Q2 2020 Syros Pharmaceuticals Inc Earnings Call
Ladies and gentlemen, please standby years euros Pharmaceuticals second quarter 2020 financial results conference call well begin momentarily. Thank you for your patience and please standby.
Operator: Ladies and gentlemen, please stand by. Your Syros Pharmaceuticals second quarter 2020 financial results conference call will begin momentarily. Thank you for your patience and please stand by. The Ultimate Parody Site! Copyright 2019 Mooji Media Ltd. All Rights Reserved.
Operator: No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. BF-WATCH TV 2021, Good morning, and welcome to Syros Pharmaceuticals' second quarter 2020 financial results conference call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Syros's website at www.syros.com. Please be advised that today's call is being Following the formal remarks, we will open up the call for your questions. At this time, I would now like to turn the call over to Naomi Ayo. Vice President of Corporate Communications and Investor Relations at Syros, with our second quarter 2020 financial results along with anticipated future milestones and recent accomplishments.
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Good morning, and welcome to see arose Pharmaceuticals second quarter 2020 financial results Conference call. At this time all participants are in listen only mode. It's called is being webcast live on the investors immediate section of cereals website www dot cereals dotcom. Please be advised the today's call is being recorded follow.
Operator: This release is available in the Investors and Media section of Syros' website at www.syros.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer; Dr. David Roth, our Chief Medical Officer; and Joe Farah, our Chief Financial Officer. We will then open the call for questions. Dr. Eric Olson, our Chief Scientific Officer, and Dr. Jeremy Springhorn, our Chief Business Officer, are also on the call and will be available for Q&A. Before we begin, I would like to remind everyone that the statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factor section of our annual report on Form 10-K, our quarterly report on Form 10-Q that we filed this morning, and any other filings that we may make with the SEC in the future.
In the formal remarks, you open up the called for your questions. At this time I would now like to turn the call over to namely Alky, Vice President corporate Communications and Investor Relations its heroes.
So with our second quarter 2020 financial results, along with anticipated future milestones and recent accomplishments. This release is available on them back.
Gerson Media section Osiris is website at www Dot Sierra Dotcom.
We began mccall with prepared remarks by Dr., Nancy Simonian, our Chief Executive Officer, Dr., David Roberts, Our Chief Medical Officer, and show Farah, Our Chief Financial Officer.
Operator: In particular, the extent to which the COVID-19 outbreak continues to impact our operations and those of third parties on which we rely will depend on future developments that are highly uncertain and cannot be predicted with confidence. Any forward-looking statements we make on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statement.
We will then open the call for questions Dr., Erik Olsson, our Chief Scientific Officer, Dr., Germany Spring Horn, our Chief business Officer are also on the call and will be available for Q1 day before we begin I would like to remind everyone that statements. We make on this conference call will include forward looking statements.
Actual events or results could differ materially from those expressed or implied by any forward looking statements. If it was all at various risks uncertainties and other factors, including those set forth in their risk factor section of our annual report on form 10-K.
Nancy A. Simonian: I would now like to turn the call over to Nancy. Thanks, Naomi. Good morning, everyone.
Our quarterly report on form 10-Q that we filed this morning and any other filings that we may make with the FCC in the future in particular, the extent of which the koeppen 19 outbreak continues to impact our operations and there was a third parties on which we rely will depend on future developments, which are highly uncertain and cannot be predicted.
Nancy A. Simonian: And thank you for joining us today as we review our progress in the second quarter of 2020. Despite all the unforeseen challenges that this year has brought, Syros is entering the second half of 2020 from a position of strength. Our team has shown remarkable resilience, dedication, and creativity in recent months, continuing to advance our two clinical stage programs, SY1425 and SY5609, toward multiple key data readouts this year and next, while also progressing our earlier stage research. The coming months promise to be an exciting time for the company. Importantly, we remain on track for clinical readouts for 1425 in two RARA-positive AML patient populations and for the first clinical data from the Phase 1 trial of 5609 in select solid tumor patients, all in the fourth quarter. These data will provide valuable insights that will help inform next steps and hopefully bring us closer to our vision of building an enduring company with medicines that provide a profound benefit for patients. Turning now to our second quarter accomplishments.
Competence.
Any forward looking statements were made on this call.
Represent our views only as of today and should not be relied upon as representing our views are there any subsequently, we specifically disclaim any obligation to update or revise any forward looking statements I would now like to turn the call over to Nancy.
Thanks Nio me good morning, everyone and thank you for joining US today as we review our progress over the second quarter of 2020.
Despite all the unforeseen challenges that this year has brought heroes is entering the second half of 2020 from a position of strength.
Our team has shown remarkable resiliency dedication and creativity in recent months continuing to advance our two clinical stage programs.
Slide 14, 25, and that's why 56, so nine toward multiple key data read out this year and next.
We also progressing our earlier stage research.
The coming months promise to be an exciting time for the company.
Importantly, we remain on track for clinical Readouts for 14, 25 into Robert positive email patient population.
Nancy A. Simonian: Consistent with our philosophy to explore combinations early in the clinic that have a mechanistic rationale and strong preclinical data, in June, we initiated enrollment in a cohort evaluating escalating doses of 5609 in combination with Sylvesterin in treatment-resistant HR-positive breast cancer patients. Also, in the second quarter, as part of the virtual ASCO meeting, we presented new preclinical data for 5609, our highly selective oral CDK7 inhibitor in colorectal cancer. As David will describe later in the call, these data, together with a mechanistic rationale, form the basis for our decision to include colorectal cancer patients in our ongoing phase one trial and support the PD markers we are using to guide dose selection in the trial. Since the inception of the company, we have been leaders in selective CDK7 inhibition, and the preclinical data in colorectal cancer and PD markers build on that leadership, further highlighting 5609 as a potentially transformative, targeted approach for difficult-to-treat cancer.
