Q4 2021 Syros Pharmaceuticals Inc Earnings Call

Operator: Good morning, and welcome to Syros Pharmaceuticals' fourth quarter and full year 2021 financial results conference call. At this time, all participants are in listen-only mode.

Good morning, and welcome to Sirius Pharmaceuticals, fourth quarter, and full year 2021 financial results Conference call.

At this time, all participants are in listen only mode.

Operator: This call is being webcast live on the Investors & Media section of Syros's website at www.syros.com. Please be advised that today's 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 Syros. Thank you.

Call is being webcast live on the investors and media section of Cra's website at Www Dot C Ross Dot com.

Please be advised that today's 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 Syros.

Courtney Solberg: This morning, we issued a press release with our fourth quarter and full year 2021 financial results, along with anticipated future milestones and recent accomplishments. The release is available on the investors and media section of Syros' website at www.syros.com. We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer, Dr. David Roth, our Chief Medical Officer, and Jason Haas, our Chief Financial Officer. We will then open the call to questions.

Thank you. This morning, we issued a press release with our fourth quarter and full year 2021 financial results, along with anticipated future milestones and recent accomplishments it releases that'd be helpful.

On the investors and media section of its website at Www Dot heroes dotcom.

We will begin the call with prepared.

Remarks, My Doctor Nancy Simonian, our Chief Executive Officer, Dr. David Roth, Our Chief Medical Officer, and Jason Hahn, Our Chief Financial Officer.

Well then open the call for questions.

Dr. Eric Olson, our Chief Scientific officer.

Christian Stephens, our Chief Development Officer, and only T. Our Chief commercial officer are also on the call it will be available for Q&A.

Courtney Solberg: Dr. Eric Olson, our Chief Scientific Officer, Kristen Stevens, our Chief Development Officer, and Conley Chee, 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 the statements we make on this call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factors section of our annual report on Form 10-K that we filed this morning and any other filings that we may make with the SEC in the future.

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

Actual events or results could differ materially from those expressed or implied.

Any forward looking statements as a result of fairness.

Uncertainties and other factors, including those set forth in the risk factors section of our annual report on Form 10-K that we filed this morning and any other filings that we may make with the S. E C in the future.

Courtney Solberg: 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. Any forward-looking statements made on this call represent our views as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statement.

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

Any forward looking statements made on this call represent our views as of today and should not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update or revise any forward looking statements I would now like to turn the call over to Nancy.

Nancy Simonian: I would now like to turn the call over to Nancy. Thank you, Courtney. Good morning, everyone, and thank you for joining us today to review our fourth quarter and full-year financial results and recent updates. 2021 was a pivotal year for Syros, driven by the expertise, commitment, and capabilities of our team. Last year, we initiated three clinical trials and one expansion cohort across our targeted hematology and CDK inhibitor portfolios, including the select MDS-1 Phase III trial, our first pivotal study of TEMI Baratine and RARA positive patients with higher risk MDS, and select AML-1 Phase 2 Study of Tammy Baratine and Rara Positive Patients with AML, a dose confirmation study of SY-2101 in APL patients.

Nancy Simonian: And finally, an expansion cohort of SY5609 in combination with chemotherapy in pancreatic cancer patients. These initiations highlight our advancement towards becoming a fully integrated biopharmaceutical company with a diversified pipeline with the potential to make a profound difference for patients. Additionally, in September, we reported promising clinical data from our phase one dose escalation trial of 5609, our highly selective and potent oral CDK7 inhibitor, based on the results, as well as mechanistic rationale and preclinical data, we are now planning to evaluate 56-09 in three distinct opportunities, pancreatic cancer, b-rath mutant colorectal cancer, and hematologic malignant [inaudible] To support the continued progress, as well as advance Syros to the next phase of our growth, we appointed two new key leadership team members.

Thank you Courtney and good morning, everyone and thank you for joining us today to review, our fourth quarter and full year financial results and recent updates.

Nancy Simonian: In September, we named Conley Chee as our first Chief Commercial Officer, who has been hard at work laying the groundwork to set us up for commercial success, and Jason Haas, appointed as our CFO in October, has been spearheading our financing effort.

2021 was a pivotal year for syros, driven by the expertise commitment and capabilities of our team at syros.

Last year, we initiated three clinical trials and one expansion cohort across our targeted hematology and CDK inhibitor portfolios.

Including the select M. D. S. One phase III trial, our first pivotal study of <unk> in RARA positive patients with higher risk Mds.

The select AML, one phase II study of Tami Barron teen in RARA positive patients with AML.

It dose confirmation study of FY 'twenty, one to one and a P L patients.

And finally, an expansion cohort of S. Y 50, 609 in combination with chemotherapy and pancreatic cancer patients.

These initiations highlight our advancement towards becoming a fully integrated biopharmaceutical company with a diversified pipeline with the potential to make a profound difference for patients.

Additionally in September we reported promising clinical data from our phase one dose escalation trial of 50 609 are highly selective and potent oral CDK seven inhibitor.

Based on the results as well as mechanistic rationale and preclinical data. We are now planning to evaluate 50 609 and three distinct opportunities.

Pancreatic cancer.

B RAF mutant colorectal cancer and hematologic malignancies.

To support the continued progress as well as advanced zero to the next phase of our growth we appointed two new key leadership team members.

In September we named finally Chi as our first Chief commercial officer, who has been hard at work laying the groundwork to set us up for commercial success.

And Jason Haas appointed as our CFO in October has been spearheading our financing efforts.

Nancy Simonian: Syros is looking forward to an exciting year in 2022 with three anticipated data readouts across our clinical portfolio. First, we will be sharing PK and safety data from our dose confirmation trial of 2101 in APL mid-year. Then, in the second half of this year, we plan to report clinical activity data from the safety lead-in portions of the SELECT-AML1 Phase 2 trial of tamivarotene in the expansion cohort of 5609 in pancreatic cancer. These results may unlock important insights into the potential of each of our programs and inform our development strategy moving forward.

Cirrhosis looking forward to an exciting year in 2022 with three anticipated data readouts across our clinical portfolio.

First we will be sharing PK and safety data from our dose confirmation trial of 21 to one and a P. L midyear.

Then in the second half of this year, we plan to report clinical activity data from the safety lead in portion of the select ammo one phase II trial of Tami Barrick team and the expansion cohort of 50 609 in pancreatic cancer.

And these results may unlock important insights into the potential of each of our programs and inform our development strategy moving forward.

Nancy Simonian: Additionally, we are looking forward to presenting an e-poster at the AACR meeting in April that shows our oral-selective CDK12 inhibitor has potent single-agent activity in vitro and in vivo in multiple cancer models, as well as enhanced antitumor effects when used in combination with DNA-damaging agents. These data support our decision to nominate our next development candidate from our CDK-12 program, which we expect to This program, as well as our other preclinical oncology programs, CDK-11 and WRN, reflect the productivity of our gene-controlled discovery engine, a key driver of our long-term goal to discover and develop highly potent and selective small molecules that target gene regulatory systems. I would now like to turn the call over to David, who will discuss our ongoing clinical programs. Thank you, Nancy.

Additionally, we are looking forward to presenting an E poster at the ACR meeting in April that shows our oral selective CDK 12 inhibitor has potent single agent activity in vitro and in vivo in multiple cancer models as well as enhanced anti tumor effect in combination with DNA damaging.

