Q3 2021 Syros Pharmaceuticals Inc Earnings Call

November 5, 2021

Operator: Good day, and thank you for standing by. Welcome to the Q3 2021 Syros Pharmaceuticals Inc. earnings conference call.

Good day, and thank you for standing by and welcome to the Q3 2021, Syros Pharmaceuticals, Inc Earnings Conference call.

Operator: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised

At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.

To ask a question during the session you will need to press star one on your telephone. Please be advised that today's conference is being recorded.

Operator: You will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would like to hand the conference over to your speaker today, Courtney Solberg from Syros. Please go ahead.

Require any further assistance please press star zero.

I'd like to hand, the conference or to your speaker today, Courtney Salzburg with tea Rose. Please go ahead.

Thank you. This morning, we issued a press release with our third quarter 2021 on annual results along with anticipated future milestones and recent accomplishments.

Courtney Solberg: This morning, we issued a press release with our third quarter 2021 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, and our Chief Executive Officer, Dr. David Roth.

This release is available on the investors and media section of cirrhosis website at Www Dot Dot Com you will begin the call with prepared remarks are Doctor Nancy Simonian, Our Chief Executive Officer, Dr. David Roth, Our Chief Medical Officer, Kristin Stephens, our Chief Development Officer.

And Jason Haas, our Chief Financial Officer.

And then open the call for a question Dr. Eric Olson, our Chief Scientific Officer, and Colin Lee Chee <unk> Chief Commercial officer are also on the call and will be available for Q&A.

Courtney Solberg: Dr. David Roth

Courtney Solberg: Before we begin, I would like to remind everyone that statements we make on this conference call will include forward-looking statements. However, actual events or results could differ materially from those expressed or implied by any forward-looking statement. 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, which was filed this morning, and any other filings that we make with the SEC in the future.

Before we begin I would like to remind everyone that statements. We make on this conference call include or 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 factors section of our annual report on Form 10-K, our quarterly report.

On Form 10-Q that were filed this morning.

And any other filings that we make with the S E C in the future.

Courtney Solberg: In particular, the extent to which the COVID-19 outbreak continues to impact our operations and those of the third parties on which we rely will depend on future developments, which are highly uncertain and cannot be predicted with confidence. Any 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

And in particular, the extent to which the COVID-19 outbreak continues to impact our operations and those of the third parties on which we rely or depend on future developments, which are highly uncertain and cannot be predicted with confidence.

Any 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 date, we specifically disclaim any obligation to update or revise any forward looking statements I would now like to turn the call over to Nancy.

Courtney Solberg: as of any subsequency. We specifically disclaim any obligation to update or revise any

Courtney Solberg: to update or revise any forward-looking statements. I would now like to turn the call over to Nancy. Thank you, Courtney.

Thank you Courtney.

Nancy A. Simonian: The third quarter of 2021 was extremely productive for Syros as we continued to execute on our three strategic priorities that we laid out at the beginning of the year. We are leveraging our leadership and expertise to build a synergistic portfolio where success in one program can inform and benefit efforts in another. We believe we are well on our way towards achieving our goal of becoming a fully integrated biopharmaceutical company that has the potential to provide profound benefits for patients with cancer and monogenic diseases.

The third quarter of 2021 was extremely productive for cerus as we continue to execute towards our three strategic priorities that we laid out in the beginning of the year.

We are leveraging our leadership and expertise to build a synergistic portfolio where success in one program kind of informed and benefit efforts in another.

We believe we are well on our way towards achieving our goal of becoming a fully integrated biopharmaceutical company that has the potential to provide profound benefit for patients with cancer and monogenic diseases.

Nancy A. Simonian: This quarter, we made two new strategic hires, adding additional strength to our experienced leadership team as we prepare for two expected NDAs in 2024. In September, we appointed Conley Chee as our first Chief Commercial Officer, bringing 20 years of pharmaceutical sales, leadership, marketing, and strategy experience. In October, Jason Haas joined Syros as our new Chief Financial Officer, bringing more than 25 years of healthcare investment banking and corporate finance experience.

This quarter, we made two new strategic hires adding additional strength to our experienced leadership team as we prepare for two expected N D as in 2024.

In September we appointed Connolly Chi as our first Chief commercial officer, bringing 20 years of pharmaceutical sales leadership marketing and strategy experience.

In October Jason Haas joined Zeros, as our new Chief Financial officer, bringing more than 25 years of health care investment banking and corporate finance experience. We are excited to have them on board.

Nancy A. Simonian: We are excited to have them on board. Importantly, as David and Kristen will review shortly, we made tremendous progress across both our hematology and CDK7 portfolios. In September, we dosed the first patient in our Select AML-1 Phase 2 trial of Tamibaratine and Rara-positive unfit AML patients, and the first patient in our dose confirmation study of SY-2101 in newly diagnosed APL patients. These milestones showcase our team's commitment to quickly advance medicines that have the potential to offer new standards of care for patients with hematologic cancer.

Importantly, as David and Christian will review shortly we made tremendous progress across both our hematology and CDK seven portfolios.

In September we dose the first patient in our select AML, one phase II trial of <unk> in RARA positive unfit AML patients and the first patient in our dose confirmation study of FY 'twenty, one O one in newly diagnosed APL patients.

These milestones showcase our team's commitment to quickly advance medicines that have the potential to offer new standards of care for patients with hematologic cancers.

Nancy A. Simonian: Furthermore, at ESMO, we presented encouraging Phase I data for SY5609, our highly selective and potent CDK7 inhibitor, which showed single-agent clinical activity at tolerable doses. We believe 5609 has the ability to attack cancer in multiple ways and could therefore become a transformative targeted therapy. With that, I'd like to turn the call over to David, who will review our progress across our hematology and CDK inhibitor programs in more detail. Thank you, Nancy.

Furthermore, at ESMO, we presented encouraging phase one data for S. Y 50, 609 are highly selective and potent CDK <unk> inhibitor, which showed single agent clinical activity at tolerable doses. We believe 50 609 has the ability to attack cancer and multiple ways. It could therefore.

Become a transformative targeted therapy.

With that I'd like to turn the call over to David who will review our progress across our hematology and CDK inhibitor programs in more detail.

Thank you Nancy.

David A. Roth: To start, I will discuss the designs of the TAMI-Baratin Select AML-1 Phase 2 and the SY-2101 Dose Confirmation Phase 1 trials in AML and APL, respectively, as well as the unmet need for each indication. Our SELECT-AML-1 randomized Phase 2 trial is now ongoing and aims to evaluate the triplet combination of tamibaritine, venetoclax, and azac The trial begins with a single-arm safety lead-in, followed by a randomized portion that will evaluate the safety and efficacy of the triplet regimen compared to the combination of venetoclax and azacitabine in approximately 80 patients randomized one-to-one. The primary endpoint of the trial will evaluate the composite CR rate, and we expect to announce initial data in 2022. There remains a tremendous unmet need in AML despite recent advances in the field.

To start I will discuss the design of the <unk> priority select AML, one phase two and the FY 'twenty one O one dose confirmation phase one trials in AML and APL, respectively, as well as the unmet need of each indication.

Our select AML, one randomized phase two trial is now ongoing and aims to evaluate the triplet combination of transparency panetta Clarks and Asus hydrogen in RARA positive newly diagnosed unfit AML patients.

The trial begins with a single arm safety, leading followed by a randomized portion, which will evaluate the safety and efficacy of the triplet regimen compared to the combination of <unk> and <unk> and <unk>.

<unk> 80 patients randomized one to one.

The primary endpoint of the trial will evaluate the composite CR rate and we expect to announce initial data in 2022.

There remains a tremendous unmet need in AML. Despite recent advances in the field.

David A. Roth: Nearly one-third of patients do not respond to the standard of care and have poor prognosis, and a majority of those with initial, ultimately LELAP. A new treatment option that provides durable benefit and is well-tolerated and convenient is what patients are looking for and need. Additionally, in September, we dosed the first APL patient in our dose confirmation study of 2101, which is our novel form of arsenic trioxide, or

Nearly one third of patients do not respond to the standard of care and have poor prognosis and a majority of those with initial response ultimately relapse.

A new treatment option that provides durable benefit and is well tolerated and convenient as what patients are looking for and need.

Additionally in September we dosed the first APL patients in our dose confirmation study of 21 to one which is our novel form of arsenic trioxide or ACO.

David A. Roth: The study is expected to enroll up to 24 new diagnosed APL patients and aims to evaluate the safety, tolerability, and pharmacokinetics of 2101. Patients will be enrolled during the consolidation phase of their APL treatment for PK assessments of single doses of 2101 in a fasted and a fed state to evaluate absorption effects on PK, as well as IV ATO to compare oral to IV direct. Patients will then have the option to enter multiple dose cohorts to provide additional steady-state PK and safety data.

This study is expected to enroll up to 24, new diagnosed APL patients and aims to evaluate the safety tolerability and pharmacokinetics of 'twenty one on one.

Patients will be enrolled during the consolidation phase of their APL treatment for PK assessments of single doses of <unk> 21 on one.

<unk> and our fed state to evaluate absorption effects on PK.

Ivy ACO to compare oral to IV directly.

Patients will then have the option to enter multiple dose cohorts to provide additional steady state PK and safety data.

David A. Roth: We expect to report dose confirmation and PK data in the first half of 2022, and we expect to initiate a phase three trial in 2020. There are approximately 2,000 APL patients diagnosed annually in the United States and Europe. Thus, an oral treatment presents a significant market opportunity.

We expect to report dose confirmation and PK data in the first half of 2022, and we expect to initiate a phase III trial in 2022.

There are approximately 2000 APL patients diagnosed annually in the United States and Europe, Thus, an oral treatment presents a significant market opportunity.

David A. Roth: The IV formulation of ATO, in combination with ATRA, is approved for use in newly diagnosed APL and is curative in more than 80% of patients. However, there is a tremendous treatment burden associated with the standard of care, requiring up to 140 infusions over the 10-month course of induction and consolidation treatment. Offering a new therapeutic option that is oral, delivers similar clinical benefits, and dramatically reduces the treatment burden has the potential to provide tremendous benefit to these patients and improve their quality of life.

The IV formulation of our CTO in combination with Natura is approved for use in newly diagnosed APL and as curative and more than 80% of patients. However, there is a tremendous treatment burden associated with the standard of care requiring up to 140 <unk> infusions over the 10 month course of induction and consolidate.

Treatment.

Offering a new therapeutic option that is oral.

Similar clinical benefit and dramatically reduces the treatment burden has the potential to provide a tremendous benefit to these patients and improve their quality of life.

David A. Roth: Now turning to our CDK inhibitor portfolio. We recently presented at ESMO our updated phase one dose escalation data of 5609. Patients were treated in cohorts, exploring continuous daily dosing, as well as intermittent dosing. As a reminder, the trial is enrolling patients with advanced breast, colorectal, lung, ovarian, and pancreatic cancer, as well as other tumor types with RB pathway alteration. As of the July 6th data cut-off... 54 patients were treated with single agent 5609 and were evaluated for safety, and 45 were valuable for clinical response analysis. The majority of adverse events were low-grade and reversed.

Now turning to our CDK inhibitor portfolio.

We recently presented at ESMO are updated phase one dose escalation data of $56 nine.

Patients were treated in cohorts exploring continuous daily dosing as well as intermittent dosing regimens.

As a reminder, the trial is enrolling patients with advanced breast colorectal lung ovarian and pancreatic cancer as well as other tumor types with RB pathway alterations.

