Q2 2022 Syros Pharmaceuticals Inc Earnings Call
Operator: Good morning and welcome to Syros Pharmaceuticals second quarter 2022 financial results conference call.
Operator: At this time, all participants are in a listen only mode.
Good morning, and welcome to Sirius Pharmaceuticals second quarter 2022 financial results Conference call. At this time, all participants are in a listen only mode.
Operator: This call is being webcast live on the investor relations and media section of Syros website at www.syros.com. Please be advised that today's call is being recorded.
This call is being webcast live on the Investor Relations and media section of Cra's website at Www Dot Sirius Dot com. Please advise please be advised that todays call is being recorded at this time I would like to turn the call over to Courtney Solberg manager of corporate Communications and Investor Relations at Crs.
Operator: At this time, I would like to turn the call over to Courtney Solberg, Manager of Corporate Communications and Investor Relations at Syros.
Courtney Solberg: Thank you.
Thank you. This morning, we issued a press release announcing our second quarter 2022 financial results and our broader business update.
The release is available on the investors and media section of this website at Www Dot Dot Com, we will begin the call with prepared remarks, I Doctor Nancy Simonian, Our Chief Executive Officer, Dr. David Roth, Our Chief Medical Officer, and Jason <unk>, Our Chief Financial Officer, We will then open the call for <unk>.
Christopher Stephens, our Chief Development Officer, Dr. Eric Olson, our Chief Scientific Officer and college, he 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 will include forward looking statements, including statements related to our planned strategic merger with time technologies and concurrent private placement I.
Actual events or results could differ materially from those expressed or implied by any forward looking statements. As a result of various risks uncertainties and other factors, including those set forth in the risk factor section of our annual report on Form 10-K.
Our quarterly report on Form 10-Q that we filed this morning and any other filings that we may make with the I V in the future.
In particular, the extent to which the COVID-19 pandemic continues to impact our operations and know that the third party that much really rely or depend on future development, which are highly uncertain.
Predicted it 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.
Now, let's turn the call over to Nancy.
Courtney Solberg: This morning we issued a press release announcing our second quarter 2022 financial results and a broader business update. The release is available on the investors and media section of Syros' website at www.syros.com.
Yeah.
Pacey, Courtney and good morning, everyone and thank you for joining us today.
In the past.
We've made important progress towards building zero into a late stage company with a portfolio of small molecule medicines that have the potential to deliver new standards of care for patients with cancer.
Courtney Solberg: Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factor section of our annual report on Form 10-K and our quarter report on Form 10-Q that we filed this morning, and any other filings that we may make with the SEC in the future. In particular, the extent to which the COVID-19 pandemic 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.
Courtney Solberg: 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.
Tara enters the second half of this year in a position of strength.
Our clinical programs are progressing well and we are on track to have multiple data readouts over the next 18 months.
This includes pivotal data from our select M. B S. One trial.
Data from the safety lead in portion of the select AML, one phase two trial and the phase one trial, that's why 50 609 in pancreatic cancer.
Today, we are pleased to report promising preliminary data from our dose confirmation study of FY 'twenty, one O one which supports advancement of 'twenty, one O one towards our phase III trial, which is expected to initiate in the second half of 2023.
Additionally, as we announced in July we expect to secure approximately a $190 million through a merger with time technologies and a concurrent pipe investment both of which are expected to close in the second half of 2022.
Together, along with the previously announced amendment to our loan agreement with Oxford, We anticipate these transactions will extend our cash runway into 2025 at least one year beyond the expected pivotal data from our ongoing select M. D. M. B S. One phase III trial.
We are incredibly grateful to our new and existing investors for their support as well as to the time team for their collaboration throughout the strategic process.
We look forward to maximizing value for patients our combined company and our shareholders in the months and years ahead.
I will now turn the call over to David who will review the recent progress we have made across our clinical and preclinical programs.
Courtney Solberg: I would now like to turn the call over to Nancy.
Thank you Nancy.
Nancy Simonian: Thank you, Courtney.
We're pleased to report promising preliminary data from our ongoing dose confirmation trial of 'twenty, one or more.
Nancy Simonian: Good morning, everyone, and thank you for joining us today. In the past month, we've made important progress towards building Seros into a late-stage company with a portfolio of small-molecule medicines that have the potential to deliver new standards of care for patients with cancer.
Nancy Simonian: Seros enters the second half of this year in a position of strength.
Our novel oral form of arsenic trioxide or Ato.
As a reminder, this is the first crossover studies directly comparing 'twenty one on one to the approved dose of IV atria.
It provides important data for our phase III dose selection.
In this trial patients with acute myeloid leukemia, or APL received a single dose of 21 O. One in the fasted and in the federal States.
As well as IV H L.
Serial PK measurements are taken after each administration.
The goal of this study is to directly compare the AUC and <unk> of 21 O One IV hei.
Safety from the ongoing study continues to support a 21, who has a favorable tolerability profile.
No severe adverse events have been reported in this study.
No new safety signals have been identified in particular with respect to liver toxicity or cardiac Qt prolongation, which have been associated with IV <unk>.
Based on preliminary data with full PK datasets for study.
21 O one at a 15 milligram dose achieved exposures based on AUC and feedbacks that were comparable to IV AGL when administered at 0.15 milligrams per kilogram.
Approved dose.
Additionally, 21 O. One showed high oral bioavailability of approximately 80%, which is the first quantitative assessment of the oral bioavailability of 'twenty, one and more in the context of this intra patient crossover study.