Agents.

These data support our decision to nominate our next development candidate from our C. D. K 12 program, which we expect to do in the second half of this year.

This program as well as our other preclinical oncology programs CDK 11, and W. R. N reflect the productivity of our gene control discovery engine, a key driver of our long term goal to discover and develop highly potent and selective small molecules that target gene regulatory systems.

I would now like to turn the call over to David who will review our ongoing clinical programs Davis.

Thank you Nancy.

David Roth: Today, I will discuss our clinical stage pipeline and review the upcoming important readouts we're anticipating this year. We have a lot to look forward to as these milestones will set us up for rich clinical and regulatory catalysts in the next two years. I'm excited to report that our select MDS-1 Pivotal Trial for RARA Positive newly diagnosed higher risk MDS patients is progressing well, and we expect to have data either late 2023 or early 2024 with a potential NDA filing in 2024.

Today, I will discuss our clinical stage pipeline and review the upcoming important readouts, we're anticipating this year.

We have a lot to look forward to as these milestones will set us up for rich clinical and regulatory catalysts in the next two years.

I'm excited to report that our select MTS, one pivotal trial for RARA positive newly diagnosed higher risk Mds patients is progressing well and we expect to have data either late 2023 or early 2024 with a potential NDA filing in 2024.

David Roth: If the trial is successful, Tamibaratine has the potential to offer higher-risk MDS patients a well-tolerated and effective treatment option. However, aside from hypomethylating agents, there have been no new therapeutics approved for this indication in over a decade.

If the trial is successful Xiaomi barraging has the potential to offer higher risk Mds patients are well tolerated and effective treatment option.

Aside from Michael Methylated patients there have been no new therapeutics are approved for this indication in over a decade.

David Roth: The unmet medical need is high for the approximately 21,000 newly diagnosed high-risk MDS patients in the U.S. and EU estimated annually. We believe tamibaritine, an oral drug with a novel mechanism of action, promising clinical activity, and a favorable tolerability profile, could change the standard of care for approximately 30 percent of these higher risk MDS patients who are RARA positive. In addition to the progress we are making, we're pleased that, in February, we received orphan drug designation from the FDA, representing an important milestone for the development of Tammy Baratine in MDS and providing certain benefits, including a seven-year period of market exclusivity if the drug is approved.

The unmet medical need is high for the approximately 21000 newly diagnosed high risk Mds patients in the U S and EU estimated annually.

We believe Tommy Barraging, an oral drug with a novel mechanism of action.

Pharmacy clinical activity and a favorable tolerability profile could change the standard of care for approximately 30% of these higher risk Mds patients who are RARA positive.

In addition to the progress we're making we're pleased that in February we received orphan drug designation from the FDA, representing an important milestone for the development of Tami Barraging in Mds, and providing certain benefits, including a seven year period of market exclusivity if the drug is approved.

David Roth: [inaudible] As we look ahead to a potential commercial launch, we entered into a master collaboration agreement with QIAGEN in March to develop and commercialize a companion diagnostic test for our proprietary RARA biomarker to identify RARA-positive higher-risk MDS patients who may benefit from using tamibaritine. Under the terms of the agreement, QIAGEN will also be responsible for obtaining and maintaining regulatory approvals for the Commercial Companion Diagnostic Test, since hematology physicians often treat both AML and MDS.

As we look ahead to a potential commercial launch we entered into a master collaboration agreement with Qiagen in March to develop and commercialize a companion diagnostic test for our proprietary RARA biomarker to identify RARA positive higher risk Mds patients, who may benefit from using <unk>.

Barra team.

Under the terms of the agreement Qiagen will also be responsible for obtaining and maintaining regulatory approvals for the commercial companion diagnostic test.

Since hematology physicians, often treat both AML and Mds.

David Roth: They are familiar with using diagnostic testing to determine the optimal targeted treatment for blood cancer. We anticipate that following potential approval, physicians will readily integrate the RARA companion diagnostic test for routine evaluation of their MDS patients and subsequently turn to our targeted therapy as the standard of care for RARA-positive higher-risk MDS. Turning to our efforts in AML, our SELECT-AML-1 Phase 2 study is ongoing and evaluating tamibarotene in combination with vanazza in RARA-positive patients with newly diagnosed unfit AML. We estimate that there are approximately 25,000 newly diagnosed unfit AML patients in the US and EU each year, of which about 30% are RARA positive, representing one of the largest targeted populations in unfit AML.

They are familiar with using diagnostic testing to determine the optimal targeted treatment for blood cancers.

We anticipate that following potential approval physicians will readily integrate the railroad companion diagnostic tests for routine evaluation of their Mds patients and subsequently turned to our targeted therapy as the standard of care for RARA positive higher risk Mds.

Turning to our efforts in AML, our select AML, one phase III study is ongoing and evaluating Tammy barraging in combination with Vanessa in RARA positive patients with newly diagnosed unfit AML.

We estimate that there are approximately 25000 newly diagnosed unfit AML patients in the U S and EU each year of which about 30% of RARA positive representing one of the largest targeted populations can unfit AML.

David Roth: We believe there's a substantial market opportunity for tamibaritine in AML, as 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 Nancy mentioned previously, we're on track to report clinical activity data from the safety lead-in cohort of the SELECT-AML1 trial in the As a reminder, this cohort is expected to enroll approximately 15 newly diagnosed, rara-positive, unfit, and ill patients.

We believe there is a substantial market opportunity for Tommy Barraging in AML.

That's our translational and clinical data support the potential for the RARA biomarker to enrich for patients more likely to respond to Tami Barron team and for whom the standard of care maybe suboptimal.

As Nancy mentioned previously we're on track to report clinical activity data from the safety lead in cohort of the select AML one trial in the second half of this year.

As a reminder, this cohort is expected to enroll approximately 15 newly diagnosed RARA positive unfit AML patients.

David Roth: If successful, we will then advance into a randomized portion of the trial, which will evaluate our triplet regimen of Tamivarotene plus Venasa compared to Venasa alone, and the primary endpoint will be the composite complete response rate. In addition, we're also developing 2101 as a novel oral form of arsenic trioxide, or ATO, for acute promyelocytic leukemia, or A

If successful we will then advance into a randomized portion of the trial, which will evaluate our triplet regimen of Tami Barraging, plus Vanessa compared to <unk> alone and the primary endpoint will be the composite complete response rate.

In addition, we're also developing 21 O one as a novel oral form of arsenic trioxide or Ato for acute <unk> leukemia or APL patients.

David Roth: 2021 has the potential to replace the IV form of HTO, which is standard of care for APL. We believe 2101 could significantly improve upon IVATO by reducing the treatment burden, increasing patient access, and limiting health care costs and utilization. The ongoing dose confirmation trial is designed to evaluate the pharmacokinetics and food effect of 2101 using CMAX and AUC, as well as tolerability, with the goal of identifying an optimal dose for the phase 3 trial.

21 O. One has the potential to replace the IV form of <unk>, which is standard of care for APL.

We believe 21 O one could significantly improve upon IV ato by reducing the treatment burden, increasing patient access and limiting health care costs and utilization.

The ongoing dose confirmation trial is designed to evaluate the pharmacokinetics and food effect of 21 O one using C Max and AUC as well as Tolerability with the goal of identifying an optimal dose for the phase III trial.

