activity in patients with PIK3CA dysregulated HNSCC.
In addition, a growing body of preclinical and clinical data support the development of <unk> in combination regiments directed at larger genetic subsets. Among these potential combinations. We've prioritized the combination of <unk> and an inhibitor of <unk> kinase Alpha.
Our preclinical data suggest that <unk> and <unk> kinase Alpha are codependent, oncogene, and <unk> FCC and combining <unk> with a <unk> kinase alpha inhibitor has potential to meaning to provide meaningfully better antitumor activity relative to inhibiting either target alone.
Furthermore, we believe this combination has potential to increase the total addressable population for typically foreign up to as much as 50% of patients with HSBC.
Last year, we announced a clinical collaboration with Novartis to evaluate the combination of <unk> and the <unk> kinase Alpha inhibitor <unk> in patients with HSBC.
<unk> is approved to treat patients with <unk> mutant breast cancer and it has demonstrated encouraging evidence of clinical activity in patients with <unk> III CA dysregulation at HSBC.
Troy Wilson: In December, we dosed the first patient in a Phase I-II study of tipefarnib in combination with alpelisib in HNSCC, a study which we call the current trial, and we're pleased with the continued pace of enrollment. The initial cohort includes patients who have PIK3CA-dependent HNSCC, and we expect to initiate an HRAS overexpression cohort by the third quarter of this year. Our goal with the current trial is to identify a recommended phase 2 dose and schedule for the combination.
In December we dosed the first patient in a phase one two study of <unk> in combination with our palisade and <unk> SEC Ah study, which we call. The current trial and we're pleased with the continued pace of enrollment. The initial cohort includes patients who have <unk> CA dependent <unk> FCC and we expect to initiate.
<unk> and HRS overexpression cohort by the third quarter of this year.
Our goal with the current trial is to identify a recommended phase II dose and schedule for the combination depending on our progress in the dose escalation, we may be in a position to provide preliminary data on safety Tolerability and clinical activity of the combination in genetically enriched head and neck patients by year end.
Troy Wilson: Depending on our progress in the dose escalation, we may be in a position to provide preliminary data on safety, tolerability, and clinical activity of the combination in genetically enriched head and neck patients by year end. Meanwhile, through our own internal efforts and our network of academic collaborations, we've identified some exciting opportunities for farnesyl transferase inhibitors, opportunities we believe represent significant potential value creation. Last year, we nominated KO2806 as our lead development candidate in our Next Generation Farnesyl Transferase Inhibitor Program. Based upon extensive preclinical work, KO2806 demonstrates improved potency, pharmacokinetic and physiochemical properties relative to tippi farnes.
<unk>.
Meanwhile, through our own internal efforts and our network of academic collaborations we've identified some exciting opportunities for foreigners feel transfer ace inhibitors opportunities, we believe represent significant potential value creation.
Last year, we nominated Kao 28 O six as our lead development candidate in our next generation Farnesol transfer Ace inhibitor program.
Based upon extensive preclinical work K O $28, six demonstrates improved potency pharmacokinetic and physiochemical properties relative to <unk>.
Troy Wilson: KO2806 is designed to target novel farnesylated proteins and address large, solid tumor indications of high unmet need through combination regimens, with a focus on delaying the onset of drug resistance. We were recently informed that an abstract from one of our academic collaborators supporting the first such opportunity in non-small cell lung cancer has been accepted for presentation at the upcoming American Association for Cancer Research Annual Meeting. We're excited about this emerging opportunity and look forward to sharing more detailed information in April. In the meantime, we are planning to perform initial clinical evaluation with Tippi Farnab in non-small cell lung cancer while continuing our IND-enabling studies of KO2806.
<unk> is designed to target novel foreign insulated proteins and address large solid tumor indications of high unmet need through combination regimens with a focus on delaying the onset of drug resistance.
We were recently informed that an abstract from one of our academic collaborators supporting the first such opportunity in non small cell lung cancer has been accepted for presentation at the upcoming American Association for cancer Research annual meeting we're excited about this emerging opportunity and look forward to sharing more.
Detailed information in April in the meantime, we are planning to perform initial clinical evaluation with <unk> in non small cell lung cancer, while continuing our IND, enabling studies of <unk> hundred 26, I believe each of our programs has potential to create significant value for patients healthcare.
Troy Wilson: I believe each of our programs has potential to create significant value for patients, health care providers, and shareholders, and I believe we have the leadership, experience and operational and financial resources to realize that value. Toward that end, we recently expanded our senior leadership team to help support and advance our mission. This expansion was driven by three key promotions, Dr. Mollie Leoni to Senior Vice President of Clinical Development, Pete Spain to Senior Vice President of Investor Relations, Corporate Communications, Tom Doyle to Senior Vice President of Finance and Accounting.
Providers and shareholders and I believe we have the leadership experience and operational and financial resources to realize that value.
Troy Wilson: In addition, Nick Scalperato, our Senior Vice President of Regulatory Affairs, has also been added to our senior leadership team. We are intentional about cultivating talent within our organization. These additions to our senior leadership team reflect the significant contributions of Mollie, Pete, Tom and Nick, as well as our confidence in their ability to help lead us into the next exciting phase of growth. In connection with his promotion, Tom's also assumed the role of principal accounting officer from Mark Grasso, who recently stepped down as chief financial and chief business officer to pursue an opportunity closer to his family.
Toward that end, we recently expanded our senior leadership team to help support and advance our mission. This expansion was driven by three key promotions, Dr. Molly Leoni Senior Vice President clinical development Pizza, Spain to senior Vice President of Investor Relations Corporate Communications, Tom Doyle Senior Vice.
<unk>, a finance and accounting in addition, Nick's Gulf <unk>, our senior Vice President of regulatory Affairs has also been added to our senior leadership team. We are intentional about cultivating talent within our organization. These additions to our senior leadership team reflect the significant contributions of Mali Pete.
And Nick as well as our confidence in their ability to help lead us into the next exciting phase of growth.