As of the July 6th data cutoff.

54 patients were treated with single agent <unk> 56.

And were evaluated for safety analyses and 45 were valuable for clinical response analyses.

The majority of adverse events were low grade and reversible.

David A. Roth: The most frequent treatment-emergent adverse events were GI-related, fatigue, thrombocytopenia, and anemia. Across the study, there were low rates of discontinuation due to adverse events. Tolerability was optimized with the seven-day on, seven-day off dosing rate, which had the lowest rates of treatment emergent age, and this regimen also demonstrated clinical activity consistent with that of other regimens. These data support the advancement of the seven-day on, seven-day off regimen in the future. We were very encouraged to see single-agent clinical activity, particularly given that our study enrolled heavily pre-treated patients, many with tumor types that are commonly refractory to treatment.

The most frequent treatment emergent adverse events were G isolated fatigue, thrombocytopenia and anemia and across the study there were low rates of discontinuation due to adverse events.

Tolerability was optimized with the seven day on seven days off dosing regimen.

Had the lowest rates of treatment emergent aes and this regimen also demonstrated clinical activity consistent with that of other regimens.

These data support the advancement of the seven day on seven days off regimen in future studies.

We were very encouraged to see single agent clinical activity, particularly given that our study enrolled heavily pretreated patients. Many with tumor types that are commonly refractory to treatment.

David A. Roth: In total, 13 of 45 response-evaluable patients achieved stable disease across multiple tumor types. Of these 13 patients, 6 had tumor regressions of up to 20%. Stable disease was observed in patients treated with both the daily and the intermittent regimens, including the 7-day on, 7-day off regimen, at doses as low as 3 milligrams per day.

In total $13 45 response, evaluable patients achieved stable disease across multiple tumor types.

Of these 13 patients six had tumor regression of up to 20%.

Stable disease was observed in patients treated with both daily and the instrument and regimens, including the seven day on seven day off regimen at doses as low as three milligrams per day.

David A. Roth: Notably, we observed the strongest clinical activity in pancreatic cancer patients. 5 of 13, or over 38%, of response-available patients with pancreatic cancer achieve stable disease, including two with tumor shrinkage. Additionally, decreases were seen in clinically relevant tumor markers that are typically used in the clinic to monitor disease progression, including decreases in three of four, or 75%, of the pancreatic cancer patients with serial tumor markers. Nearly all pancreatic cancer patients are highly refractory to existing therapies, which makes these data particularly compelling.

Notably we observed the strongest clinical activity in pancreatic cancer patients.

As of 13 or over 38% of response evaluable patients with pancreatic cancer achieved stable disease, including two tumor shrinkage.

Additionally, decreases we're seeing and clinically relevant tumor markers that are typically used in the clinic to monitor disease progression, including decreases in three or four or 75% of the pancreatic cancer patients with serial tumor markers.

Nearly all pancreatic cancer patients are highly refractory to existing therapies, which makes these data are particularly compelling.

David A. Roth: Also, across all patients in the trial, we saw the highest level of clinical activity in patients with KRAS mutations and in patients with RB pathway alteration. K-RAS mutations are potent stimulators of cell signaling and transcriptional programs for cell cycle progression and are nearly ubiquitous in patients with pancreatic cancer. Knowing this, along with our data, further supports our mechanistic understanding of how CDK7 inhibition works, as well as our go-forward plan to focus next steps in the expansion phase of the trial in patients with pancreatic cancer.

Also across all patients in the trial, we saw the highest level of clinical activity in patients with K Ras mutations.

And patients with RB pathway alterations.

K Ras mutations are potent stimulator of cell signaling and transcriptional programs for cell cycle progression and are nearly ubiquitous in patients with pancreatic cancer.

Knowing this along with our data further supports our mechanistic understanding of how CDK <unk> inhibition works as well as our go forward plan to focus next steps in the expansion phase of the trial in patients with pancreatic cancer.

David A. Roth: Additionally, as part of our ongoing study, we analyzed the degree of Pol R2a induction, which showed high correlation between target region response as assessed by research criteria. This data is important as it demonstrates the value of Pol-R2a as a PD biomarker of clinical response to CDK7 target inhibition with 56. Additionally, we observed sustained PD effects to the desired target levels that lasted at least three days after dose suspension, showing that CDK7 target coverage can last long after the time when the drug is not taken.

Additionally, as part of our ongoing study we analyzed the degree of <unk> induction, which showed high correlation between target region response as assessed by resist criteria.

This data is important as it demonstrates the value of Paul Archway has a PD biomarker of clinical response to CDK seven target inhibition with $56.

Additionally, we observed sustained PD effects to the desired target levels that lasted at least three days after dose suspension.

Showing that CDK seven target coverage can last long after the time when the drug is not taken.

This supports our confidence that we have a critical biomarker that is associated with anti tumor activity.

Additionally, the data supports the use of intermittent dosing schedules to optimize tolerability setting the stage for long term administration and our go forward combination plans in various indications.

David A. Roth: This supports our confidence that we have a critical biomarker that is associated with anti-tumor activity. Additionally, the data supports the use of intermittent dosing schedules to optimize tolerability, setting the stage for long-term administration in our go-forward combination plans in various indications. I'd now like to turn the call over to Christine to discuss our planned next steps for 5609.

I would now like to turn the call over to Christie to discuss our planned next steps for 56 of them.

Thanks, David as we've previously mentioned we plan to pursue a three pronged combination strategy for $56 nine focusing on indications with high unmet need as well as where there is strong rationale based upon available mechanistic and preclinical and clinical data.

As David alluded to earlier pancreatic cancer represents an area of tremendous unmet need as the only approved second line therapy offers that progression free survival of just three months we.

Kristen Stephens: Thanks, David. As we've previously mentioned, we plan to pursue

Kristen Stephens: to pursue a three-pronged combination strategy for 5609, focusing on indications with high unmet need, as well as where there is strong rationale based upon available mechanistic preclinical and clinical data. As David alluded to earlier, pancreatic cancer represents an area of tremendous unmet need, as the only approved second-line therapy offers a progression-free survival of just three months. We plan to initiate our expansion trial with 5609 in combination with chemotherapy in the fourth quarter of this year.

We plan to initiate our expansion trial with $56 nine in combination with chemotherapy in the fourth quarter of this year.

The trial is designed to include two arms, both of which will enroll patients with metastatic pancreatic cancer, who have progressed following first line treatment with feltl.

One arm will explore the doublet regimen of $56 nine in combination with Gemcitabine and the other arm will explore a triplet regimen of $56 nine with Gemcitabine and Nab Paclitaxel.

The endpoints for the study are safety and Tolerability as well as efficacy measures, including disease control rate and progression free survival.

Kristen Stephens: The trial is designed to include two arms, both of which will enroll patients with metastatic pancreatic cancer who have progressed following first-line treatment with Fulfurionib. One arm will explore the doublet regimen of 5609 in combination with gemcitabine, and the other arm will explore a triplet regimen of 5609 with gemcitabine.

Yes.

Next I would like to discuss our second combination strategy and mantle cell lymphoma, a subtype of B cell non hodgkin's lymphoma affecting approximately 10000 patients in the U S and EU.

This is a tumor that's driven by overexpression of cyclin D and <unk>.

RB pathway regulator and dependent on B cell receptor signaling and Nf Kappa B transcriptional program for survival and growth.

Most patients eventually relapse after their first line treatment and the median survival is three to five years.

Kristen Stephens: with Gemcitabine and NAB Paxil-Paxil.

PTK inhibitors offer a non chemotherapy option for a second line patients, but with reduced activity. After first line treatment.

Kristen Stephens: The endpoints for the study are safety and tolerability, as well as efficacy measures including disease control rate and progression-free survival. Next, I would like to discuss our second combination strategy in Mantle City.

Most patients relapse at which point they will have very limited treatment options and face poor outcomes.

We expect to initiate our phase one b trial in mantle cell lymphoma in the first half of next year.

Kristen Stephens: Affecting approximately 10,000 patients in the U.S. and E.U., this is a tumor that is driven by overexpression of cyclin D, an RB pathway regulator, and dependence on B-cell receptor signaling and NF-kappa B transcriptional programs for survival in groups.

This trial will begin with a safety evaluation of $56 nine as a single agent after which we'll move into a safety lead in in combination with a PTK inhibitor.

This will set the stage to move to combination with a beat TK inhibitor into an expansion phase in second line mantle cell lymphoma patients who have not previously been treated with the TK inhibitor.

Kristen Stephens: Most patients will eventually relapse after their first line treatment, and the median survival is three to five years. CTK inhibitors offer a non-chemotherapeutic option for second-line patients, but with reduced activity after first-line treatment. Most patients relapse, at which point they will have very limited treatment options and face poor outcomes. We expect to initiate our Phase 1b trial in mantle cell lymphoma in the first half of next year. This trial will begin with a safety evaluation of 5609 as a single agent, after which we will move into a safety lead-in in combination with a BTK inhibitor. This will set the stage.

The endpoints for this study include safety and Tolerability as well as efficacy measures such as complete response rate overall response rate and progression free survival.

Additionally, at the upcoming December Ash meeting, we will be presenting preclinical data of $56 nine as a single agent as well as in combination with the PTK inhibitor and mantle cell lymphoma cells.

Finally, I would like to discuss colorectal cancer or CRC, which is one of the leading causes of mortality and morbidity in the world.

Although early diagnosis has significantly improved outcomes many patients aren't diagnosed until the cancer is always metastasized to other parts of the body, making it very difficult to treat.

Kristen Stephens: This is a combination with a BTK inhibitor into an extension phase in second-line mantle cell lymphoma patients who have not previously been treated with a BTK inhibitor. The endpoints for this study include safety and tolerability, as well as efficacy measures such as complete response rate, overall response rate, and progression-free survival. Additionally, at the upcoming December ASH meeting, we will be presenting pre-clinical data for 5609 as a single agent as well as in combination with a BTK inhibitor in mantle cell lymphoma cells.

Adding to the complexity is that different genetic mutations cause CRC to grow.

Mutations in the BRAF gene are found in about 10% of metastatic CRC patients and are associated with a particularly dismal prognosis and a median survival of less than 12 months.

As we announced in August we recently entered into an agreement with Roche to explore 50 609 in combination with the title is the map in patients with BRAF mutant CRC.

Under the terms of this agreement we will supply 50, 609 for a combination dosing cohort and their ongoing phase one phase one be intrinsic trial.

Kristen Stephens: Finally, I would like to discuss colorectal cancer, or CRC, which is one of the leading causes of mortality and morbidity in the world. Although early diagnosis has significantly improved outcomes, many patients aren't diagnosed until the cancer has already metastasized to other parts of the body, making it very difficult to treat. Adding to the complexity is that different genetic mutations cause CRC to grow. Mutations in the BRAF gene are found in about 10% of metastatic CRC patients and are associated with a particularly dismal prognosis and a median survival of less than 12 months. As we announced in August, we recently entered into an agreement with Roche to explore 5609 in combination with

This marks the first clinical investigation of a CDK <unk> inhibitor with an immunotherapy that has the potential to demonstrate significant and broad opportunity for combinations of $56 nine with immunotherapy and other important indications.

We believe that these three studies provide a solid foundation for us to explore the full potential of $56 nine and indications where patients need better treatment options than those that are currently available.

Look forward to providing additional updates as we progress in the clinic.

