Q3 2020 Geron Corp Earnings Call

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Until that time your lines will again be placed on music hold thank you for your patience.

Operator: Until that time, your lines will again be placed on music hold. Thank you for your patience. Good afternoon.

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Lisa: My name is Lisa, and I will be your conference operator today. At this time, I would like to welcome everyone to the Q3 2020 Geron Earnings Conference Call. All lines have been placed on mute to prevent any background noise.

Good afternoon, My name is Lisa and I will be your conference operator today.

At this time I would like to welcome everyone to the Q3 2020 Geron earnings Conference call.

All lines have been placed on mute to prevent any background noise. After.

Lisa: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press the star, then the number one on your telephone keypad. If you would like to withdraw your question, press the pound.

After the speakers remarks, there will be a question and answer session.

Lisa: Thank you. I would now like to turn the call over to Ms. Suzanne Masseri. Please go ahead, ma'am.

Unknown Attendee: Thank you, Lisa. And good afternoon, everyone. Thank you for joining us for today's conference call. I am joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer, Olivia Bloom, the company's Chief Financial Officer, and Alexander Rizzo, our Chief Medical Officer. After the market closed today, we announced our third quarter 2020 financial results and recent events in a press release. It is available on our website under www.geron.com slash invest.

Unknown Attendee: In addition, a live webcast of this call is available on our website and will be archived for 30 days. 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 timeline for completion of enrollment in and the results from the eMERGE and IMPACT clinical trials, that Geron's existing financial resources will be sufficient to fund operations into the second half of 2022, and that Imitelstat has the potential to be disease-modifying. 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.

Unknown Attendee: These risks and uncertainties include, without limitation, those regarding that the COVID-19 pandemic may significantly impact the timeline for enrollment and results of the clinical trials and or drug supply. That the company may be unable to overcome all the clinical, safety, efficacy, technical, scientific, operational, manufacturing, and regulatory challenges to meet the expected timelines for eMERGE and IMPACT-MS, that in clinical trials, MS-HELPSAT may be unsafe or fail to demonstrate that it is disease-modifying or efficacious, that regulatory authorities may not permit the further development of Imitelstat on a timely basis or at all, and 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 September 30, 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.

And uncertainties include without limitation those regarding that the COVID-19 pandemic may significantly impact the timelines for enrollment and results of the clinical trials Andrew drug supply.

That the company may be unable to overcome all the clinical safety efficacy technical scientific operational manufacturing and regulatory challenges to meet the expected timelines for emerge and impact M F.

That in clinical trials and tell us that may be unsafe or failed to demonstrate that it is disease modifying or efficacious.

That regulatory authorities may not prevent the further development of M. A tell stuff on a timely basis or at all.

And that Jaron may need additional financial resources before the end of 2022 for the development and commercialization of Tulsa.

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 a forward looking statements are explains under the heading risk factors endurance quarterly report on for 10-Q for the quarter and.

It's September 30th 2020 filed with the SEC.

Undo relying 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.

On today's call Doctor Scarlet plans to make a few introductory comments after which MS. Bloom will cover the recent that financing.

Unknown Attendee: On today's call, Dr. Scarlett plans to make a few introductory comments, after which Ms. Bloom will cover the recent debt financing, third quarter financial results, and 2020 guidance. Dr. Rizzo will provide clinical development updates regarding the ongoing eMERGE Phase 3 clinical trial in lower-risk myelodysplastic syndromes, or MDS, and the upcoming IMPACT-MF Phase 3 trial in refractory myelofibrosis, or MF, and recent data announcements, including publication of the eMERGE Phase 2 data in the Journal of Clinical Oncology, also JCO, and the 10 abstract Dr. Scarlett will then finish the call with closing remarks. I will now turn the call over to Dr. John Scarlett, Jerome's Chairman and CEO. Thanks, Suzanne.

Third quarter financial results in 2020 guidance.

Dr. Rizzo will provide clinical development updates regarding the ongoing a birch Bayh Street clinical trial, and Laura risk Myelodysplastic syndrome or N D S.

And the upcoming impact amount phase three trial and refractory myelofibrosis or M. S.

And recent data announcements, including publication of the emerge phase two data in the journal of clinical oncology also G. C O S.

And the 10 abstract accepted for presentation at this year American Society of hematology or Ash annual meeting.

Doctor Scarlet will will then finish the call with closing remarks, I will now turn the call over to Doctor, John Charlotte, Gerrans, Chairman and C E O chip.

Thanks for them I'd like to welcome everyone tortured quarter Twenty-twenty conference call.