In connection with his promotion Tom has also assumed the role of principal accounting officer from Marc Grasso, who recently stepped down as chief financial and Chief business officer to pursue an opportunity closer to his family I'd.
Tom Doyle: I'd like to take this opportunity to thank Mark for his more than three years of service to Cura, during which he played an important role in ensuring our strong financial position. I respect his decision to be closer to his family and wish him well in his future endeavors. With that, I'll now turn the call over to Tom for a discussion of our financial results. Thank you, Troy. And good afternoon, everyone. I'm happy to provide a brief overview of our financial results for the fourth quarter and full year 2021.
I'd like to take this opportunity to thank mark for his more than three years of service to Curragh during which he played an important role in ensuring our strong financial position I respect his decision to be closer to his family and wish him well in his future endeavors.
With that I'll now turn the call over to Tom for a discussion of our financial results.
Tom Doyle: I invite you to review the 10-K file today for a more detailed discussion. Research and development expenses for the fourth quarter of 2021 were $21 million, compared to $17.5 million for the fourth quarter of 2020. R&D expenses for the full year 2021 were $84.7 million compared to $60.4 million for the prior year.
You Troy and good afternoon, everyone I'm happy to provide a brief overview of our financial results for the fourth quarter and full year 2021.
Tom Doyle: The increase in R&D expenses was primarily due to increases in clinical trial cost, development, and manufacturing activities related to our ZIFTO-minute program. Costs related to our registration-directed trial for Tippi Farnab. Research Activities for Discovery Stage Programs, Non-Cash Share-Based Compensation, and Other Personnel Costs. General and administrative expense for the fourth quarter of 2021 was $12.1 million compared to $8.8 million for the fourth quarter of 2020. G&A expenses for the full year 2021 were $46.5 million compared to $31.5 million for the prior year. The increase in GNA expenses were primarily due to increases in non-cash share-based compensation, personnel cost, and professional fees.
I invite you to review the 10-K filed today for a more detailed discussion.
Research and development expenses for the fourth quarter of 2021 were $21 million compared to $17 5 million for the fourth quarter of 2020.
R&D expenses for the full year 2021 were $84 7 million compared to $60 4 million for the prior year.
The increase in R&D expenses was primarily due to increases in clinical trial cost development and manufacturing activities related towards this two minute program.
Costs related to our registration directed trial for <unk> <unk>.
Research activities for discovery stage programs noncash share based compensation and other personnel costs.
General and administrative expense for the fourth quarter of 2021.
It was $12 1 million compared to $8 8 million for the fourth quarter of 2020.
G&A expenses for the full year 2021 were $46 5 million compared to 31 5 million for the prior year.
The increase in G&A expenses were primarily due to increases in noncash share based compensation personnel cost and professional fees.
Tom Doyle: Net loss for the fourth quarter of 2021 was $32.7 million, compared to a net loss of $26.2 million for the fourth quarter of 2020. Net loss for the full year 2021 was $130.5 million compared to a net loss of $89.6 million for the prior year. The net loss for the fourth quarter and full year of 2021 included non-cash share-based compensation expense of $6.4 million and $23.6 million, respectively.
Net loss for the fourth quarter of 2021 was $32 7 million compared to a net loss of $26 2 million for the fourth quarter of 2020.
Net loss for the full year 2021 was $130 5 million compared to a net loss of $89 6 million for the prior year.
The net loss for the fourth quarter and full year of 2021 included noncash share based compensation expense of $6 4 million and $23 6 million respectively.
Tom Doyle: This compares to $3.7 million and $12.8 million for the same periods in 2020. Our cash, cash equivalents and short term investments were $518 million as of December 31st, 2021, compared to $633.3 million as of December 31st, 2020. Based on our current plans, we believe that our current cash, cash equivalent, and short-term investments will be sufficient to fund operations into 2024. With that, I now turn the call back over to Troy. Thank you, Tom.
This compares to $3 7 million and $12 8 million for the same periods in 2020.
Our cash cash equivalents and short term investments were $518 million.
December 31 2021.
Compared to $633 3 million as of December 31, 2020.
Based on our current plans, we believe that our current cash cash equivalents and short term investments will be sufficient to fund operations into 2024.
With that I'll now turn the call back over to Troy.
Thank you Tom.
Tom Doyle: Before we jump into the question and answer session, let me lay out our anticipated milestones for 2022. Complete enrollment of 24 patients in the Comet 001 Phase 1b study by the second quarter. Identify the recommended Phase 2 dose of Ziftaminib and report top-line data from the Phase 1b by the third quarter. Present updated data from the Comet-001 at a medical meeting in the fourth quarter, initiate the HRAF's overexpression cohort in current by the third quarter.
Before we jump into the question and answer session. Let me lay out our anticipated milestones for 2022.
Complete enrollment of 24 patients in the comment Zero-zero, one phase <unk> study by the second quarter.
Identify the recommended phase II dose of <unk> and report topline data from the phase <unk> by the third quarter.
Updated data from the comment Zero-zero won at a medical meeting in the fourth quarter.
Initiate the HRS overexpression cohort in current by the third quarter.
Tom Doyle: Report preclinical data supporting the use of a farnesyl transferase inhibitor to delay the onset of drug resistance in non-small cell lung cancer in the second quarter and submit an IND application for KO2806 by the end of 2022.
Report preclinical data supporting the use of a farnesol transfer ace inhibitor to delay the onset of drug resistance in non small cell lung cancer in the second quarter and submitted an IND application for <unk> 28, or six by the end of 2022.
Operator: With that operator, we're now ready for questions. Ladies and gentlemen, if you have a question at this time... Please press star and then the number one key on your touchtone.
With that operator, we're now ready for questions.
Ladies and gentlemen, if you have any question at this time. Please press Star then the number one key on your Touchtone telephone.
Operator: Again, that is star 1, 2, S. Your first question is from Jonathan Chang from SVB. Hi guys, thanks for taking my questions. Congrats on the progress and congrats to the promoted individuals. First question on Zyftomeneb, what information could be provided in the top line disclosure by 3Q versus the data presentation in 4Q? Jonathan, on behalf of everyone, including the folks who we recently promoted, thank you. In terms of the data update, the top line will be just that.
