Q1 2022 Geron Corp Earnings Call

John Scarlett: In their lower-risk MDS patients, key opinion leaders and community hematologists emphasize the significant unmet need for durable transfusion independence. If the durability and safety data from our Phase 2 study are confirmed in the Phase 3 trial, then CalSTAT could represent a significant treatment advance for these patients because we believe no other product has provided the rates of 24-week and one-year transfusion independence seen in the eMERGE Phase II study. In addition, unlike currently approved therapies... IMS HealthStat offers the potential to treat both RS-positive and RS-negative patients, as well as to provide potential disease modification. We expect these characteristics to strongly differentiate Intel and to create a broad commercial opportunity.

Significant unmet need for durable transfusion independents.

If the durability and safety data from our Phase II study are confirmed in the phase III trial in a car stack could represent a significant treatment advances for these patients.

We believe no other product has provided the rates of 24 week end, one year transfusion independents scene in the emerge phase III study.

In addition, unlike currently approved therapies.

<unk> offers the potential to treat both Rs positive and Rs negative patients as well as to provide potential disease modification.

We expect these characteristics to strongly differentiate and hotel and to create a broad commercial opportunity.

John Scarlett: We're also making steady progress in opening clinical offices in 2024, and Intel Step will be the second significant data readout for Intel Step with the recent start of our Improved MF Phase I combination. Our pipeline expansion program is picking up momentum. That Pipeline Expansion Program, including the IMPROVE-MS Phase I Study in FRONTLINE-MS and the two Investigator Web Studies in AML, enables us to study the potential of Telstat as a combination therapy and raise additional capital to provide financial flexibility. We're pleased that we achieved both goals with the closing of the $70 million net public offering on April 1st.

We're also making steady progress in opening clinical trial.

Bonuses in 2024.

The second significant data readouts.

Try and kill step.

With the recent start of our improve Ms phase one combination.

Patient study our pipeline expansion program that was picking up momentum.

Yes.

Pipeline expansion program, including the improve MF phase one study in frontline MF and two investigator led studies in AML.

Enables us to study the potential of <unk> as a combination therapy raise additional capital to provide financial flexibility.

We're pleased that we achieved both goals with the closing of the $70 million net public offering on the FERC.

John Scarlett: This public offering garnered keen interest from biotech specialist investors, including Vivo Capital, RA Capital, TCGX, equal R1, the Enterprise Associates, and Health Corps Managers. We believe that Geron represents a strong investment opportunity for these and other investors, due to our compelling phase two data, the nearness of our lower risk MDF phase three readout, the commercial opportunities of our potential indications, and the strength of our internal capabilities and management. Our current financial resources, plus the net proceeds from this financing, plus additional funding in 2023 from potential warrants exercises, are expected to provide the financial resources necessary to support our planned key milestones through the end of 2023.

This type of offering garnered keen interest from biotech specialist investors, including vivo capital.

Capital TCE gx equal or one.

New enterprise associates and healthcare management.

We believe that <unk> represents a strong investment opportunity for these and other investors due to our compelling phase II data the newness of our lower risk Mds phase III readout.

The commercial opportunities of our potential indications and the strength of our internal capabilities and management team.

Our current financial resources, plus the net proceeds from this financing plus the additional funding in 2023 from potential warrant exercises are expected to provide the financial resources necessary to support our planned key milestones through the end of 2023.

John Scarlett: Assuming positive results, the trial, with a New Drug Application, or NDA, in the first half of 2023; submission of a European Marketing Authorization Application, or MAA, and preparatory activities for a potential 2024 U.S. commercial launch. We also expect these current and projected financial resources will provide us with the cash runway to consider various strategies to maximize the value of Mattel Stats for patients and shareholders. These could include partnering, additional debt, structured instruments such as royalty monetization, or other strategic options.

Assuming positive.

The trial.

These key.

With new drug application or NDA in the first half of 2023 <unk>.

Submission of a European marketing authorization application or MAA.

A tree and preparatory activities for a potential 2020 for U S commercial launch.

Thanks.

We also expect these current and projected financial resources will provide us the cash runway to <unk>.

<unk> various strategies to maximize the value of <unk> for patients and shareholders. These could include partnering additional debt structured instruments, such as royalty monetization or other strategic options.

