Q4 2020 Geron Corp Earnings Call

Ladies and gentlemen, this is the operator today's conference is scheduled to begin momentarily until that time your lines will again be placed on music hold thank you for your patience.

Operator: Welcome, this is the operator. Today's conference is scheduled to begin momentarily. Until that time, your lines will again be placed on music hold. Thank you for your patience.

unknown: Director of Photography, Edited by G.B. Weiss; Music by G.B. Weiss; Music by G.B. Weiss; Edited by G.B. Weiss

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the fourth quarter 2020 Geron Earnings conference call. At this time, all participants are in the listen-only mode.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star zero. I would now like to hand the conference over to Olivia Bloom, Geron's Chief Financial Officer. Thank you, please go ahead.

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Ladies and gentlemen, thank you for standing by and welcome to the fourth quarter 2020, Geron earnings Conference call.

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

Olivia Kyusuk Bloom: Thank you, Erica. And good afternoon, everyone. Thank you for joining us for today's conference call. I'm joined today by Dr. John Scarlett, Durham's Chairman and Chief Executive Officer, and Alexander Rizzo, our Chief Medical Officer. After the market closed today, we announced our fourth quarter and year-end 2020 financial results and operational highlights in a press release, which is available on our website under geron.com slash investors. In addition, a live webcast of this call is available on our website, and an archive will be available for 30 days. Before we begin, please note that this presentation and question and answer session will contain four looking statements relating to Geron's plans, expectations, timelines, beliefs, statements of potentiality, and projections.

Asked a question during the session you will need to press star one on your telephone if you require any further assistance. Please press star zero I would now like to hand, the conference over to Olivia Bloom, John <unk> Chief Financial Officer. Thank you. Please go ahead ma'am.

Thank you Erica and good afternoon, everyone. Thank you for joining us for today's conference call I'm joined today by Dr. John Scarlett Geron, Chairman and Chief Executive Officer, and Alexander <unk>, Our Chief Medical Officer.

After the market closed today, we announced our fourth quarter and year end 2020 financial results and operational highlights via press release, which is available on our website under geron Dot com slash inductors and.

In addition, a live webcast of this call is available on our website and an archive will be available for 30 days.

Before we begin please note that this presentation and question and answer session will contain forward looking statements relating to geron plan expectations timelines beliefs statements of potentiality and projections. These include without limitation those regarding the expected timeline for completion of.

Olivia Kyusuk Bloom: These include, without limitation, those regarding the expected timelines for completion of enrollment and the results from the eMERGE Phase III and IMPACT-MS clinical trials and submission of an NDA, the potential for positive outcomes from eMERGE Phase III and IMPACT-MS, potential approval of IMIT-HEALTH Stats by regulatory authorities, and commercialization of IMIT-HEALTH Stats. The expectation is that Geron's current financial resources will be sufficient to fund its operations until the end of 2022 and that Imitelcept has the potential to be disease-modifying and alter the course of MDS and MS. These and other forward-looking statements involve risks and uncertainty that can cause actual results to differ materially from those in such forward-looking statements.

And the results from the emerge phase III and impact MF clinical trial and submission of an NDA the potential for positive outcomes from emerge phase III and impact on NAV potential approval and was held back by regulatory authority and it's and commercialization of Intelsat.

The expectation that John current financial resources will be sufficient to fund operations until the end of 2022 and the <unk> has the potential to be disease, modifying and alter the course of Mds and MMS.

These and other forward looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward looking statements. These.

Olivia Kyusuk Bloom: These risks and uncertainties include, without limitation, those regarding that the company may be unable to overcome all the enrollment, clinical, safety, efficacy, technical, scientific, operational, manufacturing, and regulatory challenges to meet the expected timeline for eMERGE Phase 3 and IMPACT-MF due to COVID or otherwise, that in the Phase 3 clinical trials, ImatelCet may not prove to be as safe or efficacious as in the Phase 2 trials, and may not demonstrate that it is safe, efficacious, and disease-modifying, that regulatory authorities may not permit the further development of Imitelstat on a timely basis or at all, and may not approve it for commercialization, and that Geron may need additional financial resources before the end of 2022 for the development and commercialization of Imitelstat. Detailed information on the above risks and uncertainties, and additional risks, uncertainties, and factors that could cause actual results to differ maturely from those in the forward-looking statements are explained under the heading risk factors in Geron's annual report on Form 10-K for the year-ended December 31, 2020, filed with the Securities and Exchange Commission. Unviewed reliance should not be placed on forward-looking statements to speak only after the date they are made, and the facts and assumptions underlying the forward-looking statements may change.

These risks and uncertainties include without limitation those regarding that the company may be unable to overcome all the enrollment clinical safety efficacy technical scientific operational manufacturing and regulatory challenges to meet the expected timeline for emerge phase III impact MF due.

Due to COVID-19 or otherwise, but in the phase III clinical trials and hotels that may not prove to be a safer efficacious as in the phase two trials and may not demonstrate but is it safe efficacious and disease modifying.

That regulatory authorities may not permit the further development and the post that on a timely basis or at all and may not approve it for commercialization and then John May need additional financial resources before the end of 2022 per the development and commercialization of Intelsat.

Detailed information on the above risks and uncertainties and additional risks uncertainties and factors that could cause actual results to differ materially from those in the forward looking statements are explained under the heading risk factors and geron with annual report on form 10-K.

Year ended December 31, 2020 filed with the Securities and Exchange Commission.

Undue reliance should not be placed on forward looking statements, which speak only as of the day. They are made and the facts and assumptions underlying the forward looking statements may change.

Olivia Kyusuk Bloom: On today's call, Dr. Scarlett will make a few introductory comments, after which I will cover the fourth quarter and year-end financial results, as well as guidance for 2021. Dr. Lizzo will provide clinical development updates on the ongoing eMERGE Phase III trial in our target patient population with low or intermediate one-risk myelodysplastic syndrome, which we call low-risk MDS, who are transfusion-dependent, non-delphi-2, and relapsed-actyl-omopractic-2 prior treatment with an erythropoiesis-stimulating agent, or ESA. She will also provide an update on our impact MS-based retrial, which is in a population of patients with intermediate to or high-risk myofibrosis who are refracted to prior treatment with a JAK inhibitor, which we call refractory MS. Alexander will also discuss how the data and analyses we reported at the American Society of Hematology annual meeting in December 2020 have deepened our understanding on Imitel's mechanism of action and its effect on the underlying cause of the disease and the indications we're pursuing.

On today's call Dr. Chris Cabell will make a few introductory comments after which I will cover the fourth quarter and year end financial results as well as guidance for 2021 Dr.

Dr. Rizo will provide clinical development update on the ongoing emerge phase III trial in our target patient population with low or intermediate one risk Myelodysplastic syndrome, which we call low risk Mds, who are transfusion dependent and non del <unk> in relapsed after or refractory to prior treatment with <unk>.

Erythropoiesis stimulating agent or Esa.

We'll also provide an update on our impact Msas, III, CRO, which isn't a population of patients with intermediate two or high risk myelofibrosis, who are refractory to prior treatment with a JAK inhibitor, which we call refractory MF.

Alexandra will also discuss how the data and analyses we reported at the American Society of Hematology annual meeting in December 2020 has deepened our understanding on M has helped us mechanism of action and its effect on the underlying cause of the disease and the indications we're pursuing.

Olivia Kyusuk Bloom: Dr. Scarlett will then comment on the evolving low-risk MDS and MS markets and Emmett Health's positioning in those markets, given its potentially highly differentiated product profile. You'll finish the call with closing remarks on plan milestones for 2021. I'll now turn the call over to Dr. Scarlett, Geron's chairman and CEO. Thanks, Olivia.

Dr. Scarlett will then comment on the evolving low risk Mds and MMS market and <unk> positioning in those markets given its potentially highly differentiated product profile.

You'll finish the call with closing remarks on planned milestones for 2021.

Now I'll turn the call over to Dr. Scarlett Geron, Chairman and CEO Jeff.

Thanks, Olivia I'd like to welcome everyone to our fourth quarter and year end 2020 conference call.