David Roth: We plan to report data from the dose confirmation trial mid-year. From the feedback we received from the Type C meeting with the FDA in November, we have a clear development path for 2101 in frontline APL. Importantly, at this meeting, the agency reaffirmed its support for using molecular complete response rate as the primary endpoint for accelerated approval and event-free survival rate at two years as the primary endpoint for full approval. In each case, the clinical data generated in patients treated with 2101 will be compared to historic data with IVHC.

We plan to report data from the dose confirmation trial midyear.

From the feedback we received from the type C meeting with the FDA in November we have a clear development path for 'twenty, one O one in frontline APL.

Importantly at this meeting the agency reaffirmed its support for using molecular complete response rates as the primary endpoint for accelerated approval and event free survival rate at two years as the primary endpoint for full approval.

In each case, the clinical data generated in patients treated with 'twenty, one on one will be compared to historic data with IV <unk>.

David Roth: We expect to enroll approximately 215 patients in the Phase 3 study randomized 2-1 to receive 21-01 or IVATO. With the IVATO arm, allowing us to make safety and tolerability comparisons to assist in assessing the overall outcomes of the 21-01 arm. We plan to initiate the phase 3 study in the first quarter of next year with pivotal data expected in 2025. Now turning to 5609, our highly selective and potent oral CDK7 inhibitor

We expect to enroll approximately 215 patients in the phase three study randomized two to one to receive 21 O. One.

Or IV, a T O with the IV, a T O arm, allowing us to make safety and tolerability comparisons to assist in assessing the overall outcomes of the 'twenty one on one arm.

We plan to initiate the phase III study in the first quarter of next year with pivotal data expected in 2025.

Now turning to 50 609, our highly selective and potent oral CDK seven inhibitor.

David Roth: In September, we announced promising data from our phase one dose escalation study in patients with select solid tumors. We identified a dose and schedule for 5609 that achieved proof of mechanism and was generally well-tolerated with predominantly low-grade AEs and a low rate of treatment discontinuation due to AEs. Importantly, we saw the highest level of single-agent clinical activity in the relapsed refractory pancreatic cancer patients we enrolled. In this highly refractory patient population, we observed stable disease, tumor regressions, as well as tumor marker reduction. Based on these data, as well as supportive pre-clinical 5609 in vivo data, we initiated in the fourth quarter our expansion cohort evaluating 5609 in combination with chemotherapy for patients with relapsed refractory pancreatic cancer.

In September we announced promising data from our phase one dose escalation study in patients with select solid tumors.

We identify the dose and schedule for 50, 609, which achieved proof of mechanism and was generally well tolerated with predominantly low grade <unk> aes and a low rate of treatment discontinuation due to aes.

Importantly, we saw the highest level of single agent clinical activity in the relapsed refractory pancreatic cancer patients we enrolled.

In this highly refractory patient population, we observed stable disease tumor regression as well as tumor marker reductions.

Based on these data as well as supportive preclinical 50 609 in vivo data we initiated in the fourth quarter, our expansion cohort evaluating 50 609 in combination with chemotherapy for patients with relapsed refractory pancreatic cancer.

David Roth: We expect the cohort to enroll approximately 50 patients who have progressed following first-line treatment with full Farinox in first or second relapse. Starting with a biologically active dose of 5609 below the MTD of the seven-day on, seven-day off regimen, patients will be treated with 5609 in combination with gemcitabine or 5609 in combination with gemcitabine and NAB-paclitaxel using the approved doses of the combination agent. We plan to report clinical activity data from the safety lead-in portion of the trial in the second half of this year. We're also pursuing a second combination strategy with 5609 in BRAF mutant colorectal cancer.

We expect the cohort to enroll approximately 50 patients who have progressed following first line treatment with full paradox in first or second relapse.

Starting with a biologically active dose of $56 nine below the MTGE of the seven day on seven day off regimen patients will be treated with 50 609 in combination with Gemcitabine or 50 609 in combination with Gemcitabine and Nab Paclitaxel using the approved doses of the combination agents.

We plan to report clinical activity data from the safety lead in portion of the trial in the second half of this year.

We're also pursuing a second combination strategy with $56 nine in BRAF mutant colorectal cancer.

David Roth: In August 2021, we entered an agreement with Roche to evaluate 5609 in combination with their PD-L1 inhibitor, tezolizumab. Roche expects to begin enrolling patients in this arm of their ongoing phase 1, 1B intrinsic trial in the first half of this year, which will mark the first clinical investigation of a CDK7 inhibitor with an immunotherapy. Since we are supplying 5609 and Roche is sponsoring the trial, Roche will be responsible for communicating subsequent data updates.

In August 2021, we entered an agreement with Roche to evaluate 50 609 in combination with their PD L. One inhibitor. It is iliza mab.

Roche expects to begin enrolling patients in this arm of their ongoing phase one one be intrinsic trial in the first half of this year, which will mark the first clinical investigation of a CDK <unk> inhibitor with an immunotherapy.

Since we are supplying 50 609, and Roche is sponsoring the trial Roche will be responsible for communicating subsequent data updates.

David Roth: Finally, and as we announced in January, we plan to pursue 5609 in hematologic malignancies. Based on mechanistic rationale and preclinical data, which support the potential of CDK7 inhibition across a range of blood cancers, we plan to initiate a trial of 5609 in relapsed refractory hematologic malignancies to identify a maximum tolerated dose for this population and assess clinical activity. In preclinical studies, CDK7 inhibitors, including 5609, demonstrated a high level of activity across diverse hematologic cell lines and showed robust single-agent in vivo activity.

Finally, and as we announced in January we plan to pursue 50, 609 and hematologic malignancies.

On mechanistic rationale and preclinical data, which support the potential of CDK <unk> inhibition across a range of blood cancers. We plan to initiate the trial of 50 609 in relapsed refractory hematologic malignancies to identify a maximum tolerated dose for this population and assess clinical activity.

In preclinical studies, CDK <unk> inhibitors, including 56 O nine demonstrated a high level of activity across diverse hematologic cell lines.

<unk> robust single agent in vivo activity.

David Roth: In addition, we've seen synergy with a BTK inhibitor and with venetoclax in vitro. These data give us confidence in our clinical development strategy, and we look forward to initiating a phase one trial in the second half of this year. We are incredibly encouraged by recent progress across our portfolio and are looking forward to reporting data from all three of our clinical programs this year, with the potential to provide valuable insights into clinical activity, safety, tolerability, and dosing.

In addition, we've seen synergy with the <unk> inhibitor and with Venetic lax in vitro.

These data give us confidence in our clinical development strategy and we look forward to initiating a phase one trial in the second half of this year.

We are incredibly encouraged by recent progress across our portfolio and are looking forward to reporting data from all three of our clinical programs. This year with the potential to provide valuable insights into clinical activity safety Tolerability and dosing.

David Roth: With that, I'll turn the call over to Jason to review our fourth quarter and full year 2021 financial results. Thank you, David. We ended 2021 with $143.4 million in cash, cash equivalents, and marketable securities compared with $174 million at the end of 2020.

With that I'll turn the call over to Jason to review, our fourth quarter and full year financial results.

Thank you David turning now to our fourth quarter and full year of 2021 financial results. We ended 2021 with $143 4 million in cash cash equivalents and marketable securities compared with $174 million at the end of 2020 base.