Again that is starting with one to ask a question.
Your first question is from Jonathan Chang from SPV Leerink.
Hi, guys. Thanks for taking my questions.
Congrats on the progress and congrats to the promoted individuals.
First question on this tome minute.
Information can be provided in the topline disclosure by three Q versus the data presentation in <unk>.
Sure Jonathan on behalf of everyone, including the.
The folks who who we recently promoted thank you.
In terms of the data update the topline will be just that so we've said consistently that.
Troy Wilson: So, you know, we've said consistently that, 539, now Ziftamedib, has demonstrated a very encouraging safety and tolerability profile. So I think the focus will really be on what's the clinical activity at each of the two doses and how did we decide to advance one dose versus the other. It'll really be top line in terms of, you know, response rate clinical activity at those given doses. As for the presentation at a medical meeting later in the year, that's going to be the fuller picture on the full COMET-001 study, including, you know, the typical, right, safety and tolerability, PK exposure, efficacy, of course, some, you know, durability, essentially, you know, a fuller, a more fulsome presentation on all the patients that have been enrolled thus far.
539, now as if <unk> has demonstrated a very encouraging safety and tolerability profile. So I think the focus will really be on what's the clinical activity.
At each of the two doses and how did we decide to advance one dose versus the other.
It will really be top line in terms of.
Response rate clinical activity at those given doses as for the presentation at a medical meeting later in the year, that's going to be the Fuller picture on the full comment 001 study, including.
The typical right safety and Tolerability PK exposure.
Efficacy of course.
Durability Sn.
Essentially.
Fuller a more fulsome presentation on on all the patients that have been enrolled thus far.
Yeah.
Troy Wilson: Got it, thank you. And then second question, on the next gen for nasal transferase inhibitor, KO2806, and the goal of delaying onset of drug resistance, what could the opportunity and development strategy for this program look like? That's a really good question.
Got it thank you.
And then second question on the Nextgen <unk> transferase inhibitor tornadoes.
And the goal of delaying onset of drug resistance.
The opportunity in development strategy for this program look like.
Troy Wilson: And we're eager to share it with you. As we indicated, you know, the the disease area will be non small cell lung cancer. You know, there's certainly that's one of the largest areas of unmet need and one of the largest market opportunities. As for the specific development strategy, Jonathan, I think that's going to have to wait until after the the presentation at ACR. At that point, will be, a lot of the data will become clear. You'll understand what we mean when we're talking about rational combinations.
So really good question and we're eager to share it with you.
As we indicated.
The disease area will be non small cell lung cancer.
There is certainly that's one of the largest.
Areas of unmet need and one of the largest market opportunities as.
As for the specific development strategy, Jonathan I think that's going to have to wait until after the presentation at ACR at that point.
It will be a lot of the data will become clear youll understand what we mean, when we're talking about rational combinations and you'll be able to see how we intend to initially use <unk> to do some de risking.
Troy Wilson: And you'll be able to see how we intend to initially use tipefarnib to do some de-risking while we're bringing 2806 along. It'll really be a, you know, kind of a one-two punch in that area. And it's our hope and expectation that that vignette, if you will, in non-small cell lung cancer is the first of several chapters in this new story. These are entirely new farnesylated proteins that we've never really talked publicly about before.
While we're bringing 26 along.
It will really be kind of a one two punch in that area and it's our hope and expectation that vignette. If you will in non small cell lung cancer is the first of several chapters in this new story. These are entirely new foreign insulated proteins that we've never really talked publicly about before this date is.
Troy Wilson: This data's been cooking for two to three years at this point. So really looking forward to April and AACR to roll that out with, you know, actual data for people to be able to study. Got it.
Ben cooking for for two to three years at this point, so really looking forward to April and ACR to roll that out with actual data for people to be able to study.
Peter Lawson: Thank you for taking my question. Thank you. Your next question is from Peter Lawson. Great. Thank you, Troy, and congratulations on all the promotions.
Got it thank you for taking my questions.
Thank you.
Your next question is from Peter Lawson from Barclays.
Great. Thank you Troy.
And.
Congratulations on all of them will be promotions.
Because if two minutes.
Troy Wilson: Any comments around how enrollment is going with the recent lifting of the clinical hold and how sites are opening up? Yeah, yeah, Peter, thank you again. So, Prior to being put on the partial clinical hold, folks may remember, we had guided to having full enrollment of the Phase 1B cohorts by the end of Q1. That has now moved to Q2, and we're giving ourselves a little bit of time, just in case we need it, to be able to then look at the patients in the two cohorts and make a data-driven decision on which of the two doses. we would recommend moving forward with. From that, you can tell we've slipped by approximately a quarter.
Just any comments around how enrollment is going with that.
Recent initiatives clinical hold.
No.
Troy Wilson: Of the high enrolling sites, the ones that have put patients on COMET thus far, 80% of those sites are reengaged, actively screening patients. As we indicated, enrollment has resumed with multiple patients on the study. So the sites are definitely stepping up. And we feel, at this point, comfortable that we can give the guidance of full enrollment, Q2, you know, top line data, Q3, and then the medical presentation in Q4. Got you.
Yes, yes, Peter Thank you again.
No.
Prior to the prior to being put on the partial clinical hold.
Folks may remember, we had guided to having.
Full enrollment of the phase <unk> cohorts by the end of Q1 that has now moved to Q2.
And we're giving ourselves a little bit of time, just in case, we need it to be able to then look at the patients into two cohorts and make a data driven decision on which of the two <unk>.
Doses, we would recommend moving forward with from that you can tell.
We've slipped by approximately a quarter.
The.
The high enrolling sites the ones that have put patients on comment thus far 80% of those sites are re engaged actively screening patients as we indicated.
Enrollment has resumed with.
With with multiple patients on the study so the sites are definitely stepping up.
And we feel at this point comfortable that we can give the guidance of full enrollment Q2.
Topline data Q3, and then the medical presentation in Q4.
Got you. Thank you.