John Scarlett: Before I turn the call over to my colleagues, I'd like to highlight my very strong confidence in and appreciation for my remarkable Geron colleagues. It's the collective excellence and execution across the company as we approach significant milestones that will unlock value. With that, I'll turn the call over to our Chief Medical Officer, Alexandra Rizzo, for clinical... Alex. Thanks, Chip, and good afternoon to everyone on the call.

Before I turn the call over to my colleagues I would like to highlight very strong confidence in and appreciation for my remarkable geron colleagues hits the <unk>.

<unk> excellence in execution across the company as we approach significant milestones that will unlock value.

Okay.

With that I'll turn the call over to our Chief Medical Officer Alexandra Rizzo for a clinical update Alex Thanks, Chip and good afternoon to everyone on the call.

Alexandra Rizzo: As Chip mentioned, we're excited to be just eight months away from the top line results of our Phase III lower-risk MDS trial. As such, our teams are focused on preparations for a high-quality data readout, which requires collaboration and execution across the clinical operations, data management, and biostats teams, as well as partnership with our CRO investigators. We remain confident that the readout will occur in early January 2023.

As chip mentioned, we are excited to be just eight months away from the planned topline results of our phase III lower risk Mds trial as such our teams have focused on preparations for our high quality data readout, which requires collaboration and execution across our clinical operations data.

<unk> and <unk> teams as well as partnership with our hero investigator.

We remain confident that the readout will occur in early January 2023.

I'd like to remind everyone that the merge phase III trial is designed to confirm the phase II results. Since the charge you. The same patient population dosing regimen now can that tells that primary and secondary endpoints.

Alexandra Rizzo: I'd like to remind everyone that the eMERGE Phase 3 trial is designed to confirm the Phase 2 results since the trials use the same patient population, dosing regimen of hematopoietic cells, primary and secondary endpoints, and geographies for clinical sites with many of the same investigators. We believe that if the Phase 3 trial confirms similar depth, breadth, durability of transfusion independence and safety, Imetelstat could meet significant needs for all patients with low-risk MDS who have failed or are refractory to ESA treatment. Moreover, approximately 75% are negative and are underserved by current treatment options.

And geographies for clinical sites many of the same investigators.

We believe that in the phase III trial confirmed similar Bret.

Brent durability of transfusion independence and safety.

You might tell us that couldnt meet significantly for all patients with lower risk Mds, who have failed or are refractory to Esa treatment.

Moreover.

Similarly, 75%.

Who are Rs negative and are underserved by current treatment options.

Alexandra Rizzo: Furthermore, the unique telomerase inhibition mechanism provides disease-modifying potential, which we believe differentiates hematopoietin from other currently approved or investigational treatments for low-risk MDMs, in addition to preparing for a 12-plan result. Initiated NDA Submission Preparation. As Chip mentioned, assuming the results of eMERGE Phase 3 support regulatory submissions, we plan to submit an NDA in the U.

Furthermore.

The unique telomerase inhibition mechanism provides disease modifying potential, which we believe differentiates <unk> from other currently approved or investigational treatments for low risk Mds.

In addition to preparing for top line results.

<unk> NDA submission preparations.

Chip mentioned I, assuming there is also few months phase III poise regulatory submissions, we plan to submit an NDA in the U S. In the first half of 2022.

And an MAA in Europe in the second half of 2023.

Alexandra Rizzo: With regard to our Phase 3 Refract CMS clinical trial, we continue to make progress with site activation and remain confident we'll open the remaining selected sites in 2022. We believe this progress will enable completion of enrollment and a potential interim analysis in 2024. As a reminder, IMPACT-MS is the only phase 3 trial in MS using overall survival as the primary endpoint. We believe that the improvements in our eyes observed in our phase 2 trial can be confirmed in impact MS. Imatelstat would represent a potentially transformative treatment option for MS patients who no longer respond to JAK inhibitors given their dismal prognosis and lack of treatment options.

With regards to our phase III <unk> trial, we continue to make progress with site activation and remain confident we will open the remaining selected sites in 2022.

We believe this progress will enable completion of enrollment and a potential interim analysis in 2024.

As a reminder.

Impact on I think the only phase III trial on that using overall survival as the primary endpoint we.

We believe that is the improvement observed in our phase II trial can be confirmed and impact of Mezz.

Hematology start with represents a potentially transformative treatment option for MF patients, who no longer respond to JAK inhibitors.

Their diesel towards annuities and lack of treatment options.

