Q1 2021 Syros Pharmaceuticals Inc Earnings Call

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Good morning, and welcome to Zero Pharmaceuticals first quarter 2021 financial results Conference call. At this time all participants are in a listen only mode. This call is being a webcast life on the investor.

Operator: C. Rose Pharmaceuticals first quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode.

Operator: This call is being webcast live on the Investors and Media section of C-Rose's website at www.c.crowse.com. Please be advised that today's call is being recorded. Following these remarks, we will open the call up for your questions. At this time, I would like to turn the call over to Naomi Oki, Vice President of Corporate Communications and Investor Relations at C-Rose. Thank you.

And media section of see Rose website at W. W. Dot <unk> Dot com. Please be advised that today's call is being recorded following the formal remarks, we will open the call up for your questions. At this time I would like to turn the call over to Naomi Oaky, Vice President of corporate Communications and Investor Relations S. T Rose.

Thank you. This morning, we issued a press release with our first quarter 2021 financial results along with anticipated future milestones in recent accomplishment. This release is available on the investors and media section is terraces website at www Dot <unk> Dot com will.

Naomi Oki: This morning, we issued a press release with our first quarter 2021 financial results, along with anticipated future milestones and recent accomplishments. This release is available on the Investors and Media section of Seris's website at www.org. We'll begin the call with prepared remarks by Dr. Nancy Simonian, our chief executive officer, and Joe Farah, our chief financial officer. We'll then open the call to questions.

We will be getting a call with prepared remarks by a doctor Nancy Simonian, Our Chief Executive Officer, and Joe Sarah Our Chief Financial Officer will then open the call for question Doctor, David Roth, Our Chief Medical Officer, and Doctor, Eric Olsen, Our Chief Scientific Officer are also on the call and will be available.

For Q&A.

Before we begin on I would like to remind everyone that statements. We make on this conference call will include board looking statement actual events or resolved 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 for it and the risk.

Naomi Oki: Dr. David Roth, our chief medical officer, and Dr. Eric Olson, our chief scientific 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 will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors.

Doctors section of our annual report on form 10-K R. A quarterly report on form 10-Q that we buy on this morning and any other filings that we may make with Emt's day in the future in particular, the extent to which the COVID-19 outbreak continues to impact our operation and there was a third parties on which we.

Naomi Oki: Including those set forth in the risk factors section of our annual report on Form 10K, our quarterly report on Form 10Q that we filed this morning, and any other filing that we may make with the SEC in the future. In particular, the extent to which the COVID-19 outbreak continues to impact our operations and those of third parties on which we rely will depend on future developments that are highly uncertain and cannot be predicted with confidence.

Naomi Oki: 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 dates. We specifically disclaim any obligation to update or revise any forward-looking statements.

Nancy A. Simonian: I would now like to turn the call over to Nancy. Thank you, Naomi, and good morning, everyone. At Cirrus, we believe that people with cancers and monogenic diseases deserve better. At the heart of everything we do is our dedication to deliver new medicines that provide a profound benefit for patients with these difficult-to-treat diseases.

<unk> in higher risk Myelodysplastic syndrome.

Myeloid leukemia at acute promyelocyte leukemia.

Nancy A. Simonian: With that mission front and center, we are advancing a differentiated portfolio, and product candidates, each with the potential to set a new standard of care. We remain laser focused on executing against the strategy we laid out last year, with the aim of rapidly maturing Cirrus into a commercial stage company. That strategy is rooted in three priorities.

Together these programs position us for two potential new drug application filings and higher risk Mds and a T. L. In 'twenty 'twenty four with additional opportunities beyond that time frame.

We recently began dosing patients in our phase III clinical trial of 14 25 in combination with Azacitidine in RARA positive patients with newly diagnosed higher risk Mds.

The trial will compare the complete response rate of 14, 25, and eight deciding to placebo and he decided inc.

Nancy A. Simonian: Advancing a leading portfolio of targeted therapies for hematologic disorders, building on our leadership in selective CDK inhibition for difficult-to-treat cancers, and leveraging our foundational gene control discovery engine to fuel a robust and sustainable pipeline to support our long-term growth. Let me begin with our targeted chematology portfolio. We have two clinical stage programs, SI 1425 and SI201, for targeted patient populations and higher risk myeloplastic syndromes, acute myeloid leukemia, and acute promylacidic leukemia.

If successful the trial could enable an NDA filing in 2024.

The trial marks a tremendous milestone for syros is our first registration enabling study.

For patients with Mds, who remain woefully underserved despite advances in hematologic malignancies more broadly.

Hi from ethylene agents or Hma's, which are the existing standard of care for MDF provide limited efficacy and many patients continuing to suffer mortality and morbidity from deep disease related site opinions.