Jason Haas: Based on our current plans, we believe we have sufficient capital to fund our planned operating expenses and capital needs into the first quarter of 2023. We recognized $7.8 million in revenue in the fourth quarter of 2021 from our collaboration with GBT and Insight. For the full year of 2021, we recognized $23.5 million in revenue.

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

We recognized $7 $8 million in revenue in the fourth quarter of 2021 from our collaboration with GBT and insight for the full year 2021, we recognized 23 and a half million dollars in revenue.

Jason Haas: For the fourth quarter and full year 2020, we recognize a total of $5.7 million and $15.1 million under our GBT and Insight collaborations, respectively. R&D expenses were $26.8 million in the fourth quarter of 2021 and $100 million for the full year 2021 as compared to $29 million for the fourth quarter of 2020 and $76 million for the full year 2020. The increase for the year ended December 31st, 2021, was primarily due to the increase in costs associated with the continued advancement of our clinical and preclinical programs and employee-related expenses. G&A expenses were $6.4 million in the fourth quarter of 2021 and $23 million for the full year 2021.

For the fourth quarter and full year 2020, we recognized a total of $5 $7 million and $15 $1 million under our GBT and insight collaborations respectively.

R&D expenses were $26 $8 million in the fourth quarter of 2021 and $100 million for the full year 2021, as compared to $29 million for the fourth quarter of 2020 and $76 million for the full year 2020.

The increase for the year ended December 31, 2021 was primarily due to the increase in cost associated with the continued advancement of our clinical and preclinical programs and employee related expenses.

<unk> expenses were $6 $4 million in the fourth quarter of 2021 and $23 million for the full year 2021 for.

Jason Haas: For 2020, our J&A expenses were $5.9 million for the fourth quarter and $21.3 million for the full year. Finally, we reported a net loss for the fourth quarter of $23.8 million, or $0.38 per share, compared to a net loss of $30.1 million, or $0.62 per share, for the same period last year. Our net loss for the full year 2021 was $86.6 million, or $1.38 per share, compared to a net loss of $84 million, or $1.82 per share, for the full year 2020.

For 2020, our G&A expenses were $5 9 million for the fourth quarter and $21 $3 million for the full year.

Finally, we reported a net loss for the fourth quarter of $23 $8 million or <unk> 38 per share compared to a net loss of $30 $1 million or <unk> 62 per share for the same period in 2020, our net loss for the full year 2021 was $86 $6 million or $1 38 per share compared to a net loss.

<unk> of $84 million or $1 82 per share for the full year 2020.

Operator: With that, I'll turn the call over to the operator for questions. If you'd like to ask a question at this time, please press the star, then the number one key on your touchtone telephone. To withdraw your question, press the pound key.

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

If you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone telephone to.

To withdraw your question press the pound key.

Operator: Again, that is a star, then one, if you'd like to ask a question. Our first question comes from Ted Tenthoff with Piper Sandler. Great, thank you very much for taking my question, and a lot of progress that I don't think is necessarily being made. That's the market that we're currently in, and a lot of data flow that's here that hopefully is going to be recognized, and this presumably has to do with Tim McBarrattine and Select. Hey Ted,

Again that is star then one if you'd like to ask a question.

Our first question comes from Ted <unk> with Piper Sandler.

Great. Thank you very much for all ticking.

And a lot of progress.

Don't think of Mexicana.

Yes.

No that's it.

The markets that we're currently in and a lot of data for industrial look hopefully it's going to be working.

Alright.

Presumably hooker work.

Our etame Barracuda and collect.

To get a sense for sort of what the thresholds.

Might be looking for.

You know to determine.

Next steps and kind of what we should expect for the data readout for sure. Thank you.

Hey, Ted Yeah, great to hear from you I'm going to turn that over to David. Thanks.

David Roth: Great to hear from you. I'm going to turn that over to David. Thanks for the question, Ted. So with respect to the AML study, which is the Select AML-1 trial, we're in the process of what we're referring to as a safety lead-in. And we're looking forward to reporting data, sharing clinical activity, as well as safety of the triplet combination, tamibaritine plus vanadoclax plus azincitrate. And one of the things we'll be looking for, well, obviously safety will be an important parameter to assure that we can combine all three drugs and use them to move forward.

Thanks for the question Ted.

So with respect to the AML study, which is the select AML one trial.

We're in the process of what we're referring to as a safety lead in and we're looking forward to reporting data sharing.

Sharing clinical activity as well as safety of the triplet combination Tammy <unk>, plus <unk> plus as exciting and one of the things we'll be looking for we'll obviously be safety will be an important parameter to assure we can combine.

David Roth: But we'll be looking at the clinical activity, and in particular, we have benchmarks for Tammy Baratine and Asa that came from the same patient population in our phase two where we saw an approximate 61% composite complete response rate. So, we'll certainly be looking for responses that are, you know, north of that to justify adding a plan to collect data into the region. That would be a starting place, Well, and I guess that's exactly where I wanted to go.

Combine all three drugs and use them.

To move forward, but we will be looking at the clinical activity.

And in particular, we have benchmarks for.

Tammy parity in Asia that came from the same patient population in our phase II, where we saw an approximate 61% composite of complete response rate. So we'll certainly be looking for responses better.

North of that to.

To justify adding <unk> into the regimen.

That would be a starting place.

Well and I guess, that's exactly where I wanted to go and I guess. The question is are you also sort of looking at how that compares to venues.

David Roth: And I guess the question is, are you also sort of looking at how that compares to Veni's current response rates and sort of seeing where the opportunity is? Or because there are positive patients who don't respond as well, do you think you have an opportunity there? Thanks. Yeah, I think we have a great opportunity with tamibaritine in this population for multiple reasons. It's an orally administered, generally well-tolerated drug.

Hum.

Bond trades in the sort of thing where the opportunity is or because the war positive patients don't respond as well you think you'll have an opportunity there. Thanks.

Yes, I think both we think we have great opportunity with Chinese <unk> in this population for multiple reasons.

It's an orally administered generally well tolerated drug.

David Roth: The population clearly needs improvements on available therapy. We know the venetoclax regimen really hasn't, you know, benefited significantly in about a third of patients who don't achieve an initial response and the majority of patients who do ultimately lose their response. So, you know, we are hopeful that our regimen will deliver value to these patients. You know, now the translational data that we shared at the prior ASH meeting, where we were very excited to show that the majority of the patients who are RARA positive who entered our study had these features consistent with monocyticness or refractoriness to things that are known to be associated with refractoriness to venetoclax, holds yet additional potential for this therapy to address unmet needs.

The population clearly needs improvements on available therapy, we know the venetic clacks regimen.

It really has not.

Benefited significantly about a third of patients who don't achieve.

An initial response and the majority of patients who do ultimately.

Lose their response, so we are hopeful that our regimen will deliver value to these patients.

Now the translational data that we shared at the prior Ash meeting.

Where we were very excited to show that the majority of the patients who are RARA positive who had entered our study had these features consistent with monostich Miss or are refractory to <unk>.

That are known to be associated refractory Mr. Burnett o'clock.

Yet an additional potential for this therapy to address unmet needs.

David Roth: So we're very excited about the program. We see great enthusiasm from the investigators who are participating and the patients who are signing up. So look, the second half of the year is going to be a very exciting year.

And so we're very excited about the program, we see great enthusiasm from the investigators who are participating and the patients.

Who are signing up so.