John A. Scarlett: I'd like to welcome everyone to our fourth quarter and year-end 2020 conference call. Let me start by sharing our vision for Geron, which is to become a leader in the treatment of hematologic malignancies by changing the course of these diseases, and improve and extend the lives of patients. As I look back on 2020, we made significant progress towards realizing the decision. In the end, we presented compelling and differentiating data from our eMERGE Phase II Lower Risk MDS trial. These data showed high rates and exceptional durability of transfusion independence.

Let me start by sharing our vision for John which is to become a leader in the treatment of hematologic malignancies.

Changing the course of these diseases.

Improving and extending lives of patients.

As I look back on 2020, we made significant progress towards realizing this vision.

So again, we presented compelling and differentiating data from our emerge phase two low risk Mds trial.

These data showed high rates and exceptional durability of transfusion independence.

John A. Scarlett: Of any study in Mundell 5Q lower risk MDS patients who relapsed in a refractory 2EF case, the 21-month median duration of transfusion independence in eMERGE Phase II was the longest recorded to date. In our eMERGE Phase 3 Lower Risk MDS Study, enrollment gains continued, with over 50% enrollment achieved by the end of the year. We also presented exceptional overall survival data from our MBARC Phase II trial in jack-eye relapsed or refractory MF patients.

Any study and from there.

<unk> low risk Mds patients, who relapsed or refractory to your day.

20 months median duration of transfusion independence emerge phase II with the longest reported today.

And our emerge phase III lower risk Mds study enrollment gains continued with over 50% enrollment achieved by the end of the year.

We also presented exceptional overall survival data from our embarked phase II trial, and jacquie relapsed or refractory MF patients.

John A. Scarlett: In this trial, Imatelstat-treated patients had a median OS of 28 months, which is almost twice the median OS reported in the medical literature. Associates and others supporting data, and after conferring with FDA, we opened ImpactMF, our Phase 3 trial in Jack Eye Refractory MF patients. In fact, NF is the first, and to date, only, We also presented Strauss' Disease, Autism, and Anxiety Therapy, Institute of Psychic Law, RISC-MDS, and last week's Hot Re-Embed.

In this trial in the <unk> treated patients had a median of work from 28 months, which is almost twice the median of what's reported in the medical literature.

If somebody from other supporting data and after conferring with SBA, we opened impact MF, our phase III trial, and jacquard refractory MF patients.

In fact in essence, the first and to date only phase III trial with overall survival primary endpoint.

We also extended the strong.

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This low risk Mds and luxury index.

John A. Scarlett: In both indications, we saw reductions in key driver mutations of the underlying disease. Furthermore, Imitalcept is the only drug in development to establish a correlation of these and other measures of disease modification with key clinical outcomes, including durability of transfusion-independent and low-risk MDS and improvement in MS. Such correlations have given us even greater confidence in the potential positive outcomes for our ongoing A3 impact analysis. He's also stand out as important accomplishments in 2020.

And both indications we saw reductions in key driver mutations of the underlying disease.

Furthermore, <unk>, that's the only drug in development to establish a correlation of these and other measures of disease modification from key.

Key clinical outcomes, including durability of transfusion independence in low risk Mds and improvement in MF.

Such correlations have given us even greater confidence in the potential positive outcomes for our.

Ongoing phase III.

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Standout as important accomplishments from 2020.

John A. Scarlett: The first was that we successfully established our global Imitelstat supply chain, ensuring uninterrupted drug supply for clinical trials and permitting the inclusion of Geron manufactured materials in a two phase three trial. Second, we raised over $175 million in new capital from both an underwritten public offering and a new loan facility. As a result, we expect our current cash will be sufficient to fund our operations through the end of 2020. All of these accomplishments were made despite the challenges posed by the ongoing COVID pandemic. [inaudible] Through trial and error, all in a year.

The first one we successfully established our global and the <unk> supply chain.

Uninterrupted drug supply for clinical trials and permitting inclusion John manufactured materials from phase III trials.

Second we raised over $175 million in new capital from both an underwritten public offering and the new loan facility.

As a result, we expect our current cash will be sufficient to fund our operations through the end of 2022.

All of these accomplishments were made despite the challenges posed by the ongoing COVID-19 pandemic.

The effect on clinical trials.

Okay free trial.

End of year and as of today, we've achieved 65% enrollment.

John A. Scarlett: And as of today, we've achieved 65% enrollment. As a result of the COVID pandemic, ongoing enrollment continues to be challenging. These enrollment challenges have been due primarily to the reluctance of patients to participate in clinical trials, as well as delays in opening new sites.

As a result of the Covid pandemic ongoing enrollment continues to be challenging.

She's enrollment challenges have been due primarily to the reluctance of patients to participate in clinical trials as well as delays in opening new sites.

John A. Scarlett: These effects of the pandemic appear to be true for many oncology trials, not just ours. In addition, we believe enrollment in eMERGE Phase 3 may be starting to be impacted by lispatercept becoming more widely available as a treatment for patients who are RS-positive and lower-risk for MDS. From everything we can see, the enrollment constraints in this trial are not a result of eMERGE being inadequately prioritized by investigators. In our interactions with them, our investigators remain enthusiastic about our Imatelstat data and are committed to enrolling their patients in this trial.

These effects of the pandemic appear to be true for many oncology trials not just ours.

In addition, we believe enrollment in emerge phase III may be starting to be impacted by these patterson, becoming more widely available as a treatment for patients who are Rs positive and low risk Mds.

From everything we can see the enrollment constraints from this trial are not a result from emerge being inadequately prioritized by investigators and our interactions with them. Our investigators remain enthusiastic about our <unk> data and are committed to enrolling their patients from this trial.

John A. Scarlett: Based on the information we currently have, we expect Emerge Phase 3 to be fully enrolled in the second half of 2021. Depending on the exact timing when that full enrollment is achieved, we expect top line results from Emerge Phase 3 to be available from the end of 2022 to the first half of 2023. Alexander will discuss in more detail the initiatives we put in place to improve enrollment in the face of the pandemic, and he will also update our activities in the Conduct of Impact Center.

Based on the information. We currently have we expect to emerge phase III to be fully enrolled in the second half of 2021.

Depending on the exact timing when that full enrollment is achieved we expect top line results from emerge phase III to be available from the end of 2022 from the first half of 2023.

Alexandra will discuss in more detail the initiatives, we put in place to improve enrollment in the phase two was hands down.

She will also update our activities in the conduct of impact from that.

John A. Scarlett: We currently expect the interim analysis for Impact MS to occur in 2024 and the final analysis to occur in 2025. Looking ahead, our plan's strategic priorities for the next three years and commercially launching this highly differentiated drug in lower risk MDS. Now I'd like to hand the call. I'd like to call the camera call.

We currently expect the interim analysis for impact MF to occur in 2024, and the final analysis to occur in 2025.

Looking ahead, our planned strategic priorities for the next three years.

Sure.

And commercially launching this highly differentiated drug in lower risk Mds.

Now I'd like to hand the call.

Our revenue colony AMCOL over.

Go ahead.

Olivia Kyusuk Bloom: I'm sorry, you were breaking up a bit just back there, just right before for Alexandra. Okay, so we currently expect the interim analysis for IMPACT-MF to occur in 2024, and the final analysis to occur in 2025. Looking ahead, our planned strategic priorities for the next three years include achieving top-line results in eMERGE Phase 3, gaining regulatory approval for Imbetelstat, and commercially launching this highly differentiated drug in lower-risk MDF. Now, I'd like to hand the call over to Olivia to discuss our fourth quarter and year-end financial results and financial guidance for 2021. Olivia

Sorry, you were breaking up a bit just back there.

The spread before right before for Alexandra.

Okay.

We currently expect the interim analysis for impact en masse to occur in 2024, and the final analysis to occur in 2025.

Looking ahead, our planned strategic priorities for the next three years include achieving top line results emerge phase III gaming regulatory approval of <unk> and commercially launching this highly differentiated drug in lower risk Mds.

Now I'd like to hand, the call over to Olivia to discuss our fourth quarter and year end financial results and financial guidance for 2021 Olivia.

Olivia Kyusuk Bloom: Great. Thank you, Jeff. As of December 31, 2020, we had approximately $260 million in cash, cash equivalents, and current and non-current marketable security. Our cash position reflects net proceeds of approximately $140 million from a public offering in May 2020 and approximately $24 million in initial net proceeds from a non-dilutive $75 million loan facility that we closed at the end of the third quarter last year. Based on current planning assumptions, we estimate our current financial resources to be sufficient for our operations until the end of 2022.