Furthermore across multiple patients treated with 'twenty one on one at 10 milligrams or 15 milligrams, which includes goes from the original PK study conducted by force next we continue to be encouraged that we will be able to identify a dose that can achieve exposures consistent with drugs like IV Ato.
For the planned phase III trial.
This preliminary data provides further confidence at 21 O one has the potential.
We replace the standard of care IV treatment for APL, which is incredibly burdensome both for patients and the health care system.
We're continuing to enroll patients in our dose confirmation study and expect to identify the optimal dose to advance into our planned phase III trial, which is expected to initiate in the second half of 'twenty can be three.
Additionally in July we received feedback from the European Medicines Agency PMA.
On the pivotal development plans for 'twenty, one O, one, which together with prior feedback from the FDA informs our decision to move forward with a single registration trial that can support the approval of 'twenty one in both the U S and EU.
Turning to Tommy Barrick team, our selective and potent alpha agonist.
<unk> has the potential to set a new treatment paradigm for RARA positive patients who are over expressed the royalty with higher risk Mds.
In newly diagnosed unfit AML.
The select Mds one trial is on track and we expect to report pivotal data in late 2023 or early 2024.
Nancy Simonian: Our clinical programs are progressing well, and we are on track to have multiple data readouts over the next 18 months. This includes pivotal data from our Select MDS-1 trial and data from the safety-leading portions of the Select AML-1 Phase 2 trial and the Phase 1 trial of SY5609 in pancreatic cancer.
We currently have over 50 sites open globally and expect to open additional sites in the months ahead.
Importantly, and as we disclosed in June based on data from over 175 patients. We now estimate that approximately 50% with Mds patients are positive, which we believe has positive implications both for enrollment in our ongoing study.
Nancy Simonian: Today, we are pleased to report promising preliminary data from our dose confirmation study of SY2101, which supports advancement of SY2101 toward our Phase 3 trial, which is expected to initiate in the second half of 2023.
Nancy Simonian: Additionally, as we announced in July, we expect to secure approximately $190 million, through a merger with Time Technologies and a concurrent pipe investment, both of which are expected to close in the second half of 2022. Together, along with the previously announced amendment to our loan agreement with Oxford, we anticipate these transactions will extend our cash runway into 2025, at least one year beyond the expected pivotal data from our ongoing SelectMDS-1 Phase III trial.
Nancy Simonian: We are incredibly grateful to our new and existing investors for their support, as well, as to the Time team for their collaboration throughout the strategic process.
Nancy Simonian: We look forward to maximizing value for patients, our combined company, and our shareholders, in the months and years ahead.
Nancy Simonian: I will now turn the call over to David, who will review the recent progress we have made, across our clinical and preclinical programs.
One was the market opportunity long term.
Yeah.
David Roth: Thank you, Nancy.
Awesome August we announced that the EMA issued a positive opinion on our application for orphan drug designation to try and balance sheet for the treatment of M. D. S.
David Roth: We're pleased to report promising preliminary data today from our ongoing dose confirmation, trial of 2101, our novel oral form of arsenic trioxide, or ATO. As a reminder, this is the first crossover study directly comparing 2101 to the approved, dose of IV ATO and provides important data for our Phase III dose selection. In this trial, patients with acute promyelocytic leukemia, or APL, receive a single dose of, 2101 in the fasted and in the fed states, as well as IV ATO, and serial PK measurements are taken after each administration. The goal of this study is to directly compare the AUC and CMAX of 2101 to IV ATO.
David Roth: Safety from the ongoing study continues to support that 2101 has a favorable tolerability, profile. No severe adverse events have been reported in this study, and no new safety signals have, been identified, in particular with respect to liver toxicity or cardiac QT prolongation, which have been associated with IV ATO. Based on preliminary data with full PK datasets in our study, 2101 at a 15 milligram dose, achieved exposures based on AUC and CMAX that were comparable to IV ATO when administered at 0.15 milligrams per kilogram, the approved dose. Additionally, 2101 showed high oral bioavailability of approximately 80%, which is the first quantitative, assessment of the oral bioavailability of 2101 in the context of this intrapatient crossover study.
David Roth: We're continuing to enroll patients, in our dose confirmation study and expect to identify the optimal dose to advance into our Planned Phase III Trial, which is expected to initiate in the second half of 2023.
David Roth: Furthermore, across multiple patients treated with 2101 at 10 milligrams or 15 milligrams, which includes those from the original PK study conducted by Orsonix, we continue to be encouraged that we will be able to identify a dose that can achieve exposures consistent with those of IV ATO, for the Planned Phase III Trial.
David Roth: This preliminary data provides further confidence, that 2101 has the potential to replace the standard of care IV treatment for APL, which is incredibly burdensome, both for patients and the healthcare system.
David Roth: Additionally, in July, we received feedback, from the European Medicines Agency, or EMA, on the Pivotal Development Plan for 2101, which, together with prior feedback from the FDA, informs our decision to move forward with a single registration trial that can support the approval of 2101 in both the US and EU.
David Roth: Turning to tamibarotene, our selective and potent RER-alpha agonist, tamibarotene has the potential to set a new treatment paradigm for RARA-positive patients who overexpress the RARA gene, with higher-risk MDS and newly-diagnosed unfit AML.