Look second half of the year is going be very exciting year, we're going to share upcoming information about that and you'll get insights into how this is performing.

David Roth: We're going to share upcoming information about that, and you'll get insights into how it is performing. That's really helpful. And then just one last question, if I may, on this topic: when it comes to the data that you get, will that help in terms of response, will that help with any powering or sizing of the Phase 3, or is the Phase 3 already pretty much largely set? Thank you very much for all. So if you're talking about phase three in AML? Yeah, yeah. Yeah, yeah, yeah.

That's really helpful. And then just one last question if I may on this topic.

When it comes to the data that you get with that help.

In terms of response will that help with any powering.

Sure.

Sizing of the phase three or is the phase three already pretty much largely set. Thank you very much for all the questions.

Sorry, if you're talking about the phase III in AML.

Yes, having said this data later this year will it will it help you design or size the phase III select AML. Thank you.

David Roth: So the data that you get later this year, will it help you design or size the phase three select AML? Thank you. So we haven't spoken yet specifically about the next plan beyond this study. This is a randomized phase 2. And we will be presenting the data that's available to us toward the end of this year. So right now, it's a bit early for me to forecast whether that specific information is going to inform the future phase 3 design or not. But all told, I think it should be interesting information to learn about. Great. Thank you guys for your time. Thank you, Ted.

So we haven't spoken yet specifically about the the next plan beyond this the study this is a randomized phase two.

And we we will be presenting the data that's available to us towards the end of this year.

So right now it's a bit early for me to forecast whether that specific information is going to inform the future phase III design or not but all told I think it should be interesting information to learn about.

Great. Thank you guys for the time.

Thank you Ted.

David Roth: Our next question comes from Phil Nadeau with Cowen & Company. Good morning, thanks for taking our questions as well. One follow-up to Ted's on the SelectAML trial. As you look at the adverse event profile, are there specific adverse events that you're worried timibaritine could exacerbate that Venasa already has? Are there any toxicities that could potentially be overlapping that you're gonna pay particular attention to?

Our next question comes from Phil Nadeau with Cowen <unk> Company.

Good morning, Thanks for taking my questions as well one follow up to Ted's on.

The select AML trial as you look at the adverse event profile are there specific adverse events that youre worried tami Barron team could exacerbate that Vanessa already have or are there any text.

Texas sees that could potentially be overlapping that you're going to pay particular attention to.

David Roth: Phil, thanks for your question. I'm going to turn it over to David. Yeah, so I, the general safety profile of tamibaritin and AZA, we've previously described that, and we have not noted any exaggeration of toxicities that have been seen by AZCytogene. Very specifically, we have not increased myelosuppression or the cytopenias that are commonly associated with the use of venetoclax, and so we don't really anticipate that there'll be any exaggerated toxicities from the venaser regimen when we add tamibaridine to that. Of course, that's part of our clinical experiment. But we really don't expect that to be the case.

Phil Thanks for your question I'm going to turn it over to David Yeah. So.

The general safety profile of Tommy baritone as are we.

We've previously described that and we have not noted any exaggeration of toxicities that have been seen by exercising very specifically we have not incur.

Increased milo suppression or the cytopenia as that are commonly associated with.

Use of <unk>.

So we don't really anticipate.

That that there'll be any exaggerated toxicities.

From the <unk>.

And then as a regimen, where we add tammy parenting to that.

Of course, that's part of our clinical experiment, but we really don't we don't expect that to be the case.

David Roth: Great, that's helpful. And then second, on 2101, you mentioned that you're gonna collect the PK data including CMAX and AUC as well as food effects. Are there specific characteristics of the pharmacokinetics that you need to see?

Great. That's helpful and then second on 'twenty, one O one.

You mentioned that youre going to collect that.

PK data, including C, Max and AUC as well as food effect are there specific characteristics of the pharmacokinetics that you need to see.

David Roth: In order to advance 2101, or is this simply kind of a dose-finding study where there's no specific hurdles for any of those parameters? You simply need to know what dose. Yeah, so that's a good question.

In order to advanced 21 O one or is this simply kind of a dose finding study where there's no specific hurdles for any of those parameters you simply need to know what dose to move forward.

David Roth: Now, just to provide you with some important context, we already have a good insight into the fact that we believe we have a dose. We acquired this drug, and there was already a phase one study that characterized the dose and the exposures. So what we're doing here is testing that dose in direct comparison to IV arsenic trioxide to confirm in a single contemporaneously generated data set that the blood measures are consistent, and that way, we will be assured of taking the right dose forward into phase three.

Yes, so that's a good question now just to.

We will provide you with the important context, we already have good insight into the fact that we believe we have a jumps when we acquired this drug.

There already was a phase one study that characterized the dose and the exposures.

What we're doing here is we're testing that dose in direct comparison to IV arsenic trioxide to confirm.

In a single contemporary and easily generated dataset that the blood measures are consistent and that way, we will be assured of taking the right dose forward into phase III. The most important thing we can do right now to assure the technical success of the phase III is to go forward with the right dose.

David Roth: The most important thing we can do right now to assure the technical success of phase three is to go forward with the right dose. Everything else, you know, this is the same drug substance. There's already clinical proof of concept with an oral arsenic that has been used in China that shows this methodology will work. And so we have high confidence that this will be a successful program.

Everything else.

This is the same drug substance theres already a clinical proof of concept with an oral arsenic that had been used in China that shows this methodology will work.

And so we have high confidence that this will be a successful program.

David Roth: The last piece of the equation for us is just to have confidence that the right dose is being selected. And so, you know, we respect the information we reviewed when we decided to acquire this drug, but we just want to prove it to ourselves and go forward, you know, on solid footing. And the last point I'll make is that this patient population is largely cured by currently available therapy. So, really, the burden of proof is on us to make sure we protect their safety and welfare as we go into this trial.

Last piece of the equation for US is just to have confidence that the right doses being selected.

And so where we're at we respect the information we reviewed when we decided to acquire this drug but we just want to prove this to ourselves and go forward.

Uh huh.

Solid footing and the last point I'll make is that this patient population is is largely cured by the currently available therapies. So it really the burden of proof is on us to make sure we protect the safety and welfare as we go into this into this trial, but I think we're doing all the right things with all of our collective experience to assure this probe.

David Roth: But I think we're doing all the right things with all of our collective experience to assure that this program will succeed, and we feel good about our approach. When you're comparing an oral to an IV, I'd guess the shape of the PK curve must be different. Claire, correct me if I'm wrong. So what is the key parameter to show equivalents? Is it area under the curve? Does C-max matter? Can you give us some sense of how you determine comparability when you're looking at two very different types of administration?

Ram will succeed and.

And we feel good about our approach.

When you're comparing an oral to IV I'd guess the shape of the PK curve must be different.

But correct me if I'm wrong. So what is the key parameter.

To.

Showing equivalents is an area under the curve to see Max matter can you give us some sense of.

How you've determined comparability when youre looking at two very different routes of administration.

David Roth: Yeah, you're actually correct about that. I mean, clearly, an intravenously administered drug, the C-max occurs immediately at the end of the infusion, and, you know, the area under the curve largely reflects the exposure over time, which is influenced by metabolism and removal from the blood. So, you know, the specifics of those parameters may vary with oral, which will be absorbed a bit more slowly, but the exposure over time is going to be critical.