Troy Wilson: Thank you. And then just how quickly do you think you could start combination trials? Yeah, that's a good question.
<unk>.
And then just how quickly do you think you could start combination trials.
Yes, that's a good question so.
Troy Wilson: So, We are actively planning and preparing for combinations as we speak even while the determination of the recommended phase 2 dose for the monotherapy is pending. As you might expect, the expectation would be that you step down at least a dose, if not two, from the from the RP2D and do a safety run-in. We want to make sure that we balance two things, Peter. We move as aggressively as possible while not doing anything to put the program at risk from a regulatory perspective.
We are actively planning and preparing for combinations as we speak even while the determination of the recommended phase two dose for the monotherapy is pending.
As you as you might expect the expectation would be that you stepped down at least the dose if not too from the from the <unk> and do a safety run in.
And we want to make sure that we balance two things Peter we move as aggressively as possible, while not doing anything to put the program at risk from a regulatory perspective, and we're balancing that real time.
Troy Wilson: And, you know, we're balancing that real time. We'll certainly start those studies this year. I just think at this point we're not prepared to give any more granular guidance on exactly the start time. But we're actively in preparation. As I indicated, you know, we're looking both in the front line and in the early relapse setting at combination opportunities with ZIF demented. Great. Thank you so much.
We will certainly start those studies this year I just think at this point, we're not prepared to give.
To give any any more granular guidance on exactly the start time, but.
But we're actively in preparation as I indicated.
We're looking both in the frontline and any early relapse setting at combination opportunities with Ziff demanded.
Tiago Fauth: Thanks for taking the question. Your next question is from Tiago Fauth from Credit Suisse. We're taking a question, 539 still.
Great. Thank you so much thanks for taking the questions.
Your next question is from Thiago <unk> from Credit Suisse. Your line is open.
Taking the question so Pfizer nine still so.
Tiago Fauth: So you did allude to it on the prepared remarks, but I want to go back to the patients that were already enrolled in the Phase 1b expansion and were eligible to remain on study. I don't know if you can share anything additionally qualitative on those patients that could have been in a study for quite some time right now or perhaps. A different way to think about it, we've discussed in the past a benchmark of about 20-30% CRCA, as a reasonable range for the class. I don't know how good you still feel about that range or the potential to actually differentiate on efficacy relative to other benchmarks. Curious if you can share any thoughts on that. Thank you. Sure, Tiago.
You did allude to it on the prepared remarks, but wanted to go back to the patients that were already enrolled in the phase one expansion and were eligible to the maintenance study.
I don't know if you can share anything. Additionally.
Qualitatively on those spaces.
And then maybe for quite some time, right now where perhaps a different way to think about it.
As a benchmark of about 20% to 30%.
H.
As a reasonable range for the class.
I don't know how good do you still feel about that range or the potential to actually differentiate on efficacy relative to other benchmarks curious if you can share any thoughts on that thank you.
Troy Wilson: Thank you for the question. You're correct in when you formulated the question. We had a number of patients who have remained on study throughout the partial clinical hold, you know, and we're still in the midst of enrollment of the Phase I-B studies. Based on what we've seen thus far from the Phase I-B, our sort of qualitative commentary has been we believe there's an opportunity with KL-539 to be as good as, if not better, than the numbers that have been posted for competing programs.
Sure Thiago. Thank you for the question.
You are correct.
And when you formulated the question we had a number of patients who have remained on study through.
Throughout the partial clinical hold.
And we're still in the midst of enrollment.
The phase <unk> studies based on what we've seen thus far from the phase one b.
<unk> sort of qualitative qualitative commentary has been we believe there is an opportunity with <unk> $5 39 to be as good as if not better than the numbers that have been posted for competing programs.
I want to be careful, but we are seeing encouraging safety tolerability and clinical activity.
Troy Wilson: You know, I want to be careful, but we are seeing encouraging safety, tolerability, and clinical activity. But, you know, it's still early days, and I don't want expectations to get out of control, but we definitely think we've got a very, very strong compound here, and everybody is, you know, super fired up to get these Phase I-B cohorts completed. Fair enough. Great. Thank you so much.
But it's still early days, but.
I don't want expectations to get out of control, but we definitely think we've got a very very strong compound here and where.
<unk>.
Super fired up to get these phase one b cohorts completed.
Alright, great. Thank you so much.
Ren Benjamin: Your next question is from Ren Benjamin from JMP Security. Hey, good afternoon, guys. Troy, maybe just starting off, can you talk a little bit about.., and a ride from colors to how the integrates, going, and Scott Patrales, started in record time, and that... Sure, Ren.
Your next question is from Ren Benjamin from JMP Securities. Your line is open.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on all the progress.
Troy, maybe just starting off can you talk a little bit about.
I will provide some color as to how the integration of the mitigation efforts.
Has it been going I know that.
You guys got the trial started kind of restarted in record time.
Is that if you can give us some color on the on that progress and how the initial.
Troy Wilson: Yeah, thank you for the question. So, maybe just to set expectations and set understanding, we had already had a fairly fulsome section, you know, in the investigator brochure around differentiation syndrome. Now, that was bolstered through the discussions and the feedback that we received from the agency in the course of getting the clinical hold lifted, but it wasn't as though we were starting with, you know, tabula rasa. We had a pretty extensive disclosure there.
It's Luke.
Sure Brian Yes. Thank you for the question. So maybe just to set expectations and set understanding we had already had a fairly fulsome.
Section.
The.
In the investigator brochure around differentiation syndrome.
That was bolstered through the discussions and the feedback that we received from the agency in the course of getting the clinical hold lifted but it wasn't as though we were starting with Tabula Rasa. We had a we had a pretty extensive disclosure there really the focus has been around increased monitoring initially and then.
Troy Wilson: Really, the focus has been around increased monitoring initially and then sort of aggressive intervention if standard of care approaches are not effective in terms of withdrawing KL-539 from the patient to stop an ongoing episode of differentiation syndrome. So, the beginning and sort of then along the way.
Sort of aggressive intervention, if if standard of care approaches are not effective in terms of withdrawing <unk> 39 from the patient to stop.