Great. Thank you chip.

As of December 31, 2020, we had approximately $260 million in cash cash equivalents and current and non current marketable securities.

Our cash position reflects net proceeds of approximately $140 million from a public offering in may 2020, and approximately $24 million in initial net proceeds from a non dilutive $75 million loan facility that we that we closed at the end of the third quarter last year.

Based on current planning assumptions, we estimate our current financial resources to be sufficient for our operations until the end of 2022.

Olivia Kyusuk Bloom: Overall, the financial results for the fourth quarter and year-to-date period were in line with our expectations and our operating expense guidance. Operating expenses for the three- and 12-month-ended December 31, 2020, were generally higher in comparison to the same period in 2019, due to headcount increases in 2019 and 2020 across the company, increased activity for the eMERGE Phase III clinical trial in low-risk MDS, startup activities for the IMPACT-MS Phase 3 clinical trial in refractory MS, and costs associated with ongoing Imitelsat manufacturing.

Overall, the financial results for the fourth quarter and year to date period were in line with our expectations and our operating expense guidance.

Operating expenses for the three and 12 months ended December 31, 2020 were generally higher in comparison to the same periods in 2019 due to head count increases in 2019 and 2020 across the company.

Increased activity for the emerge phase III clinical trial in low risk Mds sorry.

Startup activities for the impact MF phase III clinical trial in refractory MF.

And costs associated with ongoing Intelsat manufacturing.

Olivia Kyusuk Bloom: These increased costs were partially offset by lower costs related to purchases of raw materials, drug substance, and drug products and completion of the EMBARQ clinical trial, regarding financial guidance for 2021. We expect our operating expense burn to range from $108 million to $112 million, which includes costs for two ongoing phase three clinical trials, production of validation batches of Imitelstat at contract manufacturers to enable future production of Imitelstat for clinical and commercial purposes, and preparatory activities for NDA and commercial readiness.

These increased costs were partially offset by lower costs related to purchases of raw materials drug substance and drug product and completion of the Embarq clinical trial.

Regarding financial guidance for 2021 weeks.

We expect our operating expense burn to range from $108 million to $112 million, which includes call for our two ongoing phase III clinical trials production of validation batches of <unk> that at contract manufacturers to enable future production of Intelsat preclinical.

And commercial purposes.

And preparatory activity per NDA and commercial readiness.

Olivia Kyusuk Bloom: Financial guidance is based on a set of assumptions at a point in time, and if the company's plans change, causing assumptions to be revised, then we will update guidance at that time. With that, I will now turn the call over to Alexandra to provide an update on our Phase 3 clinical development activity.

Financial guidance is based on a set of assumptions at a point in time and if the company's plans change, causing assumptions to be revised.

And we will update guidance at that time.

With that I will now turn the call over to Alexandra to provide an update on our phase III clinical development activity Alexandra.

Thanks, Louise and good afternoon, everyone.

Alexander Rizzo: Thanks, Olivia. Good afternoon, everyone. As Pete mentioned, we have now achieved 65% enrollment in our eMERGE Phase 3 trial. Also, the first meeting of the Independent Data Monitoring Committee was held in December, and the IDMC recommended that the trial continue without modification. We expect the enrollment boosting activities we started last year to become more effective as COVID cases decline and as clinical operations begin to, hopefully, return to normal over the next several months.

As Keith mentioned, we have now achieved 65% enrolment in our emerge phase III trial.

Also.

The first meeting of the independent data monitoring Committee whats held in December and the IBM theoretical mandate.

Trial continue without modification.

We expect the enrollment boosting activities, we started last year to become more effective as COVID-19 cases decline and.

And its clinical operations begin to hopefully return to normal over the next several months.

As a result, we bill.

Alexander Rizzo: As a result, we believe that clinical science liaisons we engaged in the beginning of last year will be able to interact with clinical sites more easily and with greater frequency to help alert site personnel and patients to the potential benefits of participating in eMERGE Phase 3. In addition, we believe our social media campaign will help drive patient recruitment. Over the next few months, we expect all of the approximately 20 additional files for eMERGE to be open, bringing the total number of sites in this trial to approximately 120.

I'll leave the clinical science liaisons to engage in the beginning of last year, we will be able to interact with clinical sites morisot any bleed or frequency.

To help bowlers five personnel and patients to the potential benefits of participating from the March phase III.

In addition, we believe our social media campaign will help drive patient recruitment.

Over the next few months, we expect all of the approximately 20 additional five free in March will be open.

Bringing the total number of price in this trial to approximately 120.

Alexander Rizzo: Of course, the best boost to enrollment should come as vaccinations proceed, the number and severity of COVID cases decline, and patients again become more comfortable leaving their homes to participate in clinical trials. Earlier in this call, Chief mentioned some of the more mature clinical data from our eMERGE Phase II trial in low-risk MDS, which I would like to expand on briefly. These data are very encouraging, and they continue to differentiate Matelstat from other currently approved or investigational treatments. Firstly, the metal side elicits remarkable durability for transfusion independence.

Of course, the best post enrollment should comment vaccinations precede the number and severity of Covid cases decline in patients again become more comfortable leaving their homes to participate in clinical trials.

Okay.

Earlier in this call Keith mentioned towards the more mature clinical data from our emerge phase two trial, and we'll always MBS on which I would like to expand on gluten free.

Do you think are very encouraging and we continue to differentiate from across that from other currently approved or investigational treatments.

Foremost is there's a net sales start at least it's remarkable durability for transfusion independence.

In addition to the according to percentage of patients that achieved the primary endpoint of eight week transfusion independence.

Alexander Rizzo: In addition to the 42% of patients that achieved the primary endpoint of eight-week transfusion independence, 32% of the metrostat 3D patients were transfusion-free for 24 weeks, which was a key secondary endpoint. Furthermore, 29% of the patients were transfusion-free for over a year.

32% of the <unk> treated patients were transfusion free 24 weeks, which was a key secondary endpoint.

Furthermore, 2009% compensation.

Transfusion free port over a year.

We also reported a median duration of transfusion independence of 20 months.

Alexander Rizzo: We also recorded a median duration of transfusion dependence of 20 months. That compares very favorably to the most recent available data we've seen from the Spotter test, in which a median duration of transfusion independence of seven months was recorded. I'd also like to emphasize that these results come from a patient population with a very heavy baseline transfusion burden, and then the results were similar for both RS negative as well as RS positive patients. Similar results were obtained in our eMERGE Phase 3. We believe imatelstat will be a highly differentiated and very competitive treatment for the lower risk MBS patient population. Moving on, to Miles Edwards.

That compares very favorably to the most recent available data we've seen from the spot assets in which a median duration of transfusion independence of seven months was recorded.

I'd also like to emphasize that these results have come from a patient population will be very heavy baseline transfusion burden.

And then the results were similar for both Rs negative as well as the Rs positive patients.

Similar results are obtained an hour emerge phase III.

We believe in that.

I'll start will be highly differentiated and very compelling treatment for the lower risk Mds patient population.

Moving onto myelofibrosis.

Okay.

Alexander Rizzo: In his earlier remarks, Chip mentioned that in the EMBARQ Phase 2 trial, the median overall survival was 28 months. This compared very favorably to the median age of 13 to 16 months in the medical literature. The median OS also compares favorably to the OS of 12 months observed in real-world data analysis of electrophractic MS patients who were treated with the best available therapy, and they were carefully matched with our MATELSTAT treated patients in Mumbai In addition to overall survival, patients in EMBARQ experienced other important clinical benefits, including symptom improvement, Screen Volume Reduction, and Bone Marrow Fibrosis Improvement.

In his remarks, she mentioned that in the inbox phase two trial day.

Median overall survival was 28 months.

This compares very favorably to them the interest of 13 to 16 months in the medical literature.

The meeting and I was also compares favorably to the rise of 12 months observed in real World data analysis of electric factual net patients who are treated with best available therapy.

And they were carefully matched with our metals that's treated patients in your inbox.

In addition to the overall survival patient and embark experience other important clinical benefit <unk>.

Including symptom improvement.

<unk> volume reduction.

And bone marrow fibrosis improvement.

These clinical benefits has been correlated with the improvement in overall survival.