John A. Scarlett: I'd like to welcome everyone to our third quarter 2020 conference call. Before we begin, I'd like to make a few comments on the COVID-19 pandemic and how we're managing it. In compliance with state and local rules and for the health and safety of our employees, access to our offices remains closed, and our employees are working from home. We also continue to limit business travel to essential business needs only.

Before we begin I would like to make a few comments on the COVID-19 pandemic in our management.

And compliance with state and local rules and for the health and safety of our employees.

Yes to our offices remain closed and our employees are working from home.

We also continue to limit business travel to central business needs only.

John A. Scarlett: Although all of us would like to return to our normal pre-COVID schedules and routines, employee productivity and efficiency continue to be very high. Later in the call, Alexander will comment on the effect of COVID on our clinical trials. In the third quarter, we actively pursued our clinical, regulatory, and publication plans for the MattelSTAT program. Enrollment in the ongoing IMERG Phase 3 clinical trial in low-risk MDS and start activities for the upcoming Phase 3 clinical trial in refractory MF, which we have named IMPACT-MF, continued to progress. We also secured orphan droid designation for lower risk MDS in Europe, received acceptance for presentation of all 10 abstracts submitted to the ASH annual meeting, published eMERGE Phase II data in the Journal of Clinical Oncology, and strengthened our balance sheet with a loan facility that provides additional financial flexibility to further support our plans for imitel stat development going forward. We continue to work toward completing enrollment in Emerge in the first quarter of 2021.

Although all of us would like to return to a normal pre covid scheduled and routines employee productivity and efficiency continues to be very are late.

Later in the call Alexandra will comment on the effect of Covid or clinical activities.

In the third quarter, we actively pursued are clinical regulatory and publication plans for the <unk> program.

Enrollment in the ongoing armored phase three clinical trial and lowers can be us and startup activities for the upcoming phase three clinical trial and refractory M F, which we have named impact M F.

Continue to progress we also secured orphan drive <unk> designation and lower it's gonna be a senior.

Received acceptance for presentation of all 10 abstracts submitted to the Ash annual meeting publish emerge phase two data and the journal of clinical oncology and strengthened our balance sheet with a loan facility that provides additional financial flexibility to further support our plans for <unk> development going forward.

We continue to work toward completing enrollment and emerge in the first quarter of 2021.

John A. Scarlett: However, given the recent resurgence of the COVID-19 pandemic, it's causing an uncertain and unpredictable impact on clinical trial activity. Due to these challenges, we now believe the trial will most likely be fully enrolled in the second quarter of 2020. As long as enrollment is completed by the end of the first half of 2021, we continue to expect top-line results from eMERGE to be available in the second half of 2022, as previously guided. Switching studies based on current feedback from the clinical sites that are planned to participate in IMPACT-MS, we continue to expect that trial to be open for screening and enrollment in the first quarter of 2021. So I'd like to hand over the call now to Olivia to discuss what the debt financing means for our cash position, our three-quarter financial results, and our guidance. Okay, Olivia?

However, give.

Given the recent resurgence of the COVID-19, pandemic is causing an uncertain and unpredictable impact on clinical trial activities.

Due to these challenges we now believe the trial will most likely be fully enrolled in the second quarter of 2021.

As long as enrollment is completed by the end of the first half of 2021, we continue to expect topline results from emerged to be available in the second half of 2022 as previously guidance.

Switching studies based on current feedback from the clinical sites that are planned to participate in impact M. S. We continue to expect that trial to be open for screening enrollment in the first quarter of 2021.

So I'd like to hand over the call now to Olivia to discuss what the death financing needs for our cash position or three quarter financial results and our guidance.

Olivia.

Thank you and good afternoon, everyone.

Olivia Kyusuk Bloom: Thank you, Chip. And good afternoon, everyone. As of September 30, 2020, we had approximately $274 million in cash, cash equivalents, and current and non-current marketable securities.

As of September 30th 2020, we had approximately $274 million in cash cash equivalent and current and non current marketable securities.

Our cash position reflect net proceeds of approximately $140 million from a public offering and May 2020, and approximately $24 million initial net proceeds from a non diluted 75 million dollar loan facility that closed at the end of the third quarter.

Olivia Kyusuk Bloom: 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 closed at the end of the third quarter. The loan facility will be available to Geron through year-end 2022 in three tranches, subject to certain terms and conditions, including the achievement of certain clinical, financial, and regulatory milestones. The loan facility provides us with access to non-dilutive financial resources to support the Imitelstat Development Program, as well as working capital and general corporate purposes. Based on current planning assumptions, we estimate our current financial resources to be sufficient for our operations until the end of 2022, during which time we plan to reach two significant inflection points, top-line results for the eMERGE Phase 3 clinical trial in low-risk MDS and completion of patient enrollment Overall, the financial results for the third quarter and year to date period were in line with our expectations.