And ongoing episode of differentiation syndrome, so the beginning in sort of that along the way.
Troy Wilson: Both of those have been, you know, they were generated in consultation with the study physicians. We've got, you know, a number of investigators who are, you know, among the world's experts at managing DS, so they were great. And thus far, Ren, you know, we have seen at least another episode of DS that was mild to moderate, managed very effectively using the now sort of heightened awareness and revised algorithm. It doesn't appear to have dissuaded the investigators at all. They're super excited by what they're seeing.
Both of those have been.
<unk> generated in consultation with the study physicians we've got.
A number of investigators who are among the world's experts that at managing DFS. So they were great.
Thus far we have seen.
At least another episode of DFS that was.
Mild to moderate managed very effectively using the now sort of heightened awareness.
<unk> revised algorithm.
It doesn't appear to have been to have dissuaded the investigators at all they're super excited by what they are seeing safety tolerability efficacy.
Troy Wilson: Safety, tolerability, efficacy, and I think they know what they need to do. They know how to manage it. We've given them a couple of extra tools to be able to keep the patients safe, and thus far, all indications are, you know, that was exactly what was needed. So, I don't think we're seeing any real impact at all from the revised mitigation strategy on either site engagement, investigator interest, or the pace of enrollment.
And I think they know they know what they need to do they know how to manage it.
We've given them a couple of extra tools to be able to keep the patients safe and thus far all indications are.
That was exactly what was needed so.
I don't think were seeing any any real impact at all from the revised mitigation strategy on either site engagement investigator interest or the pace of enrollment.
Troy Wilson: And when we think about, you know, the enrollment completing and you guys, I'm going to give myself a little bit more time, kind of implicit in that, me is, you know, also a greater understanding as to the durability, and not just overall. How important.., https://www.nasa.gov, Timeline, if you will, I kind of still.., or you could make. Yeah, it's a really good question, Ren.
Got it.
And when we think about the enrollment completing in you guys, giving up a little bit, giving yourself, a little bit more time kind of implicit in that.
It to me is.
Also greater understanding as to the durability.
Of of DFS right. So not just overall response rate, but then the durability.
Gordon is durability for you guys in deciding the RPT Judy and.
Yes.
As the timeline, if you will kind of still too short.
<unk> you can make the appropriate decision.
Troy Wilson: We think that the timeline we've articulated is sufficient to be able to discriminate one dose from another and to be able to come and say, we believe we've identified, you know, a recommended phase two dose. That's obviously still subject to the FDA reviewing all of the data, you know, in consultation with us around an end of phase one meeting. But we think the, you know, the activities we're conducting and the timelines we've laid out are going to be sufficient.
Yes, it's a really good question Ren.
We think that the timeline, we've articulated is sufficient to be able to discriminate one dose from another and to be able to come and say we believe we've identified.
Our recommended phase II dose, that's obviously still subject to the FDA reviewing all of the data.
In consultation with us around are around an end of phase one meeting, but we think the <unk>.
Activities, we're conducting in the timelines we've laid out are going to be sufficient part of what we're giving ourselves ran is and we've had we've seen others, who are working with Menin inhibitors comment on this you do see if you will a biphasic.
Troy Wilson: Part of what we're giving ourselves, Ren, is, and we've seen others, you know, who are working with menin inhibitors comment on this, you do see, if you will, a biphasic sort of response to drugs like this. The first phase is elimination of the leukemia. The second phase is reconstitution of the normal hematopoietic system. In order to get a CR or CRH, you need to have platelets and neutrophils, you know, at the level sufficient to call a CR or CRH.
Sort of response to drugs like this the first phase is elimination of the leukemia. The second phases reconstitution of the normal hematopoietic system in order to get a CR CRH you need to have platelets or neutrophils at the levels sufficient to call a CR CRH in our experience that can.
Troy Wilson: In our experience, that can take two or three cycles, you know, really, particularly for patients who are, you know, who've been through multiple rounds of therapy. So, you know, we've built that in as well, but it's more, our thinking is more around, let's get the patients enrolled, let's give them an opportunity to get to, you know, the best quality of response, and then the durability is going to be what it's going to be.
Take two or three cycles.
Really particularly for patients who are who've been through multiple rounds of therapy. So we've built that in as well, but it's more our thinking is more around let's get the patients enrolled let's give them an opportunity to get to the.
The best quality of response, and then the durability is going to be what it's going to be I would tell you we feel very comfortable with the guidance we've given of.
Troy Wilson: I would tell you, we feel very comfortable with the guidance we've given of, you know, we've said consistently four to six months duration of response, no reason at all to deviate from that, and ideally, again, you'd come in on the high end of that, but, you know, it's early days. But our, you know, we waited to be in a position where we could give what we believe to be, you know, pretty concrete guidance around the timing of this program and reaching the RP2D, and we feel good about that guidance.
We've said consistently four to six months duration.
Duration of response, no reason at all to deviate from that and ideally again you'd come in on the high end of that but it's early days, but.
We waited to be in a position, where we could give what we believed to be.
Pretty concrete guidance around the timing of this program and reaching the <unk> and we feel good about that guidance.
Troy Wilson: And then just one final one for me, you mentioned in your prepared remarks the flexibility of, regarding a global development. I'm going to skip a few weeks here, but when I think global development strategy, I think most ideally with a partner. Is that something that might be in the works?
Got it.
And then just one final one for me.
And in your prepared remarks the flexibility.
Regarding our global development strategy.
I might be reading too much into the tea leaves here, but.
I think global development strategy, I think probably most ideally with a partner is is that something that that might be in the works.
Something that you want to do kind of by yourselves and then evaluate a partnership at a later stage.
Troy Wilson: by yourselves, to evaluate a partner. Yeah, right. And that's a good question. So, so let's, let's tease those two things apart.
Troy Wilson: When we speak of a global development strategy, what we mean is conducting trials that are not only in the United States, but ex US, most notably Western Europe, but also, you know, places like certain countries in Asia. That's what we mean when we're talking about a global development program. We are, of course, always evaluating, you know, would we consider a partnership that would either allow us to do more, allow us to go faster, or allow us to lower the risk?