Youre actually correct about that I mean, clearly an intravenously administered drug the C. Max occurs immediately at the end of the infusion and the.

The area under the curve largely reflects the exposure over time.

Which is influenced by metabolism and removal from the blood.

So the specifics of those parameters may vary with oral which will be absorbed a bit more slowly.

And but the exposure over time is going to be critical and so we're going to be characterizing both the C. Max and the AUC and using our best judgment to pick a dose dot represents a comparable exposure.

David Roth: And so we're going to be describing both the C-max and the AUC and using our best judgment to pick a dose that represents a comparable exposure. And keep in mind, these patients are treated over prolonged periods of time. They're given this drug daily, the IV drug daily, for nearly 10 months, you know, two months for induction, eight months for consolidation, every other month. And so, you know, it sort of makes clinical intuitive sense that the overall exposure over time is going to make a difference.

And keep in mind. These patients are treated over prolonged periods of time.

They're given this drug daily the IV drug daily for nearly 10 months to months for induction eight months for consolidation every other month and so it sort of makes clinical intuitive sense that the overall exposure over time is going to make a difference.

David Roth: Great. And then the last question from us on 5609. You mentioned hematologic malignancies as being the target for one of the populations there. In the past, you specifically called out mantle cell lymphoma as perhaps being one hematologic malignancy that's particularly amenable to treatment with 5609. Is that still your thinking, or now are you more focused on just the broader hematologic malignancy group, and you'll let the data narrow down exactly which population you have?

Great and then last question from US on 50 609.

Mentioned in hematologic malignancies.

As being the target for one of the population is there in the past you specifically called out mantle cell lymphoma.

Because as perhaps being one hematologic malignancy, this particularly amenable to treatment with <unk> 56 to nine is that still your thinking right.

How are you are you more focused on just the broader Hematological malignancy group and let you know what the data narrow down exactly which population you investigate.

David Roth: So let me start by saying that mantle cell lymphoma still is a priority in many ways. I'll remind you of the really exciting data we shared at ESMO about pancreatic cancer and advanced solid tumors, where we saw the highest response rates in pancreatic cancer. We also saw very high response rates in patients who had RB pathway abnormalities, and we know the mechanism of action of a CDK7 inhibitor is very important in places where cell cycle dysregulation occurs. And that plays into the larger and more important role that cyclin D plays in mantle cell lymphoma.

So let me start by saying that.

Mantle cell lymphoma still is a priority in many ways I'll remind you of the really exciting data we shared at ESMO in pancreatic cancer, which and in advanced solid tumors, where we saw the highest response rates in pancreatic cancer. We also saw very high response rates in patients who had RB pathway abnormalities.

We know the mechanism of action of our CDK seven inhibitor.

It is very important.

Important in places where cell cycle regulation occurs.

That plays into the large and important role that cyclin D has in mantle cell lymphoma. So we see a very strong mechanistic connection to mantle cell that said.

David Roth: So we see a very strong mechanistic connection to mantle cell. That said, as we evaluated the breadth of data that we've generated across a range of hematologic malignancies, we also see other specific vulnerabilities and sensitivities that suggest a much broader opportunity than just mantle cell. So as we dug in on this initial foray into heme cancers, first, by the way, with a CDK7 inhibitor, we thought that we would be well served to explore a variety of tumor types, including mantle cell, and then let the data determine where we go.

As we evaluated the breadth of data that we've generated across a range of hematologic malignancies.

We also see other.

Specific vulnerabilities and sensitivities that suggests a much broader opportunity than just mantle cell.

So as we dug in on this initial foray in the heme cancers are first by the way for a CDK <unk> inhibitor, we thought that we would be well served to explore a variety of of tumor types, including mantle cell and then let the data determined where we go.

David Roth: So what we've done is we've really capitalized on all the information we've been generating, and we're taking a nice broad approach to initiate this program. Perfect. That is very helpful. Thanks for taking my questions. You're welcome. Our next question comes from Jason Butler at J&P Securities. Hi, it's Royansford, Jason.

So what we've done is we've really capitalized on all the information we have been generating.

And we're taking a nice broad approach to initiate this program.

Perfect. That's very helpful. Thanks for taking my questions.

Youre welcome.

Our next question comes from Jason Butler of JMP Securities.

David Roth: Thanks for taking our questions. Just a couple quick ones. I guess, um... Apologies for the crystal balling here, but about the pivotal study for 2101 and newly diagnosed ATL, I guess we're wondering about the potential for an earlier efficacy read. It seems like the median time is the complete response with about a month, a month and a half.

Hi, it's Roy in for Jason Thanks for taking our question just a couple of quick ones I guess.

Apologies for the Crystal ball here, but.

Pivotal study for 'twenty, one O one a new newly diagnosed ATL I guess were wondering about the potential.

Potential for earlier efficacy read it seems like the the median time to see a complete response within about a month to month and a half.

David Roth: Just wondering if maybe there might be the potential for an earlier look at molecular CR prior to the 2025 readout, and then we could do a quick one on CDK-12. Thanks for your question, Brian. I'm going to ask David to address the timing in phase three, maybe based on FDA feedback. Yeah, so we did meet with the agency in November.

Just wondering if maybe there might be the potential for earlier look at molecular CR prior to the 2025 readout.

And then had a quick one CDK 12.

Thanks for your question, where I'm going to ask David to address the timing in the phase III, maybe based on FDA feedback.

David Roth: We had a very productive meeting, and they reaffirmed their interest in seeing this compared to historical benchmarks. And keep in mind, we're developing this under the 5053B pathway, which relies on the pre-existing data set for the IV arsenic trioxide. So the approval benchmark from Molecular CR was assessed at the end of the third consolidation cycle.

We did meet with the agency in November you had a very productive meeting and.

They reaffirmed their.

They're.

Interest in seeing this.

Compared to historical benchmarks.

And keep in mind, we're developing this under.

Five O ICB pathway, which relies on the pre existing dataset for the IV arsenic trioxide.

So the approval benchmark for molecular CR.

It was assessed.

At the end of the third consolidation cycle.

David Roth: So, you know, that would probably be the timing that we would utilize for our molecular CR. And they've also said that the molecular CR could serve as a potential for accelerated approval with event-free survival at two years for full approval. So we think we've really got all of the guidance we need with respect to the endpoints, when they would be measured, and how they would be assessed versus the benchmarks to determine, you know, how to proceed.

So that would probably be the timing that we would utilize for our molecular CR and they have also said that the molecular CR could serve as a potential for accelerated approval with the event free survival at two years for full approval. So we think we've really got all of the.

The guidance, we need with respect to the endpoints when they would be measured and how they would be assessed versus the benchmarks to determine how to proceed. So we're very excited about having a clear path forward.

David Roth: So we're very excited about having a clear path forward. You know, it really doesn't get any better in drug development when you have crystal clear guidance from the regulatory agency to help them make a regulatory decision. Okay, great. Thank you very much.

No it really doesn't get any better in drug development. When you have crystal clear guidance from the regulatory agencies to help them make a regulatory decision.

David Roth: And just a quick one on CDK-12. So the data in AACR that's going to be using the same clinical candidate that you probably announced in the second half, and I guess just what remains gating to declare the clinical candidate. Okay, we're going to have Eric address that question. Yeah, thanks for the question.

Okay, great. Thank you very much and just a quick one on CDK 12, so the data at AAC or is that going to be using that same.