Now I'd like to turn the call over to Jason Haas, Our Chief Financial Officer to review, our third quarter financial results.

Thank you Kristen working in partnership with the team over the past month I have already experienced firsthand the passion and share commitment that drives the team everyday I could not be more excited to join them and ongoing efforts to develop new medicines that have the potential to provide profound benefit to patients now.

Kristen Stephens: Under the terms of this agreement, we will supply 5609 for a combination dose and cohort in their ongoing Phase 1, Phase 1b intrinsic trial. This marks the first clinical investigation of a CDK7 inhibitor with an immunotherapy that has the potential to demonstrate significant and broad opportunities for combinations of 5609 with immunotherapy and other important indications.

Now turning to our third quarter financial results Ciros continues to operate from a position of financial strength. We ended the third quarter with $166 $7 million in cash cash equivalents in marketable securities compared to $174 million as of December 31, 2020.

Jason Haas: We believe that these three studies provide a solid foundation for us to explore the full potential of 5609 in indications where patients need better treatment options than those that are currently available. We look forward to providing additional updates as we progress in the clinic. Now, I'd now like to turn the call over to Jason Haas, our Chief Financial Officer, to review our third quarter financial results. Thank you, Kristen.

This reflects the cash used to fund our operations during the first nine months of 2021, partially offset by gross proceeds of $75 $6 million. That's euros received from our January 2021 public offering.

Based on our current plans, we believe we have sufficient capital to fund our planned operating expenses and capital needs into 2023.

<unk> multiple expected value drivers we.

We recognized revenue of $5 7 million in the third quarter compared to $3 $8 million in the third quarter of 2020. This consisted of $5 $6 million in revenue under our collaboration with global blood Therapeutics and $100000 under our collaboration with insight.

Jason Haas: Working in partnership with the team over the past month, I have already experienced firsthand the passion and shared commitment that drives the team every day. I could not be more excited to join them in their ongoing efforts to develop new medicines that have the potential to provide profound benefits to patients. Now, turning to our third quarter financial results, Syros continues to operate from a position of financial strength. We entered the third quarter with $166.7 million in cash, cash equivalents, and marketable securities, compared to $174 million as of December 31st, 2020.

In the third quarter of 2020, we recognized $3 $5 million of revenue from our collaboration with GBT and $300000 from our collaboration with insight.

R&D expenses were $27 $3 million in the third quarter of 2021 compared to $17 $7 million for the same period in 2020.

This increase was primarily due to the continued advancement of cirrhosis clinical and preclinical programs and an increase in employee related expenses.

G&A expenses were $5 $3 million in the third quarter of 2021 compared to $5 2 million for the same period in 2020.

Finally, we reported a net loss for the third quarter of $26 million or <unk> 41 per share compared to a net loss of $19 $5 million or <unk> 43 per share for the same period in 2020.

With that I will turn the call over to the operator for questions.

Although it reminds me to ask a question you will need to press star one on your telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.

Jason Haas: This reflects the cash used to fund our operations during the first nine months of 2021, partially offset by gross proceeds of $75.6 million that Syros received from our January 2021 public office. Based on our current plans, we believe we have sufficient capital to fund our planned operating expenses and capital needs into 2023, beyond multiple expected value drivers.

Our first question comes from the line of Ted <unk> Piper Sandler Your line is now open.

Great. Thank you very much and thank you for taking my call and congrats on all the good update.

I wanted to focus on pause so laurie.

The compelling data.

<unk> demonstrated that.

Well.

Bill.

How quickly do you think we could actually start to generate data from the <unk>.

I think it was various to kind of follow the data this year.

Operator: We recognize revenue of $5.7 million in the third quarter compared to $3.8 million in the third quarter of 2020. This consisted of $5.6 million in revenue under our collaboration with Global Blood Therapeutics and $100,000 under our collaboration with Insight. In the third quarter of 2020, we recognized $3.5 million in revenue from our collaboration with GBT and $300,000 from our collaboration with Insight. R&D expenses were $27.3 million in the third quarter of 2021 compared to $17.7 million for the same period in 2020.

But are there other indications or from preclinical results.

Or anything else that might represent future opportunities and then just last question here with a focus on the hematology. Thus far has recovered ultimately represent a partnering opportunity. Thank so much.

Okay.

Thanks for the question Kristen.

Yeah, Ted Thanks for the question. So we believe that 50 690 <unk> Brian.

I'm in a large variety of unmet need kind of cancers.

That being said we are taking a very focused approach in three distinct populations.

<unk> CRC in mantle cell, so that's where our first our areas of focus is and could lead to a broad number of potential opportunities.

Beyond that we always remain open to partnering to answer that question. However, we're continuing to progress forward. The plans that we have in place.

Yeah.

Operator: This increase was primarily due to the continued advancement of Syros' clinical and preclinical programs and an increase in employee-related expenses. DNA expenses were $5.3 million in the third quarter of 2021, compared to $5.2 million for the same period in 2020. Finally, we report a net loss for the third quarter of $26 million, or $0.41 per share, compared to a net loss of $19.5 million, or $0.43 per share, for the same period in 2020. With that, I will turn the call over to the operator for questions.

Great. That's very helpful makes a lot of sense and I'm excited to see.

Continued progress.

Thank you thank you Ted.

Thank you. Our next question comes from the line of Phil NATO from Cowen <unk> Company. Your line is now open.

Good morning, Thanks for taking our questions.

Couple from US first on the select AML one trial for <unk>.

The data will be out next year is that initial data from the safety lead in portion of the study or with initial data also include.

Results from the randomized portion.

Thanks for that question.

The trial.

It is now enrolling and.

We are anticipating initial data in 2022.

We're starting with the safety lead in.

That will.

Likely be the focus of the initial data, which would include safety and Tolerability and May also include clinical activity.

Operator: As a reminder, to ask a question, you will need to press Star 1 on your telephone.

Operator: To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Ted Tenthoff, Piper Sandler.

I'm not sure what you can look forward to perfect.

Perfect. That's helpful and then on the.

21 O one dose confirmation study.

Looking at the clinical trials Dot Gov.

A couple of things that are.

Confusing to me it looks like there's two PK sequences that at least the current clinical trials to talk over exactly the same what is the difference between PK module sequence. One PK module sequence two are those two different doses of 'twenty, one or is there.

Edward Andrew Tenthoff: Your line is now open. Great, thank you very much, and thank you for taking my call and congratulations on all the good updates. I wanted to focus on 5609 and the compelling data that you demonstrated at ESMA. How quickly do you think we could actually start to generate data from that? And I think it was very astute to kind of follow the data here. But are there other indications, or from preclinical results, is there anything else that might represent future opportunities? And then this last question here, with the focus...

Some other difference that that's not obvious from the clinical trials Dot Gov entry.

Yes. So again, it's another good question. So one of the objectives of this study is to evaluate the PK profile of 21, one after it's administered orally and we're going to be doing a single dose of <unk> 21 on one.

In the fasted state as well as in the fed state and that will enable us to compare the PK.

Kristen Stephens: Thanks for the question, Ted. Kristen? Yes, thanks for the question. We believe that

Effects of absorption of the drug and we're also going to do a PK following IV and that will enable us to compare the PK of the oral to the IV directly in the same patient through some very important experiment.

Kristen Stephens: Yeah, Ted, thanks for the question. So we believe that 5609 has broad potential in a large variety of unmet needs cancers. You know, that being said, we are taking a very focused approach in three distinct populations, pancreatic CRC and mantle cell. So that's where our first area of focus is and could lead to a broad number of potential opportunities. Beyond that, you know, we always remain open to partnering to answer that question. However, you know, we're continuing to progress with the plans that we have in place.

The other module is going to allow patients to take.

The drug 'twenty one on one.

On multiple doses over the.

The course of their consolidation cycle and that will enable us to repeat the PK later on during the cycle. So we can get steady state PK assessments to see lets see what the steady state levels are during dosing and then it'll also give us an opportunity to evaluate the safety with multiple doses. So one is a single dose module.

Kristen Stephens: Thank you. Thank you, Ted.

What is the multiple dose module.

So it looks like Theres actually two single dose modules.

Philip M. Nadeau: Thank you. Our next question comes from the line of Phil Nadeau from Cowan & Company. Your line is now open.

Maybe I'm reading this correctly, but the secrets wanted sequence too or are you testing two different doses of 21 O one or.

Philip M. Nadeau: Good morning. Thanks for taking our questions. A couple from us.

I have to go back to look at how it's written in the clinical trials, but I believe the.

Philip M. Nadeau: First, on the SELECT-AML1 trial for timibaritine, you indicated the data will be out next year. Is that the initial data from the safety lead-in portion of the study, or will the initial data also include results from the randomized portion? Thanks for that question.

The sequence is refer to whether someone gets the oral or the IV first or second I got it okay.

And then.

In terms of the multiple there. So you mentioned it looks like patients will only get 21 I'm wondering.

David A. Roth: So the trial, as you know, is now enrolling, and we're anticipating initial data in 2022. We're starting with a safety lead-in, and that will likely be the focus of the initial data, which would include safety and tolerability and may also include clinical activity. And so that's what you can look forward to.

The first cycle is that is that correct. They won't be able to go on to receive 21 O one and subsequent cycles.

So basically you have to go back to IV.

Thank you.

Yes, so the patients or are undergoing.

Induction and consolidation.

Standard of care IV and Acura.

And they will be participating during their consolidation pieces during the time when they wouldn't be getting the IV arsenic.

David A. Roth: That's helpful. And then on the 2101 dose confirmation study... Looking at the entry in clinicaltrials.gov, I guess there's a couple things that are confusing to me. It looks like there are two PK sequences that, at least according to clinicaltrials.gov, are exactly the same. What is the difference between PK module sequence one and PK module sequence two? Are those two different doses of 2101, or is there not? There's some other difference that's not obvious from clinicaltrials.gov. Yeah, so again, that's another good question.

So we'll be able to include them in the study.

Along the course of their normal standard of care treatment.

And when they finish their study procedures. They can go back to continue getting their standard of care treatment with the IV.

Perfect. Thanks, again for taking my questions.

Thanks Bill.

Thank you. Our next question comes from the line of Jason Butler from JMP Securities. Your line is now Hi, Hi.

Hi, Thanks for taking the questions and I appreciate all the updates just to follow up on the 21 O. One can you just review for US the most important parameters of the PK profile that you're focused on here, obviously, you mentioned steady state AUC.

T Max and <unk> also matter here and then I have a follow up thanks.

David A. Roth: So one of the objectives of the study is to evaluate the PK profile of 2101 after it's administered orally. And we're going to be doing a single dose of 2101 in the fasted state, as well as in the fed state. And that will enable us to compare the PK effects of absorption of the drug. We're also going to do a PK following IV. And that will enable us to compare the PK of the oral to the IV directly in the same patient.

Sure so the PK parameters and just to remind you.

This drug has already been evaluated in a phase one study in non APL patients patients, who had Mds AML and CML.

And the.

The PK was assessed using the standard parameters, which C Max and AUC and it has already been shown that.

The drug can be administered and achieve equivalent exposures relative to IV arsenic basically repeating many of those procedures and APL patients using a direct crossover comparisons just to firm up our understanding of what the go forward doses using similar types of analysis and then we'll be able to start the <unk>.

David A. Roth: So it's a very important experiment. The other module is going to allow patients to take the drug 2101 at multiple doses over the course of their consolidation cycle, and that will enable us to repeat the PK later on during the cycle.

Registration trial in 2022.

