Q1 2020 Earnings Call

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Unknown Executive: Director of Photography, Edited by Stephen Willey Music by Stephen Willey Art Direction by Stephen Willey Music by Stephen Willey Art Direction by Stephen Willey [inaudible] BF-WATCH TV 2021

Unknown Executive: Ladies and gentlemen, thank you for standing by, and welcome to the Q1 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. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Head of Investor Relations, Suzanne Mafferi. Thank you. Please go ahead.

We'll be a question answer session to ask the question during the session you'll need to press star one on your telephone if you require any further assistance. Please press star zero.

I would now like to have the conference over to your speaker today head of Investor Relations Susan Missouri. Thank you. Please go ahead.

Thank you shouldn't how and good afternoon, everyone. Thank you for joining us for today's conference call I'm I'm joined today by Dr., John Scarlett, Gerons, Chairman and Chief Executive Officer, and Olivia Bloom, the company's cheapened assets financial officer.

Suzanne Mafferi: Thank you, Chantel, and good afternoon, everyone. Thank you for joining us on today's conference call. I am joined today by Dr. John Scarlett, JARN's Chairman and Chief Executive Officer, and Olivia Bloom, the company's Chief Financial Officer. Also joining me today are Alexandra Rizzo, our Chief Medical Officer, and Anil Kapur, our Head of Corporate Strategy and Chief Commercial Officer. After the market closed today, we announced our first quarter 2020 financial results via press release, which is available on our website under www.geron.com slash investors, as well as several other press releases announcing recent developments in the month of May. In addition, a live webcast of the call is available on our website and will be archived for 30 days.

Also joining me today or Alexandra, So our chief Medical Officer, and Aneel support our head of corporate strategy and Chief commercial officer.

After the market close today, we announced our first quarter 2020 financial results by a press release.

It is available on our web site under Www Dot German dot com, such investors as well as several other press releases and now see recent developments in the month of Matt.

In addition, a live webcast at the call is available on our website and will be archived for 30 days.

Suzanne Mafferi: Before we begin, please note that this presentation and question and answer session will contain forward-looking statements relating to Geron's plans, expectations, timelines, beliefs, statements of potentiality, and projections. These include, without limitation, those regarding the timelines for completion of enrollment of and the results from the ongoing Phase 3 eMERGE and planned refractory MF clinical trial. That Geron's existing financial resources will be sufficient to fund operations into the second half of 2022, potential revenues, and that Geron's 2020 operating expense burn will be in the range of $70 to $75 million. 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 risks and uncertainties include, without limitation, those regarding that the company may be able to overcome all the clinical, safety, efficacy, technical, scientific, operational, manufacturing, and regulatory challenges to enable the expected timelines for the eMERGE and CLAND refractory MF clinical trial, that regulatory authorities may not permit the further development of Imatelsa on a timely basis or at all, that the COVID-19 pandemic may significantly impact the timelines for both the enrollment and the results of the clinical trials and or drug supply, that competition or other factors result in lower than projected revenues, and that there may be unexpected operating expenses or events or changes in Geron's plans that cause the $70 to $75 million 2020 financial guidance to be revised.

Before we begin please note that this presentation and question and answer session will contain forward looking statements relating to Gerons plans expectations timeline believe statements of potentiality and projection.

These include without limitation, though is regarding the timeline for completion of enrolled enrollment and the results from the ongoing phase three emerge and planned refractory M.F. clinical trial.

That gerons existing financial resources will be sufficient to fund operations into the second half a 2022.

Potential revenues and that Gerons 2020, operating expense burn will be in the range of $70 million to $75 million.

These and other forward looking statements involve risks and uncertainties that can cause actual results to differ materially from knows in such forward looking statements. These risks and uncertainties include without limitation those regarding that the company, maybe able to overcome all the clinical safety Africa.

She technical scientific operational manufacturing and regulatory challenges to enable the expected timeline pretty emerge and clans refractory and that clinical trial.

That regulatory authorities may not permits it further development of Imetelstat on a timely basis or at all.

That's a co. Good 19 pandemic me significantly impact the timeline for both the enrollment and the result of the clinical trials and or drug supply.

The competition or other factors result in lower than projected revenues and that there may be unexpected operating expenses or events or changes insurance plans that caused the 70 to 75 million 2020 financial guidance to be revised.

Suzanne Mafferi: 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 is explained under the heading Risk Factors in Geron's quarterly report on Form 10-Q for the quarter ended March 31, 2020, filed with the SEC. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. I will now turn the call over to Dr. John Scarlett, Jones Chairman and CEO, Chip.

Detailed information on the about wrist and 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 Germans quarterly report on form 10-Q for the quarter ended March 31st 2020.

He filed with the FCC.

I do realize should not be placed on forward looking statements, which speak only as of the day, there me and the facts and assumptions underlying the forward looking statements may change I.

Ill now turn the call over to Dr. John Scarlett.

Parents, Chairman and CEO, Jeff.

Thank you Sam I'd like to welcome everyone to our first quarter 2020 conference call.

John A. Scarlett: Thank you, Suzanne. I'd like to welcome everyone to our first quarter 2020 conference call. On today's call, I'll have some introductory remarks. Olivia will cover Q1 results, 2020 guidance, and the recent financing, and Alexandra will discuss recently announced clinical development activities in MF and MPD. To start our call today, I'd like to share with you my conviction that Geron today is a fundamentally different company.

On today's call I'll have some introductory remarks, Olivia will cover Q1 results 2020 guidance and the recent financing and Alexander It will discuss recently announced clinical development activities and mm mm yes.

Just other call today.

I'd like to share with you my conviction that you're on today is fundamentally different company.

John A. Scarlett: It's a company in which all the pieces necessary to become a leader in the treatment of hematologic myeloid malignancies are now in place. We have a novel drug and a unique purpose. Meaningful clinical activity and indications with significant unmet need. Two phase three trials, one ongoing and another planned, both based on compelling phase two data, a highly experienced team to execute all aspects of drug development, and the financial resources to reach significant value in Clarkson. We've known for many years that imitalostat has a unique mechanism of action. In malignant stem, progenitor, and blood cells, telomerase is continuously upregulated, resulting in malignant hematopoiesis.

It's a company in which all the pieces necessary to become a leader in the treatment of human logic myeloid malignancies or now in place.

We have a novel drug any unique target.

Meaningful clinical activity in indications with significant unmet need.

Two phase three trials, one on going and what another planned both based on compelling phase two data.

Highly experienced team to execute all aspects of drug development.

And the financial resources to reach significant value inflection point.

We've known for many years it Imetelstat has a unique mechanism of action.

Stem for gender and blood cells telomerase is continuously regulated resulting in malignant matter polices.

John A. Scarlett: Imitelstat selectively targets malignant cells with continuously up-regulated telomerase, inducing their apoptosis, or cell death, and enabling potential recovery of normal hematopoiesis. As we continue to treat and follow patients in our Phase 2 eMERGE trial in lower-risk MDS, data continue to mature and improve. We have an increasingly differentiated profile of imitelstat compared to other agents with a high rate of transfusion independence that is similar in both RS positive and RS negative patients. A remarkable durability of transfusion independence, even in patients with high baseline transfusion rates, and substantial rises in hemoglobin levels that suggest potential recovery of normal hematopoiesis in patients treated with imetelstat.

And it helps that selectively targets malignant cells with continuously upregulate each libraries inducing there you talked to us its or cell death, and enabling potential recovery of normal medical uses.

As we continue to treat and follow patients in our phase to the merged try one lower risk Mds data continue to mature and improved.

We have an increasingly differentiated profile of imetelstat compared to other agents with a high rate of transfusion independent then similar in both our it's positive and Rs negative patients.

A remarkable durability of transfusion independence, even in patients with high baseline transfusion burden.

And substantial rises in hemoglobin levels. It suggests potential recovery of none of them out of polices and patients treated with them until stuff.

John A. Scarlett: The phase three trial in low-risk MDS continues to enroll patients, and enrollment is currently expected to be completed by the end of the first quarter of 2021, with top-line results expected in the second half of 2021. Imitalstat also represents a highly differentiated therapy designed to address the current unmet need in patients with intermediate to or high-risk myelofibrosis unresponsive to JAK inhibitor therapy. Imitelstep-treated MF patients who were relapsed or refractory to JAK inhibitors in our Phase 2 EMBARQ trial exhibited a median overall survival that compares very favorably to both historical controls and to a real-world data analysis of closely matched patients who discontinued JAK inhibitors and were treated with best available therapy. Based on these analyses and our data and the regulatory clarity we have from our recent interactions with the FDA, Both the lower-risk MDS and refractory MS indications represent very substantial and unmet medical need.