Medicines that meet the Ema's orphan designation criteria quantified for financial and regulatory incentives, including a 10 year period of market exclusivity after product approval protocol assistance from the email and reduced fees during the product development phase.
Access to centralized marketing authorization.
As a reminder, tammy by our team was granted orphan drug designation in Mds by the FDA in February of this year.
David Roth: The SelectMDS1 trial is on track, and we expect to report Pivotal data in late 2023 or early 2024. We currently have over 50 sites open globally, and expect to open additional sites in the months ahead. Importantly, and as we disclosed in June, based on data from over 175 patients, we now estimate that approximately 50% of MDS patients are RARA-positive, which we believe has positive implications both for enrollment in our ongoing study, as well as the market opportunity long-term.
David Roth: Also in August, we announced that the EMA, issued a positive opinion on our application for orphan drug designation, tamibarotene, for the treatment of MDS. Medicines that meet the EMA's orphan designation criteria, qualify for financial and regulatory incentives, including a 10-year period of market exclusivity after product approval, protocol assistance from the EMA at reduced fees during the product development phase, and access to centralized marketing authorization. As a reminder, tamibarotene was granted, orphan drug designation in MDS by the FDA in February of this year.
These agencies decisions represent an important milestone for Mds patients who are in need of effective tolerable and convenient treatment option.
David Roth: These agency's decisions represent an important milestone, for MDS patients who are in need of effective, tolerable, and convenient treatment options.
David Roth: Despite successful advancements in blood cancer more broadly, MDS has largely lagged behind in drug development.
Despite successful advancements in blood cancer more broadly MTS is largely lagged behind in drug development.
David Roth: Hypomethylating agents, or HMAs, remain the existing standard of care and provide limited efficacy.
Hyperventilating agents or Hma's remain the existing standard of care and provide limited efficacy.
David Roth: No new therapies outside of HMAs, have been approved in over a decade. We believe tamibarotene, which has a novel mechanism, and has demonstrated favorable tolerability and strong efficacy, has the potential to be the first therapy for a targeted patient population in higher-risk MDS.
No new therapies outside of patron gains had been approved in over a decade, we believe champion Barigye, which has a novel mechanism and has demonstrated favorable tolerability and strong efficacy as the potential to be the first therapy for a targeted patient population and higher risk Mds.
David Roth: As you know, we're also evaluating tamibaritine in the SELECT-AML1 Phase 2 trial in RARA-positive, patients with newly diagnosed unfit AML. About a third of unfit AML patients do not respond to the standard of care, phenetoclaxonasacitidine, and a majority relapse. Our translational and clinical data support the potential for the RARA biomarker to enrich, for patients more likely to respond to tamibaritine and for whom the standard of care may be suboptimal.
As you know we're also evaluating <unk> T in the select AML, one phase II trial in RARA positive patients with newly diagnosed unfit AML.
About a third of unfit AML patients do not respond to the standard of care Panetta classmates decided team.
A majority relapse.
Our translational and clinical data support the potential for the RARA biomarker to enrich the patients more likely to respond to Tami Barron.
The standard of care may be suboptimal.
The select and melanoma trial is.
David Roth: The SELECT-AML1 trial is evaluating the triplet regimen of tamibaritine, phenetoclax, and, azacitidine in RARA-positive patients with AML, and we look forward to providing clinical activity and safety data from the safety lead-in portion of the study in the second half of this year. We believe that data with our triplet regimen will provide an understanding of safety as, well as an early look at efficacy based on objective assessments of response rates and time to response.
Valuate, the triplet regimen, Etame barraging frenetic, lax and he's decided to do.
In RARA positive patients with AML, and we look forward to providing clinical activity and safety data from the safety lead in portion of the study in the second half of this year.
We believe that data with our triplet regimen will provide an understanding of safety as well as an early look at efficacy based on objective assessments of response rates and time to response.
David Roth: Additionally, we plan to initiate the randomized portion of the trial in approximately 80 additional, RARA-positive patients with data from the randomized portion expected in 2023 or 2024.
Additionally, we plan to initiate the randomized portion of the trial and approximately 80 additional RARA positive patients with data from the randomized portion expected in 2023 or 2024.
David Roth: Finally, I'll turn to 5609, our highly selective and potent oral CDK7 inhibitor. 5609 is being evaluated in the ongoing Phase I trial in combination with chemotherapy in, patients with relapsed refractory pancreatic cancer.
I'll turn to 50 609, our highly selective and potent oral CDK <unk> inhibitor.
56, or nine is being evaluated in the ongoing phase one trial in combination with chemotherapy in patients with relapsed refractory pancreatic cancer.
David Roth: Currently, the only approved agent for second-line pancreatic cancer is Onavide in combination, with 5-FU Leucovorin, which offers an average progression-free survival of approximately three months.
Currently the only approved agent for second line pancreatic cancer is unemployed in combination with slides a few that are born.
Which offers an average progression free survival of approximately three months.
David Roth: The Phase I trial of 5609 remains on track to report clinical activity and safety data, from the safety lead-in portion later this year.
Phase one trial of $56 nine remains on track to report clinical activity and safety data from the safety lead in portion later this year.
Based on these data we will determine the best course for further development of 50 609.
David Roth: Based on these data, we will determine the best course for further development of 5609. We're also pleased that the arm of Roche's ongoing Phase I, I-B intrinsic trial evaluating, 5609 in combination with a tezolizumab, a PD-L1 inhibitor in BRAF mutant colorectal cancer is now actively enrolling patients.
