Q3 2019 Earnings Call
Yes.
Good morning, ladies and gentlemen, and welcome to be Q3, 2019 Fierros pharmaceuticals.
Operator: Good morning, ladies and gentlemen, and welcome to the Q3 2019 earnings conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star, then zero on your touchtone telephone. I would now like to turn the conference over to your host, Ms. Naomi Aoki. Please go ahead.
Earnings Conference call.
At this time all participants are in a listen only mode.
Later, we will conduct a question and answer session and instructions will follow at that time.
If anyone CIT require assistance during the conference. Please press Star then zero on your Touchtone telephone.
I would now like to turn the conference. So first tier so Mitch Naomi Aoki. Please go ahead.
Thank you. This morning, we issued a press release with our third quarter 2019 financial results along with anticipated future milestones and recent accomplishments. This release is available on the investors and media section of Cirrus is website at www Dot theorists dot com.
Naomi Aoki: Thank you. This morning, we issued a press release with our third quarter 2019 financial results along with anticipated future milestones and recent accomplishments. This release is available on 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 to questions. Dr. Eric Olson, our Chief Financial 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 statement as a result of various risks, uncertainties, and other factors, including those set forth in the risk factors 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 addition, forward-looking statements made on this call represent our views only as of today and We specifically disclaim any obligation to update or revise any forward-looking statement. I would now like to turn the call over to Nancy.
We will begin the call, which prepared remarks by Dr., Nancy Simonian, our Chief Executive Officer, Dr., David Roberts, Our Chief Medical Officer, and Joe Farrell, Our Chief Financial Officer.
Well then open the call for questions.
Dr., Eric Colson, our Chief Financial Officer, and Dr., Jeremy springboard, our Chief business Officer 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. 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 FCC on the future. In addition forward looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent state.
We specifically disclaim any obligation to update or revise any forward looking statement.
I'd now like to turn the call over to Nancy.
Nancy A. Simonian: Thank you, Naomi. Good morning, everyone, and thank you for joining us today as we review our progress in the third quarter of 2019. Our vision at Syros is to build a great and enduring company by developing transformative gene control medicines for patients with diseases that have eluded other genomics-based approaches. To achieve that vision, we focus our people and resources where we believe we have the greatest potential to make a profound difference for patients. In the third quarter, we made important strides toward that vision.
Thank you Naomi good morning, everyone and thank you for joining US today as we review our progress over the third quarter of 29th Street.
Our vision. It's here I was just to build a great an enduring company by developing transformative gene control medicines for patients with diseases that have alluded other genomics based approaches.
To achieve that vision, we focused our people and resources, where we believe we have the greatest potential to make up the phone different for patients.
In the third quarter, we made important strides toward that vision.
Nancy A. Simonian: We reported exciting new clinical data on SY1425 in a difficult-to-treat AML population. Additionally, we presented new preclinical data on SY5609, highlighting its best-in-class potential as a highly selective and potent oral CDK7 inhibitor. And, we prioritize its development over SY1365, our IV CDK7 inhibitor, because we believe 5609 provides the best opportunity to realize the promise of selective CDK7 inhibition. Beginning with 1425, we were pleased with the clinical data we presented at the Esch conference lesson. The high complete response rates, deep CRs, and favorable tolerability profile in newly diagnosed unfit AML patients strengthen our belief in the potential of 1425 to be a foundation of care for AML patients with Aurora biomarkers. People with AML need new treatment options that are well-tolerated and can be used in combination to extend survival and improve quality of life.
We reported exciting new clinical data on that's why 14 25 in a difficult to treat A.M.L. population.
We presented new preclinical data that's why 56, so nine highlighting its best in class potential as a highly selected in potent oral TDK seven inhibitor.
And we prioritized its development over that's why 13 65, our I'd be CDK seven inhibitor, because we believe 56 or nine provides the best opportunity to realize the promise of selected CDK seven inhibition.
Beginning with Fortune 25, we were pleased with the clinical data we presented at the Ash Conference last month.
The high complete response rates deep sea ours, and favorable tolerability profile in newly diagnosed unfit AML patients strengthen our belief in the potential of 14 25 to be a foundation of care for AML patients with our up biomarker.
People with A.M.L. need new treatment options that are well tolerated and could be used in combination to extend survival and improved quality of life and we believe there was a significant opportunity for 14 25 in combination with Ace decitabine in both the frontline and relapse and refractory AML settings.
Nancy A. Simonian: And we believe there is a significant opportunity for 1425 in combination with Asacitabine in both the frontline and relapsed and refractory AML setting. As we continue to follow the newly diagnosed unfit AML patients enrolled in our trial to further characterize the profile of the combination, we are considering the best way to bring the 1425 azacitidine combination forward in the frontline setting. In parallel, we are pleased with our progress in rolling RARA-positive patients with relapsed or refractory AML into the trial and expect to announce potential proof-of-concept data in 2020 that we believe could support a fast-to-market strategy for 1425. Turning to 5609, we believe that selective CDK7 inhibition is a potentially transformative targeted approach for difficult-to-treat cancers, and we were excited to share new preclinical data on 5609 at the ENA conference last month that further support our conviction in this target and molecule.
