Q3 2020 Imara Inc Earnings Call

[music].

Good morning, and welcome to the <unk>.

Operator: Good morning, and welcome to the Amara Inc. Q3 earnings conference call and webcast. All lines have been placed on mute to prevent any background noise.

Q3 earnings conference call and webcast.

Lines have been placed on mute to prevent any background noise. After the speakers remarks, there will be a question and answer session I'd like to ask a question. During this time simply press Star then the number one on your telephone keypad. If you would like to have kind of a question press the pound key I would now like to turn the conference over to Mr., Mike Great see you may begin.

Operator: 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 and then the number 1 on your telephone keypad. If you would like to withdraw your question, press the pound key.

Operator: I would now like to turn the conference over to Mr. Mike Gray. Sir, you may begin. Okay, thank you. Good morning everyone, and welcome to tomorrow's third quarter 2020 conference call. I'd like to remind everyone that various statements we make during this conference call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual events or results could differ materially from those expressed or implied by these forward-looking statements as a result of various important factors, including those set forth in the risk factors section of our most recent quarterly report on Form 10-Q filed with the SEC this morning, as well as any other filings that we make with the SEC.

Okay. Thank you Bob Good morning, everyone and welcome to <unk> third quarter 2020 conference call I'd like to remind everyone that various statements. We make during this conference call about the company's future expectations plans.

Plans and prospects constitute forward looking statements for purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995.

Operator: Any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views should change. Therefore, you should not rely on these four statements as representing our views as of any date subsequent to today.

Mike Gray: Okay, with that, I'll turn the call over to OMAR's President and CEO, Rahul Balal. I'll return following his discussion to review our third quarter financial results, and then we'll open the call for any questions.

Rahul Balal: Thank you, Mike. Good morning, everyone, and thanks for joining us on our third quarter 2020 conference call. We've continued with what has been a productive year for Amara as we made progress across the business and accomplished several of the key objectives that we set for 2020. Importantly, in August, we dosed our first patient in our ARDENT Phase IIb clinical trial of IMR687 in patients with sickle cell disease. We then followed that milestone with the first patient dosed in the 4-tick phase 2B beta thalassemia trial of 5167 in October. In addition to dosing patients in these Phase 2b trials, our team has made important progress in receiving regulatory approval in multiple countries to conduct these studies, as well as activating multiple clinical centers to expand the global footprint of these trials. We anticipate all these efforts will further support our patient enrollment.

It has to be trials. Our team has made important progress in receiving regulatory approval in multiple countries to conduct these studies as well as the activating multiple clinical centers to expand the global.

Footprint of these trials, we anticipate all these efforts will further support our patient enrollment goals.

Rahul Balal: We've also continued to progress our ongoing clinical trials of IMR687, including our Phase IIa trial of adult patients with sickle cell disease, as well as our Open Label Extension, or OLE, trial in adult patients with sickle cell disease. Regarding the Phase 2a trial, we completed patient dosing in this study during the third quarter and are finalizing data review from this study. These steps help keep us on track to report top-line data from this trial toward the end of the fourth quarter of this year. Our OLE trial is a four-year, open-label trial that allows patients completing the Phase IIa to enroll in a longer safety and tolerability study of IMR 687 during our second quarter conference call. We reported on what we believe are two key aspects of the trial.

Also continue to progress our ongoing clinical trials of <unk> 670, including our phase Iia trial of adult patients with sickle cell disease as well as our open label extension or <unk> trial, an adult patients with sickle cell disease.

Regarding the phase Iia, we completed patient dosing in this study during the third quarter and are finalizing data review from this study.

These steps help keep us on track to report topline data from this trial towards the end of fourth quarter of this year.

Our OLED trial is a four year open label trial, which allowed to complete this 8282.

To enroll any longer safety and Tolerability study of <unk> seven.

During our second quarter Conference call. We reported on why don't believe are two key aspects of trial first we reported that we had seen increased enrollment.

Rahul Balal: First, we reported that we had seen increased enrollment, and I'm pleased today to report that trend has continued. We now have 23 patients enrolled, up from 8 that we reported during our second quarter conference call. All patients on the OLE are receiving 200 milligrams of IMR-687. We also noted that we plan to analyze data from OLE patients at approximately six-month intervals and presented what we believe to be important data on the first two patients that had crossed that mark. We plan to present additional data regarding these two patients at the upcoming ASH annual meeting in December. We also anticipate that we will report data from 10 to 15 patients, including the two previously reported patients, during the first quarter of 2020, before OLD patients progress beyond approximately six months of treatment.

And I am pleased today to report that trend has continued.

We now have twenty-three patients enrolled up from eight that we reported during our second quarter conference call.

All patients on the.

<unk> are receiving 200 milligrams of <unk> 687, we also noted that we plan to analyze data from early patients at approximately six month intervals and presented what we believe to be important data on the first two patients that across that Mark we planned to present additional data regarding these two at the.