David A. Roth: So we can get steady-state PK assessments to see what the steady-state levels are during dosing, and that'll also give us an opportunity to evaluate the safety with multiple doses. So one is a single dose module, and one is a multiple dose module. It looks like there are actually two single-dose modules. Maybe I'm reading this incorrectly, but there's sequence one and sequence two.

Got it Okay and then.

Can you give us an update on progress with the select Mds trial is everything ramping there the way you had expected.

Yes, so the select AML and Mds trial are both remaining on track, we're pleased with the progress and we remain on target to our guidance.

Great. Thanks for taking the questions.

Thanks, Jason.

Thank you. Our next question comes from the line.

Of Mark Breidenbach from Oppenheimer. Your line is now open.

Hey, good morning, and thanks for taking the questions.

David A. Roth: Are you testing two different doses of 2101 or? Well, I have to go back and look at how it's written in the clinical trials, but I believe the sequences refer to whether someone gets the oral or the IV form first or second. I got it, okay.

Just wondering with respect to the $56 nine expansion in Teaneck. If there is any specific reason for initially going after patients who received the full purion <unk> and the first one and then doing your combinations with <unk>.

So either being in the second line versus the other way around and another question I had is just with respect to the nomination of your next development candidate in 2022 is that potentially going to be associated with a milestone payment under our collaboration with GBT. Thanks for taking the questions.

David A. Roth: And then, in terms of the multiple dose that you mentioned, it looks like patients will only get 2101 during the first cycle. Is that correct? They won't be able to go on and receive 2101 in subsequent cycles. They'll basically have to go back to IV ATO.

Yes, so the answer the first question around <unk>.

Pancreatic cancer expansion. So we're starting focused in the second line. This is an area of tremendous unmet need if you think about the only approved second line therapy has a PFS of approximately three months.

In addition, we have preclinical data that support synergy with Gemcitabine and so this is a place in which we really are leveraging what we know about the underlying biology.

David A. Roth: Yeah, so the patients are undergoing induction and consolidation with standard of care IV and Astra. And they'll be participating during their consolidation phases during the time when they wouldn't be getting the IV RCA. So we'll be able to include them in the study along the course of their normal standard of care treatment. And when they finish their study procedures, they can go back and continue getting their standard of care treatment. Perfect.

The mechanistic data as well as the clinical data and preclinical data that we've generated and so this gives us an opportunity for a data readout that we think will have very clear next steps.

So that's a little bit of the rationale and.

As that continues to progress we could consider moving into the frontline, but our first focus will be in the second line, where the greatest unmet need.

In terms of partnering.

D C I'm going to turn that back to Nancy.

Thanks, Mark So we are.

Continuing to guide to having our next development candidate next year in 2022.

We have multiple programs in preclinical development, we set our most advanced is our CDK 12 program and at this point in time, we haven't.

Jason Nicholas Butler: Thanks again for taking my questions. Thanks, Phil. Thank you. Our next question comes from the line of Jason Butler from JMP Securities. Your line is now open.

Sort of.

Communicated what the development candidate will be but by having a portfolio of programs and preclinical it allows us to be able to select the one that we think is best to move forward at that at that point in time, so stay tuned for that.

Okay Super helpful. Thank you.

Okay.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw.

David A. Roth: And then I have follow-up. Sure. So, the PK parameters, and just to remind you, this drug has already been evaluated in a phase one study in non-APL patients, patients who had MDS, AML, and CMML, and the PK was assessed using the standard parameters with CMAX and AUC, and it's already been shown that the drug can be administered and achieve equivalent exposures relative to IV arsenic.

To your question.

King.

Our next question comes from the line of Gela from Roth Capital Partners. Your line is now open.

Good morning, Thanks for taking my questions. The first one I have here is on $14 25, a follow up to Phil's question, just trying to understand.

How much data, we're going to see or is it something where we're just going to be looking at initial safety and maybe some biomarker all we're going to have substantial patient numbers at the valley kind of understand I. Just know people get excited when you have any kind of combo study with vanilla class I, just kind of wanted to help set expectations for that.

David A. Roth: And we're basically repeating many of those procedures in APL patients using direct crossover comparisons just to firm up our understanding of what the go-forward dose is using similar types of analyses. And then we will be able to start the registration trial in 2020. Okay, and then can you give us an update on progress with the select MDS trial? Is everything ramping up there the way you'd expected? Yeah, so the SELECT-AML and MDS trials are both remaining on track.

Yes, It does as David said earlier, you know we we.

<unk> the trial.

Last quarter, we're very excited about the opportunity for combining <unk> with Ben Asa, We think that based on the set of biology and the data that we have with our Etame in Asia we.

David A. Roth: We're pleased with the progress, and we remain on target with our guidance. Great, thanks for taking the question. Thanks, Jason. Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer. Your line is now open. Hey, good morning, and thanks for taking the questions. I'm just wondering, with respect to the 5609 expansion in PDAC, if there's any specific reason for initially going after patients who received fulfironox in the first line and then doing your combinations with gemcitabine in the second line versus the other way around.

We have the real potential of being oral targeted drive a real potential to add benefit to those patients and at this point in time, we're guiding to initial data next year, we're starting that trial with a safety lead in but both drugs are given out there sort of full doses during that safety lead in and will present.

All of the data that we have next year, which will include safety and clinical activity from the patients that we've enrolled at the time.

David A. Roth: And another question I had is, just with respect to the nomination of your next development candidate in 2022, is that potentially going to be associated with a milestone payment under your collaboration with GDP? Thanks for taking the questions.

Thanks, and then the next one year, it's about the APL program.

I've been kind of thinking that you know this is gonna be a pretty big deal getting that those companies and got out because I think a kit.

Hum that expectations mildly Ralph boy. The actual study. So I was just wondering you know how are you guys thinking about interpretation of the results from the dose confirmation study and how that may influence the outcome of the actual study full study.

Mark Alan Breidenbach: Yeah, so to answer the first question around:

Kristen Stephens: and our Pancreatic Cancer Expansion. So we're starting focused on the second.

Kristen Stephens: This is an area of tremendous unmet need if you think about the only approved second.

Kristen Stephens: If you think about it, the only approved second-line therapy has a PFS of approximately three months. In addition, you know, we have preclinical data that supports synergy with gemcitabine. And so this is a place where we really are leveraging what we know about the underlying biology and the mechanistic data, as well as the clinical data and preclinical data that we've generated. And so this gives us an opportunity for a data readout that we think will have very clear next steps.

Yeah, I mean, I think it's as David said earlier.

We already have data with 21 O. One that it is orally bio available and that it shows sort of comparable PK parameters to IV the historic IV data and so in some ways. This next date.

Data set and it's really to hone in on the exact dose that we want to take into the phase III trial that we expect to start next year.

Kristen Stephens: So that's a little bit of the rationale, and, you know, as that continues to progress, we could consider moving into the front line, but our first focus will be on the second line, where there's the area that's greatest in that need. In terms of DC, I'm going to turn that back to Nancy. Thanks, Mark.

So we think that it's not a question of will we be able to find something to move into phase III in terms of just what what is the best dose to take forward and so we're very excited about the fact, we started that trial were already gathering data and that's what we're on track to initiate the phase III next year and.

Nancy A. Simonian: So, we are continuing to guide to having our next development candidate next year in 2022. You know, we have multiple programs in preclinical development. We said our most advanced is our CDK-12 program. And at this point in time, we haven't yet sort of communicated what the development candidate will be. But by having a portfolio of programs in preclinical, it allows us to be able to select the one that we think is best to move forward at that point in time. So, stay tuned for that.

A lot of enthusiasm for the opportunity for this to to make a big difference for patients.

Thanks, Nancy and I'm, just kind of much my last two questions here to save time by 56 or nine I know there is a bit tricky question, but was just curious as to how you're viewing the probability of success of this program in solid versus liquid tumors and then the last thing is just about your pipeline any.

Comment on indications for either candidate that could be nominated and then also trying to understand them.

Nancy A. Simonian: Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Our next question comes from the line of Zegbe Jalaa from Roth Capital Partners. Your line is now open. Good morning. Thanks for taking my questions. The first one I have here is at 1425.

There was any update on Atlas with D. D. T. I know you guys I noticed the milestone payments I was just wondering.

How things are going there and then I think that my time. This should be program is no longer ongoing so I think the first Stuart pop it up okay.

Okay, Let me make sure we get those so I think your first question was on.

How do we think about probability of technical success for $56 nine and a solid versus the heme space.

Zegbe Jalaa: A follow-up to Phil's question, just trying to understand how much data we're going to see, or is it something where we're just going to be looking at initial safety and maybe some biomarkers, or are we going to have substantial patient numbers to really kind of understand? I just know people get excited when you have any kind of combo study with another class. I just kind of want to help set expectations for that.

And here I would say I mean, one of the things that we've known we've been working on CDK seven inhibition from the time that we started the company.

We've explored.

<unk> seven inhibition pre clinically in both hematologic cancers, as well as solid tumors and we've seen a high degree of activity both in heme tumors and in solid tumors and we've always had an interest in both.

David A. Roth: Yes, as David said earlier, you know, we initiated the trial this last quarter. We're very excited about the opportunity to combine tamibaritine with benaza.

David A. Roth: We think that based on the sort of biology and the data that we have with tami and aza, we have the real potential for being an oral targeted drug, the real potential to add benefit to those patients. And at this point in time, we're guiding to initial data next year. We're starting the trial with a safety lead-in, but both of the drugs are given at their sort of full doses during that safety lead-in.

And so I think what they looked at sort of the biology the mechanism. The preclinical data we think that there is.

Very good possibility for making a difference in bulkier tumors and in solid tumors. When we initiated the program, we decided to focus on one which was in solid tumors.

David A. Roth: And we'll present, you know, the data that we have next year, which will include safety and clinical activity from the patients that we've enrolled at the time. Thanks, and then the next one here is about the APL program.

But now that we have that data and see sort of encouraging biologic activity and clinical activity and a good a good biomarker and a better sense of where might be the best place to take it in heme tumors related to the RB pathway alterations that really has opened up the door for us to know sort of some simultaneous they explored it.

Nancy A. Simonian: I've been kind of thinking that, you know, this is going to be a pretty big deal, getting that dose confirmation data, because I think it could help set expectations really well for the actual study. So, I was just wondering, you know, how are you guys thinking about interpretation of the results from the dose confirmation study and how that may influence the outcome of the actual study? Yeah, I think, as David said earlier, we already have data with 2101 that it is orally bioavailable and that it shows sort of comparable PK parameters to IV, the historic IV data.

Clinics, so I guess I'd say, we like both the opportunities and we think that they are just the also the starting out points for a greater exploration and a variety of solid tumors. So.

I'd answer I'd, we'd like we'd like both a lot.

Hum.

Eric maybe you want to take the question on G. B T and also talk a little bit about the Myotatic dystrophy program much it's continuing outgoing but Eric.

Nancy A. Simonian: And so in some ways, this next data set is really to hone in on the exact dose that we want to take into the phase three trial that we expect to start next year. So we think that it's not a question of, you know, will we be able to find something to move into phase three in terms of just what is the best dose to take forward. And so we're, you know, very excited about the fact that we have started that trial.

Yeah. Thanks for the question and of course, our sickle.

Sickle cell program and type one my atonic dystrophy programs are really built around our expertise and kind of understanding the levers are the molecular levers that control the expression of specific genes and these are both diseases, where we know exactly what Jean we need to modulate.