We're also pleased that the arm of <unk> ongoing phase one wouldn't be intrinsic trial evaluating 56 or nine in combination with it because it wasn't bad a PD one inhibitor in BRAF mutant colorectal cancer is now actively enrolling patients.
We're very encouraged by continued momentum across our clinical portfolio and look forward to sharing additional data in the coming months as we learn more about the potential of each of our investigational therapies to change the standard of care.
David Roth: We're very encouraged by continued momentum across our clinical portfolio and look forward, to sharing additional data in the coming months as we learn more about the potential of each of our investigational therapies to change the standard of care for patients.
For patients.
David Roth: Next, I'll turn to our gene control discovery engine. In July, we nominated SY12882, our oral potent and selective CDK12 inhibitor, as our next, development candidate. Preclinical data presented at AACR in April demonstrated that selective CDK12 inhibition, decreased DNA repair and caused cell cycle dysregulation and genomic instability, leading to tumor growth inhibition and apoptosis in preclinical models. Additionally, selective CDK12 inhibition as a single agent induced tumor regression to, model of small cell lung and breast cancer and demonstrated activity in combination with lorbanectin in a small cell lung model, as well as with Elaborib in a PARP-inhibitor-resistant, patient-derived xenograft model of ovarian cancer.
Next I'll turn to our gene control discovery engine.
In July we nominated S. Y 12, 882, our oral potent and selective CDK 12 inhibitor as our next development candidate.
Preclinical data presented at ACR in April demonstrated that selective CDK 12 inhibition decreased DNA repair and caused sales cycle dysregulation and genomic instability.
Adding to tumor growth inhibition of napalm choices in preclinical models.
Additionally, selective CDK <unk> inhibition as a single agent induced tumor regression to model of small cell lung and breast cancer and demonstrated activity in combination with low connectivity.
Small cell lung model.
As well as good a laggard in a PARP inhibitor resistant patient derived xenograft model of ovarian cancer.
David Roth: This nomination is a testament to our gene control discovery engine and Syros' leadership in selective CDK inhibitors.
This nomination is a testament to our gene control discovery engine and serious into leadership and selective CDK inhibitors.
David Roth: As we announced also in July, we're exploring partnerships for 12882, as well as for our CDK11 and WRN programs.
As we announced also in July we are exploring partnerships for 12 82 as well as for our CDK 11 and W are in programs.
David Roth: We're confident this approach will allow us to robustly advance each of our discovery programs as we focus our capital on our clinical assets, which have the potential to deliver the greatest benefit to patients in the near term.
We're confident this approach will allow us to robustly advance each of our discovery programs as we focus our capital on our clinical assets, which have the potential to deliver the greatest benefit to patients in the near term.
With that I'll turn the call over to Jason to review our financial results.
David Roth: With that, I'll turn the call over to Jason to review our financial results.
Thank you David we're excited to be entering the second half of 2022, and a strong financial position.
Jason Haas: Thank you, David.
Jason Haas: We are excited to be entering the second half of 2022 in a strong financial position. As Nancy mentioned, in July, we announced a definitive merger agreement with Time Technologies, where we have agreed to acquire Time, including its pipeline assets and net cash of approximately $60 million. We also announced a PIPE financing, through which new and existing investors agreed to invest $130 million in our combined company. The PIPE was led by a life sciences-focused investment fund and also included new and existing Syros shareholders, such as Flagship, Avidity, DeepTrack, Bain, Invis, Samsara, Adage, Ally Bridge, and Cowen Healthcare Investments.
As Nancy mentioned in July we announced the definitive merger agreement with time technologies, where we have agreed to acquire time, including its pipeline assets and net cash of approximately $60 million.
We also announced a pipe financing through which new and existing investors agreed to invest $130 million and our combined company.
The pipe was led by our life Sciences focused investment fund and also included new and existing Sirius shareholders, such as flagship avidity deep track being in this Sam Sarah Adage ally bridge and Cowen healthcare investments.
Jason Haas: We expect the PIPE to close concurrently with the merger in the second half of this year, subject to the approval of Syros and Time shareholders and other customary closing conditions. Finally, in July, we also announced an amendment to our senior secured loan facility with Oxford Finance, which, subject to certain conditions, will extend the interest-only payment period from March 2023 to March 2024 and upon the achievement of certain milestones all the way to September 2024.
We expect the pipes that closed concurrently with the merger in the second half of this year.
Subject to the approval of zeros in time shareholders and other customary closing conditions.
Only in July we also announced an amendment to our senior secured loan facility with Oxford, finance, which subject to certain conditions will extend the interest only payment period from March 2023 to March 2024, and upon the achievement of certain milestones all the way to September 2024.
Following the close of these transactions, we expect to have a cash balance of approximately $240 million and we believe this capital will be sufficient to fund our planned operating expenses and capital expenditure requirements into 2025.
Jason Haas: Following the close of these transactions, we expect to have a cash balance of approximately $240 million, and we believe this capital will be sufficient to fund our planned operating expenses and capital expenditure requirements into 2025, which is more than a year past our expected pivotal data readout from our select MDS-1 trial and also allow us to build out our commercial operations to support the launch of Temberitin.
Which is more than a year past our expected pivotal data readout from our select Mds, one trial and also allow us to build out our commercial operations to support the launch of a ton of Barrington.