Ash annual meeting in December we also anticipate that we will report data from 10 to 15 patients, including the two previously reported patient.

2020.

Oh that'd be patient progressed beyond approximately six months of treatment.

We also made important progress on the regulatory front during the third quarter as the European Commission quickly. The <unk> 687 orphan Dizzy designation for the treatment of sickle cell disease I.

Rahul Balal: We also made important progress on the regulatory front during the third quarter as the European Commission granted IMR 687 an Orphan Disease Designation for the treatment of Sickle Cell Disease. IMR 687 has previously been granted orphan drug, fast track, and rare pediatric disease designations from the FDA for the treatment of patients with sickle cell disease. In addition, the FDA granted orthopedic and rare pediatric designations for the treatment of patients with beta thalassemia during the third quarter of 2020, having previously granted orphan disease designation in beta thalassemia earlier in 2020. We believe that these are important designations as we continue the development of IMR-687 in these days.

<unk> 687 had previously been granted orphan drug fast track and rare pediatric disease designations from the FDA for the treatment of patients with sickle cell disease.

In addition, the FDA.

Hi back and rare pediatrics designations for the treatment of patients beta thalassemia during the third quarter of 2020, having previously granted orphan disease sake designation in beta thalassemia earlier in 2021.

We believe that these are important designations as we continue the development of <unk> and these diseases.

Rahul Balal: In the third quarter, we also began looking at clinical outcomes beyond the, which could help further differentiate IMO-67 from approved sickle cell disease therapies and therapies still in development. Specifically, with the help of well-known cardiologists, we began exploring IMR687 and its potential ability to reduce cardiovascular risk in patients with sickle cell disease. As part of that effort, an exploratory clinical analysis was conducted by Vanderbilt University Medical Center on our Phase IIa interim data, and the results were presented at the 15th Annual Sickle Cell and Thalassemia Conference, or ASCET, held virtually on October 26 to the 31st of 2020. In brief, Impact on NT-proBNP, a well-established marker of cardiovascular risk.

In the third quarter. We also began looking at clinical outcomes beyond.

If you could help further fresh.

67 from approved sickle cell disease therapies and therapy still in development.

Specifically with the help of well known cardiologist, we began exploring <unk> 687, and it's potential ability to reduce cardiovascular risk and patience with sickle cell disease as part of that effort and exploratory clinical analysis was conducted by Vanderbilt University Medical center on our face to an interim data.

And the results were presented at the 15th annual sickle cell and Thalassemia conference or ask at held virtually on October 26 to the 31st of 2023.

Briefly.

Seven impact on and T Pro BNP, a well established marker a pretty vascular risk patients treated with <unk> seven plus hydroxyurea. So a mean decrease of 27, 3% and <unk>.

Rahul Balal: Patients treated with IMR-687 plus Hydroxyurea saw a mean decrease of 27.3% in NTproBNP levels from baseline, while patients with FHU alone saw a mean increase of 27% in NTproBNP from baseline. Furthermore, among patients with higher baseline Nt-proBNP values of greater than 400 gigagram per mL, those who received IMR687 plus hydroxyurea showed a mean reduction in Nt-proBNP of 67.9% from baseline, as compared to a mean increase of 28% from baseline in patients who received HU alone. As part of our Arden and Forte Phase 2B studies, we have implemented NT-PRO-BNP as a biomarker to help further explore changes in cardiac risk when patients are treated with IMR687 in these studies. The ASCAP presentation also contained preliminary preclinical data from studies we are conducting in models of heart failure, specifically heart failure with observed ejection action, or ASPEC. Independent literature suggests the inhibition of PD-9 and resulting increases in cyclic guanosine monophosphate, or GMP, through natriuretic peptide modulation, can serve as an attractive target for the prevention and treatment of cardiovascular disease, including hepatitis.

While patient.

Issue alone so a mean increase of 27% empty pro BNP from baseline.

Furthermore, among patients with higher baseline anti pro BNP values of greater than 400, Picogram per ml, those who received <unk> seven plus hydroxyurea should a mean reduction and <unk> of 67.9% from baseline as compared to a mean inquiry.

<unk> of 28% from baseline in patients who received <unk> alone.

As part of our Arden and <unk> studies, we have implemented and T Pro BNP as a biomarker to help further explore changes in cardiac risk when patients are treated with <unk> seven on these days.

The ASCAP presentation also contain preliminary preclinical data from studies, we are conducting and models of heart failure specifically.

Josh.

Pet.

Independent literature suggests the inhibition of PD, nine and resulting increases in cycling quantity monophosphate, Berkeley G&P through natriuretic peptides modulation can serve as an attractive target for the prevention and treatment of cardiovascular disease, including half path, we are gaining confidence in this.