Alexandra Rizzo: Of note, a recent publication in Cancer Journal, co-authored by Dr. Moskarenos and Dr. Rostovchik, both principal investigators in our Phase III impact MS trial, describes the clinical dilemma for treatment of JAK-inhibitor failure. This paper reinforces the poor outcomes in many MS patients who are refractory to JAK inhibitors and highlights the unmet need for survival improvement in this patient population.

Of note our <unk>.

Recent publication in cancer Journal co authored by Dr. <unk> and October still SEC, both principal investigators in our phase III impact MF trial. This.

Describes the clinical dilemma for achievement of JAK inhibitor failures.

Paper reinforces the poor outcomes in menu mix patients, who are refractory to JAK inhibitors and highlights the unmet need for survival improvement in these patient population.

Alexandra Rizzo: Moving on to the earlier stage programs in our pipeline, the clinical side in the improved MS study. This phase one study is designed to evaluate the safety and clinical activity of hematocytes in combination with ruxolitinib in patients with front line MS. In this study, we want to explore the potential for disease modification with a metal treatment in the earlier stages of the disease. The setting.

Moving on to the earlier stage programs in our pipeline.

<unk>.

Clinical site in the improve MF study.

This phase one study is designed to evaluate the safety and clinical activity of <unk> in combination with <unk> in patients with frontline on that.

In this study we wanted to explore the potential for disease modification, leading mattel's treatment in the earlier.

D setting.

Alexandra Rizzo: As a reminder, Improve-MF is a single-arm, open-label study in patients with front-line MF consisting of two parts. Part one will enroll up to 20 patients for the combination of hematopoietin and oxaloetanib. While efficacy data are being collected in part two, we also plan to enroll approximately 20 patients identified in part one and collect further safety and efficacy data. In both parts, patients will receive Ruxolitinib, followed by Imetelstat, a dosing schedule that shows synergistic and in preclinical experiments.

As a reminder.

Improve our Matthew the single arm open label study in patients with frontline and that consisting of two parts.

<unk>, one will enroll up to 20 patients.

First for the combination of <unk> and <unk>, while efficacy data are being collected in part two we also plan to enroll approximately 20 patients.

Identified in part one and collect further safety and efficacy data.

In both product patients, who will receive <unk> sorafenib follow with buying Mattel's time, a dosing schedule that showed synergistic.

In preclinical experiments.

Alexandra Rizzo: For our investigator-led trials in high-risk MDS and acute myeloid leukemia, or AML, we continue to... expect the start in the second half of 2022. This is a non-clinical publication in the Journal of Clinical Medicine, although in pediatric AML, further supports the development of metastat in these diseases.

For our investors.

Trials in higher risk, Mds, and acute myeloid leukemia, or AML, who continue to occur.

Expect to start in the second half of 2022.

Ah.

It's a non clinical publication in the journal of clinical Medicine.

<unk> pediatric AML further supports the developments from Intelsat <unk>.

Olivia Bloom: Lastly, and in anticipation of likely questions, I want to comment that we have limited clinical trial activity in Ukraine and Russia across all of our ongoing trials. At the moment, we believe that the conflict will have no significant impact on our trials or on our timelines, including top-line results for eMERGE Phase III and enrollment and interim analysis for IMPACT-MS. I would now like to turn the call over to our Chief Financial Officer, Olivia Bloom, for a financial update. Okay, Olivia?

Lastly, and in anticipation of likely questions I want to comment that we have limited clinical trial activity in Ukraine, and Russia across all of our ongoing trials.

At the moment, we believe that the conflicts will have no significant impact in our trials or on our timelines, including topline results for emerge phase III enrollment and interim analyses or impact on that.

I would now like to turn the call over to our Chief Financial Officer, Olivia Bloom for a financial update.

Yeah.

Olivia Bloom: Thanks, Alex, and thanks to everyone on the call for joining us today. Please refer to the press release we issued this afternoon, which is available on our website, for detailed financial results. As expected, and in line with our financial guidance, overall, in our first quarter 2022 financials, there was an increase in operating expenses compared to the same period in 2021, which was primarily driven by higher development expenses. The increase in R&D expenses for the first quarter of 2022 compared to the same period in 2021 primarily reflects higher personnel-related costs for additional headcount.

Thanks, Alex and thanks to everyone on the call for joining us today.

Please refer to the press release, we issued this afternoon, which is available on our web site the detailed financial results.

As expected and in line with our financial guidance.

Overall in our first quarter 2022 financials. There was an increase in operating expenses compared to the same period in 2021, which was primarily driven by higher development expenses.

The increase in R&D expenses for the first quarter of 2022 compared to the same period in 2021.