As we continue to follow the newly diagnosed unfit AML patients enrolled in our trial to further characterize the profile of the combination we are considering the best way to bring the 14 25 eight decided in combination forward in the frontline study.
In parallel we are pleased with our progress enrolling RARA positive patients with relapsed or refractory AML in the trial and expect to announce potential proof of concept data in 2020 that we believe could support a fast to market strategy for 14 20 by.
Turning to 56 sound I, we believe that selected CDK seven inhibition, if they potentially transformative targeted approach for difficult to treat cancer and we were excited to share new preclinical data on 56, so nine at the E. N. A conference last month that further support our conviction in this target in mind.
Okay cool.
Nancy A. Simonian: These data informed our decision to prioritize 5609 and to focus our Phase I trial in patients with solid tumors, including breast, lung, and ovarian cancers, as well as in solid tumors of any hostology with RB pathway alteration. We expect to complete IND-abling studies this year and initiate a phase one trial in the first quarter of 2020. Our platform also continues to fuel a robust preclinical and discovery pipeline, which we will be highlighting in upcoming presentations at ASH and the San Antonio Breast Cancer Symposium. In an oral presentation at ASH, we will discuss our identification and validation of a novel repressor of the fetal globin gene, a discovery that will be featured in an ASH press briefing, and that stems from our broader drug discovery efforts in sickle cell
These data informed our decision to prioritize 56, so nine and to focus our phase one trial in patients with solid tumors, including breast lung and ovarian cancers.
Well was in solid tumors that any histology with RV pathway alterations.
We expect to complete I, Indeed, Ablynx studies this year and initiate a phase one trial in the first quarter of 2020.
Our platform also continues to fuel a robust preclinical and discovery pipeline, which we will be highlighting in upcoming presentations at ash and the San Antonio breast cancers symposium.
In an oral presentation at Ash, we will discuss our identification and validation of a novelty trusts are a bit fetal globin gene discovery that will be featured in ash press briefing and that stems from our broader drug discovery efforts in sickle cell disease.
Nancy A. Simonian: The poster presentation at San Antonio will share our findings from work with our collaborators at the Whitehead Institute that reveal core drivers of metastasis in triple negative breast cancer. The progress across our pipeline is a testament to the power of our platform to identify which genes to control, in which cells, for which patients, and how best to modulate the expression of those genes to provide a benefit for patients. Looking ahead to 2020 and beyond, I believe we are well positioned for success as we advance our programs to key milestones and leverage our leading platform to fuel a sustainable pipeline to support our goal of building a fully integrated pharmaceutical company. With that, I will turn the call over to David for a more detailed review of 1425 and 5609.
The poster presentation at San Antonio will share our findings from work with our collaborators at the White Institute that reveal core drivers a metastasis in triple negative breast cancer.
The progress across our pipeline is a testament to the power of our platform to identify which genes to control in which so for which patients and how best to modulate the expression of those genes to provide a benefit for patients.
Looking ahead to 2020 M. beyond I believe we are well positioned for success as we advanced our programs to key milestone and leverage our leading platform to fuel a sustainable pipeline to support our goal a building building a fully integrated biopharmaceutical company.
With that let me turn the call over to David for a more detailed review of 14, 25, and 56 or nine.
Thanks, Nancy and good morning, everybody joining us today.
David A. Roth: Thanks, Nancy, and good morning to everybody joining us today. I'm excited to walk you through the updated data from 1425 that we presented at Esch. As Nancy mentioned, the data mark an important milestone for us as they demonstrate that our novel combination of 1425 and azacitidine induces high complete response rates, deep CRs, and high rates of transfusion independence in RARA positive AML patients with a rapid onset of action, a favorable tolerability profile, and early signs of durable response. As of an August data cut, 40 newly diagnosed unfit AML patients enrolled in our Phase 2 trial Additionally, 13 RARA-positive patients and 22 RARA-negative patients were evaluable for response. In RARA-positive patients, the data showed a 62% rate of IWG complete responses, including CRs, and CRs with incomplete blood count recovery, or CRI. The CR rate was 54%, with 6 of the 7 CRs being deep, molecular, or cytogenetic.
I'm excited to walk you through the updated data for 14 25 that we presented at Ash.
As Nancy mentioned the data marked an important milestone for us as they demonstrate that our novel combination of 14, 25, and a society gene and juices high complete response rates do you see ours and high rates of transfusion independence, and Rollup positive AML patients.
Rapid onset of action.
Verbal tolerability profile and early signs of durable responses.
I was hoping August data cut 40 newly diagnosed unfit AML patients enrolled in our phase two trial and contributed to the safety analysis.
Additionally, 13, while the positive patients and 22 rolla negative patients.
Earlier, both for response.
In warmer positive patients the data showed the 62% rate I WG complete responses, including see ours and feels we didn't complete what kept recovery.