Clinical candidate that you plan to announce in the second half and I guess, just what remains gating to declare the clinical candidate.

Hey, Brian , but I haven't I'm, Eric asset type.

I Trust that question.

Yeah. Thanks for the question Yeah, we're gonna be presenting data at ACR on our C. K 12 program.

Eric Olson: Yeah, we're going to be presenting data at AACR on our CK-12 program, and we'll be highlighting a molecule. And, you know, I think it's safe to say that the profile of our development candidate that we name in the second half of the year is likely to be similar to the one that we show at AACR. Okay, thank you. Our next question comes from Zeg Vajalo with Roth International.

It will be highlighting.

Our molecule in and out.

Oh.

I think it's safe to say that the profile of our development candidate that we name in the second half of the year is likely to be similar to the one.

We show at ACR.

Okay. Thank you.

Our next.

Question comes from Doug Mitchelson with Roth International.

David Roth: Thanks for taking my question. I think I just wanted to ask a quick one here regarding 5609, you know, you're already suffering from pancreatic cancer. So I was just wondering how quickly you can dose escalate in the heme malignancies since you've already kind of seen some of that data, and then do you expect to perhaps use the same dose in the solid tumor versus that liquid tumor? I'm going to have David answer that question. Thanks, Segba.

Good morning, Thanks for taking my question I think I just wanted to ask a quick when you're recording 56 of nine and.

You know you already in pancreatic cancer. So I was just wondering how quickly can you dose escalate in the heme malignancies, I think we've already kind of seeing some of that data and then do you expect to perhaps is the same dose in the solid tumor personally is that like what's your mother's day.

He said, Bob and I have David answer that question. Thanks, Peg, but so we've learned a lot about how to dose 50 609 in patients with advanced solid tumor malignancies.

David Roth: So, we've learned a lot about how to dose 5609 in patients with advanced solid tumor malignancies, and we are going to leverage that knowledge as we move forward in heme cancers. So our plan in the heme program will be to move forward with the regimen that we've optimized the safety for, and we'll initiate it just around the MTD, the maximum tolerated dose for that. And then we'll be combining gemcitabine or gemcitabine plus NAPPAX with HAFSA using the standard of care approved levels for those combination partners. So we think that this is going to move quite swiftly, and I think that it'll be an efficient design. Did you also want to know about how we were using dosing for the heme study?

And we are going to leverage that knowledge as we move forward in the in the heme cancers. So our plan.

In the heme program will be to move forward with the regimen that we've optimized the safety for and we'll be initiating just around the MTG.

The maximum tolerate dose for that and then we will be combining with gemcitabine or gemcitabine plus Nab paclitaxel using the standard of care approved levels for those combination partners. So we think that this is going to move quite swiftly.

And I think that it'll be inefficient designs.

Yeah.

And you also wanted to know about how we're using the dosing for the heat study.

Thank you.

David Roth: Thank you. Yeah, the dosing we're starting in the heme study. Oh, I'm sorry. I must have misheard you. Forgive me.

Yes, the dosing we're starting in the heat study.

David Roth: Yeah, so in the HEIM study, we haven't really provided detailed guidance on the specifics of that trial design, but with regard to the HEIM study, we'll also be starting at around the area of the biologically active dose. So we actually have incorporated a really nice biomarker for the PD effects, the Polar2a, and we know where we can tickle the pathway with our drug over time. So we're going to be leveraging that knowledge as well, and so we're not starting from the beginning, if that's what you were asking. I'm sorry, I didn't quite answer your question correctly the first time around. No worries.

Oh I'm sorry.

I must have misheard you forgive me.

Yeah. So in the heme study, we're going to we haven't really provided detailed guidance on the on the specifics of that trial design, but with regards to the heme study will also be starting at around the area of biologically active dose.

So we actually have incorporated a really nice biomarker for the PD effects to poll, our two way and we know where we can tackle the pathway with our drug over time, so we're going to be leveraging that knowledge as well.

And so we're not starting at the beginning if thats, what youre asking I'm sorry.

I didn't quite answer your question correctly, the first time around.

David Roth: Very helpful, David. And then the last one here, I guess, is just trying to figure out whether or not you will also be needing to look at perhaps more doses for the heme malignancies, just out of curiosity, trying to figure out if you're at the right dose. And then the last bit here is about your CDK-12 program. Wanted to know if there's anything that you've seen preclinically that could suggest that it could be combined with your CDK-7, and we're looking forward to the data at AACR.

So.

Very helpful. David and then the last one here I guess is just trying to figure out.

Whether or not you will also be meeting them to.

If you look at perhaps.

Why campuses.

For the heme malignancies decided you know safeguard curiosity trying to figure out if you are at the right dose.

And the last the last that you read about the CDK talk program wanted to know if there was anything that you've seen pre clinically that could suggest that it could be combined with their CDK seven and we're looking forward to add the data at ACR.

David Roth: Great, I'll have David answer the first question and Eric the second question. Yeah, just in terms of the heme malignancies with more doses, we're going to, again, as I was mentioning, we are going to start, you know, close to the MTD and the solid tumors clearly at a biologically active dose. We are prepared to modulate that dose to achieve maximum therapeutic effects in these patients while maintaining safety. So there is some exploration that's going to be going on so we can clearly define the right dose and utilization of the drug in patients with heme malignancies. But we don't expect that to be a pretty complex clinical trial experiment.

I'll have David answer the first one and Eric the second question interesting. So in terms of the heme malignancies with more doses, we're going to again as I was mentioning we are going to be starting.

Close to.

The MTGE in the solid tumors clearly out of biologically active dose we are prepared to modulate that dose to.

To achieve maximum therapeutic effects in these patients while maintaining safety. So there there is some exploration thats going to be going on so we can clearly defined the right dose and utilization of the drug in patients with heme malignancies, but we don't expect that to be a pretty complex.

Clinical trial experiment.

David Roth: And then we're obviously setting the stage to move forward in that context either as a single agent or in combinations, as is so commonly done. So we're collecting our data and analyzing it to set ourselves up appropriately for future surveys. And for the CDK-12 study, I guess, Eric. Yeah, thanks for the question. There's certainly, our focus for the CDK-12 combinations has really been, and our thinking around that is really based on the role that CDK-12 plays in regulating DNA damage response.

And then we're obviously setting the stage to move forward.

In that context, either as a stimulation or in combination sensors. So commonly done. So so we are collecting our data and analyzing it to set ourselves up appropriately for future success.

And for the CDK <unk>.

<unk> study I guess, Eric Yeah. Thanks for the question. There is certainly our focus for the CDK 12 combinations have really been our thinking around that is really based on the role of CDK 12 plays and regulating DNA damage response.

David Roth: So, you know, our CDK-7 inhibitor is not directly a DNA damaging agent, so that hasn't been our primary focus. But in cells where there's kind of a susceptibility or dependency on DNA damage repair, that's really where we're thinking about CDK-12 combination work, whether that's genetically defined tumors, such as BRCA tumors, in combination with other agents, like DNA damaging agents, or other agents that impact other pathways involved in DNA repair, like PARP inhibitors.

So.

Our CDK <unk> inhibitor is not directly a DNA damaging agent so that hasn't been our primary focus but.

In cells, where there is a kind of a susceptibility or dependency on.

DNA damage repair.

That's really where we're thinking about CDK 12 combination work, whether thats a <unk>.