Alexander Rizzo: These clinical benefits have been correlated to improvement in overall survival, based on these data. And after conferring with FDA, we opened Impact MS in December, which was one quarter earlier than expected. As mentioned, IMPACT-MS is the first and, to date, only MS phase 3 trial with overall survival as the primary endpoint, which will be a key differentiating feature compared to other drugs in mainstay development for this population of patients.

Based on these data and after conferring with SBA.

Banking platform back in December.

Was one quarter earlier than expected.

As mentioned the impact from that is the first and to date only.

And that phase III trial with.

Overall survival is the primary endpoint.

Which will be a key differentiating feature compared to other drugs in late stage development for this population of patients.

The same dynamics affecting enrollment in the emerge phase <unk> are also affecting enrollment and the impact on net and in addition.

Alexander Rizzo: The same dynamics affecting enrollment in eMERGE Phase 3 are also affecting enrollment in IMPACT-MS, and, in addition, we've seen the start of numerous other clinical trials in MS that will compete with IMPACT-MS for patients. We're using enrollment boosting strategies for Infectonet, similar to those you have employed in Emerge Phase 3. These include expanding the number of countries on site, engaging more critical science liaisons, and implementing a social media campaign.

<unk> startup of numerous other clinical trials and a net.

It will completely impact omnicell patient.

Where you think enrollment boosting strategy for Intrexon that similar to those who have importing emerge phase III.

These include expanding the number of countries from Cy <unk>.

Gauging more clinical science, liaisons and utilizing a social media campaign.

And the current planning assumptions, we expect that impact from that will reach full enrollment in 2024.

Alexander Rizzo: Under current planning assumptions, we expect that Impact MS will reach full enrollment in 2024, and then the interim analysis may also occur in 2024. And the final analysis in 2025. Let me expand a bit on this time one. The reason that interim analysis could occur in 2024 is that the primary endpoint of the study is overall survival. As a result... The timing of the interim analysis will be based on reaching a certain number of death events since these events will occur throughout the enrollment period. It is possible that the number of events required to conduct the interim analysis could occur before enrollment is complete.

And then the interim analysis may also occur in 2024.

And the final analysis in 2025.

I can expand a bit on these timelines.

The reason the interim analysis could occur in 2020 Corp.

Because the primary endpoint of the study is overall survival.

As a result.

The timing from the interim analysis.

He will be based on reaching a certain number of death events.

Can be bad events.

Crew throughout the enrollment period.

It is possible that the number of events required to conduct the interim analysis.

Crude occur.

<unk> enrollment is complete.

I'd like to wind up my remarks by noting that we reported very important data linked to the mechanism of action from the sell side.

Alexander Rizzo: I'd like to end my remarks by noting that we reported very important data linked to the mechanism of action of inotelsat that made it responsible for this remarkable disease-modifying activity of the drug we saw in our Phase II trials in both low-risk MDS and in MS. In low-risk MDS patients, we've observed reductions in key driver mutations at a molecular level and depletion of cytogenetic abnormalities that indicate hematocytes kill malignant stem and cardiogenetor cells by targeting telomerase. These molecular data were directly correlated with a clinical benefit of transfusion independence, providing strong evidence of disease-modifying activity of hematopoietin.

Neither responsible accordingly remarkable disease modifying activity of the drug we've seen analysis two trial in booking phase two trials in both low risk Mds and AML.

In low risk Mds patients.

This reduction in key driver mutations at a molecular level.

And depletion effect of genetic abnormalities that.

Indicate human cells that kill malignant progenitor cells by targeting so on marine.

These molecular data directly correlated with a clinical benefit of transfusion independence.

Providing strong evidence of disease modifying activity I think that helps us.

Yeah.

Alexander Rizzo: And in BARC, we also saw significant dose-dependent reductions in the mutation burden of key driver mutations for MS, as well as improvement in bone marrow fibrosis. These data were also correlated with improved overall survival observed in the EMBARQ trial, further strengthening the evidence of the disease-modifying activities in the telescope. We believe that the clinical benefits of durable transfusion independence in low-risk MDs and Improvement in Overall Survival in the Met, along with the molecular data and their correlation, highlight the magnitude of Matelstat's unique mechanism of action of telomerase inhibition and provide strong evidence that the Mattel set alters the course of MDS MMS.

And embark.

Also saw significant dose dependent reduction in the mutation burden of key driver mutations for them it.

As well as improvement in bone marrow fibrosis.

Do you think there were also correlated with improved overall survival observed from the embark trial.

The strengthening of the evidence of the disease modifying activity from our sales staff.

Yeah.

We believe that the clinical benefit from durable transfusion independence in low risk Mds.

And improvement in overall survival than that.

Along with the molecular data and their correlation.

Highlights the magnitude of net sales <unk> unique mechanism of action of telomerase inhibition.

It provides strong evidence that the mitel set alter the course of MBS element.

As a result, we have further confidence that we.

Alexander Rizzo: As a result, we have further confidence that we will have potential success in both eMERGE Phase 3 and IMPACT-MS. I'd like to now hand the call back to Pete to review the current MDS and MS market rate. There's something we are, Wine.

We will have potential success in both from merch phase III and impactful net.

I'd like to now hand, the call back to chip to review the current MBS and in the marketplace.

There's something where you're.

Line.

John A. Scarlett: Historically, there have been few new treatments for hematologic malignancies, especially myeloid heme malignancies. However, in 2020, we saw a new approval for loose-pattern septum, lower-risk MDS, and several new approaches being tested for MF, including many combination therapies. First, let's discuss last year's approval of Ruth Pattersept, trade named Rebozo, and a lower risk MDF. U.S. approval took place in April 2020 based on a phase 3 trial in non-Dell 5Q lower risk MDS patients who were relapsed or refractory to EFAs and 90s to HMAs. This trial enrolled only RS-positive patients.

Let's try it again.

Thanks Alexandra historically, there have been few new treatments for hematologic malignancies, especially myeloid heme malignancies.

However in 2020, we saw a new approval from loose patterns have to low risk Mds and several new approaches being tested per MF, including many combination therapies.

First let's discuss last year's approval was Patterson trade named rebel itself in lower risk Mds.

This approval took place in April 2020, based on our phase III trial in non <unk> lower risk Mds patients, who are relapsed or refractory to Esa and my needs to Hma's. This.

This trial enrolled only Rs positive patients the launch of our Brazil by Celgene and BMS appears to be strong, which validates the high unmet need in the market potential for these are its policy of low risk Mds patients.

John A. Scarlett: The launch of rublozil by Celgene and BMS appears to be strong, which validates the high unmet need and the market potential for these RS positive lower risk MDS patients. We expect a highly differentiated profile for Imitelstat at launch and in the lower risk MDS market. Subtypes, including both RS-positive as well as RS-negative patients, low and high transfusion-burdened patients, and patients with low and high EPO levels.

We expect a highly differentiated profile for <unk> launch and the lower risk Mds margin.

Subtypes, including both are as positive as well as Rs negative patients.

Low and high transfusion burden patients and patients with low and high Epo levels.

John A. Scarlett: Because of this differentiated and advantageous profile, we continue to expect Imtelstat to play a significant role for this lower-risk MDS patient population. However, for the MS landscape, Jakafi ruxolitinib remains the primary frontline treatment. Although the number of investigational treatments, including combination therapies, has increased over time, these treatments are either another JAK inhibitor or in combination with a JAK inhibitor. They continue to be focused on the spleen, symptoms, or anelium group. These are certainly helpful, but do not address the fundamental problem of continued disease progression in these patients, which results in dismal survival.

This differentiated and advantageous profile, we continue to expect them. It helps us to play a significant role for this lower risk Mds patient population.

For the MF landscape Jakafi <unk> remains the primary frontline treatment.

Although the number of investigational treatments, including combination therapy has increased over time.

These treatments are either another JAK inhibitor for combination with a JAK inhibitor.

They continue to be focused on spleen symptoms or are newly improvements. These are certainly helpful. But do not address the fundamental problem of continued disease progression in these patients which results in dismal survival.

John A. Scarlett: Eventually, the majority of MS patients are or become non-responsive to a JAK inhibitor. As such, there remains a key unmet need for overall survival in JAK inhibitor non-responding patients. As the only therapy in development that is not a JAK inhibitor or used in combination with a JAK inhibitor, Intelstat has a clearly differentiated profile due to its potential to extend the lives of patients who either are or have become non-responsive to a JAK inhibitor.