Primarily reflect higher personnel related costs for additional headcount.

Olivia Bloom: The decrease in general and administrative expenses for the first quarter of 2022 compared to the same period in 2021 primarily reflects the net result of reduced costs related to modernizing the internal infrastructure to support commercial launch and lower legal fees, partially offset by higher personnel-related expenses for additional dollars in cash and marketable security on April 1, for the offering of common stock and warrants that Chip mentioned earlier on the call. The estimated net proceeds are approximately $70 million.

The decrease in general and administrative expenses for the first quarter of 2022 compared to the same period in 2021.

The net result of reduced costs related to modernizing the internal infrastructure to support commercial launch and lower legal fees.

Partially offset by higher personnel related expenses for additional.

And cash and marketable securities.

Okay.

On April one.

Spring of common stock and warrants that chip mentioned earlier on the call.

The estimated.

The net proceeds are approximately $70 million after you die.

Olivia Bloom: Your estimated offering expenses, payable by Us. We continue to expect non-gap operating expenses up to $150 million for the full year of 2022.

Estimated offering expenses.

Payable by Us.

We continue to expect non-GAAP .

Total operating expenses up to $150 million.

For the full year of 2022.

John Scarlett: The fiscal year 2022 financial guidance reflects costs to support clinical execution in eMERGE Phase 3 and PILAB readiness activities for top regulatory filing and pre-commercialization. Special Preparation With the additional capital from the recent financing and our existing financial resources, we expect to have approximately $130 million in cash and marketable security at the time of the lower-risk MDFS top-line results in early 2023. We also project up to $125 million in additional funding in 2023 from potential exercises of currently outstanding warrants.

For fiscal year 2022 financial guidance reflects cost to support clinical execution and emerge phase III <unk> readiness activities were top toy filings and pre commercial.

So preparation.

With the additional capital from our recent financing and our existing financial resources.

We expect to have approximately $130 million in cash and marketable securities at the time of the lower risk Mds topline results in early 2023.

We also project up to $125 million in additional funding in 2023 from potential exercises of currently outstanding warrant.

John Scarlett: When added to the projected $130 million on the balance sheet at the beginning of 2023, we expect the projected financial resources to be sufficient for Planned Milestones through the end of 2023. These milestones include regulatory filings and low-risk MDF in the U.S. and in Europe, as well as preparatory activities for the potential U.S. commercial launch of Imitelstat and low-risk MDF in the first half of 2024 With that, I will now hand the call back to Chip for closing remarks. Chip?

When added to the projected $130 million on the balance sheet at the beginning of 2023.

The projected financial resources to be sufficient.

Four planned milestones through the end of 2023.

These milestones include regulatory filings in low risk Mds in the U S and in Europe , as well as preparatory activity for potential U S commercial launch of <unk> and low risk Mds and the first half of 2024.

With that I will now hand, the call back to chip for closing remarks.

Yep.

Thanks Olivia.

John Scarlett: Thanks, Olivia. As you've heard throughout this call, 2022 marks an incipient and shareholder. So I'd like to end this call by reiterating our excitement for where we stand as a company today. We believe we have two well-designed phase 3 trials with registered... Data readouts expected to create significant, We have a tight line, opportunities for additional Immittelstead indications, and combinations who believe we're financially well-positioned to execute on key clinic runway through the end of 2020. 23.

As you've heard throughout this call 2022 marks to patients and shareholders.

So I'd like to end this.

Call by reiterating our excitement for where we stand as a company today.

We believe we have two well designed phase III trials with radius.

Data readouts expected to create CBD.

Okay.

We have a pipeline.

Opportunities for additional <unk>.

Vacations and combination regimen.

Okay.

We believe we are financially well positioned to execute on key clinical runway through the end of 2012.

John Scarlett: We expect that runway will provide for strategic optionality to maximize shareholder value, following top-line results from our lower-risk MDS phase 3 trial expected in early January 2023. We're building the capabilities to establish ourselves as a commercial company and to prepare for a potential U.S. launch, as well as a passionate, focused employee base that is deeply committed to bring intimate health statistics to patients and create value for our shareholders. We have deep belief in our ability to help patients suffering from hematologic malignancies. Thank you for listening today.

'twenty three.

We.

We expect that runway will provide for strategic optionality to maximize shareholder value.

Following top line results from our lower risk Mds Phase III trial expected in early January 2023.