Foresee normalize the CR rate was 54% with six of the southern see ours being Jeep molecular were cytogenetics yours.
David A. Roth: By contrast, in RARA-negative patients, the CRCRI rate was 27%, which is consistent with the published response rates of 18 to 29% observed in newly diagnosed unfit AML patients treated with single-agent azacitidine. We are particularly encouraged by the deep CRs we are seeing in RARA-positive patients with no detectable signs of molecular or cytogenetic abnormalities in their bone marrow following treatment. Importantly, these types of deep C.R.s are typically associated with more durable materials.
By contrast in Waller negative patients the CRC Irene was 27%, which is consistent with the published response rates of 18% to 29% observed in newly diagnosed unfit AML patients treated with single agent is a cited.
We're particularly encouraged by the deep sea ours, we're seeing in longer positive patients with no detectable signs of molecular we're cytogenetic abnormality in their bone marrow following treatment.
Importantly, these types of deep sea ours are typically associated with more durable responses and while our durability data are still maturing we're seeing durable see ours in some of the earlier patients enrolled in the trial with duration of responses to 344 days, including three of the eight responding patients having seen.
David A. Roth: And while our durability data are still maturing, we're seeing durable responses in some of the earlier patients enrolled in the trial with duration of responses of up to 344 days, including three of the eight responding patients having CRs lasting beyond seven months at the time of data cutoff. Additionally, most initial responses in RARA-positive patients were seen at the first response assessment after just 28 days on treatment. Additionally, 82% of the RARA-positive patients achieved or maintained transfusion independence. Taken together, the speed of response, which is really important for patients with leukemia, normalization of neutrophil and platelet counts, and Transfusion Independence are all important objective measures that contribute to clinical benefit for patients with AML.
Ours lasting beyond seven months at the time of the data cut off.
Most initial responses in bar positive patients were seen at the first response assessment. After just 28 days on treatment.
Additionally, 82% of the rather positive patients achieved on maintaining transfusion independence.
Taken together the speed of response, which is really important for patients with leukemia normalization of neutrophils and platelet counts and transfusion independence, all important objective measures that contribute to clinical benefit for patients with pay a mill.
David A. Roth: We are also encouraged to see these responses across AML risk groups, including patients with mutations that are typically associated with poor outcomes. Notably, we're not seeing an enrichment for genes that may be associated with responsiveness to azacitidine in our responding RARA-positive patients, supporting the distinct and synergistic mechanism of action of the 14-25 combination in this novel targeted AML patient. These new data also confirm RARA as the optimal biomarker for patient selection.
We're also encouraged to see these responses across and no risk groups, including patients with mutations that are typically associated with poor outcomes.
Notably, we're not seeing and Richmond for genes that may be associated with responsiveness to ease the psychology and are responding lora positive patients supporting to distinct and synergistic mechanism of action of the Fortune 25 combination in this novel targeted and no patient population.
These new data also confirmed rock as the optimal biomarker for patient selection.
David A. Roth: Based on data from approximately 350 newly diagnosed and relapsed or refractory patients screened for our clinical trial to date, we believe that approximately 30% of AML patients are RARA positive, representing a significant portion of the AML population. Turning to the safety analysis, updated clinical data continue to support a favorable tolerability profile of the combination. 1425 in combination with azacitidine was generally well tolerated with no evidence of increased toxicities beyond what is seen with 1425 or azacitidine alone. Rates of myelosuppression, including neutropenia, were comparable to reports of single-agent ASA, and the majority of non-hematologic adverse events were low-grade. Enrollment in the newly diagnosed cohorts is nearly complete.
Based on data from approximately 350 newly diagnosed and relapsed or refractory patients screened for our clinical trial to gauge we believe that approximately 30% of AML patients or Robert positive representing a significant portion of the ammo population.
Turning to the safety analysis, the updated clinical data continue to support a favorable tolerability profile of the combination.
14, 25 in combination with visa cited Dean was generally well tolerated with no evidence of increased toxicities beyond what has seen with fortune 25 or is this I did you alone.
Rates of Myelosuppression, including Neutropenia were comparable to reports of single agent Pizza and the majority of non hematologic adverse events were low grade.
Enrollment in the newly diagnosed cohorts is nearly complete.
David A. Roth: We plan to follow these patients to further characterize the overall profile of the combination, including safety, efficacy, and durability of response while enrolling the cohort of RARA positive relapsed or refractory AML. We're pleased with the pace of enrollment and expect to report potential proof-of-concept data from the Relapse to Refractory AML cohort next year. Strength of the Data in Newly Diagnosed Patients gives us added confidence in the relapsed or refractory setting that the 1425-asocytogene combination is highly synergistic and well-tolerated with the potential to treat RARA-positive patients across the disease spectrum. Moving now to 5609.
We plan to follow these patients to further characterize the overall profile of the combination.
Including safety efficacy and durability of response, while growing the cohort of RARA positive relapsed or refractory patients.
We're pleased with the pace of enrollment and expects to report potential proof of concept data from the relapsed refractory AML cohort next year.