Eventually the majority of MF patients are or become non responsive to a JAK inhibitor as such there remains a key unmet need of overall survival and JAK inhibitor nonresponsive patients.

As the only therapy in development that is not a JAK inhibitor or used in combination with a JAK inhibitor and Intelsat has a clearly differentiated profile due to its potential to extend the lives of patients who either are or have become non responsive to Jack.

Next I'd like to say a few words on our pre commercial planning and activities.

John A. Scarlett: Next, I'd like to say a few words on our pre-commercial planning and activity. With top-line results expected to be available from the end of 2022 to the first half of 2023, and assuming the results in Emerge Phase 3 are supportive, we plan to submit the completed NDA in 2023. In planning for those events on that timeline, in 2021, we've begun NDA readiness activities for Imitelstat and lower risk NDAs. That includes starting long lead time activities to validate drug substance and drug product manufacturing processes that are needed to keep strict standards for regulatory approval and to enable the future commercial production of Metelstat. We will also begin drafting non-clinical content for the application this year. In addition, we'll invest in building the appropriate infrastructure to support a high-growth and commercial-stage company. By 2021, other 2021.

With top line results expected to be available from the end of 2020 to the first half of 2023 and assuming the results of emerge phase III are supportive we plan to submit the completed NDA in 2023.

In planning for those events, so that timeline from 2021 we've begun NDA readiness activities for <unk> in lower risk Mds.

That includes starting long lead current activities to validate drug substance and drug product manufacturing processes that are needed to keep the standards for regulatory approval and to enable the future commercial production from Intelsat will.

We will also begin drafting non clinical content from the application this year.

In addition, we'll invest in building the appropriate infrastructure to support our high growth in commercial stage company.

Other 2021 per.

John A. Scarlett: Preliminary commercial activities include preparing the market by increasing awareness of Intel Steps' differentiated profile and building our commercial team and internal infrastructure to support commercialization. However, spending on our commercial launch plan is stage gated to achieve positive top-line results in eMERGE. In conclusion, before opening the call to questions. I'd like to reiterate our commitment to Geron's vision of being recognized as a leader in the treatment of heme malignancies. In support of that vision, in 2021, our plan is to complete enrollment in the eMERGE Phase 3 trial, advance clinical site initiation and patient enrollment in the IMPACT-MF trial, present further data and analyses from the Phase 2 eMERGE trial at medical conferences, and begin the NDA and commercial readiness activities I just described, with a strong team in place that has the expertise to advance Intel Step development and transition to the commercial stage. And having the financial resources to support our plans, we strongly believe our efforts will help establish Geron as a leader in hemologic malignancies, thus creating long-term shareholder value.

Preliminary commercial activities include preparing the market by increasing awareness of Intel steps differentiated profile and building, our commercial team and internal infrastructure to support commercialization.

However, spending on our commercial launch plan stage gated to positive topline results in March.

In conclusion before opening the call to questions.

I'd like to reiterate our commitment to geron this vision of being recognized as a leader in the treatment of heme malignancies.

Reported that vision in 2021, our plan is to complete enrollment from the emerge phase III trial advanced clinical site initiation and patient enrollment and the impact MF trial present further data analysis from the phase two emerge trial at medical conferences.

And begin the NDA and commercial readiness activities I just described.

With a strong team in place that has the expertise to advance in the Tulsa development and transition to the commercial stage.

And having the financial resources to support our plans we strongly believe our efforts will help establish <unk> as a leader in hematologic malignancies, thus, creating long term shareholder.

<unk>.

And with that we'd now like to answer your questions. So I'll call turn.

Turn the call back over to the operator.

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

Operator: And with that, we'd now like to answer your question. So I'll turn the call back over to the operator. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound sign. We'll take our first question from Chad Messer on Needham.

Your question cash.

<unk>.

Our first question from Chad Messer with Needham.

Great. Thanks, Thanks for the update and thanks for taking my questions.

Interest.

Yes.

With a little bit of drill down on Covid.

Covid impact.

Everything you said about patients.

Chad Messer: Oh, great. Thanks. Thanks for the update. Thanks for taking my question.

Sites, all obviously makes.

A lot of sense, what's going on.

Chad Messer: with a little bit of drill down on the COVID impact. You know, everything you said about patients and insights obviously makes a lot of sense in light of what's going on in the world today. But in your prepared remarks, Discussions about

In the world today, but in your.

Paired remarks.

You talked a little bit about the primary problem kind of day patient showing up per site and then in the <unk>.

The press release.

Additional discussions about.

Chad Messer: Site personnel, I guess. Site personnel, shoot.

Right.

Hi personnel.

Sure.

Chad Messer: I was wondering to what extent, you know, these two things are playing off relative to each other, me, and maybe I'm naive, it seems the patient's interest in showing up is the most obvious thing to normalize with COVID, and that site things may be more complicated. I could even be wrong about that. But I was wondering if you could give a little bit more insight on the relative impact of those two things, which are both, in my mind, logically impactful.

Wondering.

Dan.

These two things are playing off relative to each other.

To me and maybe I'm naive it's.

It's clean.

Patient interest and it's showing up.

The most obvious.

Normalized with with Covid.

Great site things may be more complicated I could be wrong about that but just wondering if you could give a little bit more.

Insight on the relative impact of those those two things which are both in my mind logically impacted by Covid.

Yeah, that's a really perceptive question. Thanks, Chad I think I'm going to turn it over to Alexandra who certainly the closest of all the people on the call to the question. She is in.

Rather constant contact with these sites and our team is of course to Alexander maybe you'd like to comment on these two different variables that Chad.

Product.

John A. Scarlett: Yeah, that's a really perceptive question. Thanks, Chad. I think I'm going to turn it over to Alexandra, who's certainly the closest of all the people on the call to the question. She's in rather constant contact with these sites, and our team is, of course, so Alexandra, maybe you'd like to comment on these two different variables that Chad brought up. Sure. Thanks for the question, Chad.

Sure.

Thanks for the question Chad I mean, you are spot on.

The two main issues that we are seeing is really the patients in <unk> guidance.

To participate in clinical trial, which actually may require more frequent visits to the horse per dollar rate than they would like or hearing call decline.

And the second one.

Enjoy your day ever.

The availability of five personnel, who appear to be no.

Maintaining trials.

Alexander Rizzo: I mean, you are spot on. The two main issues that we are seeing are really patient reluctance to participate in clinical trials, which actually may require more frequent visits to the hospital than they would like to during COVID times. And the second one is really the availability of side personnel who appear to be, you know, busy maintaining trials with, you know, again, multiple procedures due during COVID time. So it's a really mixture of these two from these two variables.

Again multiple procedures.

Nearing Colby time, I think they are really mixture of these two from these two are two variables and it's the.

We do expect that as as we spoke I went there as the Covid pandemic winds down and with the vaccinations hopefully patient flow again comfortable to come to two critical.

Come to the clinic and participate in clinical trials of.

But those are the two key reasons.

Okay Yeah.

Thanks, Greg.

A lot of sense.

And then this next one well I definitely have a comment.

Alexander Rizzo: And it's, you know, we do expect that, as we spoke, as the COVID pandemic winds down and with the vaccination, patients will feel again comfortable coming to clinics, to come to the clinic and participate in clinical trials. But those are the two key reasons, yeah.

Maybe just a question in there.

It's really interesting.

Especially when you hear about your your Ash data and you talk about <unk>.

Just defying.

Oh, yes.

OS benefit that you've seen and I get it it's a single arm. So that maybe the justification comes with kind of validating it.

Chad Messer: validating it in that context. But with things like spleen volume and symptom scores, in one way of thinking, spleen volume and symptom scores should be out there justifying their value in terms of OS, in my mind. So, I guess that was the comment. And then the question, and you guys touched on this a little bit, but, I mean... You know, talk a little bit more. And I know MS is such a unique disease in terms of the endpoints that are looked at for JAK inhibitors and other standard of care therapies. But you know, why is it that we have to work so hard here to convince people that OS benefit is, is important?

In that context, but with things like spleen volume in symptom scores.

And one way of thinking.