Nancy A. Simonian: We're already gathering data, and we're on track to initiate phase three next year and, you know, a lot of enthusiasm for the opportunity for this to make a big difference for patients. Thanks, Nancy, and I'm just going to merge my last two questions here to save time. For 5609, I know that's a bit of a tricky question, but we're just curious as to how you view the probability of success of this program in solid versus liquid tumors. And then the last bit here is just about your pipeline. Any comment on indications for the candidates that could be nominated?

The expression of in order to.

Hopefully have a therapeutic benefit.

Benefit.

So both of those programs as you know our R. R.

Our preclinical and discovery stage and very active very.

Very active chemistry programs and.

Stay tuned for further updates in terms of the sickle cell program. It's a collaboration with GBT and of course, they will be primarily responsible for communicating and updating our progress on on that program, but we're quite pleased with the.

With the with the kind of platform, we built for each of those diseases in the chemistry approaches were taking.

Zegbe Jalaa: And then also try to understand if there's any update on efforts with DVT. I know you guys noted some milestone payments. I was just wondering how things are going there. And then I think that the myotonic dystrophy program is no longer ongoing, so I think the first two are probably the most likely. Okay, let me make sure I'll get those.

Thanks for taking my questions and looking forward to the updates in 2022.

Thanks Heiko.

Yeah.

Thank you at this time I'm showing no further questions I would like to turn the call back over to Nancy Simonian for closing remarks.

Thank you operator, and thank you everyone for joining us today. We appreciate your continued support this.

This is a very exciting period for serious and we look forward to providing further updates on our progress as we continue to advance to a fully integrated biopharmaceutical company with a portfolio of targeted medicines in cancer and monogenic diseases. Please reach out to us if you have any additional questions and have a wonderful day.

Nancy A. Simonian: So I think your first question was, how do we think about the probability of technical success for 5609 in the solid versus the heme space? And, you know, here I would say, I mean, one of the things that we've known is that we've been working on CDK7 inhibition from the time that we started the company. We've explored CDK7 inhibition preclinically in both hematologic cancers as well as solid tumors, and we saw a high degree of activity both in heme tumors and in solid tumors.

This concludes today's conference call. Thank you for participating you may now disconnect.

Okay.

[music].

Nancy A. Simonian: And we've always had an interest in both. And so I think if we looked at sort of the biology, the mechanism, the preclinical data, we think that there is, you know, a very good possibility of making a difference in both heme tumors and in solid tumors. When we initiated the program, we decided to focus on one, which was in solid tumors. But now that we have that data and see sort of encouraging biological activity and clinical activity and a good biomarker and a better sense of where might be the best place to take it in heme tumors related to the RB pathway alteration, that really has opened up the door for us to now sort of simultaneously explore it in the clinic.

Nancy A. Simonian: So I guess I'd say we like both opportunities, and we think that they are just also the starting points for greater exploration in a variety of solid and heme tumors. So I'd answer, we'd like both a lot. Eric, maybe you want to take the question on GBT and also talk a little bit about the myotonic dystrophy program, which is continuing, and ongoing, but Eric? Yeah, thanks, Zegba, for the question.

Eric Olson: And of course, our... Sickle Cell Program, type 1 myotonic dystrophy programs are really built around our expertise in, And understanding the levers, the molecular levers that control kind of the expression of specific genes. And these are both diseases where we know exactly what genes. We need to modulate, the expression of in order to hopefully have a therapeutic benefit. So both of those programs, as you know, are.., preclinical in the discovery stage and very active, very active chemistry programs and you know stay tuned for further updates in terms of the sickle cell program you know it's a collaboration with GBT and Of course, they will be primarily responsible for communicating and updating progress on that program, but we're quite pleased with the, The kind of platform we've built for each of those diseases and the chemistry approach, Thanks for taking my questions and looking forward to the updates in 2022.

[music].

Operator: Thank you. At this time, I'm showing no further.

Operator: I'm showing no further questions. I would like to turn the call back over to Nancy Simonian for closing remarks. Thank you, Operator, and thank you, everyone, for joining us today. We appreciate your continued support. This is a very exciting period for Syros, and we look forward to providing further updates on our progress as we continue to advance to become a fully integrated biopharmaceutical company with a portfolio of targeted medicines for cancer and monogenic diseases.

Nancy A. Simonian: Please reach out to us if you have any additional questions, and have a wonderful day. This concludes today's conference call. Thank you for participating. You may now disconnect.

Operator: © BF-WATCH TV 2021 ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ??

Operator: Good day, and thank you for standing by. Welcome to the Q3 2021 Syros Pharmaceuticals

Operator: Irving's conference call. At this time, I'll

Operator: Participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded.

Operator: Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Courtney Solberg from Syros. Please go ahead. Thank you. This morning, we issued a press release with our third quarter 2021 financial results, along with anticipated future milestones and recent accomplishments.

Courtney Solberg: This release is available in the Investors and Media section of Syros' website at www.syros.com.

Courtney Solberg: We will begin the call with prepared remarks by Dr. Nancy Simonian.

Courtney Solberg: Chief Executive Officer, Dr. David Roth, Chief Medical Officer, Kristen Stephens, Chief

Courtney Solberg: Corey D. Miller, our Chief Development Officer, and Jason Haas, our Chief Financial Officer. We will then open the call for questions. Dr. Eric Olson, our Chief Scientific Officer, and Conley Chee, our Chief Commercial Officer, are also on the call and will be available for Q&A.

Courtney Solberg: We specifically disclaim any obligation to update or revise any such Materials.

Courtney Solberg: to update or revise any forward-looking statements. I would now like to turn the call over to Nancy. Thank you, Courtney.

Good day, and thank you for standing by and welcome to the Q3 2020 once he Rose Pharmaceuticals, Inc. Earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.

To ask a question during the session you will need to watch star one on your telephone. Please be advised that today's conference is being recorded.

Nancy A. Simonian: We are excited to have them on board. Importantly, as David and Kristen will review shortly, we made tremendous progress across both our hematology and CDK7 portfolios. In September, we dosed the first patient in our Select AML-1 Phase 2 trial of Tamibaratine and Rara-positive unfit AML patients, and the first patient in our dose confirmation study of FY2101 in newly diagnosed APL patients. These milestones showcase our team's commitment to quickly advance medicines that have the potential to offer new standards of care for patients with hematologic cancer.

If you require any further assistance. Please press star zero I would like to hand, the conference or to your speaker today, Courtney So Burke with tea Rose. Please go ahead.

Thank you. This morning, we issued a press release with our third quarter 2021 and annual results along with anticipated future milestones and recent accomplishments.

That's really used it's available on the investors and media section of cirrhosis web site at Www Dot Dot Dot Com you will begin the call with prepared remarks by Doctor Nancy Simonian, Our Chief Executive Officer, Dr. David Roth, Our Chief Medical Officer.

Christian Stephens, our Chief Development Officer, and Jason Haas, Our Chief Financial Officer, We will then open the call for a question Doctor, Eric Olson, our Chief Scientific Officer, and Connie Qi, Our Chief Commercial officer are also on the call and will be available for Q&A.

Before we begin I would like to remind everyone that statements. We make on this conference call include or looking statements.

David A. Roth: To start, I will discuss the designs of the TAMI-Baratin Select AML-1 phase 2 and the SY-2101 Dose Confirmation Phase 1 trials in AML and APL, respectively, as well as the unmet need for each indication. Our SELECT-AML1 randomized phase 2 trial is now ongoing and aims to evaluate the triplet combination of tamibaritine, venetoclax, and azac The trial begins with a single-arm safety lead-in followed by a randomized portion that will evaluate the safety and efficacy of the triplet regimen compared to the combination of venetoclax and azacitin in approximately 80 patients randomized one-to-one. The primary endpoint of the trial will evaluate the composite CR rate, and we expect to announce initial data in 2022. There remains a tremendous unmet need in AML despite recent advances in the field.

On Form 10-Q that were filed this morning.

And any other filings that we make with the S E C in the future.

And in particular, the extent to which the COVID-19 outbreak continues to impact our operations and those of the third parties, which we rely or depend on future developments, which are highly uncertain and cannot be predicted with confidence.

I would now like to turn the call over to Nancy.

Thank you Courtney.

The third quarter of 2021 was extremely productive for cerus as we continue to execute towards our three strategic priorities that we laid out in the beginning of the year.

David A. Roth: Nearly one-third of patients do not respond to the standard of care and have a poor prognosis, and a majority of those with initial, ultimately relapse. A new treatment option that provides durable benefit and is well-tolerated and convenient is what patients are looking for and need. Additionally, in September, we dosed the first APL patient in our dose confirmation study of 2101, which is our novel form of arsenic trioxide, or ATO.

We are leveraging our leadership and expertise to build a synergistic portfolio where success in one program can inform and benefit efforts at another.

This quarter, we made two new strategic hires.

Adding additional strength to our experienced leadership team as we prepare for two expected N D as in 2024.

In September we appointed Connolly Chi, it's our first chief commercial officer, bringing 20 years of pharmaceutical sales leadership marketing and strategy experience.

In October Jason Haas joined Cerus, as our new Chief Financial officer, bringing more than 25 years of health care investment banking and corporate finance experience. We are excited to have them on board.

Importantly, as David and Christian will review shortly we made tremendous progress across both our hematology and CDK seven portfolios in.

David A. Roth: We expect to report dose confirmation and PK data in the first half of 2022, and we expect to initiate a Phase 3 trial in 2022. There are approximately 2,000 APL patients diagnosed annually in the United States and Europe. Thus, an oral treatment presents a significant market opportunity.

In September we dose the first patient in our select AML, one phase two trial of <unk> in RARA positive unfit AML patients and the first patient in our dose confirmation study of FY 'twenty, one O one in newly diagnosed APL patients.

These milestones showcase our team's commitment to quickly advance medicines that have the potential to offer new standards of care for patients with hematologic cancers.

Become a transformative targeted therapy.

With that I'd like to turn the call over to David who will review our progress across our hematology and CDK inhibitor programs in more detail.

Thank you Nancy.

To start I will discuss the design of the Tommy parity select AML, one phase two and the FY 'twenty 101 dose confirmation phase one trials in AML and APL, respectively, as well as the unmet need of each indication.

Our select AML, one randomized phase II trial is now ongoing and aims to evaluate the triplet combination of Tony balancing genetic lax and Asus hydrogen in RARA positive newly diagnosed unfit AML patients.

David A. Roth: 54 patients were treated with single agent 5609 and were evaluated for safety analyses, and 45 were valuable for clinical response analysis. The majority of adverse events were low-grade and reversed. The most frequent treatment-emergent adverse events were GI-related, fatigue, thrombocytopenia, and anemia. Across the study, there were low rates of discontinuation due to adverse events. Tolerability was optimized with the seven-day on, seven-day off dosing rate, which had the lowest rates of treatment emergent AIDS, and this regimen also demonstrated clinical activity consistent with that of other regimens. These data support the advancement of the 7-day on, 7-day off regimen in future states.

Proximately 80 patients randomized one to one.

The primary endpoint of the trial will evaluate the composite CR rate and we expect to announce initial data in 2022.

There remains a tremendous unmet need in AML. Despite recent advances in the field.

Nearly one third of patients do not respond to the standard of care.

Poor prognosis and a majority of those with initial response ultimately relapse.

A new treatment option that provides durable benefit and is well tolerated and convenient here's what patients are looking for and need.