The loan facility will be available to Jarrod, two year, and 2022, and three taruntius subject to certain terms and conditions, including cheeseman, a certain clinical financial and regulatory milestone.

The loan facility provides us with access to non diluted financial resources to support the <unk> that development program as well as working capital in general corporate purposes.

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

During which time, we plan to reach two significant inflection point.

Topline results for the emerge faith be clinical trial, and low risk M. B S and completion of patient enrollment for the upcoming impact mfa's be clinical trial and refractory M F.

Overall, the financial results for the third quarter and year to date period, we're in line with our expectations.

Operating expenses for the three and nine months ended September 30th 2020, where generally higher in comparison to the same period in 2019 due to head count increases in 2019 across the company.

Olivia Kyusuk Bloom: Operating expenses for the three and nine months ended September 30, 2020, were generally higher in comparison to the same period in 2019, due to headcount increases in 2019 across the company, increased activity for the eMERGE Phase 3 clinical trial and low-risk MDS, startup activities for the upcoming IMPACT-MF Phase 3 clinical trial in refractory MF, and costs associated with validating and Mattelstat manufacturing processes.

Increased activity for the emerge phase three clinical trial and low risk M. B S.

Startup activity for the upcoming impact M. S. A three clinical trial and refractory M F.

And costs associated with validating emmetrope that manufacturing processes.

Importantly are.

Olivia Kyusuk Bloom: Our manufacturing and quality team recently accomplished an operational milestone in establishing our Imitelsat supply chain. Our clinical sites are now starting to receive Geron manufactured imitilset and placebo in the eMERGE Phase 3. This achievement helps ensure uninterrupted drug supply for both current and future clinical trials, as well as enables Geron manufactured materials to be included in the current phase three registration enabling trial. We plan to use the same manufacturers that produce these clinical materials for potential future commercial manufacture of the drug. We expect operating expenses to be higher in the second half of 2020 in comparison to the first half, as we begin to support two phase three clinical trials of Imitelstat, the ongoing eMERGE phase three, and the upcoming IMPACT-MS phase three. Regarding financial guidance for 2020, we are reiterating our expectation of operating expense burn to range from 70 to 75 million. Financial guidance is based on a set of assumptions at a point in time.

Manufacturing and quality team recently accomplished an operational milestone in establishing are <unk> that supply chain.

Are clinical psych are now starting to recede Jarrod manufactured amatol set in placebo and they emerge phase three.

Alexander Rizzo: And if the company's plans change, causing assumptions to be revised, then we expect to 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 and to discuss the data published recently in the Journal of Clinical Oncology and the multiple presentations scheduled at the ASH conference in December.

Alexander Rizzo: Thanks, Olivia, and good afternoon, everyone. Before I discuss recently published MATELSTAT data, I'd like to give a brief update on our Phase 3 clinical trials in Refractory MS and Lower Risk MDS. The clinical protocol for our upcoming phase three clinical trial in refractory MS, called Impact MS, has been finalized, and the trial is now listed on clinicaltrials.gov. We continue to expect the trial to be open for screening and enrollment in the first quarter of 2021. Startup activities are ongoing and include site selection, engagement of vendors, and building of the clinical database, among others. In the IMPACT-MS trial, the final analysis for the Primary Endpoint of Overall Survival, or OS, is event-driven and is planned to be conducted after more than 50% of the patients involved in the trial have died. An interim analysis of ORS is planned to be conducted after approximately 70% of the total projected number of death events for the final analysis have occurred.

Pack and that has been finalized and the trial is now listed on clinical trials that goal.

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

Startup activities are ongoing and include site selection engagement the vendors building of the clinical database among others.

In the impact and that trial the final analysis for the primary endpoint of overall survival or even.

The vendor even any plan to be conducted after more than 50% of the patients enrolled in the trial have died.

An interim analysis before it is planned to be conducted after approximately 70% of the total projected number of death events for the final analyses have occurred.

In the pre specified.

Alexander Rizzo: If the pre-specified statistically significant difference in OS between the two treatment arcs is met at the interim analysis, it is possible that data from the interim analysis could support a registration file moving on to the ongoing eMERGE Phase 3 clinical trial in lower-risk MDS. Enrollment for this trial continued to progress in the third quarter of this year. All 92 of the originally planned clinical sites were open for enrollment to address the enrollment delays related to the COVID-19 pandemic experienced earlier this year. We implemented several enrollment boosting activities.

Specifically significant difference in your words.

Between the two treatment arms these meds, adding terminology.

It is possible that data from the interim analysis could support registration filings.

Meaning company ongoing emerge phase three clinical trial in lower risk Mds.