Nancy A. Simonian: Together, these programs position us for two potential new drug application filings in higher risk MDS and APL in 2024, with additional opportunities beyond that time. We recently began dosing patients in our phase three clinical trials of 1425 in combination with asocytidine and RARA positive patients with newly diagnosed higher risk MDF. The trial will compare the complete response rate of 1425 with aza cytidine and placebo and aesitidine. If successful, the trial could enable an NDA filing in 2024.

Nancy A. Simonian: The trial marks a tremendous milestone for Syros as our first registration enabling study, and for patients with MDF who remain woefully underserved despite advances in hematologic malignancies more broadly. However, hypoethylating agents, or HMAs, which are the existing standard of care for MDS, provide limited efficacy, and many patients continue to suffer mortality and morbidity from disease-related cytoppenia. Aside from HMAs, no new therapies for MDS have been approved in over a decade.

To initiate a randomized phase two trial about reading the triplet regimen of 14 25, plus the net o'clock for a society and the second half of this year.

This trial will compare the composite complete response rate of the triplet a 14 twenty-five then asa to Venice alone.

Despite the emergence of then as as the standard of care in newly diagnosed a M. L y.

One third of patients remain refractory to frontline therapy and recent studies suggest that these patients are rich from monostich form of the disease.

Nancy A. Simonian: There is a clear need for new options that can deliver benefits to the thousands of people living with MDS and improve their quality of life. We believe that the combination of 1425 and asia cytidine is ideally suited to address this need. In clinical studies, 1425 has shown single agent activity in relapse or refractory, higher risk MDS. And, in combination with asocytidein, 1425 led to a 67% composite complete response rate in RARA positive patients with low blast count AML, which is close to higher risk MDS on the disease continuum.

Our data show that most RARA positive patients, including those who are a cheap complete responses with 14 twenty-five have this modest at a form of day on though.

M. L is a heterogeneous disease and we believe many patients will print that upfront with both monostich and non monothetic leukemia cells bye.

By employ a triplet strategy that combines 14 twenty-five with Ben Asa, we simultaneously target, both monothetic and non monothetic leukemia cells from the outset.

Potentially benefiting patients who are refractory to vent asa, while reducing the emergence of resistant disease.

We look forward to initiating the trial later this year I'm reporting initial data and 2022.

Turning to the second program in our hematology portfolio 21 O. One is a novel oral form of arsenic trioxide in development for the treatment of a P. L, which is a genetically defined form of a M L.

We believe 21 O one could significantly impact the lives of people with a P O.

Nancy A. Simonian: Importantly, the combination of 1425 and Aza Cytidine has been well tolerated, with no evidence of increased toxicity relative to either as a single agent. Furthermore, there was no increase in neutropenia or anemia, which is so important in treatments for patients with MDF. Taken together, these data suggest that the combination is highly differentiated.

I V. A T O the current standard of care.

Offers a cure rate of or 80 per cent, but it comes with an enormously heavy treatment burden as.

As an oral therapy, we believe that 21 O one could dramatically reduce this treatment burden without sacrificing efficacy we.

We plan to initiate a dose confirmation study and the second half of this year, followed by a phase three study and 2022.

It's successful this study could enable an N D a filing and 2024.

Nancy A. Simonian: 1425 is an oral agent that, in combination with asa cytidine, has the potential to deliver high rates of complete remissions without introducing additive cytoppenias for a targeted subset of higher risk MDSP. Turning to our efforts in AML, we remain on track to initiate a randomized phase two trial evaluating the triplet regimen of 1425 plus Venetoclaxin and asasididine in the This trial will compare the composite complete response rate of the triplet of 1425 Ven ESA to Venza alone.

Nancy A. Simonian: Despite the emergence of then-aza as the standard of care in newly diagnosed AML, one-third of patients remain refractory to frontline therapy, and recent studies suggest that these patients are enriched for a monosthetic form of the disease. Our data show that most RARA positive patients, including those who have achieved complete responses with 1425, have this monocytic form of AML. AML is a heterogeneous disease, and we believe many patients will present up front with both monocytic and non-monocytic leukemia cells.

Nancy A. Simonian: By employing a triplet strategy that combines 1425 with Vanesa, we simultaneously target both monocytic and non-monocytic leukemia cells from the outset, potentially benefiting patients who are refractive to Van Asa while reducing the emergence of resistant disease.

Nancy A. Simonian: We look forward to initiating the trial later this year and reporting initial data in 2022. Turning to the second program in our hematology portfolio, 2101 is a novel oral form of arsenic trioxide in development for the treatment of APL, which is a genetically defined form of AML. We believe 2101 could significantly impact the lives of people with APL. ID ATO, the current standard of care, offers a cure rate of over 80%, but it comes with an enormously heavy treatment burden. As an oral therapy, we believe that 2101 could dramatically reduce this treatment burden without sacrificing efficacy.