And for the first clinical data from the phase one trial, a 56, so nine in select solid tumor patients all in the fourth quarter.
These data will provide valuable insights that will help inform next steps and hopefully bring us closer to our vision a building an enduring company with medicine that provide a profound benefit for patients.
Turning now to our second quarter accomplishment.
System with our philosophy to explore combinations early in the clinic that haven't mechanistic rationale and strong preclinical data in June we initiated enrollment in a cohort evaluating escalating doses of 56, so nine in combination with pulled that strength in treatment resistant HR positive breast cancer patients.
Also in the second quarter as part of the virtual ASCO meeting, we presented new preclinical data for 56. So nine are highly selective oral CDK seven inhibitor in colorectal cancer.
As David will describe later in the call. These data together with a mechanistic rationale formed the basis for our decision to include colorectal cancer patients in our ongoing phase one trial and support the PD markers, we are using to guide dose selection in the trial.
Nancy A. Simonian: In addition to advancing our clinical stage program, we also continue to progress our preclinical and discovery efforts. As you know, building a robust and sustainable pipeline through ongoing investment in our gene control platform is a key strategic priority for us. On our first quarter call, we reported that we had reduced our lab-based operations as a result of the pandemic.
Since the inception of the company, we had been leaders in selective CDK seven inhibition and the preclinical data in colorectal cancer and PD markers build on that leadership further highlighting 56, so nice because they potentially transformative targeted approach are difficult to treat cancer.
Nancy A. Simonian: I am pleased to share today that, with the appropriate safety measures in place, our lab-based operations are now fully functional to drive forward our preclinical and discovery research. Even as the reality in which we are operating has been so dramatically altered by the ongoing pandemic, our focus here at Syros is unchanged. We are proud of the work our team has done to continue to advance our research and to prevent potential disruptions for the patients in our clinical trials, and we are deeply appreciative of the partnerships of our clinical trial sites and investigators. Every day matters for patients with cancer and monogenic diseases, and we are committed to executing with excellence to bring medicines to market that make a profound difference for these patients. With that, I'd like to turn the call over to David.
In addition to advancing our clinical stage programs. We also continued to progress our preclinical discovery efforts.
You know building, a robust and sustainable pipeline to ongoing investments in our gene control platform is a key strategic priority for us.
On our first quarter call, we reported that we had reduced our lab based operations as a result at the pandemic.
I am pleased to share today that with the appropriate safety measures in place our lab based operations are now fully functional the dry Ford our preclinical discovery research.
Even if the reality, which we are operating has been so dramatically altered by the ongoing pandemic.
David A. Roth: Thank you, Nancy, and good morning to everyone joining us today. To echo Nancy's sentiment, the second half of 2020 promises to be an exciting time for Syros as we share additional clinical data and begin charting next steps for 1425 and 5609. In anticipation of the data readouts in the fourth quarter, I want to provide a brief overview of both programs, including the nature of the data we expect to present and how we think about the opportunities in AML and in advanced solid tumors. Let me begin with 1425.
Our focus here, it's zero is unchanged.
We are proud of the work our team has done to continue to advance our research and to prevent potential disruption for the patients and our clinical trials and we are deeply appreciative of the park shipped about clinical trial sites and investigators.
Every day matters for patients with cancer and monogenic diseases, and we are committed to executing with excellence to bring medicines to market that make a profound difference for these patients.
With that I'd like to turn the call over to David.
Thank you Nancy and good morning to everyone joining us today.
Turning to Nancy sentiment to second half of 2020 promises to be an exciting time for ciros as we share additional clinical data and to begin shorting next steps for 14, Ptwenty five and 56, Illinois.
David A. Roth: We believe 1425 has broad combination potential for the approximately 30% of AML and higher risk MDS patients who are RARA positive. Our ongoing phase 2 trial is focused on 1425 in combination with azacitidine in this genomically defined subset of newly diagnosed, unfit, and relapsed or refractory AML patients. Data to date from the newly diagnosed unfit cohort has shown high rates of complete responses and transfusion independence with rapid onset of action, favorable tolerability, and early signs of durability. We completed enrollment of newly diagnosed unfit patients in November, and we expect to report mature data in the fourth quarter, which will include more patients and longer duration on study. These data will inform next steps in the frontline setting.
In anticipation of the data read outs in the fourth quarter I want to provide a brief overview of both programs, including the nature of the data we expect to present and how we think about the opportunities in and now and in advanced solid tumors.
Let me begin with 14 25.
Net of newly diagnosed unfit and relapsed or refractory AML patients.
Data to date from the newly diagnosed on the fit cohort has shown high rates of complete responses and transfusion independence with rapid onset of action favorable tolerability and early signs of durability.
We completed enrollment of newly diagnosed unfit patients in November and we expect to report mature data in the fourth quarter, which will include more patients and longer duration on study.
David A. Roth: Despite treatment advances, we're still not curing these patients. Better front-line treatment regimens are needed. Some patients are refractory to front-line therapies, and virtually all patients, in some cases, with resistance mechanisms that appear to confer an even poorer prognosis. All of this points to the ongoing need for active, well-tolerated therapies that can be used in combination, as well as the importance of identifying which patients are likely to respond to which therapies and how best to sequence those therapies. We completed enrollment in the relapsed or refractory patient cohort in May, and we expect to report the first data from this cohort in the fourth quarter. The unmet need for relapsed or refractory AML is particularly stark. Median overall survival remains low at less than six months, and recently approved therapies target limited patient subsets, leaving many patients with few alternatives.
These data will inform next steps in the frontline setting.
Despite treatment advances, we're still not curing these patients better frontline treatment regimens are needed some patients or refractory to frontline therapies and virtually all patients in some cases would have resistance mechanisms that appear to confer and even poor prognosis.