Now I'll turn to our second quarter financial results, we recognized $6 $3 million in revenues in the second quarter of 2022, consisting of $5 7 million from our collaboration with GBT and 600000 from our collaboration with insight.
Jason Haas: Now I'll turn to our second quarter financial results. We recognized $6.3 million in revenues in the second quarter of 2022, consisting of $5.7 million from our collaboration with GBT, and $600,000 from our collaboration with Insight.
Jason Haas: For the second quarter of 2021, we recognized a total of $5.2 million in revenue under our collaborations with GBT and Insight.
For the second quarter 2021, we recognized a total of $5 2 million in revenue under our collaborations with GBT and insight.
R&D expenses were $33 $1 million in the second quarter of 2022 compared to $25 eight for the second quarter of 2021.
Jason Haas: R&D expenses were $33.1 million in the second quarter of 2022 compared to $25.8 million for the second quarter of 2021. This increase was primarily due to costs associated with the continued advancement of our clinical and preclinical programs and employee-related expenses.
This increase was primarily due to costs associated with the continued advancement of our clinical and preclinical programs and employee related expenses.
Jason Haas: G&A expenses were $6.9 million in the second quarter of 22 as compared to $5.5 million for the second quarter of 21. This increase was primarily due to employee-related expenses.
G&A expenses were $6 $9 million in the second quarter of 'twenty, two as compared to $5 five volume for the second quarter of 'twenty one.
This increase was primarily due to employee related expenses.
Jason Haas: Finally, we reported a net loss in the second quarter of $34.5 million or $0.54 per share compared to a net loss of $22.5 million or $0.36 per share for the same period in 2021.
Finally, we reported a net loss for the second quarter of $34 $5 million or <unk> 54 per share.
Compared to a net loss of 22, and a half million dollars or <unk> 36 per share for the same period in 2021.
Operator: With that, I will now turn the call over to the operator for questions.
With that I will now turn the call over to the operator for questions.
Operator: We will now begin the question and answer session.
We will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad.
If youre using a speakerphone please pick up your handset before pressing the keys.
Operator: To ask a question, you may press star then 1 on your telephone keypad.
To withdraw your question. Please press Star then two.
At this time, we'll pause momentarily to assemble the roster.
Operator: If you are using a speakerphone, please pick up your handset before pressing the keys.
The first question comes from Phil Nadeau.
Of Cowen and company Cowen and company. Please go ahead.
Operator: To withdraw your question, please press star then 2.
Congrats on the progress and thanks for taking our questions. A couple of follow ups on 'twenty, one a wonderful if we could first cause.
Is there any inter patient variability and the exposures to 'twenty, one O one or is it relatively consistent across patients.
And then second I know you mentioned the Tolerability profile was it was good but what specifically are there any he's associated with oral dosing such as Gi.
Gi toxicity.
Thanks, Phil it's David.
Operator: At this time, we'll pause momentarily to assemble the roster.
So very it's a good question about variably variability is an important parameter thats going to.
Really helped to inform our actually the.
Totality of the data set that we need to generate in order to select our go forward dose and we haven't reported on that specifically, but I think what I can say is that we've been.
Operator: The first question comes from Phil Nadeau of Cowan Company.
So very encouraged by what we're seeing and we're confident that we're gonna have.
A dose to move forward with that to start our phase III trial in the second half of 2023.
Phil Nadeau: Please go ahead.
With respect to the adverse events that I mentioned, but we really haven't had any reports to date of serious adverse events.
Phil Nadeau: Phil Nadeau, Cowan Company.
No no.
Adverse events.
So tell me profile seems very encouraging obviously.
There is more opportunity for us to observe.
Potential side effects, but at the moment things are looking very encouraging and we have no reason to expect any.
Future issues with the oral form them I think to you.
That's very helpful.
Light of that the good data that you've seen thus far what still remains to be optimized through the <unk>.
In this study.
What parameters are you.
Are you trying to sell for.
Yeah.
Again, so I think the main the main thing that I think we should all appreciate us.
Is that.
The ATM as Joe said, Joseph 0.15 milligrams per kilogram, so the dosing algorithm for the intravenous form.
Wait wait based adjusted.
We've gone in.
Getting this trial without 15 milligram flat dose.
We really feel it's important to understand the characteristics of the patients. So that we understand the exposures, we're measuring and whether theres any influence on those exposures based on characteristics of the patients now weights and obviously want to look at because the IV has.
Chosen to normalize their dose by weight so.
Depending on the range of weeks of the enrolled patients.
Have a good sense as to whether that is a parameter that influences exposure. So we just need to feel good about the breadth.
Of the patients who are coming into the trial, who were getting dose to see if we can do.
To develop an adequate.
Model that helps us determine the relationship between exposure and patient probably right. Obviously, everyone comes in with the same way, we're not going to get a lot of insight into that but obviously, that's not going to be the case. So I think that's really the main thing that we're looking at now is just to build out the robustness of our dataset and go in with the appropriate model.
To assure that you might explore somewhere in the range of different types of patients who may be treated.
Phil Nadeau: Good morning.
Okay, I see that makes a lot of sense.
Phil Nadeau: Congrats on the progress and thanks for taking our questions.
Phil Nadeau: A couple follow-ups on 2101, if we could.
Second question on slipped AML.
He mentioned will get clinical activity measures at the end of the year and I think in the prepared remarks, even mentioned, perhaps a response rates or are we going to get response rates from select AML in the second half of this year or will it be earlier measures of productivity.