The phase three trial in low risk Mds continues to enroll patients enrollment is currently expected to be completed by the ended the first quarter 2021 with topline results expected in the second half of 2022.

[noise] Imetelstat also represents a highly differentiated therapy designed to address the corn unmet need in patients with intermediate two or high risk model type Brooks is unresponsive to JAK inhibitor therapy.

In the tell step treated MF patients, who were relapsed or refractory to JAK inhibitors interface to embark trial exhibited the median overall survival that compares very favorably to both historical controls into a real world data analysis of closely match patients who discontinued JAK inhibitors and were treated with best available therapy.

Based on these analyses in our data and the regulatory clarity we have from our recent interactions with the FDA. We've designed to randomize phase three trial refractory MF patients with overall survival is a primary endpoint.

Control arm, a best available therapy that excludes JAK inhibitors.

We expect that trial to be open for screening and enrollment in the first quarter of 2021 or both.

Both the low risk Mds in refractory enough indications represent very substantial unmet medical need and if we're successful in bringing mtell stuck to the market for both indications.

John A. Scarlett: And if we are successful in bringing Imitalostat to the market for both... We believe they represent a combined annual revenue potential of approximately 1.25 billion dollars in the United States and approximately 2.5 billion dollars worldwide. To execute successfully on our plans and these indications, we'll be relying on our very experienced, dedicated in-house professional drug developers. This extraordinary group includes individuals who are key team members working with Imitelstat at Janssen, including our Chief Medical Officer, Dr. Alexandra Rizzo, and our Chief Commercial Officer, Anil Kapur. These individuals have followed Imitelstat to Geron, bringing with them years of experience in clinical science, regulatory affairs, statistics, clinical operations, and commercial strategy. We've also recruited other talented professionals with experience from other very successful companies in those areas, as well as others in drug safety, manufacturing, and quality operations.

We believe they represent a combined annual revenue potential of approximately $1.25 billion into United States and approximately two $4.5 billion worldwide.

To execute successfully in our plans and these indications will be relying on are very experienced dedicated in house professional drug developers. This extraordinary group include individuals who are key team members working with Imetelstat Janssen, including our Chief Medical Officer, Dr. Alexandra resale and our Chief commercial officer before.

These individuals have followed imetelstat to cheer on bringing with them years of experience in clinical science.

Military Affairs statistics clinical operations and commercial strategy.

We've also recruiting other talented professionals with experience from other very successful companies and those areas as well as others in drug safety manufacturing and quality operations.

John A. Scarlett: And finally, due to our successful recent public offering, today we have the money to achieve our development plans for two phase three indications. It was particularly gratifying to see the response of investors to this transaction, especially leading biotechnology specialist investors, such as Eco R1, Great Point, NEA, RA Capital, and Samsara. They joined with other investors in making a very significant investment, which we believe provides strong support for both Immittelstat and Geron. Perhaps that's a good segue to Olivia's discussion of the financing and our updated financial guidance. Olivia?

And finally due to our successful recent public offering today, we have the money to achieve our development plans in two phase three indications.

It was particularly gratifying to see the response investors to this transaction, especially leading biotechnology specialists investors such as equal our one great point.

Okay, Alright capital and chance here.

They joined with other investors and making a very significant investments, which we believe provide strong affirmation for both imetelstat in German.

Perhaps that's a good segue to olivia's discussion of the financing and our updated financial guidance Olivia.

Thank you Chad and good afternoon, everyone.

Olivia Kyusuk Bloom: Thank you, Chip, and good afternoon, everyone. Before discussing the recent public offering, I will briefly summarize our financial results for the first quarter of 2020. Overall, the financial results are in line with our expectations. However, operating expenses are generally higher in comparison to the first quarter of 2019 due to increases in head count across the company as well as increased activity for the eMERGE Phase III clinical trial in lower-risk MDF. As of March 31, 2020, we had approximately $133 million in cash, cash equivalents, and current and non-current marketable securities.

Before discussing the recent public offering I will Bryce I will briefly summarize our financial results for the first quarter of Twentytwenty.

Overall, the financial results are in line with our expectation.

Operating expenses are generally higher in comparison to the first quarter of 29 team due to increases in headcount across the company as well is increasing activity for the emerge phase three clinical trial in low risk Mds.

As of March 31, Twentytwenty, we had approximately $133 million in cash cash equivalents encouraged and Noncurrent marketable securities.

Our spending in the first quarter of Twentytwenty reflected normal business activity into March and then a curtailment of certain costs due to the impacted the cobot 19 pandemic.

Olivia Kyusuk Bloom: Our spending in the first quarter of 2020 reflected normal business activities into March and then a curtailment of certain costs due to the impact of the COVID-19 pandemic. However, certain external vendor costs related to the eMERGE Phase III clinical trial are estimated to be lower in the second quarter of 2020 as a result of a reduction in clinical trial activity limited by the COVID-19 pandemic. We expect much of our personnel-related expenses to continue in line with the first quarter of 2020, with some decline as a result of travel restrictions. However, we project expenses will increase in the future as we begin to support two phase three clinical trials of Imitelcep, the ongoing eMERGE phase three clinical trial and the planned phase three clinical trial in refractory MF.

Although certain external vendor costs related to the emerged phase three clinical trial are estimated to be lower in the second quarter of Twentytwenty as a result of a reduction in clinical trial activity.

Limited by the Cobot Nike pandemic.

We expect much about personnel related expenses will continue in line with the first quarter of 2020 with some decline as a result of travel restrictions.

However, we forget expenses will increase in the future as we begin to support two phase three clinical trials of Imetelstat. The ongoing emerge phase three clinical trial and the plan phase three clinical trial in refractory enough.

Regarding financial guidance for 2020, we expect our operating expense burn to range from $70 million to $75 million.

Olivia Kyusuk Bloom: Regarding financial guidance for 2020, we expect our operating expense burn to range from $70 to $75 million. This guidance reflects cash conservation measures implemented in April due to the COVID-19 pandemic, such as suspending travel and postponing a planned Imitelstat proof of concept study. It also includes new costs for start-up activities associated with the planned phase 3 clinical trial and refractory MS, and additional costs for the expansion of clinical sites for the eMERGE Phase III clinical trial. 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 expect to update guidance at that time. Yesterday, we closed an underwritten public offering of common stock and warrants.

This guidance reflects cash conservation measures implemented in April due to the covert 19 pandemic such as the spending travel and postponing a planned and it tells that proof of concept study.

It also includes new call for start up activities associated with the plan to phase three clinical trial in refractory and out.

And additional call for the expansion of clinical sites for the emerged phase three clinical trial.

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 expect to update guidance at that time.

Yesterday, we closed an underwritten public offering of common stock anymore.

Due to the strong demand not only with the offering upsize what it was also oversubscribed.

We expect estimated net cash proceeds to gerrard from the public offering to be approximately $140 million after deducting the underwriting discounts and estimated offering expenses payable by the company.

Olivia Kyusuk Bloom: Due to the strong demand, not only was the offering upsized, but it was also oversubscribed. We expect the estimated net cash proceeds to Geron from the public offering to be approximately $140 million after deducting the underwriting discount and estimated offering expenses payable by the company. Based on current planning assumptions, we estimate that these net proceeds, together with our existing financial resources, will provide sufficient funds for our operations into the second half of 2022, when we expect top-line results for the eMERGE Phase 3 clinical trial in low-risk MDF and completion of patient enrollment for our planned Phase 3 clinical trial in Refractory MS. With that, I will now turn the call over to Alexandra to provide details around our clinical development activities. Alexandra.

Based on current planning assumption, we estimate that these net proceeds.

Together with our existing financial resources.

Well provide sufficient funds from operation into the second half of Twentytwenty too.

When we expect topline results for the emerged phase three clinical trial in low risk and yeah.

And completion of patient enrollment for our planned phase three clinical trial in refractory enough.

With that I will now turn the call over to Alexandra to provide detailed around our clinical development activities.

Alexander.

Thanks, Joey and good afternoon, everyone.