All of this points to the ongoing need for active well tolerated therapies that can be used in combination as well as the importance of identifying which patients are likely to respond to which therapies and how best to sequenced those therapies.
We completed enrollment in the relapsed or refractory patient cohort in May and we expect to report the first data from this cohort in the fourth quarter.
The unmet need in relapsed or refractory AML is particularly stark.
Median overall survival remains low at less than six months and recently approved therapies target limited patient subsets, leaving many patients with few alternatives.
Given the severity of the unmet need in the relapsed or refractory setting. We believe the data later this year have the potential to provide proof of concept in this patient population, enabling a decision about moving into a registrational trial.
David A. Roth: Given the severity of the unmet need in the relapsed or refractory setting, we believe the data later this year have the potential to provide proof of concept in this patient population, enabling a decision about moving into a registrational trial. Turning now to 5609, as Nancy mentioned, we presented data as part of the virtual ASCO meeting that provided the first insights into the role of 5609 in colorectal cancer and formed the basis for our decision to include colorectal cancer patients in the ongoing phase 1 trial. We decided to explore 5609 in colorectal cancer because increased expression of oncogenic transcription factors, as well as activating mutations in the MAP kinase pathway through KRAS or BRAF, which are potent activators of cell cycle progression, are common disease drivers.
Turning now to 56 or nine as Nancy mentioned, we presented data as part of the virtual ASCO meeting that provided the first insights into the role of 56 or nine in colorectal cancer and formed the basis for our decision to include colorectal cancer patients in the ongoing phase one trial.
We decided to explore 56 or nine in colorectal cancer, because increased expression of oncogenic transcription factors as well as activating mutations in the map kinase pathway through K, Ras or B RAF which are potent activators of cell cycle progression, our common disease drivers.
By inhibiting CDK 756, or nine attacks both of these processes, providing mechanistic rationale for 56 or nine in colorectal cancer.
David A. Roth: By inhibiting CDK7, 5609 attacks both of these processes, providing a mechanistic rationale for 5609 in colorectal cancer. The hypothesis played out in our preclinical studies. 5609 inhibited tumor growth at well-tolerated doses in colorectal cancer models, with tumor regressions seen in both BRAF mutant and very difficult-to-treat KRAS mutant models. Our preclinical studies in colorectal cancer also supported the PD markers that we're using in the ongoing trial. And with our collective work in this area, we've been able to correlate PD markers with target occupancy and preclinical efficacy. We're measuring these markers in patients to help understand the doses that are needed for biologic activities. At ASCO, we also provided additional detail on the Phase I trial design. As you know, we dosed the first patient in the trial in January. This multicenter, open-label trial is expected to enroll approximately 60 patients with advanced breast, colorectal, lung, or ovarian cancer or with solid tumors of any histology that harbor RB pathway alterations.
The hypothesis played out in our preclinical studies 56, or nine inhibited tumor growth at well tolerated doses in colorectal cancer models with tumor regressions seen in both BRAF mutant and very difficult to treat kras mutant models.
Our preclinical studies in colorectal cancer also supported the PD markers that we're using in the ongoing trial and with our collective work in this area have been able to correlate PD markers with target occupancy and preclinical efficacy.
We are measuring these markers in patients to help understand the doses that are needed for biologic activity.
And ASKO. We've also provided additional detail on the phase one trial design.
As you know we dosed the first patient in the trial in January.
This multicenter open label trial is expected to enroll approximately 60 patients with advanced breast colorectal lung or ovarian cancer or with solid tumors of any histology that harbor RB pathway alterations.
We're focusing on these patient populations based on our preclinical data a mechanistic rationale and the unmet need.
David A. Roth: We're focusing on these patient populations based on our preclinical data, a mechanistic rationale, and the unmet need. This includes the recently initiated cohort to assess 5609 in combination with Fuldestrin. In preclinical models of HR-positive CDK4-6 inhibitor-resistant breast cancer, 5609 in combination with fulvestrant shows robust antitumor activity.
This includes the recently initiated cohort to assess 56 or nine in combination with full restaurant.
In preclinical models of HR positive CDK for six inhibitor resistant breast cancer 56, or nine in combination with fulvestrant shows robust anti tumor activity.
Additionally across our preclinical studies in breast lung and ovarian cancer, we've observed deeper and more sustained responses to 56 or nine in models with RV alteration than in non RV altered models.
Joe Farah: Additionally, across our preclinical studies in breast, lung, and ovarian cancer, we've observed deeper and more sustained responses to 5609 in models with RB alteration than in non-RB altered models, and notably, RB alterations have emerged as a resistance mechanism to CDK4-6 inhibitors. The Phase I study is designed to assess the safety and tolerability of escalating doses of 5609 with the goal of establishing a Additional objectives include assessments of antitumor activity, PK, PD, and potential predictive biomarkers. We plan to report initial safety, tolerability, PK, and PD data in the fourth quarter of this year. We expect to report additional dose escalation data, including clinical activity data, in mid-2021. Additionally, as part of the trial design, we have the flexibility to expand cohorts at any dose level that has cleared the dose-limited toxicity evaluation to explore early signals while dose escalation proceeds.
And notably RB alterations have emerged as a resistance mechanism to CDK for six inhibitors.
The phase one study is designed to assess the safety and Tolerability of escalating doses of 56 or nine with the goal of establishing a maximum tolerated dose and schedule.
Additional objectives include assessments of anti tumor activity, PK, PD and potential predictive biomarkers.
We plan to report initial safety Tolerability PK and PD did it in the fourth quarter of this year, we expect to report additional dose escalation data, including clinical activity data in mid 2021, and as part of the trial design, we have the flexibility to expand cohorts at any dose level that is cleared that.
It's limited toxicity evaluation to explore early signals while dose escalation proceeds.