David A. Roth: We were very encouraged to see single-agent clinical activity, particularly given that our study enrolled heavily pre-treated patients, many with tumor types that are commonly refractory to treatment. In total, 13 of 45 response-evaluable patients achieved stable disease across multiple tumors. Of these 13 patients, 6 had tumor regressions of up to 20%. Stable disease was observed in patients treated with both the daily and the intermittent regimens, including the 7-day on, 7-day off regimen, at doses as low as 3 milligrams per day.

Additionally in September we dosed the first APL patients in our dose confirmation study of 21 to one which is our novel form of arsenic trioxide or ACO.

The study is expected to enroll up to 24 newly diagnosed APL patients and aims to evaluate the safety Tolerability and pharmacokinetics of 21 to one.

Patients will be enrolled during the consolidation phase of their APL treatment for PK assessments of single doses of 20, <unk> hundred one in a fasted and fed state to evaluate absorption effects on PK.

David A. Roth: Notably, we observed the strongest clinical activity in pancreatic cancer patients. 5 of 13, or over 38%, of response-available patients with pancreatic cancer achieve stable disease, including two with tumor shrinkage. Additionally, decreases were seen in clinically relevant tumor markers that are typically used in the clinic to monitor disease progression, including decreases in three of four or 75% of the pancreatic cancer patients with serial tumor markers. Nearly all pancreatic cancer patients are highly refractory to existing therapies, which makes these data particularly compelling.

Ivy ACO to compare oral to IV directly.

Patients will then have the option to enter multiple dose cohorts to provide additional steady state PK and safety data.

We expect to report dose confirmation and PK data in the first half of 2022 and we expect.

To initiate a phase III trial in 2022.

There are approximately 2000 APL patients diagnosed annually in the United States and Europe, Thus, an oral treatment presents a significant market opportunity.

The IV formulation of <unk> in combination with Natura is approved for use in newly diagnosed APL and as curative and more than 80% of patients. However, there is a tremendous treatment burden associated with the standard of care requiring up to 140 <unk> infusions over a 10 month course of induction and consolidate.

Treatment.

Offering a new therapeutic option that is oral delivers similar clinical benefit and dramatically reduces the treatment burden has the potential to provide a tremendous benefit to these patients and improve their quality of life.

Now turning to our CDK inhibitor portfolio.

We recently presented at ESMO, our updated phase one dose escalation data of $56 nine.

Patients were treated in cohorts exploring continuous daily dosing as well as intermittent dosing regimens.

As a reminder, the trial is enrolling patients with advanced breast colorectal lung ovarian and pancreatic cancer as well as other tumor types with RB pathway alterations.

David A. Roth: Additionally, as part of our ongoing study, we analyzed the degree of Pol-R2a induction, which showed high correlation between target region response as assessed by resist criteria. This data is important as it demonstrates the value of Pol-R2a as a PD biomarker of clinical response to CDK7 target inhibition with 56. Additionally, we observed sustained PD effects to the desired target levels that lasted at least three days after dose suspension, showing that CDK7 target coverage can last long after the time when the drug is not taken.

As of the July data cutoff.

Four patients were treated with single agent <unk> 56.

And were evaluated for safety analyses and 45 were Evaluable for clinical response analyses.

The majority of adverse events were low grade and reversed.

The most frequent treatment emergent adverse events were Gi related fatigue, thrombocytopenia and anemia and across the study there were low rates of discontinuation due to adverse events.

Tolerability was optimized with the seven day on seven days off dosing regimen, which had the lowest rates of treatment emergent aes and this regimen also demonstrated clinical activity consistent with that of other regimens.

David A. Roth: This supports our confidence that we have a critical biomarker that is associated with anti-tumor activity. Additionally, the data supports the use of intermittent dosing schedules to optimize tolerability, setting the stage for long-term administration in our go-forward combination plans in various indications. I'd now like to turn the call over to Kristin to discuss our planned next steps for 5609.

These data support the advancement of the seven day on seven days off regimen in future studies.

We were very encouraged to see single agent clinical activity, particularly given that our study enrolled heavily pretreated patients. Many with tumor types that are commonly refractory to treatment.

In total $13 45 response, evaluable patients achieved stable disease across multiple tumor types.

Kristen Stephens: Thanks, David. As we've previously mentioned, we plan to pursue a three-pronged combination strategy for 5609, focusing on indications with high

Of these 13 patients six had tumor regression of up to 20%.

Stable disease was observed in patients treated with both daily and the instrument and regimens, including the seven day on seven day off regimen at doses as low as <unk> three milligrams per day.

Kristen Stephens: I am at need, as well as where there are strong rationales based upon available mechanistic, preclinical, and clinical data. As David alluded to earlier, pancreatic cancer represents an area of tremendous unmet need as the only approved second-line therapy offers a progression-free survival of just three months. We plan to initiate our expansion trial with 5609 in combination with chemotherapy in the fourth quarter of this year. The trial is designed to include two arms, both of which will enroll patients with metastatic pancreatic cancer who have progressed following first-line treatment with Fulfurion.

Notably we observed the strongest clinical activity in pancreatic cancer patients.

Five of 13 or over 38% response, evaluable patients with pancreatic cancer achieved stable disease, including two with tumor shrinkage.

Additionally, decreases we're seeing in clinically relevant tumor markers that are typically used in the clinic to monitor disease progression, including decreases in three or four or 75% of the pancreatic cancer patients with serial tumor markers.

Nearly all pancreatic cancer patients are highly refractory to existing therapies, which makes these data are particularly compelling.

Kristen Stephens: One arm will explore the doublet regimen of 5609 in combination with gemcitabine, and the other arm will explore a triplet regimen of 5609 with gemcitabine and NAB-Paxil-Paxil. The endpoints for the study are safety and tolerability, as well as efficacy measures including disease control rate and progression-free survival. Next, I would like to discuss our second combination strategy in

Also across all patients in the trial, we saw the highest level of clinical activity in patients with K Ras mutations.

And in patients with RB pathway alterations.

K Ras mutations are potent stimulator of cell signaling and transcriptional programs for self cycle progression and are nearly ubiquitous in patients with pancreatic cancer.

Kristen Stephens: https://www.syrospharmaceuticals.com

Additionally, as part of our ongoing study we analyzed the degree of Paul <unk> induction, which showed high correlation between target region response as assessed by resist criteria.

This data is important as it demonstrates the value of Paul Archway has a PD biomarker of clinical response to CDK seven targeting tradition to six online.

Additionally, we observed sustained PD effects to the desired target levels that lasted at least three days after dosing suspension showing that CDK seven target coverage can last long after the time when the drug is not taken.

This supports our confidence that we have a critical biomarker that is associated with anti tumor activity.

Additionally, the data supports the use of intermittent dosing schedules to optimize tolerability.

Setting the stage for long term administration and our go forward compensation plans in various indications.

I would now like to turn the call over to Christie to discuss our planned next steps for 56 of them.

Thanks, David as we've previously mentioned we plan to pursue a three pronged combination strategy for 50 609, focusing on indications with high unmet need as well as where there is strong rationale based upon available mechanistic and preclinical and clinical data.

Kristen Stephens: have previously been treated with a BTK inhibitor.

As David alluded to earlier pancreatic cancer represents an area of tremendous unmet need as the only approved second line therapy offers a progression free survival of just three months.

Kristen Stephens: The endpoints for this study include safety and tolerability, as well as efficacy measures such as complete response rate, overall response rate, and progression-free survival. Additionally, at the upcoming December ASH meeting, we will be presenting pre-clinical data for 5609 as a single agent, as well as in combination with a BTK inhibitor in mantle cell lymphoma cells. Finally, I would like to discuss colorectal cancer, or CRC, which is one of the leading causes of mortality and morbidity in the world.

We plan to initiate our expansion trial with $56 nine in combination with chemotherapy in the fourth quarter of this year.

The trial is designed to include two arms.

Both of which will enroll patients with metastatic pancreatic cancer, who have progressed following first line treatment with full purion.

One arm will explore the doublet regimen of 50 609 in combination with Gemcitabine and the other arm will explore a triplet regimen of <unk> 50, 609, with Gemcitabine and Nab Paclitaxel.

Kristen Stephens: Although early diagnosis has significantly improved outcomes, many patients aren't diagnosed until the cancer has already metastasized to other parts of the body, making it very difficult to treat. Adding to the complexity is that different genetic mutations cause CRC to grow.

The endpoints for the study are safety and Tolerability as well as efficacy measures, including disease control rate and progression free survival.

Kristen Stephens: Mutations in the BRAF gene are found in about 10% of metastatic CRC patients and are associated with a particularly poor prognosis and a median survival of less than 12 months. As we announced in August, we recently entered into an agreement with Roche to explore 5609 in combination with atezolizumab in patients with D-RAF mutant CRC. Under the terms of this agreement, we will supply 5609 for a combination dose and cohort in their ongoing Phase 1, Phase 1b intrinsic trial. This marks the first clinical investigation of a CDK7 inhibitor with an immunotherapy that has the potential to demonstrate significant and broad opportunities for combinations of 5609 with immunotherapy and other important indications.

Next I would like to discuss our second combination strategy and mantle cell lymphoma, a subtype of B cell non hodgkin's lymphoma affecting approximately 10000 patients in the U S and EU.

This is a tumor that is driven by overexpression of cyclin D and RB pathway regulator and dependent on B cell receptor signaling and Nf Kappa B transcriptional program for survival and growth.

Most patients will eventually relapse after their first line treatment and the median survival is three to five years.

PTK inhibitors offer a non chemotherapy options for second line patients, but with reduced activity. After first line treatment.

Most patients relapse at which point they will have very limited treatment options and face poor outcomes.

We expect to initiate our phase one b trial in mantle cell lymphoma in the first half of next year.

This trial will begin with a safety evaluation of $56 nine as a single agent after which we'll move into a safety lead in in combination with a b TK inhibitor.

This will set the stage to move to combination with a <unk> inhibitor into an expansion phase in second line mantle cell lymphoma patients who have not previously been treated with a b TK inhibitor.

The endpoints for this study include safety and Tolerability as well as efficacy measures such as complete response rate overall response rate and progression free survival.

Additionally, at the upcoming December Ash meeting, we will be presenting preclinical data of $56 nine as a single agent as well as in combination with a <unk> inhibitor and mantle cell lymphoma cells.

Finally, I would like to discuss colorectal cancer or CRC, which is one of the leading causes of mortality and morbidity in the world.

Although early diagnosis has significantly improved outcomes many patients aren't diagnosed until the cancer is always metastasized to other parts of the body, making it very difficult to treat.

Adding to the complexity is that different genetic mutations cause CRC to grow.

Mutations in the BRAF gene are found in about 10% of metastatic CRC patients and are associated with a particularly dismal prognosis and a median survival of less than 12 months.

As we announced in August we recently entered into an agreement with Roche to explore 50 609 in combination with a table of the mab in patients with BRAF mutant CRC.

Under the terms of this agreement we will supply 50, 609 for a combination dosing cohort in their ongoing phase one phase one be intrinsic trial.

Jason Haas: We recognized revenue of $5.7 million in the third quarter compared to $3.8 million in the third quarter of 2020. This consisted of $5.6 million in revenue under our collaboration with Global Blood Therapeutics and $100,000 under our collaboration with Insight. In the third quarter of 2020, we recognized $3.5 million in revenue from our collaboration with GBT and $300,000 from our collaboration with Insight. R&D expenses were $27.3 million in the third quarter of 2021, compared to $17.7 million for the same period in 2020.