The strength of the data in newly diagnosed patients gives us added confidence in the relapsed or refractory setting up a fortune 25, eight decided in combination, it's highly synergistic and well tolerated with the potential to treat RARA positive patients across the disease spectrum.
Moving now to 56 or nine last month, we announced our decision to prioritize the development of 56 or nine and just continue further development of 30 165.
David A. Roth: Last month, we announced our decision to prioritize the development of 5609 and discontinue further development of 1365. Our rationale for this decision was based on the superior pre-clinical profile of 5609 and the advantages inherent to an oral molecule that we believe will allow us to realize the full promise of selective CDK7 inhibition for patients. Our experience with 1365 reinforced our conviction in CDK7 inhibition. We established a proof of mechanism and saw evidence of clinical activity and apoptosis in tumor tissues in patients treated at higher doses, including a durable PR in a highly refractory patient. As we treated more patients in the expansion portion of the trial, peri-infusional adverse events limited our ability to keep those patients at the higher dose.
Our rationale for this decision was based on the superior preclinical profile of 56 or nine.
And the advantages inherent to an oral molecule, but we believe will allow us to realize full promise of selective CDK seven inhibition for patients.
Our experience with searching 65 reinforced our conviction CDK several ambition.
We established a proof of mechanism and saw evidence of clinical activity and a pop toasters and tumor tissues in patients treated at higher doses, including a durable PR in a highly refractory patients.
As we treated more patients and the expansion portion of the trial Perry infusion no adverse events limited our ability to keep those patients at the higher doses.
David A. Roth: Importantly, these peri-infusional AEs tracked with peak concentrations of 1365 and not CDK7 target engagement, which is why we don't expect to see the same issues with 5609. The totality of these data leads us to believe that if we can sustain higher levels of target coverage, we can deliver on the promise of selective CDK7 inhibition. As an oral molecule, 5609 provides greater flexibility in dosing and greater opportunity to sustain target coverage with better tolerability. In preclinical studies, 5609 also outperformed 1365 on a wide range of measures demonstrating greater selectivity, potency, and anti-tumor activity in preclinical models in which both drug candidates were tested. The new preclinical data on 5609 that we presented at the ENA meeting further highlight its best-in-class potential, with at least 13,000-fold greater selectivity for CDK7 over closely related members of the CDK family.
Importantly, these perry infusion he's tracked with peak concentrations of 30 to 65 and not CDK seven target engagement, which is why we don't expect to see the same issues with 56 on art.
The totality of these data lead us to believe that if we can sustain higher levels of target coverage, we can deliver on the promise of selective CDK seven in addition.
As an oral molecule 56, or nine provides greater flexibility in dosing and greater opportunity to sustain target coverage with better tolerability.
In our preclinical studies 56, or nine also outperformed 13 65 on a wide range of measures demonstrating greater selectivity potency and anti tumor activity in preclinical models in which both drug candidates were tested.
The new preclinical data on 56 or nine that we presented at the DNA meeting further highlight its best in class potential.
At least 13000 fold greater selectivity for CDK seven over closely related members of the CDK family.
David A. Roth: 5609 demonstrated greater potency and selectivity than an oral non-covalent CDK7 inhibitor in clinical development. It also demonstrated an overall PK profile that supports daily dosage and robust anti-tumor activity at doses below the maximum tolerated dose, which was seen in preclinical models. 5609 inhibited tumor growth in 100% of the breast, lung, and ovarian cancer models studied, including inducing deep and sustained regression in 58% of these. Building off our prior work, these deeper and more sustained responses were associated with RB pathway alteration.
86 online demonstrated greater potency and selectivity set an all non covalent CDK seven Edgar.
Nickel development.
56, or nine also demonstrated an overall PK profile that supports daily dosing.
And robust anti tumor activity at doses for low a maximum tolerated dose which was seen in preclinical models.
56, or nine inhibited tumor growth and 100% of the breast lung and ovarian cancer models study.
Including reducing Jeep and sustained regressions in 58% of these models.
Building off our prior work these deeper and more sustained responses were associated with our be pathway alterations.
David A. Roth: Additionally, 5609 also induced robust anti-tumor activity in combination with fulvestrin in CDK4-6 inhibitor treatment-resistant models of ER-positive breast cancer. We expect to initiate the Phase 1 trial for 5609 in the first quarter of 2020, and we are committed to advancing the program as rapidly as possible. We're focusing on tumor types that we believe are most likely to respond to 5609, including breast, lung, and ovarian cancers, and solid tumors of any histology harboring RB pathway alterations, to increase the likelihood of seeing early signals of action. We've designed the trial in a way that we believe will allow us to more efficiently move through dose escalation and adapt quickly to explore early death. We believe we have two excellent drug candidates in 1425 and 5609, and we look forward to keeping you updated as we continue to advance these programs to key clinical milestones next year and beyond. With that, I'll turn it over to Joe to review our financial results for the quarter.
Additionally, 56 online also induced robust anti tumor activity in combination with investment.
In CDK for six inhibitor treatment resistant models of IAR positive breast cancer.