You can't novel mechanism of action that tells pledged remains unique in comparison to the currently available treatments in myelofibrosis as well as other investigational agents in phase three clinical trials today.

The overall survival data from our Imbark age two clinical tiling intermediate you or high risk MF patients relapse or refractory to JAK inhibitor highlights the potential clinical benefit achievable, we'd imetelstat treatment and indicate the potential disease modifying activity of the joc.

Alexandra Rizzo: Thanks, Olivia, and good afternoon, everyone. Due to its novel mechanism of action, Imatelstud remains unique in comparison to the currently available treatments for myelofibrosis, as well as other investigational agents in Phase III clinical trials. The overall survival data from our EMBARQ H2 clinical trial in intermediate to or high-risk MS patients who relapsed or refractory to JAK inhibitors highlight the potential clinical benefits achievable with Metelsa treatment and indicates the potential disease-modifying activity of the drug. Today, there are limited treatment options available for patients who become relapsed or refractory to JAK inhibitors and discontinue electrolytes. Approximately 75% of patients discontinue treatment with ruxolitinib, as you might know, within five years. And median survival after discontinuation is dismal and has been reported to be 14 to 16 months.

To be they're limited treatment options available for patients, who become relapse or refractory to JAK inhibitors. Indeed continue actually.

Approximately 75% of patients it's come Kenya, cheap money, which leads me that you might know within five years and median survival Aastra discrimination regional and has been reported to be 14 to succeed.

Meanwhile, as we have previously reported that the median overall survival, we need bark was 28.1 month in each with similar for both the factory NBF stations.

These potential improvement in overall survival associated to the myself by treatment [laughter] corroborated by rigorous real world data analysis from patients treated its best available therapy at the mall cancer Center, we're closely match for demographic and be east characteristics, we'd be Mattel.

Century vacation someone bought.

Alexandra Rizzo: Meanwhile, as we have previously reported, the median overall survival in EMBARQ was 28.1 months, and it was similar for both refactoring and rehab stations. This potential improvement in overall survival associated with Metelsta treatment was further corroborated by rigorous real-world data analysis from patients treated with best available therapy at the Moffitt Cancer Center, who were closely matched for demographic and disease characteristics with the Metelsta-treated patients from Inbox. In those analyses, the patients treated with BAT had a median overall survival of approximately 12 months, compared to metastat treated in BART patients who had an overall survival of approximately 30. A few weeks ago, we announced that three abstracts were accepted for poster presentations at the upcoming European Hematology Association, or EHA, annual congress. These abstracts report recent InBARC data analysis and provide further support for the OS results from InBARC.

In those analysis the patients treated the Ti had a median overall survival approximately 12 months.

Compared to the Mattel, that's really been bark patients who had an overall survival of approximately 30 months.

A few weeks ago, we announced a three abstracts were accepted for poster presentations at the upcoming European Hematology Association or E. <unk> annual Congress.

These abstracts report the recent embark detail now.

And provides further support the west results from embark.

In one of the awestruck when you do you got analysis suggested that the improvement in overall survival embark correlate with other clinical benefits observe trial motion also most notably fibrosis improvement as well it seems almost <unk> response.

The second abstract reports improved lucky noise in triple negative CMS patients treated with the Mattel budding boss.

Triple negative patients we present, a patient sub population such effects that sweet driver mutations in myelofibrosis and that have a poor prognosis.

Third outright reports biomarker data.

Indicating on target.

Pending taking so long right after treatment to them until spot and these quarterly keep with improvement in overall survival.

Alexandra Rizzo: In one of the abstracts, the new data analysis suggested that the improvement in overall survival in EMBARQ correlates with other clinical benefits observed in this trial, most notably with fibrosis improvement, as well as symptom and screening risk. The second abstract reports improvement in overall survival in triple negative MS patients treated through the Mattel Study NIMBAR. Triple negative patients represent a patient subpopulation that tracks the three driver mutations in myofibrosis and has a poor prognosis. The third abstract reports biomarker data indicating on target, dose-dependent inhibition of selenomerase after treatment with an L-Calc stat, and this correlated with improvement in overall survival in the environment.

Taken together we believe.

We met Sop strikes substantiate the O.S. data observed anymore.

The plant three clinical trials factory models.

[noise] denied claims pursuing trial in more detail.

Basically this close we discussed this trial design we DFT.

He agreed to could move horlick, we should be at Onep, all one randomized phase three trial Mattel's Dot com.

First of elbow therapy.

And Luckily, we hundred and went to patients you intermediate or high risk on that one track them to JAK inhibitor treatment.

Patients amenable for the trial will be required to be refractory to make JAK inhibitor defined as patients who have had an adequate inadequate clean response or seems arms funds.

Alexandra Rizzo: Taken together, we believe that the 3MF abstract substantiates the OS data observed in EMBARQ and supports the planned H3 clinical trial in this factory model approach. And now this is the planned phase three trial in a module. As previously disclosed, we discussed this trial design with the FDA, and they agreed that we could move forward. This will be an open-label, one-randomized, phase 3 trial of hematopoietin compared to the best available therapy in approximately 320 patients with intermediate to or high-risk MS who are refractory to JAK inhibitor treatment. Patients eligible for the trial will be required to be refractory to a JAK inhibitor, defined as patients who have had an adequate, inadequate spleen response or symptom response after treatment with a JAK inhibitor for at least six months and who had received an optimal dose of the JAK inhibitor for at least two months during the treatment period, with a gas computed. Given this definition, we believe that refractory MS patients meeting these criteria will not In the Imatelstat treatment arm, 9.4 milligrams per kilogram of Imatelstat will be administered intravenously every week.

After treatment they JAK inhibitor for at least six months.

And who had to be Heath, an optimal both with the JAK inhibitor for at least two months during the treatment.

We have a JAK inhibitor.

Given this definition, we believe that refractory AML patients meeting these criteria will not benefit some further jackie with their treatment, which is why the control arm or best available therapy will exclude JAK inhibitors, indeed, mattel that treatment arm 9.4.

And milligrams per kilogram, often the Clos that will be administered intravenously every three weeks.

As chip mentioned the primary endpoint for the trial is planned to be overall survival and we do we use the first child Healy factory myelofibrosis to use a world survival as primary endpoint.

Let me keep secondary endpoints include seem some response spleen response.

Progression free survival.

Complete and partial response cleaning going to month duration of response.

Keith pharmacokinetic.

Patients with point outcomes.

The trial design can have more than 80%, 85% powered to detect a 40% reduction in the risk of Beth Plymouth tells that treating patients.

In making these polycom completion and setting the trial size, what do you assume a husband trade show <unk> 0.6.

And the one sided alpha <unk> 0.0 25.

Alexandra Rizzo: As Chip mentioned, the primary endpoint for the trial is planned to be overall survival, and we believe this is the first trial in refractory myofibrosis to use overall survival as the primary endpoint. Planned key secondary endpoints include symptom response, screen response, Progression to Free Survival, Complete and Partial Response, Clinical Improvement, Duration of Response, Safety, Pharmacokinetics, and Patients Reported Out. The trial has been designed to have more than 85% power to detect a 40% reduction in the risk of death for metastatic patients. In making these power calculations and setting the trial size, we assumed a hazard ratio of 0.6 and a one-sided alpha of 0.025.

For example, we made the assumption that the best available therapy arm will have a median overall survival 14 months.

And be Mattel's, but arm would help a median overall survival told to three months.

The final analysis for OLED is planned to be come back after more than 50% of until we go enroll patients have dot.

An interim analysis of oils in which the alpha spend is expected to be approximately 2.01 <unk> plan to be compacted after approximately 70% of the total projected number that's hard to find on households have occurred.

At the interim analysis Youve, the pre specified statistical voice criterion Smith.

Then we expect such data me supports registrations Mattel's second factor mm.

Yes, the pre specified always criterion no not at an interim analysis, a child, who compete and finalizing.

Alexandra Rizzo: For example, we made the assumption that the best available therapy arm would have a median overall survival of 14 months, and the Matilda arm would have a median overall survival of 23 months. The final analysis for OS is planned to be conducted after more than 50% of the total enrolled patients have died. An interim analysis of OS, in which the alpha stand is expected to be approximately 0.01, is planned to be conducted after approximately 70% of the total projected number of deaths for the final analysis have occurred. At the interim analysis, if the pre-specified statistical OS criterion is met, then we expect such data may support registration as a Mattel-studying refractory MS. If the pre-specified R.S.