And the C. D. K 12, which are both involved in DNA damage repair.

Opening up several opportunities for combining a CDK <unk> inhibitor with PARP inhibitors as well as other drugs that cause DNA damage or inhibit fits recur.

In addition to our work on sickle cell disease with global Blood Therapeutics. We are also making good progress with our second monogenic disease program and my Atonic dystrophy type one a dam on.

Our goal here is to develop a trinucleotide repeat modulator to decrease the expression of the toxic copy of the DNP caging.

As we continue to advance. This program, we are gleaning key insights that could apply to other nucleotide repeat disorders.

This has the potential to unlock massive opportunity more than 40 genetic disorders are caused by nucleotide repeat expansion.

Nancy A. Simonian: We plan to initiate a dose confirmation study in the second half of this year, followed by a phase three study in 2022. If successful, this study could enable an NDA filing in 2024. Before moving to our broader portfolio, I want to take a moment to highlight the targeted hematology KOL event series that we announced this morning. Over the course of the next several months, we will be hosting three webcast conference calls focused on our hematology program. In May, Dr. Amy Dazern of Johns Hopkins will join us to speak about higher-risk MDF. In June, Dr. Daniel Pahlia of the University of Colorado School of Medicine will present on unfit AML.

Kind of mutation in which simple DNA sequences repeat and increasing copy number and induced disease like D. M. One huntington disease or fragile X syndrome.

All in I believe we are in an incredibly strong position as we thoughtfully and strategically advance on industry, leading pipeline across key areas of unmet need in cancer and monogenic disease.

Since our founding we have remained laser focused on building a synergistic portfolio, where insights gleaned in one program can be applied to advance our next wave of efforts and where we can capitalize on our expertise as well as our clinical and commercial investments to advance multiple programs forward.

Parallel.

We are entering a catalyst rich period for Cerro and look forward to updating you further as we continue to move through clinical development.

Nancy A. Simonian: And in July, Dr. Farad Rabandi of the MDA Anderson Cancer Center will speak about APL. We are very much looking forward to these webinars and hope you will join us to learn more about the unmet needs for MDS, AML, and APL, as well as the opportunities for 1425 and 2101 to set new standards of care for people with these diseases. Additional details at each call will be announced shortly. Turning to our focus on CDK-7 inhibition, we continue to enroll patients in our phase one dose escalation study of SI5509, and we remain on track to announce updated dose escalation data, including clinical activity data, in the third quarter. As a reminder, the dose escalation is enrolling patients with advanced breast, colorectal, lung, ovarian, or pancreatic cancer or with solid tumors of any histology that harbor RB pathway alteration.

With that let me turn the call over to Joe to review, our first quarter 2021 financial results.

Thank you Nancy.

We continue to operate from a position of financial strength.

We ended the first quarter with $222 million in cash cash equivalents in marketable securities compared to $174 million as of December 31, 2020.

This increase reflects gross proceeds of $75 $6 million from our public offering which closed in January 2021, partially offset by cash used to fund our operations in the first quarter.

Based on our current plans, we believe our cash position is sufficient to fund our business into 2023, enabling on aggressive investment in each of our three strategic areas of focus.

We recognized revenue of $4 $8 million in the first quarter compared to $2 4 million in the first quarter of 2020.

This $4 8 million consisted of $4 million under our collaboration with global blood Therapeutics, and <unk> $8 million under our collaboration with insight.

In the first quarter of 2020, we recognized $2 $2 million from our collaboration with GBT.

$2 million from our collaboration with insight.

R&D expenses were $20 million in the first quarter of 2021 compared to $14 6 million for the same period in 2020.

This increase was primarily due to the continued advancement of our clinical programs, including the addition of FY 'twenty one on one and an increase in employee related expenses.

Nancy A. Simonian: We are exploring various dosing regimens for 5609 as both a single and combination agent, and we expect to move into the expansion phase of the phase one trial in the second half of 2021. In parallel, we continue to invest in our gene control discovery engine, with the goal of fully exploiting the power of our platform to advance additional programs in cancer and monogenic diseases, and we remain on track to name our next development candidate in 2022.

G&A expenses were $5 $7 million in the first quarter of 2021 compared to $5 1 million for the same period in 2020.

This increase was primarily due to an increase in employee related expenses.

Finally, we reported a net loss for the first quarter of $14 $2 million or 23 per share compared to a net loss of $17 $2 million or 39 cents per share for the same period in 2020.

With that I will turn the call over to the operator for questions. Thank you all very much.

Okay.

Thank you.