We look forward to providing additional updates as we progress in the clinic.

I'd now like to turn the call over to Jason Haas, Our Chief Financial Officer to review, our third quarter financial results.

Thank you Kristen working in partnership with the team over the past month I have already experienced firsthand the passion and share commitment that drives the team every day.

Could not be more excited to join them and ongoing efforts to develop new medicines that have the potential to provide profound benefit to patients.

Jason Haas: This increase was primarily due to the continued advancement of Syros' clinical and preclinical programs and an increase in employee-related expenses. DNA expenses were $5.3 million in the third quarter of 2021, compared to $5.2 million for the same period in 2020. Finally, we report a net loss for the third quarter of $26 million, or $0.41 per share, compared to a net loss of $19.5 million, or $0.43 per share, for the same period in 2020. With that, I will turn the call over to the operator for questions.

Now turning to our third quarter financial results <unk> continues to operate from a position of financial strength. We ended the third quarter with $166 $7 million in cash cash equivalents and marketable securities compared to $174 million as of December 31, 2020.

This reflects the cash used to fund our operations during the first nine months of 2021, partially offset by gross proceeds of $75 $6 million that <unk> received from our January 2021 public offering.

Based on our current plans, we believe we have sufficient capital to fund our planned operating expenses and capital needs into 2023 beyond multiple expected value drivers.

We recognized revenue of $5 $7 million in the third quarter compared to $3 8 million in the third quarter of 2020. This consisted of $5 $6 million in revenue under our collaboration with global blood Therapeutics and $100000 under our collaboration with insight.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the power...

In the third quarter of 2020, we recognized $3 $5 million of revenue from our collaboration with GBT and $300000 from our collaboration with insight.

Operator: If you have a question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Ted Tenthoff, Piper Sandler.

R&D expenses were $27 3 million in the third quarter of 2021 compared to $17 7 million for the same period in 2020.

Edward Andrew Tenthoff: Your line is now open. Great, thank you very much, and thank you for taking my call and congratulations on all the good updates. I wanted to focus on 5609 and the compelling data that you demonstrated at ESMO. How quickly do you think we could actually start to generate data from that? And I think it was very astute to kind of follow the data here. But are there other indications, or from pre-clinical results, is there anything else that might represent future opportunities? And then this last question here, with the focus...

This increase was primarily due to the continued advancement of cirrhosis clinical and preclinical programs and an increase in employee related expenses.

G&A expenses were $5 $3 million in the third quarter of 2021 compared to $5 2 million for the same period in 2020.

Finally, we reported a net loss for the third quarter of $26 million or <unk> 41 per share compared to a net loss of $19 $5 million or <unk> 43 per share for the same period in 2020.

With that I will turn the call over to the operator for questions.

Also a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.

Kristen Stephens: Thanks for the question, Ted. Kristen? Yes, thanks for the question. So we believe that 5609 has broad potential for a large variety of unmet needs.

Our first question comes from the line of Ted <unk>.

Kristen Stephens: So, we believe that 5609 has broad potential in a large variety of unmet needs cancers. That being said, we are taking a very focused approach in three distinct populations, pancreatic CRC, and mantle cell. So, that's where our first area of focus is and could lead to a broad number of potential opportunities. Beyond that, we always remain open to partnering to answer that question. However, we're continuing to progress with the plans that we have in place.

Sandler Your line is now open.

Great. Thank you very much.

Thank you for taking my call and congrats on all the good update.

I wanted to focus on parts of co Laurie.

The compelling data that you've.

Hum.

Sure.

How quickly do you think we could actually start to generate data from that.

I think it was various to kind of follow that through this year.

But are there other indications of support from preclinical results.

Anything else that might represent future opportunities and then just last question from here with a focus on the hematology, thus far as Chicago ultimately represent a partnering opportunity. Thank so much.

Okay.

Thanks for the question Ted Kristen.

Edward Andrew Tenthoff: Great, that's very helpful, makes a lot of sense, and I'm excited to see it continued. Thank you. Thank you, Ted.

Yeah, Ted Thanks for the question. So we believe that 50 690 <unk> Brian.

I'm in a large variety of unmet need kind of cancers.

That being said we are taking a very focused approach in three distinct populations pancreatic CRC in mantle cell. So.

Philip M. Nadeau: Thank you. Our next question comes from the line of Phil Nadeau from Cowan & Company. Your line is now open.

So that's where our first store area of the focus is and could lead to a broad number of potential opportunities.

Philip M. Nadeau: Good morning. Thanks for taking our questions. A couple from us.

And that we always remain open to partnering to answer that question.

However, we're continuing to progress forward the plans that we have in place.

Okay.

Great. That's very helpful. It makes a lot of sense and I'm excited to see.

Continued progress.

Thank you thank you Ted.

Yeah.

Thank you. Our next question comes from the line of Phil Nadeau from Cowen <unk> Company. Your line is now open.

Good morning, Thanks for taking our questions.

From us first on the select AML one trial for <unk>.

The data will be out next year is that initial data from the safety lead in portion of the study or with initial data also include.

Results from the randomized portion.

Thanks for that question.

The trial.

It is now enrolling and.

We are anticipating initial data in 2022.

We're starting with the safety lead in.

Philip M. Nadeau: That's helpful. And then on the 2101 dose confirmation study, looking at the data from clinicaltrials.gov, I guess there's a couple things that are confusing to me. It looks like there are two PK sequences that, at least according to clinicaltrials.gov, are exactly the same. What is the difference between PK module sequence one and PK module sequence two?

And that will.

Likely be the focus of the initial data, which would include safety and Tolerability and May also include clinical activity.

So that's what you can look forward to.

Perfect. That's helpful and then on the.

21 O one dose confirmation study.

Looking at the clinical trials Dot Gov.

Couple of things that are.

Confusing to me it looks like there's two PK sequences that at least the current clinical trials to talk over exactly the same.

David A. Roth: Are those two different doses of 21.01, or is there some other difference that's not obvious from clinicaltrials.gov? Yeah, so again, that's another good question.

What is the difference between PK module sequence one in PK module sequence two are those two different doses of 'twenty, one or is there.

Some other difference that that's not obvious from the Clinicaltrials Gov entry.

Yes. So again, it's another good question. So one of the objectives of the study.

Is to evaluate that.

PK profile of 21, one after it's administered orally and we're going to be doing.

A single dose of <unk> 21 on one.

In the fasted state as well as in the fed state and that will enable us to compare the PK.

Effects of absorption of the drug we're also going to do a PK following IV and that will enable us to compare the PK of the oral to IV directly in the same patient through some very important experiment.

David A. Roth: The other module is going to allow patients to take the drug 2101 at multiple doses over the course of their consolidation cycle, and that will enable us to repeat the PK later on during the cycle so we can get steady state PK assessments to see what the steady state levels are during dosing. And it'll also give us an opportunity to evaluate the safety of multiple doses. So one is a single dose module, and one is a multiple dose module.

The other module is going to allow patients to take.

Good drug 'twenty one on one.

On multiple doses over.

One is a multiple dose module.

David A. Roth: It looks like there are actually two single-dose modules. Maybe I'm reading this incorrectly, but there are Sequence 1 and Sequence 2. Are you testing two different doses of 2101 or...? Well, I have to go back and look at how it's written in the clinical trials, but I believe the sequences refer to whether someone gets the oral or the IV form first or second. Okay.

It looks like Theres actually two single dose modules.

Maybe I'm reading this correctly, but the sequence sequence too or are you testing two different doses of 'twenty, one or one or.

<unk>.

I have to go back to look at how it's written in the clinical trials, but I believe the the.

Sequences refer to whether someone gets the oral or the IV first or second.

Got it Okay and then.

David A. Roth: And then in terms of the multiple dose that you mentioned, it looks like patients will only get 2101 during... The first cycle, is that correct? They won't be able to go on and receive 2101 in subsequent cycles. They'll basically have to go back to IV ATO.

In terms of the multiple dose you mentioned it looks like patients will only get 201 during the.

The first cycle is that is that correct I won't be able to go on and received 21 O one and subsequent cycles.

So basically I have to go back to IV <unk>.

David A. Roth: Yeah, so the patients are undergoing induction and consolidation with standard of care IV and ATRA, and they'll be participating during their consolidation phases during the time when they wouldn't be getting the IVR. So we'll be able to include them in the study along the course of their normal standard of care treatment. And when they finish their study procedures, they can go back and continue getting their standard of care treatment.

Yeah.

Yes, so the patients or are undergoing.

Induction and consolidation.

Standard of care IV and Acura.

And they will be participating during their consolidation pieces during the time when they wouldn't be getting the IV arsenic.

So we'll be able to include them in the study.

Along the course of their normal standard of care treatment.

And when they finish their study procedures. They can go back to continue getting their standard of care treatment with the IV.

Philip M. Nadeau: Perfect. Thanks again for taking my questions. Thanks, Phil. Thank you. Our next question comes from the line of Jason Butler from JMP Securities. Your line is now open.

Perfect. Thanks, again for taking my questions.

Thanks Bill.

Thank you. Our next question comes from the line of Jason Butler from JMP Securities. Your line is now Hi, Hi.

Jason Nicholas Butler: Hi, thanks for taking the questions and I appreciate all the updates. Just to follow up on 2101, can you just review for us the most important parameters of the PK profile that you're focused on here? Obviously, you mentioned steady-state AUC. But did TMAX and CMAX also matter here? And then I have a follow-up. Sure. So, the PK parameters, and just to remind you, this drug has already been evaluated in a phase one study in non-APL patients, patients who had MDS, AML, and CMML, and the PK was assessed using the standard parameters with CMAX and AUC, and it's already been shown that the drug can be administered and achieve equivalent exposures relative to IV arsenic.

Hi, Thanks for taking the questions and I appreciate all the updates just to follow up on the 21 O. One can you just review for US the most important parameters and the PK profile that Youre focused on here, obviously, you mentioned steady state AUC.

<unk> also matter here and then I have a follow up thanks.

Sure so the.

The PK parameters and just to remind you. This this drug has already been evaluated.

Phase one study in non APL patients patients, who had Mds AML and CML and the.

The PK was assessed using the standard parameters, which C Max and AUC and it's already been shown that.

The drug can be administered achieve equivalent exposures relative to IV arsenic basically repeating many of those procedures and APL patients using a direct crossover comparisons just to firm up our understanding of what the go forward doses using similar types of analysis and then we'll be able to start the <unk>.

Jason Nicholas Butler: And we're basically repeating many of those procedures in APL patients using a direct crossover comparison just to firm up our understanding of what the go-forward dose is using similar types of analyses. And then we will be able to start the registration trial in 2020.

Registration trial in 2022.

David A. Roth: Yeah, so the SELECT-AML and MDS trials are both remaining on track. We're pleased with the progress, and we remain, you know, on target with our guidance.

Got it Okay and then.

Can you give us an update on progress with the select Mds trial is everything ramping there the way you had expected.

Yes, so the select AML and Mds trial are both remaining on track.

Pleased with the progress and we remain on target to our guidance.

Great. Thanks for taking the questions.

Mark Alan Breidenbach: Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer. Your line is now open. Hey, good morning, and thanks for taking the questions. Just wondering, with respect to the 5609 expansion in PDAC, if there's any specific reason for initially going after patients who received fulfirinox in the first line and then doing your combinations with gemcitabine in the second line versus the other way around. And another question I had is just with respect to the nomination of your next development candidate in 2022, is that potentially going to be associated with a milestone payment under your collaboration with GBP? Thanks for taking the questions.