Yes, that's a good question so let's take let's tease those two things apart when we speak of a global development strategy. What we mean is conducting trials that are not only in the United States, but ex U S. Most notably Western Europe , but also places like certain countries in Asia, that's what we mean when we.
Talking about a global development program, we are of course always evaluating.
Would we consider a partnership that would either allow us to do more allow us to go faster or allow us to lower the risk.
Troy Wilson: There's certainly strong interest across the portfolio. These are things that we have to weigh is, you know, what's best for shareholders, what's best for the programs and the patients. But, but most immediately to your question, when I talk about us moving into a global development program, think of that as, at least in the most immediate case, a trial that's going to be conducted in the US and then, you know, identified ex US countries, really to help drive enrollment, which is what you need in these, in these rarer populations.
There is certainly strong interest across the portfolio. These are things that we have to weigh is what's best for shareholders, What's best for the programs and the patience, but but most immediately to your question when.
When I talk about us moving into a global development program think of that as at least in the most immediate case a trial that's going to be conducted in the U S. And then identified ex U S countries really to help drive enrollment, which is what you need in these in these rare populations.
Troy Wilson: The BD question or the strategic question, if you will, that's a second question. And that's one that's always out there. But that's not what we were, that's not what I was referring to in my comments specifically.
BD question or the strategic question. If you will that's a second question and Thats, one thats always out there, but thats not what we were what I was referring to in my comments specifically.
Terrific. Thanks for the clarification and good luck moving forward.
Troy Wilson: Thank you. Your next question is from Ron Roger Song from Jeffrey's Real Life. Great, congrats for all the progress. A few quick ones from me.
Your next question is from non grocery saw from Jefferies. Your line is open.
Great.
For all the progress.
Roger Song: So the first one is, I think, Troy, When would you meet FDA to discuss the potential pivotal plan for the 539? Do you need to weigh the full results, maybe a little bit kind of durability, or you actually can meet them after the top-line data? Yeah, Roger, it's a good question.
A few quick ones from me. So the first one is I think Troy.
Where would you need FDA to discuss the potential pivotal for that by 39.
Need to waive a full rollout maybe amendable kind of durability are you actually can be done after the topline data items in Q.
Troy Wilson: So it's our understanding, you know, Once we're in a position where we believe we've identified a recommended Phase 2 dose, obviously there's a lot of supporting information that goes into that determination. There's the safety and tolerability, there's the PK and exposure, and there's the clinical activity. And each of those is, you know, has to be handled completely and correctly.
Yes, Roger it's a good question so it's hard to understanding.
Once we're in a position where we believe we have identified a recommended phase II dose. Obviously, there is a lot of supporting information that goes into into that determination. There is the safety and Tolerability. There is the PK exposure and there is the clinical activity and each of those is.
It has to be handled completely and correctly.
Troy Wilson: It's not our view, Roger, that we'd be waiting on durability. It's more how quickly can we hustle to get all that data together, to get it clean, to get it into a format where we can deliver it to the agency in a way that addresses any questions that the reviewers might have. So our view is, you know, you can imagine we're doing everything we can at risk to save time.
It's not our view Roger that we'd be waiting on durability. It's more how quickly can we hustle to get all that data together to get a clean to get it into a format, where we can deliver it to the agency in a way that there.
Addresses any questions that the reviewers might have so.
Our view is.
You can imagine we're doing everything we can at risk too to save time.
Troy Wilson: Ultimately, we do have to say, is it this dose or that dose, plug that in, and then have the narrative descriptions and the data supporting it. But I don't think we need to, I don't think we're going to be waiting on durability, you know, to be able to provide those materials and, if necessary, answer any questions that the agency might have. Got it, that's very helpful, thank you. Maybe just another one.
Ultimately, we do have to say is that this dose or that dose plug that in and then and then have the narrative descriptions and the data supporting it but I don't think we need to I don't think were going to be waiting on durability to be able to provide those materials and if and if necessary answer any questions that the agency might have.
Got it that's very helpful. Thank you maybe just another one.
Troy Wilson: Understanding you are doing the TIPI up-listed combo data, potentially initial data by the end of this year. So if the data looks very impressive, how would you kind of incorporate this into your monotherapy pivotal, which is ongoing? Yeah, that's a good question.
Understanding youre doing the.
Optimistic combo data potentially initiative by the end of this year. So if the data looks very impressive how would you kind of incorporate this into your monotherapy pivotal which.
Which is ongoing.
Troy Wilson: So ultimately, what one does is in combination is quite different from what one would do as a monotherapy. You know, the monotherapy is a trial where confirmed response rate is the is the you know, the in the in the high VAF population is the primary endpoint. And it's a single arm trial in the combination setting, one would need to you'd need to do some sort of randomization. You'd also, you want to make sure that you addressed the contributions of the individual drugs to you know, to the activity that you're seeing.
Yes, that's a good question so ultimately.
One does this combination is quite different from what one would do as a monotherapy.
The monotherapy is a trial where.
Confirmed response rate is that is the.
In the high VHF population.
<unk> is the primary endpoint.
And it's a single arm trial in the combination setting one would need to you would need to do some sort of randomization you'd also.
Troy Wilson: What what we can tell you is, you know, you don't see high rates of response with either tippy, you certainly don't see them with tippy in the PIK3CA population, you don't see them at all. And with alpelicative, they're relatively rare.
You want to make sure that you addressed the contributions of the individual drugs to to the activity that youre seeing.
What we can tell you is you don't see high rates of response with either typically.
We don't see them with <unk> in the <unk> population, you don't see them at all and without palisade. They are relatively rare. So if youre seeing objective responses that's a good sign.
Troy Wilson: So if you're seeing objective responses, that's a good sign. You know, you probably would need to do some sort of randomization. At this point, we're really looking to see, can we recapitulate clinically, what we've seen preclinically? Namely, can we drive up, you know, responses? And can we maintain durable responses in this much broader set of patients? It's early days that we're encouraged by what we're seeing. You know, we're really trying to get our arms right now around safety and tolerability of the payer.