We expect to initiate the phase one trial for 56 online.
The first quarter of 20 Twond.
And we're committed to advancing the program as rapidly as possible.
Focusing on tumor types that we believe our most likely to respond to 56 or nine including breast lung and ovarian cancers.
End solid tumors of any histology harboring RB halfway alterations to increase the likelihood obscene early signals of activity.
We've designed to trial in a way that we believe will allow us to more efficiently move to dose escalation and adapt quickly to explore early signals.
We believe we have two excellent drug candidates in 14, 25, and 56 online and we look forward to keeping you updated as we continue to advance. These programs two key clinical milestones next year and beyond.
With that I'll turn it over to Joe to review, our financial results for the quarter.
Thank you David.
Joe Farah: Thank you, David. As we prepare for these key developments across our pipeline next year, we continue to maintain a strong financial position. We are updating our cash guidance to reflect that we now expect our existing cash, cash equivalents, and marketable securities to fund our planned operating expenses and capital requirements through the end of the second quarter of 2021. We ended the third quarter with $108.1 million in cash, cash equivalents, and marketable securities, compared with $99.7 million on December 31, 2018. We recognized $0.6 million of revenue in the third quarter of 2019, compared to $0.4 million for the third quarter of 2018. Revenues in both periods were earned entirely from our collaboration within. R&D expenses were $15.9 million for the third quarter of 2019, compared to $12.9 million for the same period in 2018.
As we prepare for these key developments across our pipeline next year, we continue to maintain a strong financial position.
We are updating our cash guidance to reflect that we now expect our existing cash cash equivalents in marketable securities to fund our planned operating expenses in capital requirements. So we ended the second quarter of 2021.
We ended the third quarter with 108.1 million in cash cash equivalents in marketable securities compared with 99.7 million on December 30, Onest 2018.
We recognized a point 6 million of revenue in the third quarter of 2019, comparing 2.4 million for the fourth quarter in 2018.
Revenues in both periods were earned entirely from our collaboration with insight.
R&D expenses were 15.9 million for the third quarter of 2019.
Eric to 12.9 million for the same period in 2018.
Joe Farah: This increase was primarily due to the continued advancement of our existing clinical trials and preclinical programs, including conducting IND-enabling studies to support the planned initiation of a Phase I trial for 5609 in the first quarter of 2020. G&A expenses were $5 million for the third quarter of 2019 compared to $3.9 million for the same period in 2018. This increase was primarily due to an increase in employee-related... Finally, we reported a net loss for the third quarter of $19.8 million, or $0.47 per share, compared to a net loss of $15.7 million, or $0.47 per share, for the same period in 2018.
This increase was primarily due to the continued advancement of our existing clinical trials in preclinical programs, including conducting R&D, enabling studies to support the planned initiation of phase one trial for 56 or nine in the first quarter of 2020.
Gina expenses were five union for the third quarter of 2019 compared to 3.9 million for the same period in 2018.
This increase was primarily due to an increase in employee related expenses.
Finally, we reported a net loss for the third quarter of 19.8 million or 47 cents per share.
Compared to a net loss of 15.7 million or 47 cents per share for the same period in 2018.
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. Ladies and gentlemen, if you have a question at this time, please press star and then the number one on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. My first question comes from the line of Kenneth Atkins with Cohen. Thanks for taking my questions.
Ladies and gentlemen, if you have a question at this time, please press star and in the number one audio test town telephone. If your question has been answered or you wish to remove yourself from the Q. Please press the pound key.
Your first question comes from the line of Kenneth Atkins with Cowen.
Okay. Thanks for taking my questions.
Kenneth Atkins: You showed some pretty impressive data at ASH with 1425 in terms of depth of response. Could you just remind us what the criteria are for patients achieving a molecular CR? What's the cutoff there?
You should some pretty impressive data at ash with Fortune 25 in terms of step. The response could you just remind us what further criteria for patients achieving a molecular CR cut off there.
Hi, Ken I'm going to turn I'm going ask David answer that question sure. Thanks for that question.
Nancy A. Simonian: I'm going to turn around, and I'm going to ask David to answer that question.
David A. Roth: Sure, thanks for that question. A complete response requires having fewer than 5% blasts on a follow-up bone marrow biopsy associated with normalization of the neutrophils and platelets. And in order for it to be as deep as a molecular CR, mutations that were present at baseline can no longer be detected by PCR, which is the most sensitive test we have for screening the marrow.
A complete response requires having fewer than 5% blasts on a follow up though now a biopsy associated with normalization of the neutrophils and placements and in order for it to be as deep as a molecular CR mutations that were present their baseline how can no longer be detected by PCR, which is the most sensitive.
Test we have for screening the merit.
Okay. Thanks, and then what do you need to see from the ongoing cohort in frontline AML with 14 65 to justify pursuing pivotal development and then.
Nancy A. Simonian: Okay, thanks. And then, what do you need to see from the ongoing cohort in frontline AML with 1465 to justify pursuing pivotal development? And then, if you were to pursue that, what would that study look like, you think?