Currently we are expecting each over 150 sites across North America, South America, Europe and Asia.

Start up activities have already begun and we plan to open the trial for screening and enrollment in the first quarter 2021.

On their current assumptions, we expect to complete patient enrollment in the second half of 20 to 22.

To conduct an interim analysis in the first top 20 to 23.

To conduct a final analysis in best first half of 20 to 24.

However, both things dream, a decline on hours and sorry, then treatment and could occur on a different timelines and currently expected.

We believe that he'd be planned phase three trial in Frac sand that's a successful.

That will be the first park demonstrate survival benefit in these poor prognosis patient population.

Moving onto the ongoing emerge suite to suite clinical trial in loans and yes.

Alexandra Rizzo: If the criterion is not met in the interim analysis, the trial will continue to the final analysis. Currently, we expect to involve over 150 sites across North America, South America, Europe, and Asia. Startup activities have already begun, and we plan to open the trial for screening and enrollment in the first quarter of 2021. Under current assumptions, we expect to complete patient enrollment in the second half of 2022, conduct an interim analysis in the first half of 2023, and conduct a final analysis in the first half of 2024. However, both the interim and the final analysis are event-driven and could occur on a different timeline than currently expected.

As of the end of April 2020, approximately 68% of get a regional claimed clinical sites for the emergency he clinical trial, even though it's Kevin yes.

Oh, great home.

We previously announced covert 19 has had a significant impact on site initiation enrollment this trial.

Everything we can to ensure we need all enrollment goals in the March has included consistent contacts with dollar clinically investigators and working with our zero on enrollment boosting the TV.

Now on top of those activities currently evaluating additional potentially six new countries and approximately 40, new clinical sites for participation in the trial, which could result in a total up to approximately 835.

As for topline results. The protocol defined final analysis will be conducted speech two months after July patients enrolled and that's based on our updated enrollment the sections, we expect to topline results to be available in the second half of 20 to 22.

Alexandra Rizzo: We believe that if this planned phase 3 trial in refractory MS is successful, methotrexate will be the first drug to demonstrate a survival benefit in this poor prognosis patient population. Moving on to the ongoing eMERGE Phase 2-3 clinical trial in lower-risk MDs. As of the end of April 2020, approximately 68% of the originally planned clinical sites for the eMERGE Phase 3 clinical trial in lower risk MDs were open for enrollment. As we previously announced, COVID-19 has had a significant impact on site initiation and enrollment in this trial. We are doing everything we can to ensure that we meet our enrollment goals in eMERGE.

[noise] compelling data from the phase two portion will emerge continue to highlight the differentiating effect, okay, Mattel thought in lowering scams and speech.

Hers, Oh, we're dealing become meaningful transfusion independence yeah.

She was mostly going to tell such nice.

42% accretions achieve the primary end 0.8 weeks T I.

68% achieve hematologic improvements are right.

Second.

Similarly, nickel benefiting couldn't yacht had been observed goes ours, because it's an hour negative patient subgroups.

Alexandra Rizzo: This has included consistent contact with our clinical investigators and working with our CRO on enrollment-boosting activities. Now, on top of those activities, they're currently evaluating the addition of potentially six new countries and approximately 40 new clinical sites for participation in the trial, which could result in a total of up to approximately 130. As for top-line results, the protocol-defined final analysis will be conducted 15 months after the last patient is enrolled, and that's based on our updated enrollment assumptions. We expect top-line results to be available in the second half of 2022.

Our cost because patients represent approximately 10% to 25% low risk mds patients while our negative.

Patients, we presented approximately 75% to 90%.

The lowering scale patient.

Being cable show transfusion dependent accrual be patient subgroups allows him to close that to potentially address abroad to patient population.

Third and the most significant differentiator in the Eutelsat in lower risk Mds.

Which is observed to date, you said your ability of transfusion independence, namely the here. He asked strikes which was accepted for an oral presentation.

When it at 24 weeks T I read 32%.

For the first time, where not only pointing a one year T. I read a 29% is presenting patient being transfusion. He for at least one year, we the longest trumped seizure free TV I think 2.7 years.

Alexandra Rizzo: Compelling data from the Phase II portion of eMERGE continue to highlight the differentiating effect of hematelstat in lower-risk MDS patients. First, our data indicate meaningful transfusion independence, or TR, achievable within a TELSTAT framework. At 42% of patients achieved the primary endpoint of 8-week TI, and 68% achieved hematologic improvement erythroids.

In addition, the new medium duration of transfusion independence, 88 weeks, which is our knowledge the longest reported to date in the non Delphi Q lowering scandals said.

Finally, 75% of the eight we carved ctr sponsors sure I'm moving lives Creek, and then three grams per deciliter, you into transfusion free interval when compared to their pretreatment level.

Alexandra Rizzo: Similar rates of clinical benefit, including CI, have been observed in both RS-positive and RS-negative patients. RS-positive patients represent approximately 10 to 25% of low-risk MDS patients, while RS-negative patients represent approximately 75 to 90% of low-risk MDM patients. Being able to show transfusion independence across these patient subgroups allows hematocytes to potentially address a broad patient population. Third, and the most significant differentiator from the Telstat in low-risk MDIs that has been observed to date, is the durability of transfusion independence. This year's EHA abstract, which was accepted for an oral presentation, reported a 24-week, For the first time, we're now reporting a one-year T.I. rate of 29%, representing patients being transfusion-free for at least one year, with the longest transfusion-free period being 2.7 years.

I chemo looking right of these magnitude is not achievable with a blood transfusion port growth factor treats.

We believe the being creek hemoglobin together with your ability of T.I.s because piece of the disease modifying activity the myself that treatment, which a line we can itself. So I couldn't come up action.

Telomerase inhibition.

Tell us that has potential to keep the I'm control of cooperation of malignancy, <unk> and progenitor cells and potentially enable recovery normal and much of please.

Now collecting a hand the call back.

She.

Hey, keep our maybe on mute.

Thank you.

The trials and tribulations of doing era.

So thank you Alexander with all the pieces known place to capture the value from two significant indications. We believe we have strategically position drawn to become a leader in the treatment of human logic myeloid malignancies, perhaps would that we'd like to answer your question. So I'll turn the call back tour operator operator.

As a reminder to ask a question you'll need to press star one on your telephone to withdraw your question press the pound or Husky. Please standby heavily compiled acuity roster.

Your first question comes from Charles Duncan with Cantor Fitzgerald. Your line is open.

Thank you hi, chip and team thanks for taking my question and.

Alexandra Rizzo: In addition, the new median duration of transfusion independence is 88 weeks, which is, to our knowledge, the longest reported to date in the non-Delphi-scale lower Iskandian set. Finally, 75% of the eight-week RBCTR responders showed a rise greater than three grams per deciliter during the transfusion-free interval when compared to their pre-treatment level. A hemoglobin rise of this magnitude is not achievable with a blood transfusion or growth factor treatment. We believe that the increase in hemoglobin, together with the durability of TI, is indicative of the disease-modifying activity of Telstra treatment. [inaudible] As a telomerase inhibitor, imetelsat has the potential to inhibit the uncontrolled proliferation of malignant stem and progenitor cells and potentially enable recovery of normal hematopoiesis. Now, I'd like to hand the call back to James. Hey, Chip, are you maybe on mute?

Congratulations on the recent equity raise as well is the plan dropped forward in Myelofibrosis. In addition to Mds I had a couple of questions on the pipeline and just a one operational.

So first question is regarding the pipeline up in Mds.

You know.

I'm not sure if I'm reading this right, but in the corporate debt.

It looks like there is 29% of patients are so achieved a 24 week you know red Red blood cell transfusion independent.

But even the E hi, abstracted it seemed longer and I think Alexander.

Just a dresses, but I'm I'm assuming these are the same patients. Please correct me if I'm wrong and in addition, I'm wondering if you could compare the patient sample characteristics and durability of treatment or transfusion independence to that of the emerging H. English.

And are set.

Thanks, Charles well Alexander perhaps.

John A. Scarlett: The Trials and Tribulations of the Era. So thank you, Alexander. With all the pieces now in place to capture the value from two significant indications, we believe we have strategically positioned Geron to become a leader in the treatment of hematologic myeloid malignancies. And perhaps with that, we'd like to answer your questions, so I'll turn the call back to our operator. Operator?