As a reminder to ask a question you will need to press Star then one on your telephone to withdraw your question. Please press the pound key.

Please standby, while we compile the Q&A roster.

Yes.

Our first question will come from the line of Phil Nadeau with Cowen and company. Your line is now open good morning.

Congrats on the progress.

Two questions from US first on the phase III in HR Mds.

What's the most recent count for sites that are enrolling patients today and have you experienced any COVID-19 related issues and getting sites open and recruiting.

Nancy A. Simonian: As we've shared before, our most advanced preclinical program targets CDK 12, another member of the transcriptional CDK family. Preclinical studies show a synthetic lethal relationship between PARP and CDK12, which are both involved in DNA damage repair, opening up several opportunities for combining a CDK 12 inhibitor with PARP inhibitors, as well as other drugs that cause DNA damage or inhibit its repair. In addition to our work on sickle cell disease with global blood therapeutics, we are also making good progress with our second monogenic disease program in Miotonic Dystrophy type 1, or DM1. Our goal here is to develop a trinucleotide repeat modulator to decrease the expression of the toxic copy of the DNPKG.

Thanks, So David you want to take that.

Oh sure so.

As you know we've.

Recently initiated the trial and we're actively dosing patients we haven't specifically guided to.

On a specific number of sites where patients at this time.

And but we do want to remind you that as we move forward on all works out.

Successful outcome, we are.

On anticipating the potential to file an NDA in 2024 time frame as it relates to COVID-19.

Managing through COVID-19 I think that there.

On those specific challenges that we've confronted that we don't feel can be mitigated and we remain on track moving forward right now.

Great and then.

On 50 609.

Could you give us some sense of how many patients will be in that Q3 update maybe what the duration of follow up is likely to be and also some sense of the efficacy measures that you'll be able to disclose at that time.

Nancy A. Simonian: If we continue to advance this program, we are gleaning key insights that could apply to other nucleotide repeat disorders. This has the potential to unlock massive opportunities. More than 40 genetic disorders are caused by nucleotide repeat expansion, a kind of mutation in which simple DNA sequences repeat, an increasing copy number, and cause disease, like DM1, Huntington disease, or fragile X syndrome.

So for 56 and on we are planning for a data update in the third quarter of this year and that update will include.

You know more information around the safety and Tolerability PK and PD that we've reported on previously on we're also gonna have a focus on clinical activity we haven't.

Specifically guided to the numbers of patients.

Joe Farah: All in all, I believe we are in an incredibly strong position as we thoughtfully and strategically advance an industry-leading pipeline across key areas of unmet need in cancer and monogenic disease. Since our founding, we have remained laser-focused on building a synergistic portfolio where insights gleaned from one program can be applied to advance our next wave of efforts, and where we can capitalize on our expertise, as well as our clinical and commercial investments, to advance multiple programs forward in parallel.

That would be included in our presentation, but I think you can anticipate we will report the available data we have.

To us at the time on the presentation.

Great and then last question is for that update is there a specific form is that likely to be in.

In conjunction with a medical meeting or whether it could be a serious.

On itself.

So you know on a general practice has been to.

Report data from trials at medical meetings.

So.

That's been sort of our standard practice, you know obviously last year with COVID-19. There was big questions on with that general they change, but but I think we are you know that that's that's the general approach with them okay.

Got it.

For taking the questions.

Sure. Thanks, Bill appreciate it.

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

Joe Farah: We are entering a catalyst-rich period for seros and look forward to updating you further as we continue to move through clinical development. With that, let me turn the call over to Joe to review our first quarter 2021 financial results. Thank you, Nancy. We continue to operate from a position of financial strength. We ended the first quarter with $22 million in cash, cash equivalence, and marketable securities, compared to $174 million as of December 31, 2020.

Hi, Thanks for taking the questions I just have two.

You've had the asset for several months now just wondering if you've had the opportunity for any dialog with regulators or with Kols to confirm your development plans and on the approval path.

Oh.

Sorry, you cut out a little bit on for which program I missed that.

For 'twenty one on one.

Oh for 'twenty, one on one okay.

Well you know I think we certainly have had and I think we've shared with you on discussions with.

Many kols I think that I would just say, there's a huge amount of interest and enthusiasm I think what's really speaks to is a big need.

For an.

On oral therapy, and APL, just given how burdensome on the idea. So we've had a lot of input and as you know we're going to have one of those kols I speak at an upcoming events I don't believe it's on July from from MD Anderson.

Oh, the Bondi Doctor of on it he he.

But there's a lot of interest and enthusiasm in terms of.

Joe Farah: This increase reflects gross proceeds of $75.6 million from our public offering, which closed in January 2021, partially offset by cash used to fund our operations in the first quarter. Based on our current plans, we believe our cash position is sufficient to fund our business into 2023, enabling aggressive investment in each of our three strategic areas of focus. We recognized revenue of $4.8 million in the first quarter, compared to $2.4 million in the first quarter of 2020.