If you were to proceed of what would that study looked like you. Thanks.
Nancy A. Simonian: Hey Ken, we were very pleased with the data in the newly diagnosed cohort, and as we said, we're continuing to follow the patients, particularly to look at durability. At the same time, we're looking at the overall kind of landscape in the newly diagnosed unfit setting and figuring out what's the best path forward in the newly diagnosed setting. So that's an ongoing work that we're doing really assessing the competitive landscape, but I think importantly these data are very strong, and we think that that gives us a lot of conviction that this will be an important therapy also in the earlier lines of setting. Okay, thanks. That's helpful.
Hey, Ken.
We were very pleased with the data in the newly diagnosed cohort.
And as we said, we're continuing to follow the patients, particularly to look at the durability.
At the same time, we're looking at the overall kind of landscape in the newly diagnosed uncut setting and figuring out what's the best path forward in the newly diagnosed setting. So that's an ongoing work that we're doing really assessing the competitive landscape, but I think importantly, these data are very strong.
And we think that that gives us a lot of conviction that this will be an important therapy also in earlier lines the upsetting.
Okay. Thanks, that's helpful.
Your next question comes from the line of Ted Tenthoff with Piper Jaffray.
Operator: Your next question comes from the line of Ted Tenhoff with Piper Jaffray. All right. Thank you.
Great. Thank you very much oral CPT code seven.
Edward Andrew Tenthoff: Thank you very much. On Oral CDK7, what should we be into?
What should we be anticipating.
Nancy A. Simonian: are anticipating as a potential development path beyond the Phase I. Is this still very much in line with how you were planning on developing the IV? And maybe you can comment on what potential combination therapies make sense with oral CDK7. Thanks so much.
Short development path.
The phase was still very much in line with sort of hard we're planning on developing VIP, maybe he can comment or what potential combination therapies that serves oral ceded to seven thanks. So much.
David A. Roth: Yeah, thanks, Ted. I'll start, and then I'll turn it over to David. And I think, as we've just discussed before and illustrated by what we did with 1365, we, first of all, are always going to be thinking about, you know, what is the optimal patient population where we think we have the greatest likelihood of seeing activity. And we're taking a lot of the learnings from both 1365 and our preclinical data with 5609, as illustrated by already doing that enrichment in this. And then we will look at the drug and evaluate it both as a single agent. Are there potential opportunities with more of a fast track opportunity as a single agent? And at the same time, we'll also be thinking about combination because we think, ultimately, combination is going to be most important, but we will continue to look for opportunities. And, you know, we were encouraged by the fact that we saw some single agent activity with 1365. So we think that there is that potential opportunity, but of course, will the data play out? But David, do you want to add anything?
Yes, Thanks, Ted I'll start that I'd turn it over to David and I think as Weve discussed before and as illustrated by what we did but 13 65.
We first of all we're always going to be thinking about what is the optimal patient population, where we think we have the greatest likelihood of seeing activity.
We're taking a lot of the learnings from.
13, 65 in our preclinical data with 56 or nine as illustrated by already doing that enriching and this and.
And then we will look at the drug and evaluated both as a single agent are there potential.
Opportunities with more of a fast to market opportunity of the single agent and at the same time will be thinking also about combination could we think ultimately the combination is going to be most important but we will now can you always and look for opportunities and we it's I think we were encouraged by the fact that we saw something.
Angle agent activity with 13 65, so we think that there is that potential opportunity, but of course will be data will play out, but David you want to add anything no I think you largely covered it obviously we're exploring.
David A. Roth: No, I think you've largely covered it. Obviously, we're exploring a single agent at the start of the program in tumor types, selected tumors, which we anticipate may be enriched for response to the drug. And, you know, we're obviously positioned to evaluate combinations with a focus. We have lots of preclinical data that support a range of combination opportunities to pursue, and we'll let the data guide that.
Single agent at the start of the program in tumor types select tumors, which we anticipate maybe enriched for response to the drug and we're obviously positions to evaluate combinations with a focus obviously, we have lots of preclinical data that support a range of combination opportunities.
Pursue and we'll have to data guidance.
Yes.
Yes.
Your next question.
Operator: Your next question... Your next question comes from the line of Jason Butler with JMP Securities. Hi, thanks for taking the questions. First one, just on the 5609 phase one study, can you just speak to any clinical site overlap with the 1365 or anything else that gives you confidence that you can get the trial up and running quickly? And then secondly, just in context of your updated cash burn or cash runway guidance, can you speak to how you're thinking about advancing the preclinical portfolio and to what extent business development comes into your priorities? Thanks.
Your next question comes from the line of Jason Butler with JMP Securities.
Hi, Thanks for taking the questions.
First one just on the 56 or nine phase. One study can you just speak to any clinical site overlap with the.
30, and 65 or anything else that gives you confidence that you can get the trial from running quickly and then secondly, just in context of your your updated cash burn or cash runway guidance can you speak to how you're thinking about advancing the preclinical portfolio and to what extent business development comes into your priorities.