We are building the capabilities to establish ourselves as a commercial company and to prepare for a potential U S launches as well as attachment focused employee.

Employee base that is.

We committed to bring <unk> to patients and create value for our shareholders sure Jerome and understand our.

Deep belief in our ability to help.

Patients suffering from hematologic malignancies.

Thank you for listening today.

Operator: And operator, please open the call to questions. Thank you. At this time, I would like to remind everyone that in order to ask a question, press star, then number one on your telephone keypad, and we'll pause for just a moment to compile the Q&A roster. Good afternoon, everyone.

And operator, please open the call to questions.

Thank you at this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad and we'll pause for just a moment to compile the Q&A roster.

Good afternoon, everyone.

Anil Kapur: So maybe a question for the MF Study: how do you think the positioning in Telstat might look like for additional drugs that may be approved by that time in the second-line setting, for example, momoletinib? I think Anil is going to take that question. Thank you, Gil. With multiple mechanisms under investigation, patients to be treated with combination therapy. Peace, Herapies that are addressed in traumatic patients and also address the needs of the general population, which represents a fragment of the eligible patients for our study.

So maybe.

Okay.

For the.

MF study.

How do you think the positioning of <unk>.

And the cost up might look like in <unk>.

Additional drugs that may be approved by that time in the second line setting up of for example, more malignant.

I think Neil is going to take that question. Thank you Joseph importantly, those fees.

With multiple mechanisms underinvest.

Patients to retreat.

Greg.

<unk> competitive.

These therapies that address symptomatic patients and also addressing the needs of CA release cycle is and are transfusion dependent.

Evolution, which represents.

Segment of the eligible patients for our study.

Anil Kapur: Our study, as you know, I, the faculty, patient-only study with overall survival as a primary end point. In all our market research, discussion with physicians, and KOLs, this is expected to be a highly compelling study and, if the results are proven, we would expect it to become part of the standard of care for myelofibrosis. That makes a lot of sense. An OSN point is definitely differentiated.

Our study as you noted.

Hi, feedstock III patients.

Only study with overall survival.

As a primary endpoint.

And all.

Market research and discussions with physicians Kols.

This is expected to be a highly compelling study results.

So proven we would expect to become part of the standard of care for myelofibrosis.

Alexandra Rizzo: Maybe a related question. So we're going to be looking at a frontline combination study with Roth, and I noticed that the primary endpoint is TSS and SVR35, which is kind of the usual endpoint. But any thoughts on other assessments like response rates or, you know, something a little more outside of the SVR realm? Thank you. Alex will take that, Gil.

That makes a lot of sense and OS endpoint as the main differentiator maybe.

Related question.

So.

But we're going to be looking at frontline combination study with rocks.

I noticed that the primary endpoint is to assess the message. We are 35, which is kind of the usual, but any thoughts on the other assessment bike response rates or.

Something a little more outside of the SVR wrong. Thank you.

Alexandra Rizzo: Yeah, thank you. So again, let me repeat that this is a phase one dose finding study. We want to first confirm that we can combine the two drugs, identify a safe dose, and then, in the second part of the study, we want to confirm this dose. So while we're doing this, we will be collecting all the efficacy data that is out there known for myelofibrosis in addition to SVR and TSS. We will be collecting all the biomarker data for which we believe we can distinguish it from other drugs in development.

Hi.

Yes, Alex we will take that Joe.

Sure. Thank Gil so.

Again, let's shrink keypad speaking a phase one dose finding study we wanted to first confirm that we can combine the two drugs.

Identify a dose and borrowing in the second part of the study we want to confirm this dose so why while.

While we're doing this we will be collecting every efficacy data.

Are there.

Known for Myelofibrosis. In addition to SCR in PSS will be collecting all the biomarker data for which we believe will distinguish.

From other drugs in development.

Alexandra Rizzo: So that is one. We will be collecting fibrosis data, or we will be conducting marrow assessments, for potential PRs and for regular PRs as well. So it will be a comprehensive data collection that we believe will inform us about the next step. Thank you. That's very helpful.

So that is one we will be collecting fibrosis data or improve we will be conducting a.

Narrow assessments.

For <unk> potential Prs and Prs.

Well.

So it will be a comprehensive data collection that we believe will inform us.

On the next steps.

Thank you that's very helpful.

Hum.

Thanks for taking our questions.

You bet. Thanks Bill.

Yeah.

Stephen Willey: And thanks for taking our questions. You bet. Thanks, Gil. We will take our next question from Stephen Willey with Stifel. Your line is open.