Compare some of those numbers, which I'm confident in or.

Correct.

I'll take the Luspatercept com comments the.

I think that the things that really distinguish the imetelstat in low risk Mds.

Our first of all that we are treating both auris positive and ours negative patients.

The Rs positive as you recall or somewhere around.

20 ish, 25% quoted is anywhere from 10% to 25% of patients with low risk Mds and that will be that is both the limitation within the accepted labeling for the U.S. for at least cut or so.

Unknown Executive: As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound or hash key. Please stand by while we compile the Q&A roster. Your first question comes from Charles Duncan with Cantor Fitzgerald. Your line is open.

Cost of patients in the future MP patent pending also mentions that.

We include both Horace caused an artist negative patients in our studies and would anticipate heading in that direction from a from a submission perspective. The second is that we had significantly higher baseline transfusion burden in in our phase two study compared to the medalist piece.

Charles Duncan: Thank you. Hi Chip and team. Thanks for taking my question. And congratulations on the recent equity raise as well as the planned route forward in myelofibrosis.

Unknown Executive: and Milo Fibro.

Charles Duncan: I had a couple of questions on the pipeline and just one operational. So, the first question is regarding the pipeline for MDS. You know, I'm not sure if I'm reading this right, but on the corporate deck, it looked like 29% of patients or so achieved 24-week red blood cell transfusion independence, but in the EHA abstract, just addressed this, but I'm assuming these are the same patients. Please correct me if I'm wrong. In addition, I'm wondering if you could compare the patient sample characteristics and durability of treatment or of transfusion independence to that of the emerging agent Lispatercept.

Three study.

The median baseline translation burden was eight units create weeks compared to five for metals and.

The interesting feature about metal was was that they did include patients in medalist who had less than four units for eight weeks are they the RBC transfusion burden about 29% of their patients had less than four units.

When you sort of just look at the patients who had greater than or equal to four units per eight weeks is the baseline transfusion burden, which was the case for both studies for arc study and if you take only those patients in the medalist you end up with transfusion eight week RBC PCI rates of 42%.

John A. Scarlett: Thanks, Charles. While Alexander, perhaps,

Unknown Executive: [inaudible] I'll take the Luz Pattersept comments. I think that the things that really distinguish Imitalstat in low-risk MDS are, first of all, that we are treating both RS positive and RS negative patients. The RS positive, as you recall, are somewhere around 20-ish, 25 percent, quoted as anywhere from 10-25 percent of patients with low-risk MDS. And that is both the limitation within the accepted labeling for the U.S. for Luz Pattersept in RS positive patients, and the CHMP positive opinion also mentions that. We include both RS positive and RS negative patients in our studies and would anticipate heading in that direction from a submission perspective.

Emerge and 32% for Mentalist.

And as we commented earlier that 24 week RBC T I read of 32% and 29% for the one year RBC T I read.

Have not for going to tell said that those rates. The 24 weaken the one we have not been reported for the medalist study any where we've been able to fund.

Finally, the last point is that in if you look at the medium duration of RBC tea.

It's 88 weeks, where the emerge data.

The phase two and it was 31 weeks for the median duration of the T <unk>.

Medalist now I would hasten to add debt.

The.

Emerge study was it was a phase two study in metal since of course, the Sthree and second I would make the point that metals has a.

John A. Scarlett: The second is that we had a significantly higher baseline transfusion burden in our Phase 2 study compared to the MEDLIST Phase 3 study. The median baseline translation burden was 8 units per 8 weeks compared to 5 for MEDLIST. And the interesting feature about Metalist was that they did include patients in Metalist who had less than four units per eight weeks of the RBC transfusion burden. About 29% of their patients had less than four units.

Very I would say benign side effect profile.

So the drugs or the drugs are not entirely comparable but I think that when you look across the opportunity I think we feel very good about where imetelstat stacks up, particularly in the higher transfusion burden and the Irish negative it's walls are supposed to patients.

Oh centered did you have any other further comments about about members.

John A. Scarlett: When you sort of just look at the patients who had greater than or equal to four units per eight weeks as the baseline transfusion burden, which was the case for both studies, for our study, and if you take only those patients and the medalists, you end up with transfusion eight-week RBCTI rates of 42% for eMERGE and 32% for medalists. And, as we commented earlier, the 24-week RBCTI rate of 32% and 29% for the one-year RBCTI rate have not, for Imitel. Those rates, the 24-week and the one-week, have not been reported for the Medal of Study anywhere we've been able to find. Finally, the last point is that if you look at the median duration of RBCTI, it's 88 weeks for the eMERGE data in Phase II, and it was 31 weeks for the median duration of the TI in MED-EL-LIST.

Now the chip actually to cover the everything Charles Please let us know theres I'm not sure.

No I think.

That was very clear and I appreciate the added color.

My second question was regarding the Myelofibrosis protocol and you know, which I think it's pretty interesting because I believe it's quite well suited to show Mechanistically driven differentiation.

Clinical profile for Imetelstat relative to standard of care. However for the planned control arm, which is you know best available therapy. Since it does not include a JAK inhibitor. How would you characterize what B P is if if in any way.

And then given that it's an open label study you know I know over overall survival, probably pretty hard to sake, but in terms of some of the secondary.

John A. Scarlett: Now, I would hasten to add that the eMERGE study was a Phase II study, and MED-EL-LIST was, of course, Phase III. And second, I would make the point that MED-EL-LIST has a very, I would say, benign side effect profile. So, the drugs are not entirely comparable, but I think that when you look across the opportunity, I think we feel very good about where Imitel stacks up, particularly in the higher transfusion burden and the RS negative as well as RS positive. Alexander, did you have any other further comments about numbers?

Im point like some of the patient reported outcomes.

You plan to maintain some level control regarding patient communication.

That's why don't you start off and I'll supplements needed I came close.

Yeah, it's cheaper shirt so so.

Let me start to get that we've got a begs the question around the best available therapies. So.

We have to find the patient cultivation and our study very carefully and the patient population as such right has exhausted or has that had has had the chance to respond to a jackups to meet their treatment.

John A. Scarlett: Now Chip, I think you covered everything. Charles, please let us know if there's anything to be announced.

He would have had mentioned seeks mines all treatments for the Jack and cubic yard and two months of those without being honest people those for the Jack and keep it therefore be concerned patients would not need a treatment a further treatment because the Jack.

Charles Duncan: Yeah, no. I think that was very clear, and I appreciate the added color. My second question was regarding the myelofibrosis protocol and, you know, which I think is pretty interesting because I believe it's quite well suited to show mechanistically driven differentiation of the Clinical Profile for Imitelstat relative to standard of care. However, for the planned control arm, which is, you know, the best available therapy since it does not include a JAK inhibitor, how would you characterize BAP if it is any way different? And then given that it's an open-label study, you know, I know overall survival is probably pretty hard to fake, but in terms of some of the secondary endpoints, like some of the patient-reported outcomes, how do you plan to maintain some level of control regarding patient control?

Mr. fear for the beat the arm can exclude the Jack and keep it now in this setting a BTR will include most likely agents like Hydroxyurea stewards danijel image potentially HMH right. So so we do we backed with.

We I trust and support that defined patient population.

I believe that helpful <unk>.

And then relative to the secondary endpoint.

You know just kind of [laughter].

I guess exercising some control around patient communication and how those readout given it's an open label study.

Unknown Executive: Why don't you start off, and I'll supplement if needed? I can, please.

Alexandra Rizzo: Yes, for sure. So let me start with the question about the best available therapy. So we have defined the patient population in our study very carefully. And the patient population, as such, has exhausted or has had the chance to respond to a JAK inhibitor treatment. They would have had, as I mentioned, six months of treatment with a JAK inhibitor, and two months of that would have been on a stable dose of that JAK inhibitor. Therefore, with this definition, patients would not need further treatment with a JAK inhibitor. Therefore, the BAT arm can exclude the JAK inhibitor. Now in this setting, the BAT arm will likely include agents like hydroxyurea, steroids, and damazole in its potentially HMAs, right? So we believe that with this, we've addressed the need for the defined patient population. I believe that... So far.

So that's a fair question. It's a question that has an overall survival as an endpoint.

Though applies to two and study with an overall survival endpoint.

Thank you as you mentioned right I mean over the primary endpoint you cannot think MD eightys what it is.

And for the you know where that came to my assessment or Simulcrypt heroes.