Yeah. So.
The trial is testing our triplet Tommy Barentine of earnings.
And what we're calling a safety lead in and that's a prelude to opening the randomized portion of the trial, where we will compare that to the doublet in Asia.
Obviously, we're looking at safety right. So that's the main thing that we need to demonstrate but.
All of these patients are being treated actively for newly diagnosed unfit AML. So we're gonna have responses.
There are aspects of being done and all the usual times after one to three months and so on and thereafter, So I think it's reasonable to expect that you'll.
You'll see activity. In addition in addition to safety and that's those are all the usual measures right. So our primary endpoint is the CR cri rate.
So obviously it will be you know looking for patients who have that and we'll be looking at speed to determining the response and so on and so forth.
Got it that's very helpful. Thanks for taking our questions and congrats again on the progress. Thank you so much thanks Bill.
The next question comes from Jason Butler of JMP Securities. Please go ahead.
Hi, Thanks for taking the questions a couple more on plenty of one on one I guess just to confirm is the plan to advance one dose in phase III or could you explore potentially you know a lower dose as well and then and then secondly can you just remind us of the <unk>.
Phil Nadeau: First, is there any interpatient variability in the exposures to 2101, or is it relatively consistent across patients?
Phil Nadeau: And then second, I know you mentioned the tolerability profile was good, but specifically, are there any AEs associated with oral dosing, such as GI toxicity?
It'll work do you need to do after confirming the dose in the profile in the PK study, but before initiating the phase III trial. Thanks.
Phil Nadeau: Thanks, Phil.
David Roth: It's David.
David Roth: So, it's a good question about variability.
David Roth: Variability is an important parameter that's going to really help to inform, actually, the totality of the data set that we need to generate in order to select our go-forward dose.
Yeah. So.
David Roth: We haven't reported on that specifically, but I think what I can say is that we've been very encouraged by what we're seeing, and we're confident that we're going to have a dose to move forward with to start our Phase 3 trial in the second half of 2023.
We would.
We're going to establish the dose.
That we're going to recommend to treat patients with moving into <unk> into the phase III.
David Roth: With respect to the adverse events that I mentioned, we really haven't had any reports to date of serious adverse events, and we've had no real adverse events.
David Roth: So, the totality profile seems very encouraging.
We haven't specifically, we haven't finalized that determination. That's why you know the trial is still ongoing.
David Roth: Obviously, there's more opportunity for us to observe potential side effects, but at the moment, things are looking very encouraging, and we have no reason to expect any future issues with the oral form of ATO.
It may be.
David Roth: That's very helpful.
A specific dose where it may be a weight adjusted dose. So I think that's really I think where we're leaning right now.
David Roth: In light of the good data that you've seen thus far, what still remains to be optimized through the continuation of the study?
But in terms of other things that need to be done obviously, the obvious things that relate to the trials startup.
David Roth: What parameters are you trying to solve for?
David Roth: Again, I think the main thing that I think we should all appreciate is that IV ATO is dosed at a dose of 0.15 milligrams per kilogram.
David Roth: So, the dosing algorithm for the adrenous form is weight-based adjusted.
You know Nancy if you have any other comments about.
David Roth: We've gone in initiating this trial with a 15-milligram flat dose, and we really feel it's important to understand the characteristics of the patients so that we understand the exposures we're measuring and whether there's any influence on those exposures based on characteristics of the patients. Now, weight is an obvious one to look at because the IV has chosen to normalize their dose by weight.
David Roth: So, depending on the range of weights of the enrolled patients, We'll have a good sense as to whether that is a parameter that influences exposure.
David Roth: So we just need to feel good about the breadth of the patients who are coming into the trial, who are getting dosed to see if we can develop an adequate model that helps us determine the relationship between exposure and patient body weight.
There are activities that are going to happen between now and the initiation of the trial feel free yeah. No I just I was just going to add Jason that obviously the cats.
David Roth: Obviously, if everyone comes in with the same weight, we're not going to get a lot of insight, into that. But obviously, that's not going to be the case.
Selecting the dose on finalizing the protocol and then of course, then there's all the manufacturing necessary without phase III material to start the phase III.
One of the things that we're working on right now and feel very confident that we're on on track here.
With all of those activities and are needed to start the phase III.
Great and then just on the earlier stage pipeline programs.
You said your Youre looking to progress partnership discussions can you just give us a sense of what the priority level there is or how.
How early are advanced into those discussions are obviously I understand you can't give timelines here, but just a sense of how active those discussions are.
Yeah. So first of all I'll, just say that you know we.
We remain very excited and bullish on our gene control discovery engine.
The CDK <unk> inhibitor development candidate nomination is I think it's a great Testament to.
What our scientists can do in terms of collected.
David Roth: So I think that's really the main thing that we're looking at now is just to build out, the robustness of our data set and go in with the appropriate model to assure the right exposures on the range of different types of patients who may be treated.
Collective very potent inhibitors of these important regulatory targets.
It is you know as we're focusing now on kind of our late stage clinical pipeline, we think that it's in the best interest of these programs that we seek our partnerships to ensure that we have adequate capital to robustly.
Phil Nadeau: Okay.
Those early programs. So we have ongoing discussions going on on the oncology.
Discovery programs and we feel.
Confidence in terms of being able to enter into one or more partnerships, but well keep you apprised of that.
Okay, great. Thanks for taking the questions.
Mhm.
As a reminder, if you have a question please press star one.