Regulatory updates in discussions I think we've shared with you that when we acquired the asset orphan ex had had discussions with the agency and sort of developed a plan on that.

We're kind of on our current operating assumptions on that so you know clearly as we move forward and do you have any further updates will almost certainly on a price you have that.

Okay, Great and then second question on 2014 25 mm.

And in the Triple combo.

With that as a are are you screening for patients with monistat excels or or or stratify on on that basis, and then just thinking forward to how that could change standard of the standard of care our patients typically screen from on a snick sells today or would you not envisage that that would be necessary.

Joe Farah: This $4.8 million consisted of $4 million under our collaboration with Global Blood Therapeutics and $0.8 million under a collaboration with Insulyte. In the first quarter of 2020, we recognized $2.2 million from our collaboration with GBT and 0.2 million from our collaboration with Insulyte. R&D expenses were $20 million in the first quarter of 2021 compared to $14.6 million for the same period in 2020. This increase was primarily due to the continued advancement of our clinical programs, including the addition of SI201, and an increase in employee-related expenses.

You you you you wouldnt need to do that.

In clinical practice.

Yeah. Good question. So we are focused on RARA positive.

We diagnosed unfit AML for that study.

And so we are not specifically looking for patients who have monothetic features where we're screening for RARA. What we showed at the Ash meeting was that.

The majority of the patients who are RARA positive where indeed.

Those monosomic type patients, but we don't foresee a need to further screen for those additional features since the vast majority of.

From a positive patients R&D those patients so on.

That simplifies things for us greatly which is really nice.

And we really do anticipate that this could significantly address.

Our newly created unmet need because about one third of patients don't respond to that as a combo.

Joe Farah: GNA expenses were $5.7 million in the first quarter of 2021, compared to $5.1 million for the same period in 2020. This increase was primarily due to an increase in employee-related expectations. Finally, we reported a net loss for the first quarter of $14.2 million, or 23 cents per share, compared to a net loss of $17.2 million, or 39 cents per share, for the same period in 2020.

And the majority of which are considered these types of patients as far as the patient analyses when they come in there.

Classified that way more traditionally just based on the appearances of the cells are certain.

Cell surface markers or genetic expression levels.

Sometimes these are done as part of their routine work up there.

We're not consistently done certainly the research study that's been done on it has helped us make this connection.

Okay great.

Thanks for taking the questions.

Thanks, Jason.

Thank you.

As a reminder to ask a question you will need to press Star then one on your telephone.

Our next question comes from the line of Mark Breidenbach.

Operator: With that, I will turn the call over to the operator for questions. Thank you all very much. Thank you. As a reminder, to ask a question, you would need to press Star, then one on your telephone.

Oppenheimer. Your line is now open.

Hey, good morning, guys and thanks for taking our question.

I'm just wondering if you can offer any early observations from the patient screening success rate in the phase III Mds trial, I guess I'm just wondering if you see any potential challenges in finding RARA positive MD Mds patients, who also qualified for high risk classification by I guess, that's the criteria.

Operator: To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Phil Nadeau with Cowan and Company. Your line is now open. Good morning, congrats on the progress. A few questions from Oz. First, on phase three in HRMDS, what's the most recent count for sites that are enrolling patients today? And have you experienced any COVID-related issues in getting sites open and recriminated against?

Thanks.

Sure.

Thanks for that question.

Oh, we have analyzed our.

Screening of well over 350 patients sometime back and the data continues to trend.

Consistently overtime.

In patients with AML or high.

High risk Mds, who have been previously eligible for our studies and we see a 30% rate of <unk> positivity. So you know 30 per cent of patients have this and we foresee no.

Specific challenges or obstacles to identifying 30 per cent of patients who are higher risk Mds. So those patients are out there.

David A. Roth: Thanks, Phil. David, do you want to take this? Sure, so as you know, we've recently initiated the trial, and we're actively dosing patients. We haven't specifically guided to a specific number of sites or patients at this time. But we do want to remind you that as we move forward, if all works out with a successful outcome, we are anticipating the potential to file an NDA in the 2024 timeframe. As it relates to COVID, you know, we're managing through COVID. I think that there are no specific challenges that we've encountered that we don't feel can be mitigated, and we remain on track moving forward.

And we're very excited about the opportunity.

To participate on a trial that offers an oral medicine.

Which is really convenient because you know keep in mind. These higher risk Mds patients are typically still managed in the outpatient setting.

And when you are enrolling in studies that require you get an IV drug it's sort of it's an extra burden. So I think that's very appealing and having a targeted agents in that kind of disease space.