<unk> defined tumors, such as <unk> tumors in combination with other agents.

DNA damaging agents or other agents that impacts other pathways involved in DNA repair like PARP inhibitors. So that's really been our focus in the combination.

Eric Olson: So that's really been our focus in the combination. Thanks, Eric. Thanks, everybody. As a reminder, if you'd like to ask a question at this time, that is star, then 1. Our next question comes from Matthew Cross with Alliance Global Partners. Hi, all.

Thanks, Eric.

Thanks and goodbye.

As a reminder, if you'd like to ask a question at this time that is star then one.

Our next question comes from Matthew Cross with Alliance Global Partners.

Matthew Cross: Good morning, and thanks for taking a couple of quick confirmatory questions from me. I wanted to start off by congratulating you on the arrangement with QIAGEN around the companion diagnostic. I was curious, because you had called out the terms of that being around MDS in particular, given that you're also looking, obviously, at Roger Positations in the AML setting, which is curious if that part of it can be expanded or, separate there, if that's even necessary, and then kind of the development commercialization strategy you're pursuing for timobaracene.

Hi, all good morning, and thanks for taking a couple of quick confirmatory questions for me.

Wanted to start off first congrats on the arrangement with a key agenda around the companion diagnostic was curious because you had called out.

In terms of that being around Mds in particular.

Given that you're also looking obviously at.

RARA positive patients in AML setting, but was just curious if that partnership can be expanded or do something separate there if that's even necessary.

And then kind of the steady development commercialization strategy, you're pursuing for their team.

Kristen Stephens: And then secondly, you know, David, you gave a good or great coverage of kind of the rationale for the confirmatory study in APL, but I was curious between the kind of timing of the initial confirmatory data and the initiation of phase three in 2023. That couple of quarters gap was curious if you need to discuss those results with the agency, or, as you said, it's really just kind of confirmation for your own sake, making sure But do you need to talk with the agency and review that confirmatory data before moving into phase three? Does that explain the couple of quarters gap there?

And then secondly.

Was curious David you gave a good or great.

Or kind of the rationale for the confirmatory study in APL.

But was curious between the timing.

Timing of initial confirmatory data and the.

Initiation of the phase III in 2023 that couple of quarters GAAP was curious if you need to discuss those results.

With the agency or as you said, it's really just kind of confirmation for your own sake, I'm, making sure you're confident of the dose going into phase III, but do you need to talk with the agency and review that confirmatory data before moving into the phase III does that explain the couple quarter gap. There just want to make sure we understand that the kind of limiting steps on those timelines. Thanks.

David Roth: I just want to make sure we understand the kind of limiting steps on those timelines. Thanks. Thanks Matt. I'm going to have Kristen Stephens take the first question on the QIAGEN. Kristen?

Thanks, Matt I'm going to have Kristin Stephens take the first question on the Qiagen Kristen.

Kristen Stephens: Yeah, thanks for the question. So we have been using a centralized clinical trial assay that was developed for use in our original phase 2 AML study. And that assay had input from the CDRH division of the FDA and was operated under IDE requirements. And so this is the same assay that's been used across all of our studies with Tammy Baratine, and it serves as a foundation for the development of the commercial CDX.

Yeah. Thanks for the question. So we have been using a centralized clinical trial assay that was developed for use on our original phase two AML study.

That assay had input from the C. D. R. H division of the FDA and we've operated under I D requirements and so this is the same assay that's been used across all of our studies of Tami Barron team and it serves as a foundation for the development of the commercial CTX.

Kristen Stephens: So while we haven't provided further detail beyond our agreement with QIAGEN, you can imagine where that will lead. Great. Okay. Very helpful. Appreciate it. And then on 2101, David, do you want to take that?

So while we haven't provided further detail beyond our agreement with Qiagen and you can imagine where that will land.

Okay.

Great. Okay very helpful. I appreciate it and then on 'twenty one on one.

David you want take that.

David Roth: Yeah. So I think that, you know, we're guided to reporting data on PK and safety from the ongoing trial, you know, mid-year. And, you know, we're going to be initiating phase three in the first quarter of 2023. That's our current plan. You know, we haven't specifically explained the details of what, you know, what is transpiring, but, you know, we're activating a global phase three. You know, it requires some effort, and I didn't think that there was any particular challenge to getting that done over the period of time between collecting that data and initiating the trial.

So I think that.

We've guided to reporting the data on the PK and safety from the ongoing trial midyear.

And we're going to be initiating the phase III in first quarter of 2023, that's our current plan.

We haven't specifically explained that.

The details of what what is transpiring, but.

Activating our global Phase III.

It requires some effort.

I didn't think that there was any any particular.

Challenge to getting that done over the period of time between collecting that data and initiating the trial.

David Roth: Yeah, I'll just say, Matt, we're obviously moving as swiftly as we can. There are multiple things necessary to initiate phase three, which includes the dose, the phase three material, and then all the things that we need to initiate a large global study.

We're obviously moving as swiftly as we can there's multiple things necessary to initiate the phase III, which includes.

The dose the phase III material.

And then all the things that we need to activate a large global study so MMO outwear and we think that this is sort of the best timing related to having all of those things are ready to go.

Nancy Simonian: So, I mean, we think that this is sort of the best timing related to having all those things ready to go. And the nice thing is we can work in advance now to kind of get ready for all those things, because we actually know with the feedback that we've gotten from the agency, and we know exactly the trial that we need to do. So that's going to give us a great way to launch this very quickly when we initiate it.

And where are the nice thing is we don't know.

We can work in advance now to kind of get ready for all of those things because we actually know the feedback we've gotten from the agency and we know exactly the trial that we need to do so that's kind of give us a great way to launch this very quickly when we initiate it.

Nancy Simonian: I didn't mean in any way to imply that that was a long timeline; just wanted to confirm that you wouldn't need to run that data, I guess, by the FDA again and that it sounds like, based on what Nancy just said, that they're pretty clear with the plan moving into the pivotal study and that it's really just more of an internal confirmation of dose. Yep. Okay, but yeah, that covers it. I appreciate it, guys. Thanks for all the answers.

Understood no. It didn't mean in any way to avoid that that was a long timeline just wanted to confirm that you wouldn't need to run that data I guess by the FDA again, it sounds like based on what you said that there are pretty clear with the.

The plan moving into the into the pivotal study and that its really just more of an internal confirmation of dose.

Yep.

Yeah that covers it I appreciate it guys. Thanks for all the answers.

Okay.

Nancy Simonian: That concludes today's question and answer session. I'd like to turn the call back to Nancy Simonian for her closing remarks. Thank you, Operator, and thank you, everyone, for joining us today. We appreciate your continued support and look forward to providing further updates on our progress as we continue to advance to becoming a fully integrated biopharmaceutical company. Please reach out to us if you have any additional questions, and have a wonderful day. This concludes today's conference call. Thank you for participating. You may now disconnect. [music]

That concludes today's question and answer session I'd like to turn the call back to Nancy Simonian for closing remarks.

Thank you operator, and thank you everyone for joining US today. We appreciate your continued support and look forward to providing further updates on our progress as we continue to advance to becoming a fully integrated biopharmaceutical company.

Please reach out to us if you have any additional questions and have a wonderful day.

Okay.

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

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Yeah.

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Okay.

Yes.

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Okay.

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Sure.

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