Spleen volume and symptom scores should be out there just define fair value in terms of in my mind.

So I guess that was the comment.

And then the question and you guys touched on this a little bit but I mean.

Talk a little bit more and I know.

Unique.

Disease in terms of the endpoints that are looked at per JAK inhibitors and other standard of care.

<unk>.

Sarah.

But.

Why is it that you have to work so hard here.

To convince people that.

Benefited us.

John A. Scarlett: I'll take the first part and then I think Alexander would probably like to comment on this. I don't think we feel that there's any need to justify the OS benefit.

Sure.

It is important.

I'll take the first part and then I think Alexander again, we'd like to probably comment on this I don't think.

We feel that there's any need to justify the OS benefit I think it's plain and simple and incredibly obvious.

John A. Scarlett: I think it's plain and simple and incredibly obvious. I think we make the point, and perhaps our continued commentary on this could be taken the wrong way, but I think we're trying to make the point that we're the only drug that we're aware of that is actively engaged in a phase three trial that will, in fact, use OS as an outcome. And it takes some courage to do that, right? These are long trials. You've heard the date.

We make the point.

Perhaps our continued.

Our commentary on this could be taken the wrong way, but I think we're trying to make the point that we're the only drug that we're aware of that is actively engaged in the phase III trials that will in fact use OAS as an outcome.

And it takes some courage to do that right. We took these are long trials.

Per the dates.

John A. Scarlett: They require a fairly large number of patients, and it's breaking out of the mold. Most people just do a landmark analysis at a certain number of months after being treated with a combination, usually containing a JAK inhibitor and a new drug or simply a new JAK inhibitor alone. And you're kind of done.

They require a fairly large number of patients and it's breaking out of the mold.

Most people just do a landmark analysis at certain number of months after being treated with <unk>.

Combination, usually containing a JAK inhibitor and a new drug.

We're simply addressing new JAK inhibitor alone.

And youre kind of done, but what you don't see are the real benefits of changing the course of the disease, which had we think that that's the big news Big story and frankly, the big benefit of this drug I don't think anybody else has any kind of data like we do in that regard so thats been our primary focus.

John A. Scarlett: But what you don't see are the real benefits of changing the course of the disease. And Chad, we think that's the big news, the big story, and, frankly, the big benefit of this drug. I don't think anybody else has any kind of data like we do in that regard. So that's been our primary focus and why we've tried to talk about OS more than anybody else, because we also have the correlations of the changes in the course of the disease, both clinical and, more importantly, perhaps in some ways, molecularly, with the actual improvement in OS in our phase two study. So I hope that that puts it in some context. Alexander, I don't know if there's anything else to add, or Chad, if you would like to jump back in, that's fine. Um, no.

And why we've tried to talk about our reps more than anyone else because we and we also have the correlations.

The changes in the course of the disease.

<unk> clinical and more importantly, perhaps in some ways molecularly with the actual.

Improvement in OS in a phase II study, so I hope that that puts it in some context.

Alexandra I don't if there is anything else to add or Chad, if you would like to jump back and that's fine.

Yes.

No look those are those are really helpful comments in context. Thank you.

John A. Scarlett: Um, no, look, those are really helpful comments and contacts. Thank you.

Sure.

Anything else on that.

That's been from me.

Operator: Thank you. Okay, go ahead. Unknown Speaker.

Okay go ahead.

Your line is a good question is from Justin Walsh with B Riley's Securities.

Unknown Attendee: Hi, thanks for taking the question. Can you provide any color on feedback that you've received from your initial marketing research and outreach efforts? How eager are MDS versus MS physicians and patients for new treatment options? And how have they reacted to the telestats profile?

Alright, Thanks for taking my question can.

Can you provide any color on feedback you've received from your initial marketing research and outreach efforts, how eager our mds versus MF physicians and patients per new treatment options and how they reacted to Covid health.

Profile.

John A. Scarlett: Right. Well, I'm going to let Alexandra talk about the individual physicians that we've spoken to. We've done market research, and we're in the process of planning for additional market research this year that will really drive those points, Justin. But I think that the benefits of MDS in MDS are really quite evident to a lot of physicians, particularly those who take care of more ill patients. Remember that all of our patients have very high transfusion burdens, and that's an area that can be particularly difficult for these physicians to get traction on.

Right.

<unk>.

Im going to let al.

Alexandra talk about the individual physicians that we've spoken to.

We've done.

We've done market research who were in the processes.

Planning for additional market research this year that will really drive into those points Justin but.

I think that the.

Benefits of Mds in Mds are really quite evident to a lot of physicians, particularly those who take care of more patients remember that all of our patients had very high transfusion burdens and that's an area that can be particularly difficult.

For for these physicians to get traction with now.

John A. Scarlett: Now they've certainly adopted, or are in the process of adopting, Lispatercept, and we again call that out, and we think that's good because prior to Lispatercept coming on the market, there hadn't been anything new since the HMAs over 10-12 years ago. So I think that the rapid uptake has been good, but there's a lot of room left for a drug like Inatelstat that does a One, we treat RS negative patients as well as RS positive patients.

Now they certainly adopted or they are in the process of adopting these patterns theft, and we again, we call that out and we think that's good because prior to the scatter set coming on the market there hasn't been anything new since the HMA has over 10 to 12 years ago. So I think that the rapid uptake has been good but there's a lot of room left for.

Or a drug like <unk> that does a bunch of things one we treat rs negative patients as well as our as positive two we can treat patients with very high baseline transfusion burdens and still get excellent outcomes three durability repeat it the durability of the durability of <unk> activity.

John A. Scarlett: Two, we can treat patients with very high baseline transfusion burdens and still get excellent outcomes. Three, the durability, repeat it, the durability, of Inatelstat's activity in these patients is really dramatic and far greater than anything we've seen at least in print or at meetings from the folks studying Lispatercept.

In these patients is really dramatic and far greater than anything we've seen at least in print.

Or at meetings from from the folks settings Patterson.

So I think that those.

John A. Scarlett: So I think that those then factor into the underlying cause of all of this, which is when we see decreases in SF3B1 and decreases in cytogenetic abnormalities, it's pretty clear that we have disease-modifying activity going on. I won't characterize other products in low-risk MDS, but all of those are really powerful differentiating factors. And I think that they'll play very, very well.

Then factor into the underlying cause of all of this which is when we see decreases in NSF <unk> decreases entitled genetic abnormalities, it's pretty clear that we have disease modifying activity going on.

Characterize other products in low risk Mds, but all of those are really powerful differentiating factors and I think they'll play very very well Alexandra do you want to comment on the specifics of investigator interaction and okay, well interaction because youre very close John sure Sharon I can I can.

Alexander Rizzo: Xander, do you want to comment on the specifics of investigator interaction and KOL interaction? Because you're very close to a number of these folks. Sure, sure. I can talk about that.

Talk about that I mean are we.

Alexander Rizzo: I mean, we obviously are in very close contact with participating PIs, as well as community opinion leaders. So, and I can just reiterate, there's really a great enthusiasm for a drug that works across different subtypes of low-risk MDS. That's to start with, right?

Obviously, we are in very.

Very close contact free play.

She brings in Pi's as well as our key opinion leaders. So I can just reiterate there is really a great enthusiasm for a drug that works across.

Different subtypes of ultra low risk Mds that historically right so for them there.

Alexander Rizzo: So, for them, there's, you know, just the fact that they don't need to subtype whether you're RS positive or RS negative. It makes their clinical and everyday work very, very easy, right? I mean, we weren't subtyping for RS positivity prior to Roblosio's approval, let's put it that way. So this kind of is one convenience for them, right?

Just the fact that they don't need to subsidize whether your Rs positive where of Rs negative.

Makes their clinical and everyday work very very easy right. I mean, we were non truck typing for Rs upwards at TVT.

Prior to that low with your per.

Well, let's put it that way so these kind of.

It is one convenience for that rain.

Alexander Rizzo: And then, I mean, the fact that we have durability of 20 months versus the seven months of an already approved drug that is doing very well on the market is really another convenience, if you will, for patients. You know, you don't have to come back to the clinic for multiple transfusions to which they're used. And I have to say something, and we often discuss this internally. I mean, what really gets these investigators excited is the molecular data.