You probably would need to do some sort of randomization at this point, we're really looking to see can we recapitulate clinically what we've seen pre clinically.
Namely can we drive.
Sponsors and can we maintain durable responses in this much broader set of patients. It's early days, but we're encouraged by what we're seeing.
We're really trying to get our arms right now around safety and Tolerability of the Payor.
Troy Wilson: The overall development strategy in head and neck squamous, Roger, I think that's a that's a longer discussion. And one that we're, you know, we're preparing for and we'll be in a position to speak to sort of later in the year, I hope. Great. Look forward to it.
The overall development strategy in head and neck squamous, Roger I think that that's a longer discussion and one that we're preparing for and we'll be in a position to speak to sort of later in the year I hope.
Roger Song: Thank you. That's all from me. Congrats again. Thank you. Again, that is star and then the number one on your telephone keypad to ask.
Great look forward to.
Thank you that's all for me.
Again.
Thank you.
Again that is star then the number one on your telephone keypad to ask a question.
Operator: Your next question is from Philip Nadeau from Covenant Company, here live. Good afternoon, thanks for taking our questions and congratulations for the promotion. First, a question on Ziftaminib. In terms of MLLR versus NPM1 patients. Is there... Do you have expected numbers of each of those?
Your next question is from Phil Nadeau from Cowen <unk> Company. Your line is open.
Good afternoon, Thanks for taking my questions and congratulations for the.
The promotions first a question on just a minute in terms of MLR versus NPM one patients is there.
Do you have expected numbers of each of those.
Philip Nadeau: genotypes in the trial, and do you hope to get an assessment of response rate? for both of those at both doses, or are you fairly confident that the response rate for MLLR and NPM1 similar, so you won't, you won't differentiate. Yeah, Phil, that's a really good question.
Genotypes in the trial and do you hope to get an assessment of response rate.
For both of those are both data at both doses or are.
Are you fairly confident that the response rate for MLR in NPM, one won't be similar so you won't you won't differentiate between the two.
Troy Wilson: So, the Phase 1b portion of Comet is not designed to enrich, it's not designed to, sorry, it's enriched in KMT2A and NPM1, but there's no requirement of, you know, some minimum number of patients from each genotype. So we're getting what we're going to get. I think we've commented in the past, we are seeing more KMT2A rearranged patients than the relative epidemiology might suggest, probably because those patients do not have a lot of options and they tend to just blow through lines of therapy, as opposed to the NPM1 mutant patients sometimes have co-mutations and are eligible to go, for example, into a FLT3 trial.
Yes, Phil.
Good question.
So.
The phase <unk> portion of comment is not designed to enrich its not designed to sorry.
It's enriched in Kmt <unk> and NPM, one, but there is no requirement of.
Some minimum number of patients from each genotype.
So we're getting what we're going to get.
We've commented in the past, we are seeing more Kmt <unk> rearranged patients than the relative epidemiology might suggest probably because those patients do not have a lot of options and they tend to just blow through lines of therapy.
As opposed to the NPM, one mutant patients sometimes have co mutations and are eligible to go for example into a <unk> trial. So we are seeing more Kmt two way than than than one would predict if thats, 5% to 10% of the population in NPM. One is 30% we think overall that's right but in the in this really.
Troy Wilson: So we are seeing more KMT2A than one would predict if that's 5-10% of the population and NPM1 is 30%. We think overall that's right, but in this relapsed refractory setting, it's perhaps a little tilted. It's our view, you know, does that matter?
Refractory setting, it's perhaps a little tilted it's al.
Troy Wilson: We don't think so. We haven't seen any indication that tells us either that we need a different dose between the two genotypes or that we should expect a different result. In fact, it seems to have more to do, the quality of clinical benefit has more to do with the patient's overall fitness and perhaps other co-mutations such as P53 than, you know, is it NPM1 or KMT2A. It's early days, it's small numbers, but I don't think we're going, it's not our view right now that we would need a lot more. And I'll just remind you and the audience of one final thing.
Our view does that matter, we don't think so we haven't seen any indication that tells us either that we need a different dose between the two genotypes or that we should expect a different result in fact the seams.
It seems to have more to do that.
The quality of clinical benefit has more to do with the patient's overall fitness.
And perhaps other co mutations such as P. 53, then it then is it NPM Warner Kmt <unk>. It's early days, it's small numbers, but I don't think we're going it is not our view right now that we would need a lot more and I will just remind you in the audience of one final thing remember that once we enroll.
Troy Wilson: Remember that once we enroll these 24 patients, 12 in each cohort, we then can transition and enroll an additional 18 patients at whichever dose we've identified. That gives us the opportunity prior to going into the formal portion of the Phase 2 of getting even a little bit better clarity and better precision, if you will, around exactly what it is we're seeing. So in totality, at the recommended Phase 2 dose, we'll have, we expect to have 30 patients' worth of data by the time we formally transition into Phase 2.
These 24 patients 12 in each cohort, we then can transition and enroll an additional 18 patients at whichever dose we've identified.
That gives us the opportunity prior to going into the formal portion of the phase II of getting even a little bit better clarity and better precision. If you will around exactly what it is we're seeing so in totality at the recommended phase II dose, we expect to have 30 patients worth of data by the time, we formally.
Troy Wilson: Now, all of those patients, we hope and expect, will be treated as though they're eligible to be in the registrational population, but that'll allow us to do any tweaking that we need to do. At this point, we don't think we need to do any, Phil, but, you know, you don't know what you don't know.
Transition into phase II now all of those patients, we hope and expect will be treated as though they are eligible to be in the registrational population, but that will allow us to do any tweaking that we need to do at this point, we don't think we need to do any fill but.
You don't know what you don't know so this will give us a lot of a lot of ability to to make sure. We're on the right path.