We'll take our next question from Stephen Willey with Stifel. Your line is open.

Alexandra Rizzo: Yeah, thanks for taking the questions. Maybe just to follow up on the last question with respect to improved MF, I know the intention here is to evaluate the potential for disease modification in frontline patients, but, I'd be curious what you think the efficacy bar and tolerance for incremental toxicities is here, given the treatment of front-line patients with neuropathies is currently very focused on symptomatic improvement. And I guess I'm a follower. Yeah. Go ahead, Alex.

Yes, thanks for taking the questions.

Maybe just a follow up on on the last question with respect to improve on that if I look at your attention here to evaluate the potential for disease modification.

One patient but.

Just curious what you think.

The key bars tolerance for incremental toxicities here just.

Given the.

The treatment of frontline patients with <unk>.

As is currently very focused on symptomatic improvement.

And then just have a follow up.

Alexandra Rizzo: I can take that. I can see. So, there are a couple of points I believe are important to make. Thresholds in terms of safety or toxicity are very important. Our drugs do have overlapping thrombocytopenias, and for that reason, we are starting very carefully with the dosing of the two drugs. We stabilize RAX first, and then we add Gematelstat.

Yeah go ahead, Alex I can think of ion intensities, though I mean couple of points I believe here are also important to me so.

In terms of safety or toxicity are very important our drugs that do have overlapping thrombocytopenia for batteries and we are starting.

Carefully.

With that dosing of the two drugs, we're stabilizing rock burst and then theyre, adding mattel's bug and weed and no I think we believe that with this approach we will find the best tolerated.

Alexandra Rizzo: And, you know, I think we believe that with this approach we will find the best tolerated dose for the combination. In terms of efficacy, I mean, the bars are set in front line, they're being set in second line as well, but we believe that, again, we will see, or we hope to see, right, other improvements in addition to the SVR and the TSS, and I think the disease modifying potential that we hope for in terms of reduction in allele burden, improvement in fibrosis is something that, you know, will take our drug, right, in a different position than the other drugs in development.

Those for the for the combination.

In terms of.

Secrecy.

The bars are.

Or said in frontline there.

In second line as well, but we believe that again, we view.

Are we hope to see right either.

Improvements in addition to the SVR and the TSS and I think the disease modifying potential that we hope for in terms of reductions in allele burden improvements in fibrosis as something that.

We'll take the hour drive right.

In a different position than the other drugs in development.

Okay.

Alexandra Rizzo: Okay, and then just on the disease modification front. Are you going to be requiring patients to undergo Marrow assessments and fibrotic assessments, and I guess with respect to fibrosis, I know it's kind of a bit of a subjective endpoint. Would you also be looking at mutant allele frequencies in these patients and, if so, can you remind me what the rate of secondary mutation is? Aron, and these frontline patients are those observed at the same kinetics that are seen in the Jack refractory patients.

Okay, and then just on the disease modification fronts.

Are you going to be requiring patients to.

To undergo.

Marrow assessments.

And fibrotic assessments.

Yes, with respect to fibrosis, I know, it's kind of a bit of a subjective endpoint.

Would you also be looking at.

<unk> frequencies in these patients and if so can you remind me does the railroads.

Secondary mutations.

These frontline patients or are those observed that youre seeing.

The same kinetics that is seen in.

In the Jack refractory mutations.

Alexandra Rizzo: So a couple of points. I think you had a couple of very good points. Let me address them one by one. So we do, or we will be, collecting marrows to assess fibrosis as well as allele frequencies for various mutations. The fibrosis assessment that we have done in our studies so far, and we plan to continue doing in the same way, is done by an independent review committee. So while it is, you know, some people say it's subjective, I think we're doing a fairly good job in having that done by an IRC, which kind of makes us confident about the fibrosis improvement or the fibrosis data that we will be collecting and assessing. So, So he has two fibrosis, right?

So a couple of I think you had couple of very good points, let me address them one by one.

Do you are we will be collecting.

Mero.

To assess fibrosis as well as <unk> fragrances.

For variance.

<unk> mutations.

Thus fibrosis assessment that we have gone on our study so far and.

Plan to continue.

Testing of the same way is done by an independent review committee so while it is.

No.

Some people say subjective I think are doing fairly good job.

Having been done by an IRC, which kind of.

<unk>.

It makes us confident about the fibrosis improvement or the fibrosis data that we will be collecting in assessing.