Well, we though where we will just be sure, but there are taken into the high compliance.

And report the data sets it just because it's a club almost every survival study.

Got it and last question operational do you have sufficient quantities of Imetelstat for both studies and.

If not.

Assuming you've contemplated that with regard to the balance sheet and and if you need to do.

Two additional manufacturing.

Yeah, we have sufficient we have sufficient to to complete the.

The Mds study and to go Weve at least very far into the M.F. study Alexander I don't know if you have any update on that or not.

Unknown Executive: And then relative to the secondary endpoints, you know, just kind of exercising some control around patient communication and how those read out, given it's an open-label study.

No. That's that's accurate I suppose that yep.

Yeah. So we have multiple years worth of a drug supply discipline and a very well start manufacturing.

Unknown Executive: So that's a fair question. It's a question that has overall survival as an end point and applies to any study with an overall survival end point.

Process.

I became Olivia I, what I would add to that Charles I'm, because you asked about the spend at that time in in the in the guidance I gave 'em does include car for CMC as you know I'm a in a tough at his contract manufactured out and so we haven't validating all those vendor.

Unknown Executive: And as you mentioned, right, I mean, overall, the primary end point, you cannot fake it is, it is what it is. And for the, you know, for the symptom assessment or some of the PROs, we will, you know, we will just ensure that they're taken with high compliance and report the data as such. It's difficult. It's a problem with every survival study.

As part of the process in in readiness for potential not only for phase three trial of supply, but also for potential commercialization down the road and so those activities are ongoing right now.

Charles Duncan: Got it. And last question, operational. Do you have sufficient quantities of imitel staff for both studies? And if not, do you assume you've contemplated that with regard to the balance sheet and whether you need to do additional manufacturing?

Okay. Thanks for taking my questions.

Okay, great progress.

Thank you very much.

Your next question comes from Chad Messer Needham and company. Your line is open.

John A. Scarlett: Yeah, we have sufficient funding to complete the MDS study and to go at least very far into the MF study. Alexander, I don't know if you have any update on that or not.

Oh, Thanks for taking my questions and Mike Congratulations on all the progress, particularly with Ah getting this.

Protocol worked out and things moving forward there.

Alexandra Rizzo: No, that's that's accurate. That's well said. Yep.

I'm just wondering if there's one thing [noise].

Unknown Executive: Yeah, so we have multiple years' worth of drug supply at this point, and it is very well-established.

Can maybe share your thoughts on with me with regards to imagine that's you know all all other drugs approved or or late stage development.

Olivia Kyusuk Bloom: This is Olivia. What I would add to that...

Unknown Executive: [inaudible]

Our current giving away.

Unknown Executive: Okay, thanks for taking my question. Thank you.

Sure the hybrid.

After endpoint.

Unknown Executive: Thank you very much, Jeff.

And you guys kind of being held to the sort of high bar.

Chad Metzer: Your next question comes from Chad Metzer with Needham and Company. Your line is open. Thanks for taking my questions and let me give you my congratulations on all the progress, particularly with getting this MS protocol worked out and things moving forward there. It's just one of those things you can maybe share your thoughts on with me with regard to MS. And that's you know, all the other drugs approved or late-stage development are kind of getting away with it, and you guys are kind of being held to the sort of high bar of OS. [inaudible]

20 give any.

Blocks on why that may be and whether or not you're really strong oh less data from from the phase twos small smallish, though it may be somehow Ah.

Well I'm actually working against you.

Well, let me take that first of all and then I'll invite Oh invite Alex to to make additional comments.

I would actually look at it differently I think that we view the ability the confidence we haven't and a central Wes.

Benefit.

As you commented on came from both the real World data.

Analyses that we did.

Reported previously and also the just the comparison in the Imbark study to the historical controls. We only saw that is not a burden to bear but actually.

Unknown Executive: Well, let me take that first of all, and then I'll invite Alex to make additional comments. I would actually look at it differently. I think that we view the ability, the confidence we have in a potential OS benefit, which, as you commented on, came from both the real-world data analyses that we did and reported previously, and also just the comparison in the EMBARQ study to the historical controls. We always saw that as not a burden to bear, but actually an incredibly valuable finding and a deeply differentiating element for our drug, Emetelstat. So, far from viewing it as something that we are going to be held to a higher standard than anyone else, it may be true that it's a higher standard. It takes a little bit longer, and it takes substantial resources to do.

Incredibly valuable.

Finding and in a deeply differentiating.

Element to to our to our drug to Imetelstat. So far from viewing it is something that we were going to be helped to higher standards than anyone else. It may be true that it's a higher standards. It takes a little bit longer and it takes you know substantial resources to do but on the other hand.

Coming out at the other end of this I think we expect to have the only drugs that will have been through the the only drug in Jack refractory patients, who make up a very substantial part of the market.

John A. Scarlett: But on the other hand, coming out at the other end of this, I think we expect to have the only drug that will have been through the, the only drug in JAK refractory patients who make up a very substantial part of the market, the only drug that will have actually demonstrated a survival benefit in such patients, and a survival benefit in SACCHAT is a primary outcome measure. So this is actually new ground, but with new ground also comes high barriers to entry, potentially, and also great differentiation. I can tell you the investigators that we engaged in working through the details of this type of approach were just simply extremely excited about the possibility of getting a drug that would have this type of benefit demonstrated. So that was our real approach to it, and I think we feel pretty terrific about the opportunity to go there.

The only drug that will was actually demonstrated survival benefit in such patients and survival benefit benefit in fact chat is a primary outcome measure. So this is this is actually new ground, but with new ground also comes high barriers to entry potentially and also a great differentiation.

I can tell you the investigators that we engaged in working through the details of.

This type of approach, we're just simply extremely excited about the possibility of getting getting a drug that would have this type of benefit demonstrated so that was our real approach to it I think we feel pretty terrific about the opportunity to go there.

I leave anything else Alex.

Yeah, maybe I can just reinforce a cheap I mean that we lost the fact that we have a driveshafts can I know improve overall survival in these relapse refractory setting that there's no. Other trackers actually mentioned that has shown that and as you know right other other drugs.

Our having primary endpoint, but are addressing that seemed to come off that.

Unknown Executive: Yeah, maybe I can just reinforce Chip. We love the fact that we have a drug that can, you know, improve overall survival in these relapses.

Whether that's a screen or same time response or am I mean cool month or a combination of your boss right. So what we have here isn't overall survival and I think that we have about the possibility or the chance to have a paradigm shift into thinking about how you approach treatment, we might look like.

Unknown Attendee: Unknown Attendee, Anil Kapur, Aron Feingold, Faye Feller, Robert Driscoll, Ethan Markowski, [inaudible]

Yes.

Unknown Executive: All right, yes, no; I appreciate that perspective and certainly don't disagree with anything you're saying. It's the go big or go home approach.

No I appreciate that perspective, and certainly don't disagree with anything you're saying, it's 60 go bigger go home approach.

Chad Metzer: Thanks Ash. Maybe just with regard to the upcoming EHOP, congrats on the strong, sort of top line, one year data that came out in the abstract. What other analyses, are there any other analyses that you would sort of highlight you should be looking out for in the full oral presentation?

I ask maybe [laughter], maybe just with.

Regarding upcoming Jihad.

Congrats on the strong sort of topline one your data that came out.

Can be abstract.

What other analyses ours or any other analyses that you would.

Sort of highlight you should be looking out for in the oral presentation.

In all federal his presentation.

Alexandra Rizzo: In the myelofibrosis presentation, there is one key, I guess, data point that I would definitely want to bring to the attention, and that's the correlation that we are now showing of fibrosis improvement with significantly longer overall survival in these patients, right? So this is the first time ever that in myelofibrosis, we are showing the fact that if you have an improvement in fibrosis, you have a better So I guess that would be the data that I would really highlight from the myelofibrosis abstract. In terms of the MDS, it will certainly be durability, right? The one year transfusion-free period.

There is a wine key I guess at the Guy that I would definitely one green our who he attention.

That's a b on incredibly Sean odd, but we are now showing all I drove this improvement with both significantly longer old girls survival. In these patients right. So I think the first time ever at that that in myelofibrosis is being facts that you have an improvement.

Fibrosis, you have a better shands commute to these longer so I guess that would be the data that I thought I would really highlights from back myelofibrosis from the myelofibrosis abstract income could be MTS will certainly good could your ability IRI Burger one were touched.