<unk> is also very exciting in particular, given the data that we've shown where we have such a high response rate in AML and <unk>.

As high or even higher in the lower blast count AML, which is more closely aligned with the high risk diagnosis. So I think our data sets.

The nature of our drug on the Tolerability profile all support enthusiasm for the investigators.

David A. Roth: Great Then second, on 5609, could you give us some sense of how many patients will be in that Q3 update, maybe what the duration of follow-up is likely to be, and also some sense of the efficacy measures that you'll be able to disclose at that time? So for 56 and 9, we are planning for a data update in the third quarter of this year, and that update will include, you know, more information around safety and tolerability, the PK and PD that we've reported on previously, and we're also going to have to focus on the clinical activity, specifically directed to the numbers of patients that would be included in that presentation, but I think you can anticipate we'll report, you know, the available data And then last question, for that update, is there a specific forum?

Direct patients into our study.

Alright terrific. Thanks for taking my question.

Okay.

Thanks Mark.

Yeah.

Thank you. Our next question comes from the line of Zach <unk> with Roth Capital partners.

Your line is now open.

Good morning, guys and congrats on the progress just had a real quick question here just about any additional assays to kind of educate clinicians on you know of our biomarker, especially you know since you're saying that if particularly kisses predict if a patient that may not responsive to net o'clock and then any additional progress on your companion.

Okay.

Exactly what I have David answer that.

Sure. So you.

I would say that it's it's really important that.

There continues to be increasing awareness of our study and I think the.

Availability now of the data that we shared at ash are coupled with the outreach that we've done too.

Initiate a global study has really helped us a great deal in and communicating our data our results and our hopefulness for this drug in helping patients in the future.

So I think we've already made some really good progress in explaining that and I can say.

The data that we share.

The poster on the on the correlation of our biomarker with resistance phenotype <unk> really.

Caught people's attention because the physicians are really looking for I can why doesn't that work and how can we still address those patients. We don't typically select from them, but now there may be other options. So so the idea that one could select ferraro positivity.

David A. Roth: Is that likely to be in conjunction with the medical meeting, or will it likely be a Pesiros event? So, you know, our general practice has been to, you know, report data from trials at medical meetings. So that's been sort of our standard practice. You know, obviously last year with COVID, there were big questions on whether that would generally change.

And channel those patients to our drug has really captured the imagination and I think we're seeing that in.

In the interest and participating in our studies. So so we're working really hard to get that word out and we think that the data are helping us do our job.

David A. Roth: But, but I think we, you know, that's the general approach we've been taking. Good. Thanks for taking the questions. Sure, thanks, Phil. I appreciate it.

Yeah.

Yeah, I would just add.

Stay I think as you know where where we have these two K O all of them. The first one is this month.

On a higher risk Mds with any designs on them and in June and AML, So I think that'll.

Operator: Thank you. Our next question comes from the line of Jason Butler with JMP Securities. Your line is now open.

That would be a great opportunity for you to do.

To hear directly from the Kols in terms on how they think about that.

Okay and then just one other question you had about the companion diagnostic I mean, I know that.

Operator: Hi, thanks for taking the questions. I just took two. You've had them for several months now. Just wondering if you've had the opportunity for any dialogue with regulators or with KOLs to confirm your development plans and the approval path. Jason, you cut out a little bit and for which program I missed it. For 21-0-1.

We've shared with you that we we had enrolled be RARA negative patients.

Early on in that study just to make that observation that there was indeed.

Our selection advantage or the biomarker yourself is operating as we had anticipated on its enriching for patients who are likely to respond and we're making great progress towards the development.

Development of a commercial companion diagnostics, such that its available coordinate Lee with the approval and launch of the truck.

Thanks, Congrats on the progress on looking forward to that came on we bank.

Nancy A. Simonian: Oh, for 21-01. Okay. Great. Well, you know, I think we certainly have had, and I think we've shared with you, discussions with many KOLs. I think that I would just say there's a huge amount of interest and enthusiasm, which really speaks to the big need for an oral therapy, an APL, just given how burdensome the ID is. So we've had a lot of input. And as you know, we're going to have one of those KOLs speak at an upcoming event, I think, believe it's in July from M.D.

Thank you goodbye.

Thank you.

Our next question comes from the line of per panel with Piper Sandler. Your line is now open come on.

Development has become such a bigger part of the company, but I still don't understand I feel like there's so much still to do with this platform. So maybe you can give us some updates on what's going on on the discovery side at least from Cook.

Future potential partnerships. Thank you.

Yes.

Okay. Thanks for that and we couldn't agree more I think you know on.

I'm Gonna have Eric addressed your question, but we.