Enrollment for this trial continues to progress in the third quarter.

In August.

Only two of the originally planned clinical sites were opened for enrollment.

To address the Olin believes you read through to the COVID-19, but demick experienced earlier this year.

We implemented several enrollment boosting activities.

These include engage in clinical science liaisons to interface directly with the clinical side.

Alexander Rizzo: These include engaging clinical science liaisons to interface directly with the clinical side, establishing a digital presence for the trial, and expanding the number of clinical sites in existing and new countries. We currently expect to open approximately 30 new clinical sites, although at this time, only a handful are open. As a result, we believe the full benefits of the additional sites have not yet been realized.

That machine, a digital presence where to trial.

And expanding the number of clinical sites in existing and new countries.

We currently expect to open approximately 30, new clinical sites, although at this time only a handful or open.

As a result.

We believe the full benefit of the additional sites have not had been realized.

We expect almost all of the sites to be open for screening and enrollment by the end of 2012.

Alexander Rizzo: We expect almost all of these sites to be open for screening and enrollment by the end of 2020. Our team internally is continuing to target completion of enrollment in eMERGE by the end of the first quarter. Despite our efforts,

Our team internally is continuing to target completion of enrollment in the marriage by the end of the first quarter.

Despite our efforts.

Given the recent resurgence of the core 19 pandemic, particularly in many of the countries where enriches being conducted.

Alexander Rizzo: Given the recent resurgence of the COVID-19 pandemic, particularly in many of the countries where eMERGE is being conducted, and the uncertainty and unpredictability regarding its impact on Clinical Trials Activities this coming fall and winter, we now believe it is most likely the trial will be fully enrolled sometime in the second quarter of 2021. However, it is important to note that as long as enrollment is completed by the end of the first half of 2021, we continue to expect top-line results to be available in the second half of 2022, which is consistent with our previous guidance, as announced in a press release last week. The data from the eMERGE Phase II trial in low-risk MDs were published in the well-respected Journal of Clinical Oncology, or JCO. We believe this publication further indicates the recognition of the importance of eMERGE data by experts in the MDS field. As you may recall,

And the uncertainty and unpredictability regarding the impact.

Clinical trial activities this coming fall and winter. We now believe it is most likely the trial will be fully enrolled sometime in the second quarter 2021.

However, it is important to note that as long as the enrollment is completed by the end of the first half of 2021 sequence.

We continue to expect topline results to be available in the second half of 2022.

Which is consistent with our previous guidance.

As announced in a press release last week.

The data from numerous phase two trial in lower risk Mds was published in November well respected journal of clinical oncology.

We believe these publications further indicates the recognition of the importance of being merged data by experts in India sales.

As you may recall.

Alexander Rizzo: Meaningful and Durable Transfusion Independence with Imatelsta Treatment has been highlighted consistently in previous medical conference presentations, as it is in the JCO article. The median duration of transdruzion independence of 21 months is a critical clinical outcome for this transfusion-dependent patient. Moreover, it's reported that approximately 30% of the patients were transfusion-free for over a year. To our knowledge, this is the longest duration of transfusion independence reported in lower risk MDS patients, in addition to the Durable Transfusion Independent, a decrease in SF3B1. One of the key mutations correlated with ineffective erythropoiesis in lower-risk MDS was observed in the trial, although only a small number of patient samples were available for testing, of Critical Importance. The duration of the transfusion-free period was correlated with the decrease of the SX3B1 mutation, and patients that had the highest decrease of SF301 also had the longest transfusion sleep period, to put these data in context Recall that telomerase is continuously upregulated in malignant stem and progenitor cells, resulting in malignant hematopoiesis, as its alumnus and key contributor. Immatile fat selectively targets malignant cells, with continuously upregulated telomerase to induce their death and enable potential recovery of normal hematopoiesis.

Meaningful and durable transfusion independence, we imetelstat treatment has been highlighted consistently in previous medical conference presentations as any in the June to your article.

The median duration of terrestrial independents of 21 mines.

He is a critical clinical outcome for these transfusion dependent patients.

Moreover, as reported approximately 30% of the patients were transfusion free for over a year.

To our knowledge base.

Alexander Rizzo: Decreasing disease mutations, such as the SF3B1 mutation, is an indicator of potential impact on the malignant cells of the underlying disease, which suggests disease-modifying activity. In addition, observations of clinical outcomes, such as the durable transfusion-free period experienced by the patients in the eMERGE Phase II, indicate potential recovery of normal hematopoiesis, suggesting disease-modifying activity. Therefore, we believe both the durable transcription dependence and the reduction in the SF3B1 mutation observed in the eMERGE phase 2 suggest disease-modifying activity for Telstra treatment in these patients. Regarding, Yesterday we announced that a total of 10 abstracts have been accepted, of which four will be oral presentations. In summary, the data and analysis reported in all of the abstracts support our Phase 3 clinical trials and highlight the clinical benefits observed in both the Phase 3 eMERGE and eMERG trials.