Troy Wilson: So this will give us a lot of ability to make sure we're on the right path. Perfect, and then second question, in terms of determining the recommended phase two dose, you mentioned that exposure is one of the criteria in addition, obviously, to safety and efficacy. Do you have specific criteria for exposure, so IC90s that you want to maintain for? some time, or PD biomarkers that you're assessing, as well. Can you can you give us some sense of how you are going to, Yes, so it's that's a great question.
Perfect and then second question in terms of determining the recommended phase two dose you mentioned that exposure is one of the criteria.
In addition, obviously the safety and efficacy do you have specific criteria for exposure. So IC 90 days that you want to maintain for some point in time.
<unk> or PD biomarkers that youre assessing.
As well can you can you give us some sense of how you are going to look at exposure.
Troy Wilson: So we are looking at them, that we don't believe they're gating on making a determination of identifying the recommended phase two dose for the following reason. The you know, KO539 exhibits time dependent accumulation. We see exposures at steady state that are multiples of the exposure on cycle one day one. And we don't have the sort of periodicity that you see from once daily or twice daily dosing. You're basically, you know, you're basically bathing the target in 539.
So that's a great question. So we are looking at them.
We don't believe there gating on making a determination of identifying the recommended phase two dose for the following reason.
<unk>.
<unk> hundred 39 exhibits time dependent accumulation.
We see exposures that steady state that are multiples of the exposure on cycle. One day, one and we don't have the sort of periodicity that you see from once daily or twice daily dosing you basically you basically bathing the target in 539 now you do see a difference if you take the <unk>.
Troy Wilson: Now you do see a difference, you know, if you take the mean or the median exposure of patients at the 200 milligram dose versus the 600 milligram dose, you see more, you see greater exposure at the 600 milligram dose. But both of those doses appear to be covering the target sufficiently to drive clinical activity. So it's going to be part of the package built to make sure that we're giving as consistent, you know, dose and exposure as possible, but probably not going to be gating on making the ultimate determination of one dose versus the other to move forward. Perfect.
Mean, or the median exposure of patients at the 200 milligram dose versus the 600 milligram dose you see more youll see greater exposure at the 600 milligram dose, but both of those doses appear to be covering the target sufficiently to drive clinical activity. So it's it's it's going to be part of the package built.
To make sure that we're giving is consistent.
Both dose and exposure as possible, but probably not going to be gating on on making the ultimate determination of one dose versus the other to move forward.
Philip Nadeau: And then last question from us is on Tippi Farnab in the AIM-HN study. ClinicalTrials.gov still lists that trial as completing in May 2022, but we did notice that you didn't call out a date or event for that trial this year. Any sense when that could complete and when data could be released?
And then last question from Us.
No.
<unk> HN study clinical trials Dot Gov still with the trial was completed in May 2022, but we didn't know so you didn't call out particular event for that.
A trial this year.
Any sense when that could complete and when data could be released.
Troy Wilson: Yeah, so we haven't reinstated guidance, Phil, on that. You know, we have been, I hope, pretty transparent with folks that, you know, the trial's ongoing, we are seeing clinical activity that's consistent with RUN. The biggest challenge, frankly, for us has been, and this is in contrast to what we saw with RUN, the ability to convert patients that we identify, HRAS mutant patients, and actually get them on the study is much lower than we had predicted.
Yes, so we haven't reinstated guidance Phil on that.
We have been I hope pretty transparent with folks that.
The trials ongoing we are seeing clinical activity, that's consistent with run the.
The biggest challenge frankly for us has been.
And this is in contrast to what we saw with run.
The ability to convert patients that we identify a trust mutant patients and actually get them on the study is much lower than we had predicted it's it's probably one in four meaning we have to find for HRS mutant Hi, Hi.
Troy Wilson: It's probably one in four, meaning we have to find four HRAS mutant, you know, high VAF patients for every one that we successfully convert onto the study. That has, much to our frustration, kind of delayed and enlarged the timelines around recruitment. And, you know, that's also part of why it's been interesting to bring the current study online, because there you're dealing with 20 to 50% of head and neck. We've been very pleasantly surprised with the rate of enrollment in the current study.
<unk> patients for everyone that we successfully convert onto the study that has much to our frustration kind of delayed and enlarge the timelines around recruitment.
And.
That's also part of why.
It's been interesting to bring current the current study online because there youre dealing with 20% to 50% of head and neck.
We've been very pleasantly surprised with the rate of enrollment in the current study.
Troy Wilson: You know, the fact that you're looking at one in two or one in three patients, it's just a completely different ballgame. So, you know, the team's doing their best to soldier on. You know, recurrent and metastatic head and neck is a tough indication. There's no approved small molecule targeted therapies.
Fact that Youre looking at one and two or one in three patients. It's just a completely different ballgame.
So.
The team is doing is doing their best to soldier on.
Recurrent and metastatic head and neck is is a tough indication there is no approved small molecule targeted therapies.
Troy Wilson: They're slogging through it to get those patients on study. Ultimately, you know, combination and going to a broader population may help to address the challenges that we're seeing. Perfect. That's very helpful. Thanks again for taking our, Our pleasure. I am showing no further questions. I would now like to turn the call back to CEO Mr. Troy Wilson for a close, Thank you, operator. And thank you all once again for joining our call today.
Theyre slogging through it to get those patients on study ultimately combination and going to a broader population may help to address that the challenges that we're seeing.
Perfect. That's very helpful. Thanks, again for taking my questions.
Our pleasure.
I am showing no further question at this time I would now like to turn the call back to CEO , Mr. Troy Wilson for closing comments.
Troy Wilson: We'll be participating in the Cowan and Barclays Healthcare Conferences over the next several weeks, 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 myself. Thank you again, and have a good evening, everyone. Ladies and gentlemen, this does conclude the... Thank you for participating. In the next video, we'll see you in the next video.
Thank you operator, and thank you all once again for joining our call today, we will be participating in the Cowen and Barclays healthcare conferences over the next several weeks and we look forward to seeing many of you there in.
In the meantime, if you have any additional questions. Please feel free to contact Pete Tom or myself. Thank you again and have a good evening everyone.
Ladies and gentlemen, this does conclude today's conference. Thank you for participating you may now disconnect.
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