Nancy A. Simonian: Anderson, Robandi, Dr. Rivandi, he, he, but we, but there's a lot of interest and enthusiasm. In terms of regulatory updates and discussions, I think we've shared with you that when we acquired the asset, Orsonics had discussions with the agency and sort of developed a plan that we're kind of on our current operating assumptions on that. So, you know, clearly, as we move forward and we have any further updates, we'll certainly apprise you of those. Okay, great. And then the second question on 1425.

Free capabilities isn't this platform space of how do you turn up or how do you turn down a G.

You know that program is designed to a multiple approaches to <unk> small molecules that will turn up the expression of fetal globin.

David A. Roth: In the triple combo with Benaza, are you screening for patients with monocytic cells or stratifying on that basis? And then just thinking forward to how that could change standard of care, are patients typically screened for monositic cells today? Or would you not envisage that to be necessary? You wouldn't need to do that.

And then kind of Ah Ah Ah a third area is the the whole field of kind of transcription and gene regulation as a as it impacts.

Impacts diseases across several several different therapeutic areas, there's really exploding. This what we said early at that the company. That's 98 per cent of the genome that doesn't code for jeans.

David A. Roth: That, clinical practice. Yeah, no, good question. So we are focused on RARA positive, newly diagnosed unfit AML for that study, and so we are not specifically looking for patients who have monocytic features. We're screening for RARA. What we showed at the Ash meeting was that the majority of the patients who were rather positive were indeed those monocytic type patients, but we don't foresee a need to further screen for those additional features since the vast majority of the Raropososite patients are indeed those patients.

There's just been an explosion of information over the last few years, what what that out of the genome is doing and more specifically how it's linked to specific pieces and we're we're actively looking at at all of that data and thinking about a brand new program. So.

You know like the very rich and exciting time to be in that type of the gene control space.

So a lot of future, but also you know executed on the on the programs that are right in front of us.

Excellent well. Thank you so much cheaper per grade work.

Thanks <unk>.

Thank you there are no further questions I would now turn the call back to Nancy Simonian for closing remarks.

Thank you operator, and thank you everyone for joining us. This morning, we are grateful for your continued support as we execute against our three strategic priority.

David A. Roth: So that simplifies things for us greatly, which is really nice. And we really do anticipate that this could significantly address a newly created unmet need because about one-third of patients don't respond to the Van Aza combo. and the majority of which are considered these types of patients. As far as patient analyses when they come in, they're classified that way, more traditionally, just based on the appearances of the cells or certain cell surface markers or genetic expression levels. Sometimes these are done as part of a routine workup.

And look forward to update on you further as we pursue our ultimate goal a maturing Sarah into a fully integrated biopharmaceutical company and deliberating a portfolio of targeted small molecule medicine, the profoundly impact the lives of patients.

Ladies and gentlemen, this concludes today's conference call.

Thank you for your participation you may now disconnect.

David A. Roth: They're not consistently done. Certainly, the research setting that's been done and has helped us make this connection. Okay, great. Appreciate it. Thanks for taking the question. Thanks, Jason. Thank you. As a reminder, to ask a question, you would need to press star, then one on your telephone. Our next question comes from the line of Mark Breitlock with Oppenheimer. Your line is now open.

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Operator: Hey, good morning, guys, and thanks for taking our question. I'm just wondering if you can offer any early observations on the patient screening success rate in the Phase 3 MDS trial. I guess I'm just wondering if you see any potential challenges in finding RAA positive MDS patients who also qualify for high-risk classification by IPS criteria. Thanks. Sure, thanks for that question. And, you know, we analyzed our screening of well over 350 patients some time ago, and the data continues to trend consistently over time in patients with AML or higher risk MDS who've been previously eligible for our studies.

Operator: And we see a 30% rate of RARA positivity. So, you know, 30% of patients have this, and we foresee no specific challenges or obstacles to identifying 30% of patients. or higher-risk MDS. Those patients are out there, and they're very excited about the opportunity to participate in a trial that offers an oral medicine, which is really convenient because, keep in mind, these higher-risk MDS patients are typically still managed in the outpatient setting. And when you are enrolling in studies that require you to get an IV drug, it's an extra burden.

David A. Roth: So I think that's very appealing, and having a targeted agent in that kind of disease space is also very exciting, in particular, given the data that we've shown, where we have such a high response rate in AML, and even higher, even higher, in the lower blast count AML, which is more closely aligned with the high-risk diagnosis. So I think our data sets, the nature of our drug, and the tolerability profile all support enthusiasm for the investigators to direct patients to our stuff. All right, perfect. Thanks for taking the time to answer the question. Thanks, Mark. Thank you. Our next question comes from the line of Zegh Bajala with Roth Capital Partners. Your line is not open.