Once dose escalation is completed we plan to initiate multiple expansion cohorts to further evaluate the safety and efficacy of 56 or nine as both a single and combination agent.
Joe Farah: Once dose escalation is completed, we plan to initiate multiple expansion cohorts to further evaluate the safety and efficacy of 5609 as both a single and combination agent. We have two excellent product candidates in 1425 and 5609, reflecting our deep understanding of how genes are controlled and our ability to systematically analyze regulatory regions to home in on which genes to control in which patients to maximize the chances of providing a therapeutic benefit. We look forward to reporting data for both programs that we hope will bring us closer to our goal of bringing much-needed new medicines to market for patients. With that, I'll pass the call over to Joe to review our financial results for the second quarter. Thank you, David. We ended the second quarter in a strong financial position, with $108.7 million in cash, cash equivalents, and marketable security, compared to $91.4 million on December 31st, 2019.
We have two excellent product candidates in 14, 25, and 56 or nine reflecting our deep understanding of how genes are controlled and our ability to systematically analyzed regulatory regions to homing in on which genes to control in which patients to maximize the chances of providing a thorough.
Uptick benefit.
We look forward to reporting data for both programs that we hope will bring us closer to our goal of bringing much needed new medicines to market for patients.
With that I'll pass the call over to Joe to review, our financial results for the second quarter.
Thank you David.
We ended the second quarter, and a strong financial position with $108.7 million in cash cash equivalents and marketable securities compared to 91.4 million on December 30, Onest 2019.
Based on our current plans, we believe we have sufficient cash to fund our operating expenses and capital requirements into 2022.
Joe Farah: Based on our current plans, we believe we have sufficient cash to fund our operating expenses and capital requirements into 2022, beyond multiple expected data readouts for 1425 and 5609, while also continuing to invest in our preclinical programs and in discovery. We recognized $3.2 million of revenue in the second quarter of 2020, as compared to $0.5 million in the second quarter of 2019. This $3.2 million consisted of $2.5 million under our collaboration with GBT and $0.7 million under our collaboration with Insight. All revenues recognized in the second quarter of 2019 were under our collaboration with NCI. R&D expenses were $14.8 million in the second quarter of 2020, compared to $15.5 million for the same period in 2019. This decrease was primarily due to deprioritizing SY-1366. G&A expenses were $5.1 million in the second quarter of 2020 compared to $5.2 million for the same period in 2019. Finally, we reported a net loss for the second quarter of $17.2 million, or $0.38 per share, compared to a net loss of $19.5 million, or $0.47 per share.
Beyond multiple expected data Readouts for 14, 25, and 56 or nine while also continuing to invest in our preclinical programs and discover.
We recognized $3.2 million of of revenue in the second quarter of 2020.
As compared to point 5 million in the second quarter of 2019.
This 3.2 million consisting of 2.5 million and our collaboration with GBT.
And point 7 million under our collaboration with Incyte.
All revenues recognized in the second quarter of 2019 were under our collaboration insight.
R&D expenses were $14.8 million and the second quarter of 2020 compared to 15.5 million for the same period. In 2019. This decrease was primarily due to de prioritizing slide 13 65.
Gionee expenses were $5.1 million in the second quarter of 2020 compared to $5.2 million for the same period in 2019.
Finally, we reported a net loss for the second quarter of $17.2 million or 38 cents per share compared to a net loss of 19.5 million or 47 cents.
With that I will turn the call over to the operator for questions. Thank you.
Operator: With that, I will turn the call over to the operator for questions. Thank you. Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. Do I request you press the pound?
Thank you as a reminder, asking questions. Please press star 100 telecom.
Good question, Chris the balance sheet.
Please standby generators.
Operator: Stand by while we compile the Q&A. Our first question comes from Phil Nadeau with Town & Company. You may proceed with your question. Morning, thanks for taking my questions. First question: just generally on the ongoing studies, are you seeing any impact from COVID on the trials, whether it's the ability of patients to get the drug or get interim evaluations in the clinical trials? Hey Phil.
Our first question comes from terminating with Cowen and company. You May proceed with your question.
Good morning, Thanks for taking my questions.
First question just generally on the ongoing studies are you seeing any impact from covered on the trials whether its.
For your patience to getrag or get interim evaluations that the clinical trial sites.
Hey, though.
We have not seen any.
David A. Roth: We have not seen any major disruptions with the trials. I think having an oral cancer drug in a relapsed or high-medical-need oncology population has really not been affected. We've instituted measures, telemedicine, remote monitoring, and other things like that, but we have not seen any major impact on our ability to enroll or follow the patients in the trial, which is great. And again, it's a great testament to our team at Syros for all that work, as well as, I think, the enthusiasm of the investigators on our program. That's great. Second, maybe a question on 1425.
No disruptions, let the trials I think having them.
Oral cancer drug and they.
Relapse store high unmet medical need oncology population.
Really has not been affected we instituted a lot measure as you know telemedicine remote monitoring.
And other things like that but we have not seen any major impact on our ability to enroll our politicians and the trial, which is which is great and again, it's a great Testament to our team at zero for all that work as well as I think the ability of them of the investigators on on our program.
Great.
Second maybe a question for 25 relapse refractory population can you give us some sense of.
David A. Roth: In the relapsed refractory population, can you give us some sense of what you would consider proof of concept? What quality of data would encourage you to continue developing 1425? You know, Phil, as you know, there's a very high medical need in that patient population. Once people relapse, you know, certainly meeting an overall survival of less than six months. And I think even with some of the newer therapies coming into the frontline setting, patients are becoming even more refractory. If you just look at precedent in terms of regulatory approvals, there have been agents approved in the relapse setting with response rates between, you know, 20 and 35 percent with duration of response between four and six months. So that's at least a regulatory benchmark and precedent for approvals in that setting, and I think it just denotes the very high level of medical need in that population and the real need for new therapies there. That's great. And last question on 5609, have you disclosed how many cohorts have been dosed thus far in the dose escalation study? Have you seen any evidence of a headache, nausea, and vomiting since 1365 or so far?