Mm derivations of clinical outcomes, such as the durable transfusion free period experienced by the patients medium marchbanks too.

Indicate potential recovery of normal Kimoto. Please.

Just think disease modifying activity.

Therefore, we believe.

Both the gerbil transfer your independence and the reduction in DSS there'll be one mutation of European do much face to suggest td's modifying activity Corina Tulsa treatment. These patients.

Regarding S yesterday right now is that a total of 10 abstracts has an acceptance of which four will be oral presentation.

Alexander Rizzo: There are several abstracts covering EMBARQ Stage 2, including new data on patient-reported outcomes, data on improved OS in triple negative MS patients, as well as biomarker data and analysis supporting the on-target activity of the drug. Also, there are two abstracts called Trials in Progress that provide further detail of the trial design for the ongoing eMERGE Phase III and the upcoming IMPACT and MET Phase III. This afternoon, I would like to focus on the data suggesting potential disease-modifying activity of metal sets from the INBARG Phase II trial in relapsed refractory mass that were reported in two of the ASH abstracts. Why not the Eshob track?

Alexander Rizzo: No. 346 and is scheduled for an oral presentation, report new analysis from the EMBARQ Phase 2 trial that shows significant dose-dependent reduction of the mutation burden of key driver mutations for MS, as measured by a reduction in the variant allele frequency, or VAS, of the mutation. The data showed that the patients who had reduction, NVS had prolonged median OS for 31 months, versus 21 months for those patients that did not have reduction in BAS. The abstract concludes. The depletion of cytogenetically abnormal clones and reduction in mutation burden, together with the improvement in median OS, further demonstrate that Imatelstat has disease-modifying activity by targeting malignant cells.

It did not have reduction.

The abstract concludes.

The depletion of size of genetically abnormal cost and reduction in utilization burden together with the improvement in median.

Further demonstrate the imetelstat has disease modifying activity by targeting malignant cells.

The second I'm starting on that number.

Alexander Rizzo: The second abstract in the mess, number 658, which is scheduled for an oral presentation, described a set of data from the EMBARQ stage 2 showing that there was a correlation between improvement in fibrosis and improved median OS. In other words, the patients that had at least one degree of fibrosis improvement had significantly longer survival than those who had worsening of fibrosis.

Number 658, which is scheduled for an oral presentation.

Describes a set of data from the Imbark phase G.

Showing that there was a correlation between the improvement in fibrosis and improved media analyst.

Alexander Rizzo: In conclusion, we believe that the data from the JCO publication and these two abstracts highlight Mattelstat's impact on the malignant cells responsible for the underlying disease, as well as the clinical outcomes of durable transfusion-independent or low-risk MDS patients and improved overall survival for relapsed and refractory MS patients. Taken together, these data continue to build the clinical and biomarker evidence suggesting disease-modifying activity, which really differentiates hematocytes from other treatments for low-risk MDS and refractory MS. Now, I'd like to hand the call back to Chip. Thanks, Alexandra. In closing, I'd like to reiterate that we continue to advance both the eMERGE and IMPACT MS Phase 3 clinical trials. Through medical conferences like ASH and in scientific and clinical journals, we continue to raise awareness of Imtelstat's disease-modifying data. We are also pleased to report that we have established our own Inmatel stat supply chain, which will allow Geron manufactured materials to be included in the current phase three registration enabling trials, which is an important step in NDA readiness. Finally, we've also strengthened our balance sheet to further support our plans for Mattelstat development going forward.

John A. Scarlett: We believe that these efforts will help establish Geron as a leader in hematologic myeloid malignancies, thus creating long-term shareholder value. So with that, we'd like to answer your questions. I'll turn the call back over to our operator, Lisa. At this time, I would like to remind everyone that if you would like to ask a question, please press star and the number one on your telephone keypad. Your first question comes from the line of Gil Blum with an 8 minute copy. Good afternoon, everyone. And thank you for taking our questions. I mean, I'm here for Chad.

Lisa: So maybe, maybe a bit of a strange question. Is there any overlap between the iMERGE and Impact MS study sites? Alexandra, can you take that overlap between the two studies and sites in terms of sites? Yes, there are sites that are overlapping for sure between the two studies. Gotcha. And it looks like you have a very big ash ahead of you.

Gil Joseph Blum: Lots of presentations. What can you share about some plans for KOL outreach and those kinds of activities, considering this is a virtual format? Go ahead. Yeah, and I mean, it's a good question. And then again, he just gave the answer, I guess, because it's a virtual meeting. At the moment, we have not planned any KOL activities, but it's best at the moment.