Operator: Good morning, guys, and congrats on the progress. Just had a really quick question here, about any additional

Operator: any additional efforts to kind of educate clinicians on, you know, the Rara Barbar marker, especially since you're saying that it particularly could be predicted for patients that may not respond to Phenetoclast and then any additional progress on your companion diagnosis. Hey, Victor, I'm going to have David answer this question. Sure.

David A. Roth: So, you know, I would say that it's really important that there continues to be increasing awareness of our study. And I think the availability now of the data that we shared, Ash, coupled with the outreach that we've done to initiate a global study, has really helped us a great deal in communicating our data, our results, and our hopefulness for this drug in helping patients in the future. And so I think we've already made some really good progress in explaining that.

David A. Roth: And I can say the data that we shared on that poster about the correlation of our biomarker with a resistance phenotype to Venetaclax really caught people's attention because, you know, physicians are really looking for like, well, why doesn't that work, and how can we still address those patients? We don't typically select for them, but now there may be other options.

David A. Roth: So the idea that one could select Ferrara positivity and channel those patients to our drug has really captured their imagination, and I think we're seeing that in the interest in participating in our study. So we're working really hard to get that word out, and we think that the data are helping us do our job. Yeah, I would just add, say, as you know, we have these two KOL events. The first one is this month on a higher risk MDS with Amy DeZerns and then in June on AML.

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Nancy A. Simonian: So I think that will be a great opportunity for you to hear directly from the KOLs in terms of how they think about this. Okay, and then there was one other question you had about the companion diagnostic, and I know that we shared with you that we enrolled the RARA negative patients early on in that study, just to make that observation that there was indeed a selection advantage. You know, the biomarker itself is operating as we had anticipated, and it's enriching for patients who are likely to respond, and we're making great progress toward the development of the commercial campaign diagnostics such that it's available coordinately with the approval and launch of. Thanks, congratulations on the progress, and looking forward to the KOL event. Thanks, begs.

Operator: Thank you. Our next question comes from the line of Ted Tindell with Piper Sandler. Your line is not open. Good morning, everyone. How are you doing?

Operator: Thanks so much for the update. I wanted to ask a little bit about sort of the discovery efforts and appreciate that you guys are kind of moving down the chain a little bit here, and development has become such a bigger part of the company. But I still want to understand; I feel like there's so much still to do with this platform. So maybe you can give us some updates on what the company is like. going on on the discovery side and even future potential partnership. Thank you. So, Ted, thanks for that, and we couldn't agree more.

Nancy A. Simonian: I think, you know, I'm going to have Eric address your question, but we have made just tremendous progress and insights with our gene control platform. And it's interesting to see so many other companies cropping up today in exactly that same space, but we've been doing this for, you know, seven, eight years. And I think we have gleaned so many great insights in terms of how to develop important new drugs. So, Erica, let me turn the meat of the question over to you. Sure, thanks, Ted, for the question. Obviously, I'll kind of take it in a couple of parts.

Eric Olson: First is, you know, our early pipeline itself. And, you know, as Nancy said in her remarks, CDK12 is looking like a really, really good addressing target. We think there's a great opportunity to be combining a molecule like that with other DNA damage or DDR agents such as PARP inhibitor. You know, our collaboration with global blood therapeutics has really, really allowed us to kind of accelerate our drug discovery capabilities in this platform space of how do you turn up or how do you turn down a gene. As you know, that program is designed to be multiple approaches to find small molecules that will turn up the expression of

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Eric Olson: And then kind of a third area is the whole field of transcription and gene regulation as it impacts diseases across several, you know, several different therapeutic areas is really exploding. You know, this, what we said earlier at the company, that 98% of the genome that doesn't code for genes. There's just been an explosion of information over the last few years on what that part of the genome is doing, and more specifically how it's linked to specific diseases, and we're, you know, actively looking at all of that data and thinking about brand new programs.

Eric Olson: So you know, it's a very rich and exciting time to be in the gene control space. A lot of future, but also, you know, executing on the programs that are right in front of us. Sure. Excellent. Well, thank you so much and keep up the great work. Thanks, Ted. Thank you. There are no further questions. I would now turn the call back to Nancy Simonium for closing remarks.

Eric Olson: Thank you, operator, and thank you everyone for joining us this morning. We are grateful for your continued support as we execute against our three strategic priorities and look forward to updating you further as we pursue our ultimate goal of maturing Seros into a fully integrated biopharmaceutical company and delivering a portfolio of targeted small molecule medicines that profoundly impact the lives of patients. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

Nancy A. Simonian: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, Thee, and and and You're I'm thanking you, thank you, and and Thank you, Thee, and Thank you.

Operator: Thank you. Thank you. Thank you. Thank you, and so on the Thank you. Thank you. Thank you.