You would consider proof of concept where quality of data would would.
Encourage you to continue developing fortune 25 in that population.
Yes, Bill as you know there is a very high unmet medical need and that patient population.
Once people overlaps.
Certainly a median overall survival up less than six months and I think even with some of the newer therapies.
Going into the frontline study.
Cases are becoming even more refractory you just look at precedence in terms of the regulatory approvals there have been agents approved in the relapse setting with response rates between 20 and 35%.
Net duration of response between four and six months so that's at least.
Regulatory benchmarking precedence for.
For approvals in that setting I think it just.
No. It's a very high unmet medical need in that population and that in the real deep forget therapies there.
That's right at the last question on 56 or nine have you disclosed how many cohorts have been dosed.
Thus far in the dose escalation study in.
If you've seen any evidence of a headache, nausea, and vomiting from 30, and 65 or thus far.
To those those events seem to be.
Nancy A. Simonian: Do those events seem to be... a molecule specific to 1366? You know, as you heard from David, we started enrollment in January. We're planning to report the initial data from the dose escalation in the fourth quarter, and we haven't given any further details in terms of the number of patients enrolled, other than that the trial's enrolling kind of well. And at this point, we have not communicated anything about, you know, the data from that cohort. So that's what to expect in the fourth quarter or from that trial. Sorry
Molecule specific to searching 65.
It is the as you heard from David We started enrollment in January right planning to report.
The initial data from the dose escalation of the fourth quarter and we haven't given any further details in terms of a number of patients enrolled other than that the trials enrolling kind of well and at this point, we have not communicated anything about.
The data on that cohort so thats, what you expect in the fourth quarter.
Childlike.
Operator: Fair enough. Thanks for taking my, All right, Paul, thank you. Thank you. Our next question... Ted Tenthoff with Piper Sandler, you may proceed with your question. What would be viewed as sufficient to proceed in different indications from the readout in 4Q? Do you guys have specific bars, or are you just looking for general activity?
Fair enough thanks for taking my questions.
Alright, thank you.
Your next question comes from Ted Tenthoff fiber Sandler you May proceed with your question.
Great. Thank you good morning, everyone.
Alright.
Sure.
Yes.
Yes.
Our.
From there.
Okay.
Yes.
Okay.
Nancy A. Simonian: Thank you very much. So, you know, the goal of a dose escalation study, like the one that we have, is really to establish a dose and schedule to take forward into the expansion arm. So, the focus is really on safety, tolerability, PK, and PD. As you know, Dave and the team have done a great job designing a trial that gives us the flexibility to do what we call sort of extension arms, and so we can focus on particular patient populations at particular doses. But I think I would just focus on the main focus for the dose escalation portion is safety, PK, and PD.
Hey, Todd.
So the goal that dose escalation study like the one that we have is really to establish.
Dosing schedule to take forward into the expansion arm. So that the focus is really on safety Tolerability PK and PD.
As you know, Dave and the team had done a great job designing a trial that gives us also flexibility to do what we call sort of that extension arms and that we can focus on particular patient population at particular doses, but I think I would just focus on that the main focus for that dose escalation portion is.
On the safety PK PD, we learned a lot from working in CDK seven inhibition por for a long time in terms of good markers to assess biologic activity were taking the learnings from our first generation program as well as what we've learned with 56 or nine and incorporating.
Operator: We learned a lot from working in CDK7 inhibition for a long time in terms of good markers to assess biological activity. We're taking the learnings from our first generation program, as well as what we've learned with 5609, and incorporating that so that we can identify sort of biologically active doses. And we've learned a lot about potential patient populations that we think are most likely to respond, and we're enriching for those. Excellent. Thank you very much.
So that we can identify biologically active doses and we've learned a lot also about potential patient populations that we think most are most likely to respond enriching for those.
Thanks.
Thank you.
Thank you.
Operator: Thank you. Thank you. Our next question comes from Jason Butler with JMP Securities. Great.
Thank you. Our next question comes on Jason Butler with JMP Securities.
Proceed with your question.
Great. Thanks for the the questions.
David A. Roth: Thanks for the questions. First one, just for the newly diagnosed data that we're going to see for 14-25 later this year, obviously, you've already shown some compelling response rate data in the RARA population, but can you maybe talk about how you think about the bar for success or threshold that you need to see in terms of durability? And then just secondly, looking forward, obviously you're also going to wait for the relapsed refractory data, but in the newly diagnosed population, do you think there's still a strategy to focus on a combination of AZA alone, or do you think that anything going forward would need to include venetoclax as well? Thanks for the question, Jason. I'm going to take the second question, and I'll start first, and then I'll turn it over to David for durability.
First one just for the newly newly diagnosed data that we're going to see.
14, 25 later this year, obviously, you've already shown some some compelling response rate data on the rural population, but can you maybe talk about how you think about the barkey success with threshold.
You need to see in terms of durability and amend just secondly, looking forward.
As the year olds going to wait for the rack relapse refractory data, but in newly diagnosed population do you think theres still a strategy to focus on a a combination with visa alone or do you think that anything going forward would need to include phonetic lacks as well. Thanks.
Thanks for the question, Jason I'm going to take the for the second question and I'll start first and then I'll turn it over to David on that are on the durability.