Thanks.
Hey, Jason I'm going to ask David to take the first question around the.
Jason Nicholas Butler: Hey Jason, I'm going to ask David to take the first question on the sites and the overlap and potential for quick start-ups.
The sites in the overlap and potential for quick startup, yes, I saw interests.
David A. Roth: Yeah, so just, thanks for that question again, and just to comment. I'm really pleased to say that our sites have been incredibly engaged, and we have excellent relationships and good working rapport with all of the sites that have been working on the 1365 program. We don't see any concerns with respect to site overlap and operationalizing the 5609 program, and our team is very well positioned for an effective and efficient SWIFT startup. And I'll turn over the secondary questions to Joe.
Thanks for the question begin to just to comment I mean, I'm really pleased to say that on our sites have been incredibly engaged and we have excellent relationships with a good working report with all of the sites that were working on the searching 65 program. We don't see any concerns respect with respect to site overlap.
Operationalizing were 56 or nine program and our team is very well positioned for an effective and efficient swift startup.
So and then I'll turn over the secondary question Joel So.
Joe Farah: I'll take the next question, Jason, related to business development. Corporate development has always been part of the strategy for the company, and we're continuing to look at what could be the right partnership that would allow us to accelerate or move forward as quickly as possible our medicines to patients. So it has always been and will continue to be an important part, and as things arise from that, we will let you know.
Ill take the next question, Jason that related to business development.
Corporate development has always been part of the strategy for the company and we're continuing to look at what could be the right partnership that would allow us to.
Accelerate or move forward as quickly as possible on medicines to patients. So it has always been and we'll continue to be an important part and.
We will.
Things arise from that we will let you know.
Great. Thanks, again for taking the questions.
Operator: Great. Thanks, Kevin, for taking the question. And once again, if you would like to ask a question, please press star, then the number 1 on your telephone keypad. Again, that is star 1.
And once again, if you would like to ask your question. Please press Star then the number one on your telephone keypad again that star one.
Your next question comes from the lineup Mark Breidenbach with Oppenheimer.
Mark Alan Breidenbach: Your next question comes from the line of Mark Breidenbach with Oppenheimer. Hey, good morning, guys, and thanks for taking the question. Just a quick one from me, and it's probably directed toward David.
Hey, good morning, guys and thanks for taking your question.
Just a quick one from me and is probably directed towards David I was wondering if you could give us a little bit more color on on how you're defining RV pathway alterations in the CDK seven trial.
David A. Roth: I was wondering if you could give us a little bit more color on how you're defining RB pathway alterations in the CDK7 trial. And I'm just trying to get a sense if you're planning to use a specific companion diagnostic as part of this trial, or if you're really just enriching for tumor types that are already known to be... And I'm just trying to get a sense if you're planning to use a specific companion diagnostic as part of this trial, or if you're really just enriching for tumor types that are already, Enriched for RB pathway alteration. So I'm just trying to get a sense for if this will be a simple diagnostic test that will be implemented or if that's gonna come in later clinical trials.
And I'm, just trying to get a sense, if you're if you're planning to use a specific companion diagnostic as part of this trial or if you're really just enriching for.
Tumor types that are already known to be.
Enriched for RV pathways.
Alterations Im just trying to get a sense for it if this will be as a simple.
Diagnostic tests that will be implemented or is that that's that's going to come in later later clinical trials.
Great. Thanks, Marc I mean to ask David to answer that question. So we will be.
David A. Roth: Great. Thanks, Mark. I'm going to ask David to answer that question.
Utilizing readily available diagnostic tests for patients as they come into the trial and we don't anticipate there being any specific challenges associated with defining those patients when we sort of closer to the time that this study starts we can provide you with a little bit more context around specifically what will be looking forward, though.
David A. Roth: So we will be utilizing readily available diagnostic tests for patients as they come into the trial, and we don't anticipate there being any specific challenges associated with defining those patients. When we get closer to the time that the study starts, we can provide you with a little bit more context around specifically what we'll be looking for.
And just to add to what they say, where you were kind of doing two things where both.
David A. Roth: And just to add to what David was saying, we're kind of doing two things; we're both enriching for populations that have RB pathway alterations, and we'll be measuring those. We're not, in those ovarian, breast, and lung cancers, selecting those patients; we'll be measuring them. And then we actually then have another cohort that's really selecting for other cell tumors that have them, but as David said, based on existing ways to detect those that the sites have.
Enriching for populations have RB pathway alterations and will be measuring though is we're not in those ovarian breast and lung were not selecting patients what would be measuring them.
And then we actually then have another cohort that's really selecting for other solid tumors that have them, but as David said based on existing ways to detect those but the flight test.
Operator: Okay, that's helpful. All right, thanks for taking the question and congrats on the progress. Yeah, thanks, Mark. Your next question comes from the line of Zek Bajala with Roth Capital. Apologies for the noise in the background, but I just kind of wanted to ask a question about the Sickle Cell Program. I was really excited about the announcement, about the data coming from ASH, but wanted to know any thoughts about the market or any other thoughts that went into making that decision, and then any additional details on the program. Any incremental bit of information that you can give ahead of ASH that could kind of get people excited about the data readout.