And then I mean, the fact that we have <unk> 20 months to seven months of already approved drugs and doing very well in the market is really another convenience. If you will force for patients don't have to come back to the to the cleaning per multiple transfusions. So each day.

Our used to prior to treat margin.

And I have to say something and we often discuss this internally I mean, what can really make these investigator excited is the molecular data. It's really and this was you know that that maybe even the best reason.

Why the paper ended up in <unk> and you know.

So it's really.

Alexander Rizzo: It's really, and this was, you know, that's maybe even the best reason or why the paper ended up in JCO, you know. So it's really the decrease in not only SF3B1. SF3B1 is just an example that we are using, you know, here to illustrate the effect.

B B.

The decrease in not only <unk> one as a hidden line is just an example that we are using here.

To illustrate the effect, but.

It's really multiple.

Hum.

Insurance that we've seen and also cytogenetics right right between us.

In these patients that.

<unk> believes that our cows NPI that Mattel studies really altering the course of disease in low risk Mds patients.

Thank God I E beyond three to four four Mbas I don't know Jack if you wanted to cover from that but it is pristine Susan might really be.

Alexander Rizzo: But it's really multiple mutations that we've seen and also cytogenetic decrease in these patients that make believe our care of NPIs, that Mattel study is really altering the cause of disease in low-risk NPS patients, in new compounds, right, showing that, you know, we can improve anemia with one drug, we can improve symptoms, right? New endpoints have been established. And now we can't do it.

The molecular data an enemy.

Chad also it'll be to go to your question line about.

Data has been evolving and the agency has been more incentive to different endpoint tried to historic Covid SPR into coffee was on the market for so long, but as you move EBITDA in <unk>.

With new compiling trade show that.

We can improve anemia with the one drag we can improve symptoms riding new endpoint has been established and now we come we go ahead.

unknown: [inaudible] Unknown Attendee, Anil Kapur, Aron Feingold, Faye Feller, Robert Driscoll, Ethan Markowski, Corinne Jenkins, Anil Kapur, Aron Feingold, Faye Feller, Robert Driscoll, Ethan Markowski, Corinne Jenkins, Anil Kapur, Aron Feingold, Faye Feller, Robert Driscoll, Ethan Markowski Maybe just a quick follow-up to that. One, can you maybe quickly just remind us of how many of the low-risk MDS patients are RS-positive versus RS-negative? And do you think that there could be potential for patients to use Catarsept and Metelstat and Sequence if they fail therapy with one or the other?

The other question that the crown of the endpoints I mean, the ultimate endpoint of every clinical trial right. So when you win when you show such data.

Granted at the moment is just from two different doses of <unk>.

And some of the items is high I don't think we had needs to justify.

You know the RF is there as an endpoint to any of our investigators nor to regulators. So far from it we remain enthusiastic its long and Thats what makes it you know.

A challenge it is a long study or IV is a day from endpoint, but other than that Thats really low.

Really no other.

The reason to believe that.

But we have any.

It's about the data.

Thank you that's very helpful and maybe just a quick follow up to that.

So one can you could you maybe quickly just remind us of how many of those are low low risk Mds patients are Rs positive versus RF negative and do you think that there could be potential for patients to use with patterns theft in the Carlsbad in sequence, if they fail therapy with one or the other.

So typically there are the.

Alexander Rizzo: So typically, the numbers for RS positive patients in the literature, you know, range anywhere from 10 to 25%. It depends which paper you take, right? So, let's say at most a quarter of the patients are RS positive, right? So the majority, you know, a lot of the patients are negative. Again, as we've spoken multiple times, we work across both subsets. Uh, so, um... I think that was one question. And can you remind me what the second part of your question was? Yes. Is there potential to use those pattern steps and subsetting sequence?

The numbers for Rs positive patients in the literature now range anywhere from 10% to 25% right.

You can switch paper you take Craig so so let's say at most.

Quarter of the patients are on.

Rs positive right. So my yard are low.

A lot of the patients are Rs negative again, ive just spoken multiple times, we work across both Bose.

Subtypes.

So.

I think that was one question and can you remind me what was the second part of it yes.

Is there potential to use the cash that's there.

Good day.

Alexander Rizzo: Bye! So for our response, it is, Patients, right, potentially, right. But, you know, for patients that are heavily transfused, you know, I really don't know, right, what would be the clinical preference, I would say, by Thank you very much. That's it for me. Okay, thanks. Your next question is from Stephen Wiley with Stiefel.

So for Rs positive.

Right.

So right now for patients that are.

Heavily transfused.

I really don't know right what would one would be you know that day.

The clinical preference.

I would say.

Thank you very much that's it from me.

Okay. Thanks, Thanks, guys.

Your next question is from Stephen Wiley with Stifel.

Yes, good afternoon, thanks for taking the questions.

Stephen Douglas Willey: Yeah, good afternoon. Thanks for taking the questions. So maybe just with respect to

So maybe just with respect to the impact.

MF guidance.

Stephen Douglas Willey: MF Guidance. So I'm just kind of curious as to, you know, there's obviously a lot of competitive happenings within the space. And I'm just kind of curious.

So.

I'm just kind of curious as to you know.

There's obviously a lot of it.

Competitive happenings within the space.

I'm, just kind of curious as to.

Stephen Douglas Willey: as to, you know, how the guidance, if at all, contemplates the competitive environment in terms of competition for some of these host rock patients. I guess, specifically just given the number of trials we're kind of seeing in a nutshell.

How the guidance if at all contemplates the competitive environment in terms of competition for some of these.

Most rux patients.

I guess, specifically just given the number of trials, we're kind of seeing.

Within that show.

Alexander Rizzo: Yeah, that's a great question. I mean, just as we announced the study, there had been three new trials, three trials in a mess, right, that had been started because the competition is really high. For us, at this moment, it's difficult to give, you know, a very precise guideline. But, as you can imagine, we have conducted a feasibility study and a base, and that feasibility is taken into account, as well as, right, as well as competitive trials.

Yeah. That's it that's a great question, Steve I mean.

Just quickly I know the study there had been any new trials phase III trials in EMEA side that had been started to competition really high.

For us at this moment, it's difficult to give.

A very precise guideline, but as you can imagine we have conducted.

Ah study feasibility.

And base and that visibility.

<unk> <unk> co.

As well as right as well as competitive trials.

Alexander Rizzo: So, based on the current knowledge we have and, you know, our current planning assumptions are that we will reach full enrollment in 2024, which is different guidance than what we've given so far.

So that's how you know based on the current knowledge, we have now in our current planning assumptions are that.

We will reach the full enrollment in 2024, which is a different guidance than what we've given so far.

Okay.

Stephen Douglas Willey: Okay, and maybe I'll just go back to eMERGE for a minute.

And then maybe just going back to emerge for a minute.

Stephen Douglas Willey: And Chip, you had made the comment with respect to Liz Pattersett's availability potentially impacting patient involvement in the study. So.

And the ship you had made the comment with respect to <unk>.

Pattern.

Availability potentially impacting.

Patient enrollment into the study.

Stephen Douglas Willey: Is there a scenario whereby...

Is there a scenario whereby.

Stephen Douglas Willey: Emerge maybe ends up representing kind of an over-enrichment of RS negative patients. And do you think that there's any potential labeling or ramifications as a result of that? I'm just kind of curious to get your opinion there.

Emerge maybe ends up representing kind of.

Over enrichment of Rs negative patients.

Do you think that there is any potential labeling limitations as a result of that I'm just kind of curious too.

Uh huh.

To get your opinion, there and just whether or not you have kind of real time insight into the baseline characteristics of patients that are coming into the study and if that's something that you see.

Alexander Rizzo: And just whether or not, you know, you have kind of real-time insight into the baseline characteristics of patients that are coming into the study, if that's something that you're Yeah. So I'll start with the last one, Steve. I mean, we have no insight into what type of patients are being enrolled in the study because it's a double-blind placebo control study, right? So it's very difficult to not very difficult.

Thanks.

Again, I think Alex is in the best.

Physician to answer those questions.

Yeah.

I'll start with the last from Steve I mean, we have no insight into it.

Type of patients are being enrolled in the study because it's a double blind placebo control study right. So it's very difficult to not very difficult, it's impossible to comment or to know what patient arc.