And I mean it could.

Good question and then I guess when he discusses the answer I guess because its a virtual.

A meeting at the moment, we have not planned carrawell activities, but thats at the moment.

Alexander Rizzo: However, we will be sponsoring a few of the educational sessions that will be at AASH. And, kind of last, we know that getting your own supply of limit health gives you flexibility and control over your own supply chain. Is there any situation in which that supply chain would be affected by the ongoing pandemic? So far, Gil, we don't see that as a major risk. Much of our supply chain is in South Korea, which is probably one of the best controlled countries so far.

Moreover, we will be sponsoring a few of the educational sessions that will be at ash.

And.

Last week.

We know that getting your own supply of the metals that gives you flexibility and control over your own supply chain is there any situation in which that supply chain would be affected by the ongoing pandemic.

Okay.

We we so far.

Gil we don't see that as a major risk.

Much more supply chains in South Korea, which is probably one of the best controlled countries. So far.

John A. Scarlett: So I would comment on that. Second of all, we managed all of this, all of these activities, which were, [inaudible] Excellent. Thank you for taking our questions and congratulations on all the progress. Thanks. Thanks. Your next question comes from the line of Bonnie Quash with Stiefel. Hi, this is Bonnie. I'm from Steve Willey.

So I would comment on that second of all we managed all of this all of these activities which were.

Very substantial during the height of the pandemic so while it's impossible to you know never say never.

We shouldn't say never say never I think it's pretty low risk right now.

Excellent. Thank.

Thank you for taking our questions and congratulations on all the progress.

Bonnie Quash: Thanks for taking my questions. I wanted to ask more about the enrollment in the eMERGE study. Is the patient population that you're enrolling so far somewhat similar to the patient population enrolled in the Phase 2 trial in terms of RS positive and RS negative, as well as transfusion burden? Because I remember the Phase 2 patients had a pretty high transfusion burden. Correct. I'll let Alexandra answer that first. If you have more, I may take them.

Alexander Rizzo: Go ahead. Right? So the inclusion and the exclusion criteria for the phase three part of the study have not changed to those of the phase two part of the study that were defined for the target patient population, which means that we are still enrolling patients regardless of the presence or absence of ring cedroblast, and we are still enrolling patients that had at least four units prior to the enrollment in the study prior to the randomization into the study. So again, we are enrolling the same patient population from the target population. Thank you. And for the MDS patients who achieve transfusion independence but then end up requiring transfusions again, is there any evidence of the potential for achieving durable transfusion independence, or achieving that transfusion independence again, with continued treatment? Is this something you have looked into?

Alexander Rizzo: Absolutely. And that has already been reported by a few of the patients at last IHOP. So we do have patients that achieved transfusion independence, but for some reason had to stop or had to, sorry, had to receive a transfusion and then again became transfusion independent. And just a small follow-up to that, how do you see this playing out in a real-world setting in terms of keeping patients on drugs once they've gone back to receiving transfusions again? So the question, if I understand the question correctly, was, so what happens in the real world if a patient has achieved transfusion independence and then they require a transfusion? Are they going to just stop the drug, or are they going to potentially continue on? Is that your question? Yes. Okay, I'll let Alexandra know.

Alrighty reported and a few of the patients at loss.

So we do have patience with that.

A chief transfusion independence for some reason had to talk for or art in the head to sorry had to receive.

Transfusion and then again became transfusion independence.

Just a small follow up with that how do you see this playing out in the real world studying in terms of keeping peace was on drugs.

Wednesday is going back to Jones receive some seasons again.

[noise], how we from a question. So the question if I understand the question. It was so what happens in the real world if a patient.

Has achieved transfusion independence and then they require a transfusion are they going to just stop the drug or are they going to.

Potentially continue on is is that your question.

Yeah.

Okay outlet Alexander.

John A. Scarlett: Right. So I mean, at the moment, I really don't see a reason why they wouldn't continue, right? If you are transfusion independent, and you are benefiting from the drug, you're feeling better, you don't need a transfusion.

So I mean at the moment I really don't see a reason why being hidden continue right. If you are transfusion independence and you are benefiting from the drug feeling better you don't need transfusions.

I believe you would like to.

Alexander Rizzo: I believe you would like to continue receiving treatment, so I don't see a problem in keeping patients on treatment. Yeah, and to answer the question very directly, I think if a patient for whatever reason requires a transfusion, these patients are used to requiring, you know, different levels of transfusion, etc. So if they require a transfusion, I think our experience suggests that they would likely continue to give imidaclostat an opportunity to keep them transfusion-free. Again, it goes back to the question that you asked before. What happens to patients who stop having transfusion independence? Do they then reestablish transfusion independence after getting a transfusion? Can the drug continue to work?