Great.

Okay, great. Thanks, I'll, you looking out for those.

Chad Metzer: Great, thanks; I'll be looking out for those.

Unknown Executive: Thanks, Chad.

Thanks, Chad.

Again, if you would like to ask a question press star one on your telephone keypad. Our next question comes from Andrew Dsilva with B. Riley FBR. Your line is open.

Andrew De Silva: Again, if you would like to ask a question, press star one on your telephone keypad. Our next question comes from Andrew De Silva on B Riley FBR. Your line is open.

Andrew De Silva: Yeah, thanks for taking my questions and congrats on the progress. So, you know, lots to unpack here.

Yeah, Thanks for taking my questions and congrats on the progress.

Lots to unpack here I'll, just start as far as embark the M.F. phase three.

Andrew De Silva: I'll just start as far as EMBARQ, the MF phase 3, and connecting, you know, the recent abstracts and the benefits seen in overall survival in patients that experience other clinical benefits. And then, you know, tying that into the stronger results that we're seeing in the triple negative patient group that, you know, further align with the other clinical benefit statement. Are you looking to have... Protocols designed in Phase III in a manner where we should expect triple negative patients to be a focal point of the enrollment criteria.

And conducting the recent abstraction the benefit seen an overall survival in patients that.

Experience other clinical benefits.

And then you know tying that into the stronger results that that we're seeing in the triple negative patient group that further align with the other clinical benefit statement or are you looking to have.

Protocols designed in the phase three in a manner, where we should expect triple negative patients to be.

I would be a focal point of the enrollment criteria.

Alex.

Yes, the answer to that he yes, however, our focus and priority all the moment east the phase three study in refractory myelofibrosis patients.

Unknown Executive: Yes, the answer to that is yes. However, our focus and priority at the moment is a phase three study in refractory myelofibrosis patients.

I think a andy might have been asking.

Unknown Executive: I think Andy might have been asking, within the phase three study, within the refractory phase three study, will there be a particular focus on triple negative patients within that broader patient population? And in other words, is there either a major stratification for triple negatives, or do we have a particular focus on that?

In the phase three study within the Refractories phase three study will there be a particular focus on triple negative patients would be about that broader patient population.

And.

In other words is there either a major stratification for triple negative or do we have particular focus on that GLADO.

Unknown Executive: Go ahead, Alex.

Alexandra Rizzo: Well, triple negative patients will also be allowed to enter the current, refractory study. At the moment, if that was the question, we have not planned for stratification for triple negative patients.

Well triple negative patients will be also allowed to and third the the current that the refractory study.

At the moment is that with the question we have not planned for stratification for triple net to prison.

Unknown Executive: Right, there's a particular focus on them, Andy.

Right, Okay particular focus on them Andy.

Okay. Okay. Thank you for that.

Andrew De Silva: Okay, okay, thank you for that. And then you notice that enrollment, or you noted enrollment from that standpoint would exclude JAK inhibitors. Did that happen in the real-world data Moffitt ran? Their bat population also excluded jacks.

And then Oh, you noticed the enrollment Oh, you noted the enrollment.

From from that standpoint would exclude a JAK inhibitors did that the real world data Moffett ran.

There there that population also exclude jacks.

Alexandra Rizzo: Yes, yes, the BAT in the Moffitt patient did not also exclude jack and sitters.

Yes, yes, but be 80 on them in the most me in a in the most of that patients did not include also excluded JAK inhibitors.

Andrew De Silva: So it's a fairly clean comparison, then, as far as, okay. [inaudible] Perfect.

So it's a fairly clean comparison, then as far as okay. Okay. Good.

Turning to the outcomes expected yes.

Andrew De Silva: And then this last question for me, as far as guidance goes, you know, no change really from a numbers standpoint. Can you help me crosswalk how it's different today than it was in March? Obviously, you're increasing spend with MF and then reducing enrollment, or just enrollment is going slower with MDS due to COVID-19, and you're pushing out proof of concept studies a little bit. Could you help me get to the same number as far as where the gives and takes are?

Okay. Okay perfect and then we'll just last question for me as far as guidance goes no.

No change really from from a number standpoint, but they'll be crosswalk, how how it's different today than it then it was in March obviously, you're you're increasing spend.

With M.F., and then reducing enrollment or just your almost going slower Mds due to covert 19.

And your you're pushing out a proof of concept studies a little bit could you could you help me get to the same number as far as where the gives and takes our there.

Olivia Kyusuk Bloom: Yeah, Annie, this is Olivia. Sure, I can.

Yeah any this Olivia sure I can't so you're right overall you know the range is the same as what we guided earlier this year, but you're right, there's kind of pluses and minuses in many areas and and then we ended up you know in the same range. So I would say that the composition of the guidance is.

Olivia Kyusuk Bloom: So, you're right. Overall, the range is the same as what we guided earlier this year, but you're right. There's kind of pluses and minuses in many areas, and then we ended up in the same range. So, I would say that the composition of the guidance is relatively unchanged. It's just that, again, there was some pushing from one category to another as the different expenditures were going along. So, just to let you know, for the current guidance and its composition, the clinical trial costs, which include the startup activities that I mentioned for the refractory MF trial, as well as the ongoing support for the eMERGE Phase III, probably represent a little less than a fifth of the total guidance. FTE costs are a little over a third. The manufacturing costs that I mentioned earlier when we were talking with Charles, that's a little over a fourth, and then overall GNA, you know, kind of supporting the public company, that kind of thing is a little less than a fifth.

Relatively same Mississippi again, there were some pushing from one category to another as as the different expenditures were going along so just to let you know for the current guidance of <unk> and the composition the clinical trial costs, which include the startup activities.

For the refractory Nf trial as well as the ongoing support for the emerge phase three but on that is probably represents a little less than a fifth.

The total guidance.

S. T E com are a little over a third.

The manufacturing costs and I mentioned early when we're talking with Charles that's a little over a four.

And it and then overall Gionee you know kind of supporting the public company that kind of thing is a little less than a stat.

Okay.

Andrew De Silva: Okay. Great color. Thank you very much. I'll take everything else offline. Best of luck going forward this year. Thank you.

Great. Thank you very much I'll take everything else offline best of luck on for this year [noise].

Thank you.

Paul Schrader: Your next question comes from Paul Schrader with VTIG. Your line is open.

Your next question comes from all Schrader with BTG. Your line is open.

Well good afternoon, I like the echo the sentiment that kind of amazingly vol coal congratulations on getting this at this stage no stuff.

Paul Schrader: Good afternoon. I'd like to echo the sentiment. It's been an amazingly long poll. Congratulations on getting this to this stage. I know it's not been easy. So my first question is:

So my first question is that the M.F. control arm.

Unknown Executive: Alarm. Does Fidratinib, is that a complexity for you? They have retreatment data, I know it's highly contentious, but is it a worry for you that as you talk to clinicians, they would want to try Fidratinib and Rux failures?

Those were threatened.

Complexity for you, but they have retreatment data I know, it's probably just but is it a worry for you that as you talk clinicians that they would want to try but were threatened they've been brooks failures.

Alex did you get the question of course.

Alexandra Rizzo: Alex, did you get the question correct? Yeah, go ahead.

Right I mean, I I don't know rate is not ignore it Ah I worry right again keep them. The definition all that patient population and our study we do believe that no patients or pie investigators would not want to treat patients with a JAK inhibitor. So.

Unknown Executive: Right. I mean, I don't know.

Alexandra Rizzo: It is not. It is not a worry, right? Again, taking the definition of the patient population in our study, we do believe that, you know, patients or PIs, investigators would not want to treat patients with a jack and signature. So I don't, I don't think we see that as a worry.

I don't I don't think we see that as a word.

Okay, and then I'm kind of a so I'm I'm intrigued by your abstract with it.

Paul Schrader: Okay, and then a kind of a remark on your EHA abstract with the telomere length. My memory is that that's been very difficult to measure historically and, in fact, I think didn't correlate with early data because you couldn't measure it. Is it now a robust assay, and you could actually look at all MF patients as a function of telomere length, irrespective of treatment, and you might have a subgroup? What are your thoughts on that? Is that a new assay, and how robust is it? Because my memory is telomere length was historically nearly impossible to measure.

Telomere length.