<unk>.

So.

Yes to fibrosis rise that we our agreement in.

Alexandra Rizzo: So we are doing this in an independent review manner, and we will be collecting samples to assess allele frequency. And in addition to that, we will be coordinating these two with the outcomes. Now, your last question, whether these mutations occur at the same frequency in the front line and second line setting, I think we'll have to discuss which ones because as the patients progress, I would guess, I would say in their disease, they tend to have high-risk molecular characteristics, but nevertheless, a lot of these mutations are linked to the disease itself, right? So just like the driver mutations itself.

Independent review manner, and we will be collecting.

Samples to assess elio frequency.

And in addition to that he will be coordinating this too.

<unk> outcome.

Now to your last question, whether these frequent whether these mutations occur in.

The theme of frequency in frontline and second line setting.

I think it will have to discuss which one because.

The patients.

For Chris I would guess I would say they're in there.

<unk>.

They tend to be.

To have the high risk molecular characteristics.

But nevertheless, a lot of these.

Mutations are linked to the disease itself right. So just like the driver mutations itself. So I don't know exactly about the frequency of each of them, but I would say that at least a combination of all of them. For example, the <unk> do increase over time as the patients progress.

Alexandra Rizzo: So I don't know exactly about the frequency of each of them, but I would say that at least the combination of all of them, and, for example, the HMRs do increase over time as the patients progress. Okay, that's very helpful. Thanks for taking the question. Thank you. And we will take our next question from Joel Beatty with Baird. Your line is open. Hello, this is Benjamin on behalf of Joel.

Okay. That's very helpful. Thanks for taking questions.

Thanks Vic.

And we will take our next question from Joel Beatty with Baird. Your line is open.

Hmm.

Anil Kapur: Just a few questions for us. Could you maybe describe the level of physician engagement in enrolling patients in IMPACT-MS, and maybe you can provide a little bit of color on the number of sites coming online? Thank you. I'll take that one as well.

Hello. This is Benjamin on for Joel just a few questions for us.

Yeah.

Could you maybe describe the level of physician engagement and enrolling patients in impact.

And maybe you can.

Provide a little bit of color on a number of sites coming online. Thank you.

Anil Kapur: So I think that's what we've guided so far is that we've opened more than 50% of our sites and we do remain confident that we will open the rest of the sites by the end of the year. I don't think we have really put a number there, but this is what we are expecting to do. The space is competitive, as I'm sure you know.

I'll take that one as well so.

I think thats, what <unk> guided so far because we've opened more than 50% of our size and we do remain confident that we will open the rest of the sites by the selected sites by the end of the year I don't think we have really put a number there but.

This is where this is where they are we are expecting to do.

The space is competitive as im sure.

Anil Kapur: However, taken the fact that we have overall survival as a primary endpoint, which has been multiple times repeated at EDs, an endpoint that is needed in this space, and our PIs really remain enthusiastic about it, we do see enrollment moving in the right direction. Great, thanks. And then just one more.

No.

However, it taken thus.

The fact that we have an overall survival as the primary endpoint, which has been multiple times repeated at E <unk> Barry.

It is.

An endpoint that is.

Needed in this space and our <unk>.

We remain enthusiastic about it.

Hugh.

We do see enrollment.

Moving in the right direction.

Anil Kapur: On the lower-risk MDS, are there any early commercial preparations underway for the readout anticipated in early January? Thank you. Joel, this is Anil.

Great. Thanks, and then just one more on the lower risk Mds or are there any early commercial breadth underway for the readout dissipated in early January thank you.

Okay.

Yeah.

Anil Kapur: I'll take that question. So yes, there is an extensive effort underway for us to characterize the market, understand the physician base, really see where all the treatments are coming from, and also extensive efforts, which you will start to see over the next 12 months as we bring Imitelstat data to the market and start to educate physicians around the unique mechanism of action from our perspective. All of these events are stage gated.

Joe This is <unk> I'll take that question. So yes that is extensive effort under way for us to characterize the market.

This time, the physician is really to see where all the treatments are coming from and also our extensive efforts, which you will start to see over the next 12 months as we bring in Windows star data to the market and start to educate physicians around the unique mechanism of action from our perspective all of these events are a stage gated.

Anil Kapur: They are all tailored post-low risk MDS, and I want to remind you one more time that the vast majority of our commercial hiring is gated post-ELR as well. So I'll just stop here to see if I answered your question. Yep, all set.