The next question comes from Mark Breidenbach of Oppenheimer. Please go ahead.
Phil Nadeau: I see.
Hey, good morning, guys and thanks for taking our questions.
Just a few quick ones for me.
First with regard to the EMA feedback.
Phil Nadeau: That makes a lot of sense.
On FY 'twenty, one or one.
Did that feedback substantially influence or or or cause you to change your plans for the design of your pivotal trial in terms of size.
Phil Nadeau: Second question on SelectAML, you mentioned we'll get clinical activity measures at the, end of the year. And I think in the prepared remarks, you even mentioned perhaps response rates.
Another question is is what's the timing looking like for the initiation of the randomized portion of the select AML. One study is that something we can expect to kick off kind of.
Phil Nadeau: Are we going to get response rates from SelectAML during the second half of this year, or will, it be earlier measures of activity?
David Roth: Yeah.
Later this year as soon as we see that the safety lead in data and one final one for me.
Very quickly does the pending GBT acquisition by Pfizer, what does that mean for your collaboration are you getting any indications that Pfizer would want to continue developing fetal hemoglobin inducers. Thanks for taking the questions.
Sure.
Okay. So the first question was related to the EMA feedback on 'twenty one to one so we had.
Already received feedback from a very fruitful dialogue with the food and drug administration on our proposed strategy and it really.
Was important corroborating our approach.
Giving us a solid foundation upon which we can move forward with endpoints.
Our.
Benchmarks to assessments endpoints and various.
Various things like that so we had a good structure for study designed to take forward and also in terms of size, we took that strategy to the EMEA and vetted our approach there and we've received general alignment that strategy, but solid and so we come back from that meeting now emboldened with the notion that we have.
An opportunity to use one protocol to seek global approvals in both the U S and in Europe . So that's really very exciting and very strong positive.
Feedback from our go forward plan.
David Roth: So, look, the trial is testing our triplet of tamibaritine and venasa in what we're calling, a safety lead-in. And that's a prelude to opening the randomized portion of the trial, where we'll compare that, to the doublet of venasa. Obviously, we're looking at safety, right?
The AML trial, obviously, we're on target to report data coming out of the safety lead in.
In the second half of this year absent later this year.
And our current plan is to move forward with the randomized portion you know as we get closer to that will give you an update on.
David Roth: So, that's the main thing that we need to demonstrate.
On the specific timing of opening the randomized portion of the trial.
David Roth: But all these patients are being treated actively for newly diagnosed unfit AML.
David Roth: So, we're going to have responses, you know, bone marrow aspirates are being done at all, the usual times after one, two, three months, and so on and thereafter.
David Roth: So, I think it's reasonable to expect that you'll see activity in addition to safety.
And then the last one with regard to the G. P T and I'll, let you take that one.
David Roth: And those are all the usual measures, right?
David Roth: So, our primary endpoint is the CR-CRI rate.
Yeah.
We are.
We remain really excited about our ongoing collaboration with GBT, which is to develop.
David Roth: So, obviously, we'll be, you know, looking for patients who have that, and we'll be looking, at the speed to determining the response, and so on and so forth.
Small molecule inducer of fetal hemoglobin, which we think is a really great opportunity.
Phil Nadeau: Got it.
To treat kind of give a functional cure of sickle cell disease patients with <unk>.
Phil Nadeau: That is very helpful.
Oral medicine.
Phil Nadeau: Thanks for taking our questions, and congrats again on the progress.
And obviously, we're incredibly excited for GTT with the news yesterday about the Pfizer acquisition and I think.
Phil Nadeau: Thank you so much.
Phil Nadeau: Thanks, Bill.
Suggests to me that there's a real interest in sickle cell disease and thinking about all the ways that we can improve that disease, which had been neglected for so long and I think it's a very exciting overall for that for the field to have that potential 10, a pending acquisition.
Operator: The next question comes from Jason Butler of JMP Securities.
Jason Butler: Please go ahead.
Jason Butler: Hi.
Jason Butler: Thanks for taking the questions.
Yes.
Jason Butler: A couple more on 2101.
In terms of what we're doing right now it doesn't impact our collaboration but as we've learned more.
Jason Butler: I guess just to confirm, is the plan to advance one dose into Phase 3, or could you explore, potentially, you know, a lower dose as well?
Jason Butler: And then, secondly, can you just remind us of the, you know, additional work you need, to do after confirming the dose and the profile in the PK study, but before initiating the, Phase 3 trial?
Jason Butler: Thanks.
David Roth: Yeah.
David Roth: So first, I would just say that, you know, we we remain very excited and bullish on our gene, control discovery engine.
David Roth: Yeah, so, you know, we would, you know, we're going to establish the dose that we're going, to recommend to treat patients with moving into the Phase 3.
David Roth: The CDK-12 inhibitor development candidate nomination, as I think, is a great testament to what our scientists can do in terms of selective, very potent inhibitors of these important regulatory targets.
David Roth: You know, we haven't, you know, finalized that determination.
More from discussions with GBT will have a better idea about where that's going but it's.
David Roth: As you know, as we're focusing now on kind of our late stage clinical pipeline, we think that it's in the best interest of these programs that we seek a partnership to ensure that we have adequate capital to robustly develop those early programs.
David Roth: That's why, you know, the trial is still ongoing.
David Roth: So, you know, we have ongoing discussions going on on these oncology discovery programs, and we, feel, you know, confident in terms of being able to enter into one or more partnerships.