Nancy A. Simonian: You know, as you know, the landscape has been changing in AML, and it's great for patients. There are many more options available. Obviously, the Venn-AIDS approval and, most recently, the Phase III data, I think, are really solidifying that as a very important standard of care in the frontline setting in the unfit patient population. But I think we also know that about a third of the patients don't respond to Venn-AIDS. We know that even those patients that respond, which is great, and they benefit, we could do better there. And so when you think a little bit about the strategy that one could take going forward, you think about, and you just think about how drug development is done. You just harken back to the myeloma days, when we had active drugs as a single or a doublet, then we would look for triplets. And so, you know, one opportunity was to add on to a standard of care like Venn-AIDS. Think about where there may be resistance to Venn-AIDS that you could consider developing, and then other related conditions to AML where maybe Venn-AIDS is not yet the standard of care.
As you know the landscape.
Consulting and ammo.
And it's great for patients that many more options available obviously, the then A's approval and most recently the phase three data I think are really solidify and that is a very important as standard of care in the frontline setting and the unmet patient population.
I think we also know that about a third of the patients don't respond to Venezuela.
We know that even those patients that respond.
Which is great and they benefit they they could do better there.
And so any think a little bit about the strategy that one could take going forward you think about and you just think about how drug development is done in like is harken back to the myeloma days when we had active drug as a single or double. It then we would look for triplets and so one up opportunity was to add.
On to a standard of care like beneath us think about where there may be resistance to their names that you could consider a developing and then other related conditions to malware maybe bodies as not yet the standard of care. So all of those are opportunities to think about enough in the upfront setting I would just say that there continues.
David A. Roth: So all of those are opportunities to think about in the upfront setting. I would just say that there continues to be a very important unmet medical need in that space, and I think what's really great about 1425 is not only is it active, it works quickly, it gives deep and durable responses, but it's also very well tolerated.
To be a very important unmet medical need in that space and I think whats really great. About 14 25 is not only is that act. If it works quickly. It gives deepen durable responses. It's also very well tolerated and I think that's really important when you think about a combination.
David A. Roth: And I think that's really important when you think about a combination agent that you want to be able to add on and not get overlapping toxicity. So that's just the overview of kind of how we think about this continued important need for active new agents. I'm going to ask David to address the question of kind of what are we thinking about for the bar for durability in the newly diagnosed study. Yeah, sure. So, you know, it's really important to appreciate that we will be evaluating the totality of the data that we have as we consider next steps, and durability certainly is a very important component of the overall picture, but it's really just one piece of the puzzle.
Agent on that you want to be able to add on and not get overlapping toxicity. So that's the that's just the overview on kind of how we think about this continued important need and for active new agents.
I'm going to as David to address the question on kind of that what are we thinking about for the bar for the durability.
For in the newly diagnosed study.
Yeah sure. So it's really important to appreciate that we will be evaluating the totality of of the data that we have.
As we consider next steps and durability certainly is very important component of the overall picture, but it's really just one piece piece of the puzzle and.
David A. Roth: And, you know, we also will be considering, you know, the percentage of patients who have responses, the depth of the responses, which are often associated with long-lasting responses, and also safety and tolerability. That's obviously very key. You know, so when we look at it, we'll probably be looking at that in the context of a relevant historical benchmark, which would be single-agent azacitidine. I mean, that's the backbone used in our combination.
We also will be considering the percentage of patients who have responses the depth of the responses, which are often associated with long lasting responses and also the safety Tolerability. That's obviously very key.
So when we look at it will probably be.
Looking at that.
In the context of a relevant historical benchmark, which would be single agent siding I mean that that's the backbone using our combination and we know very well that Pat has a median duration of response of about 10 months and so that would certainly be a context in which to interpret and then just not to repeat.
David A. Roth: And, you know, we know very well that that has a median duration of response of about 10 months. And so that would certainly be a context in which to interpret it. And then just, you know, not to repeat what Nancy just said, but really, the broad opportunity in the, you know, in the emerging landscape, given, you know, what we're seeing evolve, it really speaks volumes to the importance of having well-tolerated combinations that we can deploy in a targeted way where we expect patients to respond based on selection and things of that nature. So that's the overall context in which we'll be interpreting the Okay, great. Thanks for the color and thanks for taking the questions. Thanks, Jason!
What Nancy just said, but.
Really the broad opportunity.
In the emerging landscape given what we're seeing evolve really speaks volumes to the importance of having well tolerated combinations that we can.
Deployed in targeted way, where we expect patients to respond based on selection and things of that nature. So so that's the overall context I will be interpreting the data.
Okay, great, thanks sort of color and thanks for taking my questions.
Thanks, Jason.
Operator: Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. You may proceed with your question. Hey, good morning, and thanks for taking my questions. Just a few for me, and kind of all focused on 5609, probably aimed toward David. First of all, based on the preclinical models with 5609, I'm wondering if you can make any extrapolations regarding what steady-state exposure levels you'll have to achieve before potentially seeing clinical activity. Sure.
Thank you. Our next question comes from Mark Greenberg with Oppenheimer. You May proceed with your question.
Hey, good morning, and thanks for taking my questions.
Just looking for me and kind of all focused on 56 or nine probably into or David.
First of all based on preclinical models with its in line I'm wondering if it didn't make any extrapolations regarding what steady state exposure levels, you will have through two before potentially seeing clinical activity.
Sure so.
David A. Roth: So, you know, we've obviously developed the 5609 and have moved into phase one testing starting this past January, and we're very excited about that and the progress we're making. But when we look back at the preclinical models, we obviously did a range of tests in various models of different tumor types. We've measured drug exposures in blood, and we've correlated those exposures with very important pharmacodynamic markers, PD markers that are going to help us understand the biological activity that we're getting and correlate that to exposure.
We've obviously developed the 56 or nine and.
Have moved into a phase one testing starting this past January and we're very excited about about that in the progress were making but when we look back at the preclinical models. We've we've obviously done a range of testing various.
Models of different tumor types.