Thanks, Jason.

Thank you. Our next question comes from the line.

Mark Breidenbach from Oppenheimer. Your line is now open.

Hey, good morning, and thanks for taking the questions.

Just wondering with respect to the $56 nine expansion in Teaneck. If there is any specific reason for initially going after patients who received <unk> in the first one and then doing your combinations with German side of being in the second line versus the other way around and another question I had is just with respect to the nama.

A nation of your next development candidate in 2022 is that potentially going to be associated with a milestone payment under our collaboration with GBT. Thanks for taking the questions.

Kristen Stephens: Yeah, so to answer the first question about our pancreatic cancer expansion, we're

Yes, so to answer the first question around.

Kristen Stephens: on Pancreatic Cancer Expansion. So we're starting focused on the second line. This is an area of tremendous unmet need. If you think about it, the only approved second-line therapy has a PFS of approximately three months. In addition, we have preclinical data that supports synergy with gemcitabine. And so this is a place in which we really are leveraging what we know about the underlying biology and the mechanistic data, as well as the clinical data and the preclinical data that we've generated. And so this gives us an opportunity for a data readout that we think will have very clear next steps. So that's a little bit of the rationale.

In addition, we have preclinical data that supports synergy with Gemcitabine and so this is a place in which we really are leveraging what we know about the underlying biology.

The mechanistic data as well as the clinical data and preclinical data that we've generated and so this gives us an opportunity for a data readout that we think will have very clear next steps.

So that's a little bit of the rationale.

Kristen Stephens: And as that continues to progress, we could consider moving into the front line, but our first focus will be on the second line, where there's the area of greatest unmet need. In terms of DC, I'm going to turn that back to Nancy. Thanks, Mark.

As that continues to progress we could consider moving into the frontline, but our first focus will be in the second line, whether it's the area of greatest unmet need.

Terms of partnering.

I'll now turn it back to Nancy.

Thanks, Mark So we are.

Continuing to guide to having our next development candidate next year in 2022.

We have multiple programs in preclinical development, we set our most advanced is our CDK 12 program and at this point in time, we haven't.

That sort of communicated.

Communicated what the development candidate will be but by having a portfolio of programs and preclinical it allows us to be able to select the one that we think is.

Best to move forward at the at that point in time, so stay tuned for that.

Okay Super helpful. Thank you.

Okay.

Operator: Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Our next question comes from the line of Zegbe Jala from Roth Capital Partners. Your line is now open. Good morning. Thanks for taking my questions. The first one I have here is on 1425. A follow-up to Phil's question, just trying to understand how much data we're going to see, or is it something where we're just going to be looking at initial safety and maybe some biomarkers, or are we going to have substantial patient numbers to really kind of understand? I just know people get excited when you have any kind of combo study with Vanetta Class. I just kind of want to help set expectations for that.

Thank you as a reminder to ask a question you will need to press star one on your telephone.

Joe Your question press the pound key.

Our next question comes from the line of Gela from Roth Capital Partners. Your line is now open.

Good morning, Thanks for taking my questions. The first one I have here is on.

On Fortune 25, a follow up to Phil's question, just trying to understand.

How much data, we're going to see or is it something where we're just going to be looking at initial safety and maybe some biomarker all we're going to have substantial patient numbers at the rally kind of understand I. Just know people get excited when you have any kind of combo study with vanilla class I, just kind of want to help the expectations for that.

Zegbe Jalaa: Yeah, Zegba, as David said earlier, you know, we initiated the trial this last quarter. We're very excited about the opportunity to combine Tamibaratine with Venazza. We think that based on the sort of biology and the data that we have with Tami and Aza, we have the real potential for being an oral targeted drug, the real potential to add benefit to those patients. And at this point in time, we're guiding to initial data next year.

Yes, It does as David said earlier, you know, we we initiated the trial.

Last quarter, we're very excited about the opportunity for combining <unk> with Ben Asa, We think that based on the set of biology and the data that we have with our Etame in Asia.

We have the real potential of being oral targeted drug a real potential to add benefit to those patients and at this point in time, we're guiding to initial data next year, we're starting that trial with a safety lead in but boats. Other drugs are given out there sort of full doses during that safety lead in and we will present.

Zegbe Jalaa: We're starting the trial with a safety lead-in, but both of the drugs are given at their sort of full doses during that safety lead-in. And we'll present the data that we have next year, which will include safety and clinical activity from the patients that we've enrolled at the time. Thanks, and then the next question here is about the APL program.

All of the data that we have next year, which will include safety and clinical activity from the patients that we've enrolled at the time.

Thanks, and then the next one year, it's about the APL program.

Nancy A. Simonian: I've been kind of thinking that, you know, this is going to be a pretty big deal, getting that dose confirmation data, because I think it could help set expectations really well for the actual study. So I was just wondering, you know, how are you guys thinking about interpretation of the results from the dose confirmation study and how that may influence the outcome of the actual study, folks? Yeah, I think, as David said earlier, we already have data with 2101 that it is orally bioavailable and that it shows sort of comparable PK parameters to IV, the historic IV data.

I've been kind of thinking that this is gonna be a pretty big deal getting that those compensation data because I think it could.

Hum that expectations really well for the actual studies. So I was just wondering how are you guys thinking about interpretation of the results from the dose confirmation study and how that may influence the outcome of the actual study full study.

Yeah, I mean, I think it's as David said earlier.

We already have data with 21 O. One that it is orally bio available and that it shows sort of comparable PK parameters to IV, the historic IV data and so in some ways. This next.

Data set and is really hone in on the exact dose that we want to take into the phase III trial that we expect to start next year. So we think that it's not a question of.

Will we be able to find something to move into phase III in terms of just what is the best dose to take forward and so we're very excited about the fact, we started that trial were already gathering data and that's what we're on track to initiate the phase III next year and.

A lot of enthusiasm for the opportunity for this to make a big difference for patients.

Thanks, Nancy and I am just kind of much my last two questions here to save time by 56 or nine I know there is a bit tricky question, but was just curious as to how you're viewing the <unk>.

Zegbe Jalaa: We're just curious as to how you view the probability of success of this program in solid versus liquid tumors. And then the last bit is just about your pipeline, any comment on indications for the candidates that could be nominated, and then also trying to understand if there's any update on efforts with DBT. I know you guys noted the milestone payments, so I was just wondering how things are going there. And I think the Myotonic Dystrophy Program is no longer ongoing, so I think the first two are probably the best. Okay. Let me make sure I'll get those.

Pablo the success of this program in solid versus liquid tumors and then the last thing is just about your pipeline any comment on indications for either candidate that could be nominated and then also trying to understand if there.

Any update on Atlas with JBT I know you guys I noticed the milestone payments I was just wondering.

How things are going there and then I think that my time. This should be program is no longer ongoing. So I think the first two are probably enough okay.

Okay. So let me make sure we get those so I think your first question was on <unk>.

Nancy A. Simonian: So I think your first question was, how do we think about the probability of technical success for 5609 in the solid versus the heme space? And, you know, here I would say, I mean, one of the things that we've known. We've been working on CDK7 inhibition from the time that we started the company. We've explored CDK7 inhibition preclinically in both hematologic cancers as well as solid tumors, and we saw a high degree of activity both in heme tumors and in solid tumors.

How do we think about probability of technical success for 50 609 in solid versus the heme space.

And here I would say I mean, one of the things that we've known we've been working on CDK seven inhibition from the time that we started the company we've explored.

CDK <unk> inhibition pre clinically in both hematologic cancers, as well as solid tumors and we've seen a high degree of activity both in heme tumors and in solid tumors and we've always had an interest in both.

And so I think what they looked at sort of the biology the mechanism. The preclinical data we think that there is.

A very good possibility for making a difference in both heme tumors and in solid tumors. When we initiated the program, we decided to focus on one which was in solid tumors.

But now that we have that data and see sort of encouraging biologic activity and clinical activity and a good a good biomarker and a better sense of where it might be the best place to take it in heme tumors related to the RB pathway alterations that really has opened up the door for us to know sort of simultaneously exploring.

Nancy A. Simonian: So I guess I'd say we like both opportunities and think that they are just also the starting points for greater exploration in a variety of solid and heme tumors. So I would answer, we like both a lot.

Our clinic, so I guess I'd say, we like both the opportunities.

Think that they are just the also the starting out points for a greater exploration and a variety of solid tumors. So.

I'd answer why we'd like we'd like both a lot.

Eric Olson: Eric, maybe you want to take the question on GBP and also talk a little bit about the myotonic dystrophy program, which is continuing, ongoing. But Eric? Yeah, thanks, Zegba, for the question. Of course, our... Sickle Cell Program and type 1 myotonic dystrophy programs are really built around our expertise in and understanding the levers, the molecular levers that control the expression of specific genes. And these are both diseases where we know exactly what gene.

On the Eric maybe you want to take the question on GBT and also talk a little bit about the Myotatic dystrophy program, which is continuing outgoing but Eric.

Yes. Thanks for the question of course are.

Sickle cell program and type one my iconic dystrophy programs are really built around our expertise and.

And understanding the levers the molecular levers that control the expression of specific genes and these are both diseases, where we know exactly what we need to modulate.

Eric Olson: We need to modulate the expression of these genes in order to hopefully have a therapeutic benefit. So both of those programs, as you know, are preclinical in the discovery stage and very active, very active chemistry programs, and stay tuned for further updates. In terms of the Sickle Cell Program, it's a collaboration with GBT, and of course, they will be primarily responsible for communicating and updating progress on that program.

The expression of in order to.

Hopefully have a therapeutic benefit.

Benefit.

So both of those programs as you know our R. R.

Our preclinical and discovery stage and very active.

Very active chemistry programs and.

Stay tuned for further updates in terms of the sickle cell program, it's a collaboration with GBT and and of course, they will be primarily responsible for communicating and updating our progress on on that program, but we're quite pleased with the.

Zegbe Jalaa: But we're quite pleased with the kind of platform we've built for each of those diseases and the chemistry approaches. Thanks for taking my questions and looking forward to the updates in 2022. Thanks, Rebecca. Thank you. At this time, I'm showing no further questions. I would like to turn the call back over to Nancy Simonian for closing remarks. Thank you, Operator, and thank you, everyone, for joining us today. We appreciate your continued support.

The with the kind of platform, we built for each of those diseases in the chemistry approaches were taking.

Thanks for taking my questions and looking forward to the updates in 2022.

Thanks Deborah.

Thank you at this time I'm showing no further questions I would like to turn the call back over to Nancy Simonian for closing remarks.

Thank you operator, and thank you everyone for joining us today. We appreciate your continued support.

Zegbe Jalaa: This is a very exciting period for Syros, and we look forward to providing further updates on our progress as we continue to advance to a fully integrated biopharmaceutical company with a portfolio of targeted medicines in cancer and monogenic diseases. Please reach out to us if you have any additional questions, and have a wonderful day. This concludes today's conference call. Thank you for participating. You may now disconnect.

This is a very exciting period for <unk> and we look forward to providing further updates on our progress as we continue to advance to a fully integrated biopharmaceutical company with a portfolio of targeted medicines in cancer and monogenic diseases. Please reach out to us if you have any additional questions and have a wonderful day.

This concludes today's conference call. Thank you for participating you may now disconnect.

Q3 2021 Syros Pharmaceuticals Inc Earnings Call

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