Continue receiving treatment so I don't see a problem in keeping the patients on treatment.

They have potentially yeah sorry.

And I think just to answer the question very directly I think if a patient for whatever reason requires a transfusion.

These patients are used to require different levels of transfusion et cetera. So if they require a transfusion I think.

Our experience suggests that they would likely continue to give <unk> that.

An opportunity to keep them transfusion free again it goes back to the question that you asked before what happens to patients.

Who quit having transfusion independence do they then re establish transfusion independents after getting a transfusion.

Can the drug continue to work the answer is unequivocally, yes, so I think because of that.

John A. Scarlett: The answer is unequivocally yes. So I think because of that. The likelihood is that investigators, or, sorry, in this case, treating physicians, and patients would have a very high incentive to continue on the drug even if there was an interruption of their transfusion period of time. Yeah, yeah.

The likelihood is that investigated or sorry in this case treating physicians and patients would have a very high.

Incentive to continue along the driver even if there wasn't interruption of their transfer region free.

Period of time.

Yeah.

Alexander Rizzo: If I just wanted to add, "Oh, I'm sorry. Go ahead. But, no, I had nothing."

I just wanted to add Oh, I'm sorry go ahead.

Oh, no I have no clue.

Bonnie Quash: Please go ahead. I just wanted to add one more item. I know we're discussing transfusion independence, but recall in our study, we had 68, about 70% of the patients who had hematologic improvement. And those are the patients that actually decreased in the need for transfusions. So it's a large proportion of patients that benefit from our drug, regardless of whether they would eventually achieve transfusion independence, which still happens in a large, you know, 42% of the patients. But again, 68% have hematologic improvement and decrease in transfusion needs, right? I believe that's really, you know, a good reason to stay on drugs.

Go ahead.

I just wanted to add one more item I know, we're discussing transfusion independence, but we call in our study we have to 68 about 70% of the patients who have him into logic improvement.

And those are the patients that actually had between using the need of chest fuchsia.

Alexander Rizzo: Thank you so much for answering all my questions. Okay, great. Thank you. Your next question comes from the line of Charles Duncan with Counter Fitzgerald. Hi, John, and team.

Charles Duncan: Congratulations on continued enrollment in iMERGE and the manufacturing milestone, as well as the AASH abstracts. Thanks for taking the time to answer my questions. I had a couple, so I'm going to try to be quick. First of all, with regard to iMERGE and the enrollment discussion around 1Q or 2Q next year, is that the result of an observed change in enrollment patterns or getting new sites up and running in terms of executing on that, or just prudence? I'll take that, Chas.

I'll I'll take that chance. Thanks, thanks for the question.

John A. Scarlett: Thanks for the question. First of all, let me make a couple of comments. Look, we debated a long time about how to characterize the uncertainty that was caused by COVID and also the comment that many experts believe that the worst is yet to come, right? So at the same time, we have not yet begun to see broad-based, self-imposed holds, similar to what we saw early in spring and summer of the year when sites were initially feeling the first effects of COVID. So what we are seeing is that sites are beginning to adapt in order to enable patient treatment to continue. So these are kind of the unknowns at the point. What, how severe is the increase gonna be this fall and winter?

So first of all let me make a couple of comments look we debate a long time about how to characterize the uncertainty that was caused by Covid and.

And also the comment that many experts believe that the worst is yet to come right.

John A. Scarlett: How effective are the measures employed by these sites to stay open? How effective are they going to be despite the increasing numbers of COVID cases? How effective is our enrollment boosting activities going to be at the existing sites? And how effective will we have, you know? How many of these new sites will come online by the end of the year? As we said, we hope that that most will come on. But again, COVID makes this all pretty tough.

John A. Scarlett: So our best assessment was that we believe it's most likely that we'll be fully enrolled in the second quarter. But I really want to make the point that, and we did, by the way, feel like that was the best and most responsible way to weigh and communicate these various scenarios. But I do want to be really clear that if we achieve that by the end of the second quarter, we will still be on track and on time for our top line results as previously communicated. Okay. Yeah, and I understand that's an event-driven study, so there may be a little bit of conservativism in that as well. And it sounds like it's a prudence thing in terms of enrollment on iMERGE.

John A. Scarlett: Are you detecting the same kind of level of enthusiasm around the profile of Imitelstat for investigators in terms of enrolling patients as you did when you launched this study? Yeah, I'll let Alexandra comment on that. Yeah, yeah, I can just, you know, reaffirm and reconfirm that that's the case. The data that was published in JCO has really even further raised enthusiasm. We work very closely together.