My memory of the that's been very difficult to major historically in effect I think didn't correlate with early data because you couldn't measure it didn't know robot, that's where you could actually look at all into patients as a function of telomere length irrespective of treatment and you might have a subgroup just your thoughts on you've got a new capacity.

And how robust is that if my memory is caliber like what's historically nearly impossible to measure.

You are great whoever drilling is a very difficult to measure, especially uses a fact that you're mixing in Oakland, sorry, malignant as well as normal cells.

Alexandra Rizzo: You are correct. Telomere length is very difficult to measure, especially due to the fact that you're mixing, you know, potentially malignant as well as normal cells. However, as you indicated, we've improved on the assay. And now, again, in a limited number of patients, I guess that's still a caveat, but in a limited number of patients that had paired analysis, it is the first time that we are able to, you know, introduce some correlation between the TL, the telomere length, and the outcome.

Her oh, so he indicated we've improved on the acetate and now yeah Im a limited number of patients I guess, that's your coffee has been a limited number of patients that had appears analyses and he's the first time, but we are able to you know to up to do.

Some correlation between Oh, the two on the alone.

Paul Schrader: Do you think it will be a biomarker? Is that something that kind of has you excited, or is it still very exploratory?

Uh huh.

And do you think it will be a biomarker that something is kind of has accelerated or is it still very export or.

I think we'll look at all.

Alexandra Rizzo: I think we look at all of the three PD parameters, if you will, right, the telomere length, the polymer effectivity, and the H-Turks expression, right? We look equally at them. I don't think we're thinking of any biomarker at the moment, but it is really good to have them as PD pharmacodynamic markers in order to know to confirm the own target mechanism of adenine

We PD parameters, if you will ramp that you on your Lang, the telomerase activity and the H her in a express one right. We will look inquiry at them I don't think are thinking of any up bio marker.

Home runs if I could be really good to have them as a BD pharmacodynamic markers in order to know to kind of where I'm.

On target mechanism of action so.

Paul Schrader: All right, and then one quick, maybe slightly annoying question, because the horse is out of the barn, but in the eMERGE trial, you have such a different drug profile, where three-quarters of the patients that get an eight-week transfusion get a year. Do you... Are you sorry you chose such a short end point, which will be much noisier, or do you think that you're confident that eight weeks is long enough so that the placebo rate is going to be very low?

Third and then one quick maybe slightly annoying question, though because of the horses out of a barn, but like EMEA merged trial, you have such different drug profile, where three quarters of the patients to get an eight week transfusion get a year.

Do you do.

Are you saw you chose such a short pinpoint would flow.

The Wifi or where do you think that.

You're confident that eight weeks as long enough. So that the placebo rate is going to be very.

John A. Scarlett: Maybe I can just comment that the eight-week RBCTI is, Alexander, I'm sure we'll have a few other comments, but you know, Tom, the eight-week RBCTI is kind of the accepted or approved regulatory outcome or regulatory endpoint, and so you're, it's really common in virtually all of these studies in low-risk MDS to use that as the primary outcome measure. I think we have a very robust outcome measure, and even in the medalists, when you got into the higher transfusion-burdened patients, such as we will have in our study, in our phase three, and as we have in our phase two, you know, the noise really goes down low, much lower. You're bringing up a really interesting point.

Maybe I can just comment that the eight week.

Alexandra I'm sure we'll have a few other comments that you're told the eight week RBC T.I. is kind of the accepted or approved.

Regulatory outcome or regulatory endpoint until you're you're it's really common.

In virtually all of these studies and low risk Mds to use that as the primary outcome measure.

I think we have a very robust in the phase two we saw very robust outcome measure and even in the medalist when you got into the higher transfusion burden patient such as we will have in our study in our phase three unless we have interface to.

You know the noise really goes down low much lower you're bringing up or really interesting point. So for example, with the medalist study, which I just use metal us in this case not to two to harp on anything with regard to luspatercept that because it is a study with a wide variety of patients in the baseline try.

John A. Scarlett: So, for example, with the medalist study, which I just use medalist in this case, not to harp on anything with regard to Luz Patterson, but because it is a study with a wide variety of patients in the baseline transfusion burden. So when you looked at the patients, just at the placebo rates, because that's what you're actually kind of getting at, right? So when you looked at the patient's placebo outcome, in their study as a whole, which included, remember, from, you know, from two units of transfusion burden up to actually 20. Their placebo response rate was 16%. And I have to say, when we looked at that, we went, Oh, holy cow. What was that?

Fusion Burton.

So when you looked at the patience it just at the placebo rates, because that's what you're actually kind of getting it right. So when you looked at the patients placebo outcomes in their study as a whole which included remember from you know from two units transfusion burden up to.

Actually 20, they're placebo response rate was 16% and I have to say when we looked at that we went home Holy cow, what was that but the reality is that when you knock out the patients who have the less than four units pretty weak transfusion burden. So the two and three patients okay.

John A. Scarlett: But the reality is that when you knock out the patient who had the less than four units per eight week transfusion burden, so the two and three patients, okay, that placebo rate comes down to seven. In the MDS005 study, which Celgene did a couple of years ago and was reported, well, yeah, a couple of years ago at ASH, that was Revlimid versus placebo. The placebo rate, as I recall, was 4 or 5 percent. So I think we don't see a signal-to-noise ratio here as long as you have a sufficiently high transfusion burden. And if memory serves me correctly, if you then flip the analysis and you look at the patients in the Luz-Patterson study that had only 2 units or 3 units per 8 weeks, and just that subgroup alone, their placebo response rate was extremely high.

Backing people rate comes down to seven person in the.

In the Mds 005 study, which celgene did or couple of years ago and was reported.

A couple of years ago. It at Ash that was revlimid versus placebo the placebo or is it raises I recall was four or 5%. So I think we don't see a signal to noise ratio here as long as you have a sufficiently high.

Transfusion burden and if memory serves me correct. If you then slipped that analysis. If you look at the the patients in that Luspatercept city that had only two units.

Were three units a pre weeks and just that subgroup alone. There placebo response rate was extremely high so it. It I think there it's really defined by the baseline transfusion burden and that signal whose ratio in those patients it will be studying.

John A. Scarlett: So I think it's really defined by the baseline transfusion burden, and that signal-to-noise ratio in the patients that we'll be studying is more than adequately high. The additional durability is the icing on the cake, right? And I think everyone will pay a great deal of attention to the durability because we would expect an exceptionally low, I expect a very low, placebo response rate there. And I think that will not be an issue at all in the signal-to-noise ratio. I hope that didn't expand too much and confuse it.

I think is more than adequate behind the additional durability is is is the icing on the cake right and I think everyone will pay a great deal of attention to the durability, because we would expect an exceptionally low.

Specs at very low placebo response rate, there and I think that will not be an issue at all and second one always ratio I hope that didn't have turned much shouldn't confuse that [laughter]. So those who are actually we're looking for and thank you very much but it's like a.

Paul Schrader: Absolutely what I was looking for. Thank you very much, guys.

Unknown Executive: Okay, sure.

Sure.

There are no further questions at this time I'll now turn the call back over to John Scarlett for closing remarks.

John A. Scarlett: There are no further questions at this time. I'll now turn the call back over to John Scarlett for closing remarks.

John A. Scarlett: Well, I'd just like to thank everybody for participating in this conference call. We're exceptionally pleased by the progress that we've been able to make. I think that we have a really great opportunity to now drive forward with two Phase III studies, us, our new investors, who we're excited to have, and also just simply want to thank all the patients and the investigators who have helped us get to this point. We still have a lot of wood to chop, as they say, but I feel really, really good going into the next several years, when we have some exciting times to come. So thank you all very much, and we look forward to taking the journey with all of you. I think that concludes our call, Operator.

Well I just like to thank everybody for participating in this conference call were exceptionally pleased by the progress that we've been able to make I think that we have.

I'm, a really great opportunity to now drive forward with two.

Phase three studies.

Yep.

The company's get this far we thank all of our investors are long time investors who've been with the company and supported US our new investors who were excited to have and also just simply want to thank all the patients and the investigators who helped us get to this so at this level, we still have a lot of wood to chop as they.

Say, but I feel really really good going into the next several years, where we have someone excite exciting times to come. So thank you all very much we look forward to taking the journey with all of you.

I think that concludes our drug on our call Oh operator.

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

Unknown Executive: This concludes today's conference call. You may now disconnect.

Okay. Thanks very much.

Unknown Executive: Okay, thanks very much.

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