Okay. That's helpful. Alright, Thanks for taking your question and congrats from progress progress.
Thanks, Mike.
Your next question comes from the line of setback shallow with Roth capital.
College is for the noise in the background, but just kind of wanted to ask a question about this because I'll tell them as really excited about the announcement about the data coming at us, but wanted to know any thoughts about market or any other thoughts that went into making that decision and then.
Any additional details on.
The.
And the incremental bit of information.
As head of aspect that kind of get excited about that data read out.
Now let me start another turn it over to Eric Yes, we are really excited about the sickle cell program that we it's part of our broader strategy to identify ways to modulate the level of expression of a single gene for therapeutic benefit and we think the.
Nancy A. Simonian: Let me start and then I'm going to turn it over to Eric. We are really excited about the Sickle Cell Program that we have. It's part of our broader strategy to identify ways to modulate the level of expression of a single gene for therapeutic benefit. And we think this could be broadly applied to many monogenic diseases; our first one that we selected was sickle cell, and to see the progress that's been made and to see this highlighted at ASH, it's really kind of one of the really important new breakthroughs. I think it's a real testament to the work of Eric and his discovery organization. Eric, I'm going to turn that over to you in terms of...
Could be broadly applied to many monogenic diseases that first one that we collected the sickle cell and to see the progress that's been made and to see it's highlighted at ash.
Well, they kind of one of the really important new breakthrough so think of the real Testament to the work Eric and his discovery organization.
Eric.
Turn it over to you in terms of.
Yes. Thanks, Thanks for asking the question Yeah. We're really excited we've been working on this for a couple of years really building all the pieces.
Eric Olson: Thanks for asking the question. We're really excited. We've been working on this for a couple of years, really building all the pieces, all the assays, all the tools to launch a drug discovery program in this space. And one of the key aspects of that was to really tear apart and understand the differentiation process and what happens to this locus as cells differentiate toward more mature erythrocytes. So that's really the highlight of the poster is demonstrating our ability to understand this locus and assay for the types of targets that may be druggable and effective therapeutic approaches for sickle cell. So I urge you to read the abstract; there are several figures that are online. I think they really demonstrate well what we're up to.
All the assays all the tools.
To launch a drug discovery program in this space and one of the key aspects of that was to really tear apart and understand the differentiation process and what happens to this locus as cells differentiate towards more mature a retro sites. So that's really the highlight of the of the of the poster is demonstrating our.
Ability to understand this locus and assay for the types of targets.
Maybe druggable and.
Effective therapeutic approaches for sickle cell. So I urge you to on the in the abstract or several figures that are online I think they really demonstrate well what we're up to I.
Nancy A. Simonian: I think just to add to what Eric said related to sickle cell, we think that one can get a potential functional cure by altering the level of expression of fetal globin so that we can, and we think that, therefore, taking a pill could have a benefit for a very large number of people across the globe that have this disease. So while we think that other approaches may also have benefits, we think that this approach has really the potential to have a fairly broad impact, and I think the fact that at ASH they selected this for their press briefing is just an indication of the potential for this approach.
I think just to add to what Eric said it related to sickle cell Inc.
We think that.
One can get a potential functional cheered by altering the level of expression of fetal globin and so that we can.
We think that.
Therefore, taking a pill could have a benefit for a very large number of people across the globe that have this disease. So while we think that.
The other approaches May also have benefit we just we think that this approach has really the potential to have a fairly broad impact and.
I think is is illustrated by the fact that you know at Ash. They selected this for their press briefing I think isn't just an indication of the potential for this approach.
Thanks, Nancy I think it's very evident that community is supportive and obviously there is really looking forward to seeing.
Nancy A. Simonian: Thanks, Nancy. I think it's really evident that the community is supportive, and obviously, the FDA is really looking forward to seeing new therapies for sickle cell.
After the first if that's all.
Okay.
Operator: Thanks, everyone.
Thanks.
I'm showing no further questions at this time I would now like to turn the conference back over to the company.
Nancy A. Simonian: I am showing no further questions at this time. I would now like to turn the conference back over to the company.
Thank you operator in closing we are focused on executing on our clinical development plans for 14, 25, and 56 or nine as rapidly and efficiently as possible and we look forward to keeping you updated as we work toward our ultimate goal of bringing much needed therapies to market for patients. Thanks.
Nancy A. Simonian: Thank you, Operator. In closing, we are focused on executing on our clinical development plans for 1425 and 5609 as rapidly and efficiently as possible, and we look forward to keeping you updated as we work toward our ultimate goal of bringing much-needed therapies to market for patients. Thank you all for joining us today and for your continued support of Syros. Have a good day.
You all for joining us today and for your continued support.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation and have a wonderful day. You may now disconnect.
I have a bit.
Ladies and gentlemen. This concludes today's conference call. Thank you for your participation and have a wonderful day you may now disconnect.