You detecting the same kind of levels enthusiasm around the.

Ill profile of Imetelstat for investigators in terms of enrolling patients as you did when when you launch this study.

Alexander Rizzo: I mean, even though I answered, we're not maybe having an event at ASH. We're working very, very closely with all of the key opinion leaders in the field. So we feel confident about the outreach to the KOLs and the interest from the KOLs in our study and the sites that just the PIs that are participating in our study. Okay, that's helpful.

Charles Duncan: And then with regard to the IMPACT-MF trial, which I got to tell you I really like because it says something more to me than the previous study names. Can you just remind me or or maybe I should go to ClinTrials, but can you remind me the event rate that you were assuming in IMPACT-MF or the kind of time to event that you're looking at going in on that? So in terms of, I don't think that information will be on cleantrials.gov.

Alexander Rizzo: So we have not published that. But as I was saying, the study is eventually going to be published, and we do plan to have an interim analysis when 70% of the events that were planned for the final analysis to occur will happen. So at that point, is there a statistically significant difference between the two arms? It is possible that that data could be used to support a filing, which is 70% of the 50% that are required at the end of the study. Okay, but the kind of time to that you really haven't published, and I can understand why. Is that clear? Is that the answer? Oh, Chas, this is Olivia, just to remind you. So as of now, we're projecting that it's in the first half of 2023, potentially for the interim. Okay, and the final and the final, potentially in the first half of 2024.

I would think the study is event reason as you said, we do plan to have an internal team I'm obviously.

70% of the Ben said were planned for the final analysis to occur.

Hi, Brian.

John A. Scarlett: Okay, and then last question is regarding manufacturing. So it's cool to see that you folks have been able to get that up and running despite the challenges of COVID. I guess I'm wondering if any patients have been dosed with the older drug or the drug from Janssen and if there is any bridging or anything or can you handle, you know, kind of the comparisons through analytical methods? So, let me comment on that. So, fundamentally, we're using the same manufacturing process. The sponsorship changed the vast majority of the processes, and even the companies involved and the contract manufacturing groups involved are the same. But this is now being done completely under our sponsorship. Now, all of the patients treated so far in the MDS study have been using material made by Janssen and under Janssen sponsorship.

The vast majority of the.

The vast majority of the processes and even the the companies involved in the contract manufacturing groups involved or at the same but this is now made completely under our aegis under our sponsorship.

Now the all of the patients treated so far in in the Mtf's study have been using material made when the you know by Jansen I'm under Jansen sponsorship now what's changing as it will be feeding the new material made under our sponsorship into.

John A. Scarlett: Now, what's changing is that it will be feeding the new material made under our sponsorship into this study as it progresses. As you may know, although it's not a high-risk situation because it's all the same process, it is a kind of regulatory box to tick that what is expected to be the final commercial process and group is being used in the phase three study. So, I think we've avoided a footfall here certainly and likely have ticked off an important but tickish regulatory box to check. Got it. Okay. Congratulations on the progress. Excuse me.

This study is at progressive as you may know that although it's it's not a high risk situation because it's all the same process.

Charles Duncan: Thanks for taking my question. Sure. Your next question comes from the line of Tom Schrader with BTIG. Good afternoon.

Tom Schrader: Thanks for the update, as always. A quick question on impact. The interim look, is that a tiny alpha spin, so the bar is very high? Is that reasonable for us to expect, or is that a real, would the drug have to just perform spectacularly? So I would say that it's a reasonable alpha that we've allocated for the interim analysis. Okay. And I was a little surprised by the first half interim score of 23 and the first half full score of 24.

Alexander Rizzo: A lot of these trials enroll sort of very slowly, and once they get rolling, they enroll like mad. Do you expect us to enroll more linearly because all the centers are well established and the patients are pretty well known? That's kind of an unusually linear forecast you see enrollment. Yeah, I don't think we can predict the pattern for this study specifically. However, again, based on clinical oncology experience in general, as you say, most enrollment happens towards the end of the study. But I mean, I just don't think I can comment or I can predict how that will be for this study. All right, one more. So you're starting to talk about mutant clones and treatment rates, and do telomerase lengths correlate with any of the mutant clones? You know, at this point, it's not so relevant, but is it validating the mechanism of the drug as originally proposed? If I had to choose between Telomere and Territua...

Like the station.

Okay got it and I was a little surprised by first have interim and twenty-three and first half full for 24.

A lot of these trials enrolls sort of very slowly and once they get rolling the enrolled like Mad do you expect this to enroll more linearly because all the centers are well established in the patients are pretty well known this kind of an unusually linear forecasts you see enrollment.