They're all tailored post low risk Mds and <unk> as a reminder, one more time that vast majority of our commercial hiring.

Is it both <unk> as well so I would just stop here to see if I answered.

To your question.

Yes. Thank you.

Justin Walsh: Thanks. And that's a reminder. It is Star One if you would like to ask a question. And we will take our next question from Justin Walsh with B Reilly Securities. Your line is open.

Remainder exam.

<unk>.

It is star one if you would like to ask a question.

And we will take our next question from Justin Walsh with B Riley Securities. Your line is open.

Alexandra Rizzo: Hi, thanks for taking the questions. With respect to improved MF, do you anticipate front-line MF patients having any hesitancy about starting with a front-line combo, given that RUX alone can provide benefit in patients for some time before they inevitably relapse? Thanks for that question. I don't see why I think that, you know, just in addition to the benefits that they can have with RUX, they might have additional benefits from treatment with Metelstat.

Hi, Thanks for taking the questions.

With respect to improve MFS, you anticipate frontline MF patients, having any hesitancy about starting with the frontline combo given that rux alone can provide benefit in patients for some time before they inevitably relapse.

Alexandra Rizzo: So we have not heard that concern, nor do we have any hesitancy about that. Just to add to what Alex said, there are multiple trials underway in myelofibrosis, upwards of 10 phase 3 trials, 6 of them in frontline with combination strategies with JACI. So our expectation is what we would hope to bring to the table is the potential for disease modification with a novel non-JACI mechanism over time as the improved MF data starts to establish itself.

Thanks for that question I don't see why I think that just in addition to the benefits that they can have right they might have.

Additional benefits from treatment with <unk>. So we have not heard that concern nor we have any hesitancy about that.

Got it so just to add on to what Alex said.

There are multiple trials underway in myelofibrosis.

Purchased 10 phase III trials six of them in frontline with combination strategies with <unk>.

So our expectation is what we would hope to bring to the table is the potential for disease modification with a novel non <unk> mechanism.

Overtime as the improved by Merck data starts supposed ambitious.

Alexandra Rizzo: Got it. And maybe building on that, as my last question, do you have any concern that there'll be challenges in enrolling patients since you'll be competing with all of those other trials that you just mentioned? I'm not sure about which study you're talking about.

Got it and maybe building on that as my my last question.

Do you have any concern that there'll be challenges in enrolling patients since you'll be competing with.

With all of those other trials that you just mentioned.

I'm not sure for which study IMMU improve MF.

Alexandra Rizzo: Improved MS. Improved MS for the front-line study? Maybe, but I guess we could... That's true for impact as well.

<unk> for the frontline.

Improve MF, but I guess, we could.

That's true for <unk>.

In fact as well.

Alexandra Rizzo: Right. I don't think so. I don't think so. I mean, again, the drug offers a really different benefit and distinct value, right, for the patient.

Brian I don't think so I don't think so I mean again the drug offers.

Read different benefits and distinct value add for it for the patients.

The potential for overall survival in that refractory space, it's really received with enthusiasm and bringing that does disease modification to the frontline setting where patients should respond even better right. Because these are less sick patients I think it still uniquely attractive to both the eye.

Alexandra Rizzo: You know, the potential for overall survival in the refractory space is really received with enthusiasm and bringing the disease modification to the frontline setting where patients should respond even better, right, because these are elastic patients. I think it's still uniquely attractive to both PIs and investigators. So with that, at least, I don't expect any problems with enrollment. The field is competitive, nevertheless, but we do stand out for a couple of good reasons, I believe.

And investigators.

So with that at least I don't expect any.

Any problems with enrollment the fill this competitive nevertheless, but we do stand out for it for a couple of good reasons I believe.

Alexandra Rizzo: Great, thanks for taking the questions. Thank you. Thank you. And there are no further questions at this time. I would like to turn the call back to Aron Feingold for his closing remarks. Thanks so much to everyone for joining us today and for your questions. We look forward to keeping you posted on our progress. See you all. And ladies and gentlemen, this concludes today's conference call. We thank you for your participation, and you may now disconnect. Thanks for watching!

Great. Thanks for taking the questions.

Thanks Joseph.

And there are no further questions at this time I would like to turn the call back to Aaron <unk> for closing remark.

Thanks, so much to everyone for joining us today and for your questions. We look forward to keeping you posted on our progress seawell.

And ladies and gentlemen. This concludes today's conference call. We thank you for your participation and you may now disconnect.

[music].

Yeah.