We've measured drug exposures in blood and Weve correlated those exposures with very important pharmacodynamic markers PD markers that are going to help us understand the biological activity that we're getting and correlated to exposure, but more importantly, we've looked at those correlations and sort of pin them into.
David A. Roth: But more importantly, we've looked at those correlations and sort of pinned them into the types of tumor regressions one might see. And so those are very important PK-PD efficacy relationships that are helping to inform our dosing decisions as we go through the escalation process. You know, obviously, we're going to need to measure the drug levels in humans to directly connect the dots between the preclinical models and the humans. And that's really going to be the main focus of our presentation in the fourth quarter, where we're going to have initial data that focus on safety tolerability, PK, and PD. So we look forward to giving you more updates on that type of information at that time. Okay, fair enough.
The types of tumor regression as one might see and so those are very important PK PD efficacy relationships that are helping to inform.
Our dosing decisions as we go through the escalation.
Obviously, we're going to lead to measure the drug levels in humans to directly connect the dots between the preclinical models in humans and that's really going to be the main focus of our presentation in the fourth quarter, where we're going to have initial data that's going to focus on the safety Tolerability and the PK and PD. So we look forward to give you more updates on that.
Good information at that time.
Okay fair enough.
David A. Roth: And I'm wondering if the preclinical activity you saw in the MAP kinase pathway mutants in your CRC models is unique to CRC? Or would you expect activity in those types of mutants across other solid tumor types? So, you know, that's a really good question.
I'm wondering if the preclinical I can be so in the map kinase pathway.
And your CRC models, you think that's unique to CRC or or would you expect activity in those types of.
Meetings across other solid tumor types.
David A. Roth: So, we, you know, you're referring to the data that we presented back in May at the virtual ASCO. Yeah, and in that system, just so everyone knows specifically what you're asking, we did demonstrate fairly significant preclinical activity in colorectal cancer models. And what was notable about that presentation was the abundance of tumor growth inhibition we saw in two-thirds of our models. We had 30 PDX models, and two-thirds of them demonstrated tumor growth inhibition. And a quarter of them had complete regressions, with a very significant number, about I think half of the BRAF mutant models and certainly some of the KRAS mutant models also demonstrating regression.
So that's really good question. So we just you're referring to the data that we present is back in.
In may of this virtual Alaska, yes, and and in that and that's isn't just so everyone knows something where you are asking we did demonstrate.
Fairly significant preclinical activity in colorectal cancer models.
And what was notable about that.
Presentation was the.
Abundance of tumor growth inhibition, we had two thirds of our models. We have 30 pdx models, two thirds of them demonstrated tumor growth inhibition in a quarter of them a complete regressions.
With a very significant number about I think half of the B RAF view models and certainly some of the K raspy models also demonstrating regression. So it was really exciting to see that now we know that at times certain pathways may have a tumor specific.
David A. Roth: So, it was really exciting to see that. Now, we know that at times certain pathways may have a tumor-specific context in which they demonstrate activity, but we also know these are common mutations that are relevant in other tumor types. And so, I think there really does represent a broad opportunity for the drug in a range of solid tumor cancers. Okay, fantastic.
Context in which they demonstrate the activity, but we also know these are common mutations that are relevant in other tumor types.
And so I think there really does represent a broad opportunity.
For for the drug in arrangement of solid tumor cancers.
Okay fantastic.
And last one from me.
David A. Roth: And last one for me, just because I know fulvestrin is maybe increasingly used in combination with a CDK4-6 inhibitor. Now that you're running a combination study with 5609 and fulvestrin, I'm wondering if that's open to patients who have had prior fulvestrin therapy or if those are being specifically excluded.
Just because I know that strength is maybe increasingly used in combination with CDK port six inhibitor.
Now that you're running combination study with six or nine and pull best trend I'm wondering if that's opened for patients who have had our oldest rent or or those are been specifically excluded.
Yes, so really the main domain inclusion criteria for that and that's.
David A. Roth: So, you know, really, the main inclusion criteria for that, and that's a combination that we've already added into the dose escalation to help explore the tolerability and ultimately the clinical activity of that combination, require having progressed after a CDK4-6 inhibitor. And it's understood that patients may have had a range of different hormonal agents in combination, but, you know, they probably would not have previously had full vests.
A combination of we've already added into the dose escalation.
To help explore.
Tolerability and ultimately the clinical activity of that combination requires having progressed after a CDK for six inhibitor.
And it's understood that patients may have had a range of different hormonal agents in combination.
But they probably would not have previously had for western.
David A. Roth: Okay, that's helpful. Thanks so much for taking the questions, and congrats on the quarter. Thank you. Thank you. And as a reminder, if you're asked a question, you'll need to press star 1.
Okay. That's helpful. Thanks, so much for taking the questions on congrats on the core.
Thank you.
Thank you as a reminder, basket caution you will need press Star one. Our next question comes from my job with Roth Capital Partners. You May proceed with your question.
Operator: Our next question comes from Zegba Jaha with Roth Capital Partners. You may proceed. Good morning, guys.
Good morning, guys. Thanks for taking my question and David I really appreciated add that detail at eight so just a couple of clarifications Boy me I thought that benchmarks for an hour how far enough. You later, Sam that you know your exceeded their level would you know fired with both in newly diagnosed and the real.
Nancy A. Simonian: Thanks for taking my question, and David, I really appreciated the detailed update. So, just a couple of clarifications for me. I thought the benchmarks for AML were helpful, and if you were to assume that, you know, you exceeded those levels, would you move forward with both the newly diagnosed and the relapsed refractory patient studies in parallel, or would you just be moving forward with the relapsed refractory AML cohort? And then just a quick question here as well for 5609, again, as you know, I'm quite bullish about CDK7, but just wanted, again, clarification with regards to what we may see later this year relative to what we might see next year in terms of data, and how you're thinking about the expansion, assuming that you do, or extension arms, assuming that you do see, again, positive data in that, would you just start with colorectal, or how you're thinking about, you know, moving forward with that, or, you know, with the breast cancer or something like that?