Alexander Rizzo: It's impossible to comment or to know what patients are enrolled. Now, your first question is whether Lusparacept or Lusparacept approval might have an impact, so Lusparacept usage, right, might have an impact in a way that we now enroll RS positive patients only, sorry, RS negative patients the other way around, because they will be treated. I don't think so. Remember, Lusparacept has just been approved, and it is used now in patients. I assume, you know, for the RS positive patients, they would initially be treated with Lusparacept, and then they'll be put on our trial.

<unk> enrolled.

Now your first question.

<unk>.

John.

Mike are in these fires that approval might have impact. So it requires the usage right might have impact in a way that we know will Rs positive patients only on.

That's alright Rs negative patients the other way because they will be treating eye.

Items think salary remember I was product has just been approved it is news now patients I assume you know from the Rs positive patients.

Would initially be treated with most providers have growth annually they'll put them on our trial. So I honestly do not think right that we will end up being reaching four one or four another patient population and therefore I don't see a problem in the label in the label I mean.

Alexander Rizzo: So I honestly do not think, right, that we will end up reaching for one or for another patient population. And therefore, I don't see a problem in the label, in the labeling, I mean, at the moment. Steve, I think also, I don't know.

At the moment.

Steve I think also I don't know yeah, Yeah, Yeah, Steve I think also we should comment that when we talk to investigators their views on the on the fees are really quite different drugs right.

John A. Scarlett: Yeah. Yeah. Yeah, Steve.

John A. Scarlett: I think also we should comment that when we talk to investigators, their views on these are that these are really quite different drugs, right? I mean, the effects of Imitelstat in high transfusion burden patients, greater than 4 units, and especially greater than 6 units, are quite dramatically different, at least if you look at sort of the phase 2 comparisons to phase 3 comparisons between the two drugs. So I think that there are probably so many different ways to cut this.

John.

The effects of <unk> in.

High transfusion burden patients greater than four units and especially greater than six units is quite dramatically different at least if you look at sort of the phase III to comparisons to phase III comparisons between the two drugs.

So I think that there is probably so many different ways to cut this.

John A. Scarlett: I agree with Alexandra. We were, I think we'll be surprised to see a meaningful enrichment of one RS positive versus RS negative. And I think we'll be surprised, but we don't know yet. And we'll see.

Agree with Alexandra.

I think we will be surprised to see me.

Meaningful enrichment of one Rs positive versus negative.

And.

I think we'll be surprised but we don't know yet and we'll see.

Stephen Douglas Willey: And I was just, as you were talking to me, sorry, if I just want to jump in. I mean, we got about 50% in our trial before the spotter set became available or reimbursed in the European countries where most of our sites are. So I, I, I bet we do have a sufficient number, you know, in those patients that are RS positive as well as RS negative. Very good. That's a fair point.

And I was just as you were talking cheap maintenance at first if I just wanted an open.

I mean, both about 50% on our trials before the spiders that became available or reimbursed from the European countries, where most of our sites are.

So I.

Ben we do have sufficient number you know standard.

And those patients that are Rs positive as well as ours.

Great That's fair point.

For taking the questions.

Sure. Thank you.

Yes.

Your next question is from Tom Shrader with <unk>.

Stephen Douglas Willey: Thanks for taking the question. Sure. Thank you. You kind of just talked about my question, but you see no reason to stratify for RS-positive versus RS-negative. It kind of kicked to your point that these patients either... Physicians would know are going to get almost nothing out of what's happening.

Well you kind of just talked about my question, but.

You see no reason to stratify for Rs positive versus Rs negative kind of chip to your point that these patients either.

Physicians would know we're going to get almost nothing out of less bad or separate probably did get almost nothing out of those Patterson is that accurate that you just don't think it confounds your study much.

John A. Scarlett: Is that accurate? You just don't think it confounds your study much? I think the question, if I understand it correctly, Tom, is whether we're stratifying in the analysis for RS-positive versus RS-negative, and stratification in this case usually would mean if you were stratifying in the randomization. We're not stratifying, as far as I know, at least in the randomization. Will we look at the effects of, you know, the subtypes? Absolutely, of course we will. So we'll look at it, but we're not preferentially making sure that we take a specific group. I mean, I need to say this.

I think the question if I understand it Thomas.

Whether were stratified and the analysis for Rs positive <unk> negative and stratification. In this case you usually would mean, if you stratify randomization, where not stratified for diagnosis system implementation.

Well, we look at the effects of.

The subtypes absolutely of course, we will so we will look at it but we're not preferentially making sure that we that we take a specific group I.

I need to say this we don't completely understand why.

John A. Scarlett: We don't completely understand why Mouspattercept has this effect and appears to have this effect, a big enough effect that Acceleron and Celgene decided to really restrict their phase three, their initial phase three trial meta-study to RS-positive patients. But what I can tell you is that when we look at our data, it doesn't really matter whether you're RS-positive or RS-negative. You get very similar results.

Patterson has this effect in appears to have this effect in a big enough effect that accelerant on Celgene decided to really.

Correct.

Phase III that initial phase III trial metal study to Rs positive, but what I can tell you is that when we look at our data it doesn't really matter, whether you are Rs positive or negative you can get very similar results. So I think thats the real bottom line for us.

John A. Scarlett: So I think that's the real bottom line for us, and I think that will show equally good results in either group. Okay, and then there's a kind of interesting comment about a reasonable R&D build going forward. Are you still looking for a way forward in AML? Is that still on the table? Are you looking for a subgroup that makes a lot of sense? Or am I misreading the tea leaves?

That will show equally good results from either group.

Yeah.

Okay, and then there's a kind of an interesting comment about a reasonable RNA or indeed build.

Going forward it is.

Are you still looking for looking for a way forward in AML is that is that still on the table you're looking for a subgroup that makes a lot of sense or am I misreading tea leaves.

John A. Scarlett: Um, no, I mean, let's just say this: I don't know that the R&D build necessarily reflects that. But what it does reflect is a maturing development organization for a drug that's going to be on the market in, you know, however many years. And one that we think has a very unique mechanism of action as well and has properties and capabilities that aren't shared by other products. So we'd be crazy not to try to take advantage of that.

No I mean, let's just say this I don't know that the R&D build necessarily reflects that but what it does reflect is a maturing.

Our.

Development organization for a drug that's going to be on the market.

However, many years and.

One that we think has a very unique mechanism of action as well and has properties and capabilities that arent chaired by other other products. So we'd be crazy not to try to take advantage of that and I think thats kind of the real answer.

John A. Scarlett: And I think that's kind of the real answer. I don't think we're prepared to talk today about the specifics of what the next indication would be, or when it would come, or how much it will cost, or any of that, or how many people will be required to support it. But we certainly have are going through the cafeteria line of hematologic delinquencies.

I don't think we're prepared to talk today about the specifics of what the next indication would be or when it would come or how much it will cost or any of that or how many people will be required to support it but we certainly have.

Our.

Going through the cafeteria line of hematologic malignancies.

John A. Scarlett: We're certainly interested in putting more on our plate than simply low-risk MDF and MF and relapsed retractor MF, for that matter. So I think that you can assume that we have a very keen interest in that. But we'll just have to wait a little bit longer for us to really come out and do the, do the, have the commentary that I think you're looking for.

We're certainly intra.

Interest in putting more on our plate and simply low risk Mds and MMS.

In relapsed refractory method or for that matter. So I think that you can assume that we have a very keen interest in that but we'll just have to wait a little bit longer for us to really come out and do the deal.

The commentary that I think youre looking forward from.

Okay, great. Thank you.

John A. Scarlett: Okay, great. Thank you. I will now turn the call back. Well, thanks a lot.

Sure.

This concludes our Q&A session I will now turn the call back over to Dr. Scarlett for closing remarks.

Well, thanks a lot.

Right.

Operator: It was a very spirited discussion, which I think we really appreciate and thank everyone who participated. We thank all the people who listened to the call, and we hope you have a good rest of this week and onward, and we will talk to you again surely at the next quarterly earnings call. Thank you all very much for participating. Bye-bye. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

A very.

Spirited discussion, which I think we really appreciate it and thank everyone who participated.

We thank all the people who listen to the call and we hope you have a good rest of this week and onward, and we will talk to you again.

Surely if the next.

Quarterly.

Earnings call. Thank you all very much for participating.

Yes.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.

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