David Roth: It may be a specific dose or it may be a weight-adjusted dose, so, you know, I think that's really, I think where we're leaning right now, and, you know, in terms of other things that need to be done, obviously, the obvious things that relate to trial start-up, you know, Nancy, if you have any other comments about.., other activities that are going to happen between now and the initiation of the trial.
David Roth: But, you know, we'll we'll keep you apprised of that.
David Roth: Feel free.
Nancy Simonian: Yeah, no, I just I was just going to add, Jason, that obviously the, selecting the dose, finalizing the protocol, and of course, then there's all the manufacturing necessary for that phase three material to start the phase three are kind of the things that we're working on right now and feel very confident that we're on on track to with all of those activities that are needed to start the phase three.
Nancy Simonian: Great.
Relates to our clubs our relationship but we we think gets I'd say overall really positive news for the sickle cell disease community.
Jason Butler: And then just on the the earlier stage pipeline programs, you said you're you're looking to progress partnership discussions.
Jason Butler: Can you just give us a sense of what the priority level there is or how how early or advanced into those discussions are?
Jason Butler: Obviously, I understand you can't give timelines here, but just a sense of how active those discussions are.
Jason Butler: Okay, great.
Jason Butler: Thanks for taking the questions.
Alright, thanks, so much and congrats again.
Operator: As a reminder, if you have a question, please press star one.
Operator: The next question comes from Mark Bradenbach of Oppenheimer.
Mark Bradenbach: Please go ahead.
Mark Bradenbach: Hey, good morning, guys, and thanks for taking our questions.
Mark Bradenbach: Just a few quick ones for me.
Seeing that there are no further questions I would like to turn the conference back over to Nancy Simonian for closing remarks.
Mark Bradenbach: First, with regard to the EMA feedback on SY2101, did that feedback substantially influence or, cause you to change your plans for the design of your pivotal trial in terms of size and endpoints?
Mark Bradenbach: Another question is, what's timing looking like for the initiation of the randomized portion of, the select AML1 study?
Mark Bradenbach: Is that something we can expect to kick off kind of later this year, as soon as we see that the safety lead-in data?
Mark Bradenbach: And one final one for me, you know, very quickly, does the pending GBT acquisition by Pfizer, you know, what does that mean for your collaboration?
Mark Bradenbach: Are you getting any indications that Pfizer would want to continue developing fetal hemoglobin, inducers?
Mark Bradenbach: Thanks for taking the questions.
David Roth: Sure.
David Roth: Okay, so the first question was related to the EMA feedback on 2101.
Thank you operator, and thank you everyone for joining us today and for your continued support.
David Roth: So, you know, we had already received feedback from a very fruitful, dialogue with the Food and Drug Administration on our proposed strategy, and it really was important in corroborating our approach and giving us a solid foundation upon which we can move forward, you know, with endpoints and… and Benchmarks to assess those endpoints and various things like that.
David Roth: And then the last one, which relates to GBT, and I'll let Nancy take that one.
David Roth: So we had a good structure for study design to take forward also in terms of size. We took that strategy to the EMA and vetted our approach there, and we received general, alignment that that strategy was solid.
David Roth: And so we come back from that meeting now emboldened with the notion that we have an, opportunity to use one protocol to seek global approvals in both the U.S. and then Europe.
David Roth: So that's really very exciting and very strong positive feedback for our Go Forward plan.
David Roth: With the AML trial, obviously we're on target to report data coming out of the safety lead-in, in the second half of this year, so later this year.
Nancy Simonian: Yeah.
David Roth: And our current plan is to move forward with the randomized portion. As we get closer to that, we'll give you an update on the specific timing of opening, the randomized portion of the trial.
Nancy Simonian: So, you know, we remain really excited about our ongoing collaboration with GBT, which, is to develop, you know, sort of small molecule inducers of fetal hemoglobin, which we think is a really great opportunity to treat, kind of give a functional cure to sickle cell disease patients with an oral medicine.
We look forward to updating you again soon as we advance our portfolio and work to build <unk> into a leading biopharmaceutical company.
Nancy Simonian: And obviously we're incredibly excited for GBT with the news yesterday about the Pfizer, acquisition.
Nancy Simonian: And I think, you know, it suggests to me that there's a real interest in sickle cell disease, and thinking about all the ways that we can improve that disease, which has been neglected for so long.
Nancy Simonian: So I think it's very exciting overall for the field to have that potential pending acquisition.
Nancy Simonian: You know, in terms of what we're doing right now, it doesn't impact our collaboration, but as we learn more from discussions with GBT, we'll have a better idea about where that's going, but it relates to our relationship.
Nancy Simonian: But we think it's actually overall really positive news for the sickle cell disease, community.
Mark Bradenbach: All right.
Operator: Thanks so much and congrats again.
Nancy Simonian: Seeing that there are no further questions, I would like to turn the conference back over, to Nancy Simonian for closing remarks.
These reach out if you have any further questions. Thank you.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
Nancy Simonian: Thank you, operator, and thank you everyone for joining us today and for your continued, support of Seros.
Nancy Simonian: We look forward to updating you again soon as we advance our portfolio and work to build, Seros into a leading biopharmaceutical company.
Operator: You may now disconnect.
Nancy Simonian: Please reach out if you have any further questions.
Operator: Thank you.
Operator: The conference is now concluded.
Operator: Thank you for attending today's presentation.