Lapse you factor patient studies in parallel we must be moving fired Abbott with day relapse refractory at now.
Cohort and then just a quick question, yet well pursue 56 to nine.
Again, as you know quite bullish about as CDK, seven but gigawatt. It again clarification with regards to what we may see at later this year relative to what we might see next year in terms of data and how you're thinking about as Dick mentioned see me that you.
Or extension arms, assuming that you do see again, our positive data and that would you just start with colorectal or how you're thinking about loving the board out with that or you know with the breast cancer or something like that.
Hey, guys nice to hear from you so with the answer to the 14 25 question, we're going to let the data kind of drive our decisions in the context of.
Nancy A. Simonian: Hey Zeitgeist, nice to hear from you. So with the answer to the 1425 question, we're going to let the data kind of drive our decisions in the context of the strength of the data, the competitive landscape, and also, I wouldn't, you know, if the data are strong in both populations, we'll move forward with both. If it's in one, it would be with one or the other. So it really relates to what the data are. It's not that we would necessarily only seek one or the other.
The strength of the data.
The competitive landscape at all so I don't wouldn't.
If the data are strong in both populations will move forward, but both of it in one it would be with one or the other so it will it really relates to what the data our it's not that we would necessarily only seek one or the other I think we believe that there isn't a high unmet medical need both patient population.
Nancy A. Simonian: I think we believe that there's a high-end medical need in both patient populations, and it will be a data-driven decision. And probably a similar answer to the next question: obviously, we've been, you know, we've enriched the population in phase one on tumor types that we think are most likely to respond, where there's a high-end medical need. And again, I think we're going to let the data drive the decision, as well as, you know, the development paths in terms of what we take forward into the expansion.
And it will be a data driven decision.
It probably a similar answer to.
Question [laughter] itself.
Obviously, we've been we've been rich the population in the phase one on a tumor types that we think are most likely to respond whether its high unmet medical need and again I think we're going to let the data derived the decision.
As well as.
The development has in terms of but we take forward into the expansion and you know I think is as we've said that data do you expect in a fourth quarter of the here is really focused around PK PD.
Nancy A. Simonian: And, you know, I think, as we've said, the data to expect in the fourth quarter of this year is really focused around PK, PD, and Tolerability. As David mentioned, we developed PD markers that give us a good sense of sort of where there are biologically active doses, and we correlated that with preclinical efficacy. So that's really the focus of Q4 and then, you know, mid next year, the more robust dose escalation data, including clinical activity.
The Tolerability as David mentioned, we developed a PD markers that give us a have a good sense of sort of where the biologically active.
Mrs. We correlated that preclinical efficacy. So that's really the focus of the Q4 and then mid next year, the more robust sales escalation data, including clinical activity.
Thanks, and Nancy really appreciate and just a quick clarification I feel like the data. We saw we didn't really the plant that this molecule is a lot more you know it then your last molecule, which is encouraging but is there anything else that we should be looking for attempt that you know, saying that this is really a differentiated a molecule.
Nancy A. Simonian: Thanks Nancy, really appreciate it. And just a quick clarification, I feel like the data we saw was really supportive that this molecule is a lot more potent than your last molecule, which is encouraging. But is there anything else that we should be looking for in terms of, you know, seeing that this is really a differentiated molecule?
Nancy A. Simonian: Well, as you know, we, you know, when we profiled 5609 against 1365, it is obviously one's covalent, the other one, 5609 is not covalent, but it was more potent and more selective. And in preclinical models, where we ran it head to head against 1365, it showed superior activity and also worked more consistently at doses below the maximum tolerated dose. So, I think the preclinical data supports the superiority of 5609 over 1365. And, you know, we were excited. We, you know, with 1365, not only learned a lot, but we saw evidence of biological and clinical activity. So, that gave us a lot of confidence in CDK7 inhibition as an important therapeutic approach, and we think we have the optimal molecule of 5609.
Well as as you know we.
When we profiled 56 or nine again 30 and 65 you know it is obviously one covalent the other way in a 56 or nine if not clearvale and but it's a 56 or nine was more potent and more selective.
And in preclinical models, where we ran it head to head against 13 65, it showed superior activity.
And also worked a more consistently at doses below the maximum tolerated dose.
So I think the preclinical data to support the superiority of 56 or nine over 13 65 and yeah. We were excited we know what 30 65, we not only learned a lot, but we saw evidence of biologic and clinical activity.
So that gave us a lot of confidence in CDK seven inhibition.
As an important therapeutic approach and we think we have the optimal molecule it at the six or nine.
Thanks Nancy.
Thank you.
I'm not showing any further questions at this time I'll now turn the call back over to Nancy's ammonium for any further remarks.
Nancy A. Simonian: Thanks, Nancy. Thank you. I'm not showing any further questions at this time. I would now like to turn the call back over to Nancy Simonian for any further...
Thank you operator.
In closing I want to thank you all for joining us today and for your continued interest in Sarah we look forward to updating you as we continue to advance our vision of building a fully integrated biopharmaceutical company with a portfolio medicine that provide a profound benefit for people, but cancer and lot of genetic diseases.
Nancy A. Simonian: Thank you, operator. In closing, I want to thank you all for joining us today and for your continued interest in Syros. We look forward to updating you as we continue to advance our vision of building a fully integrated biopharmaceutical company with a portfolio of medicines that provide profound benefits for people with cancer and monogenic diseases. Stay well. Thank you, ladies and gentlemen. This concludes today's conference call. Thank you for participating. [inaudible] BF-WATCH TV 2021
Well.
Thank you ladies and gentlemen, this concludes todays conference call. Thank you for participation you may now disconnect.
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