Rahul Balal: We are gaining confidence in this indication from our recent preclinical work. In a model that recapitulates the HFPAF phenotype, we show that treatment of IMR687 attenuates cardiac hypertrophy, reduces cardiac fibrosis, and increases cardiac inflammation in a dose-dependent manner. Lastly, we believe that there could be an important link between our sickle cell studies that examine cardiovascular biomarkers, like NT-proBNP, and future HF-TEST efforts with IMR680. I would now like to spend a few minutes with further details on our core programs before returning the call back to Michael for you financially. Beginning with the Phase IIa clinical trial of IMR687 sickle cell, we presented interim results in adult patients with sickle cell disease at the virtual EHA Congress in January. In the higher dose cohort, where patients started at 100 mg per day for 3 months and their dose escalated to 200 mg per day for 3 months, IMR 687 monotherapy showed a statistically significant increase in F cells, which are red blood cells containing fetal hemoglobin, as well as a dose-dependent increase in fetal hemoglobin levels. We believe that these data provide important proof of concept for the potential of IMR-687 to be developed as an oral once daily disease-modifying treatment for sickle cell disease.

Vacation from a recent preclinical work in a model that recapitulates the half theft phenotype, we showed that treatment of <unk> 687.

Attenuates cardiac hypertrophy reduces.

Cypress's increases cardiac inflammation in a dose dependent manner.

Lastly, we believe that there could be an important link between our sickle cell studies that examined cardiovascular biomarkers like anti pro BNP and future half past efforts with <unk>.

I would now like to spend a few minutes with further details on our core programs.

Turning the call back.

Financial reports.

Beginning with the phase two a clinical trial <unk> 67, sickle cell disease, we presented interim results an adult patients with sickle cell disease at the virtual <unk> Congress in June.

And the higher dose cohort were patient started at 100 per.

Per day for three months and there were dose escalated to 200 Meg per day for.

Rahul Balal: As I mentioned earlier, we expect to report top line data late in the fourth quarter. Patients completing the phase 2A study can enroll in an open-linked consent trial, and we are pleased with the increased enrollment in this study over the last few months. We currently have 23 enrolled patients, all of which are on the 200 mg dose. If patients were on a stable dose of HU in the Phase 2a trial, they continue that same dose of HU for the open-label extension trial. We plan to analyze data from the OLE patients at approximately six-month intervals and present a data from two patients during our second quarter conference call. Patient 1 was originally randomized to the 100mg-200mg dose group of the monotherapy substudy of the phase 2 clinical trial, and completed one year of treatment on the OLE in June of 2020. Data from this patient at the one-year mark indicated potential benefits of IMR-687 for this patient with respect to reported vaso-occlusive crises or VOCs. Trends in Healthcare Facility Use and Quality of Life Metrics and Design.

Rahul Balal: Patient 2 recently entered the Phase 2a trial as part of the HU Combination sub-study and was randomized to the placebo dose group, therefore never receiving IMR 687 during the Phase 2a clinical trial. However, data from this patient at the six-month mark also indicated potential benefits of IMR 687 for this patient with respect to VOC disease biomarkers. We view data from both of these patients as encouraging with regard to potential longer-term effects of IMR687 administration in these patients. We look forward to updating data from these patients as well as several additional patients on this trial during the first quarter of 2021 and its future period.

And you should too.

Entered the phase III trials part of the H U combination subsidy.

And was randomized placebo dose group, therefore never receiving <unk> during the phase two a clinical trial.

Patients who had completed six months of treatment on the early as of August of 2020 data from this patient at the six month, Mark also indicated potential benefits Weimar succeed Kevin for this patient with respect to Coc's disease Biomarkers.

We view data from both these patients as encouraging with regards to potential longer duration effects of <unk> seven administration and these patients we look forward to updating data from these patients as well as several additional patients on this trial during the first quarter of 2021 and his future periods.

I wouldn't like to turn to our phase <unk> study studies of <unk> 67, including are ardent trials in patients with sickle cell disease.

Rahul Balal: I would now like to turn to our Phase 2B study, studies of IMR-687, including our ARDENT trials in patients with sickle cell disease and our TATE trial in patients with sickle cell disease. We expended substantial effort this year in initiating these trials and are pleased to have begun dosing in patients from both these trials in recent months. In addition, we have continued to increase the number of active clinical sites and expand the global footprint in which these studies will operate. Briefly, the ARDENT Phase 2b trial will enroll 99 patients with sickle cell disease and is a double-blind, randomized trial where patients will be stratified by the use of HU as well as by region. We are utilizing weight-based dosing to maximize exposure across weight-based doses up to 300 and 400 mg. Recall that 200 mg was the top dose in our Phase IIa trial, and the ARDENT Phase IIb trial tests higher doses and extended duration with IMR 687.

Wow.

Yeah.

We expended.

Substantial efforts this year and initiating these trials and are pleased to have begun dosing in patients from both these trials in recent months. In addition, we have continued to increase the number of active clinical sites and expand the global footprint in which the sales will operate.

Rahul Balal: The primary efficacy objective is to evaluate the proportion of patients with a human enrollment response, meaning an increase of HBF of 3% or greater from baseline to week 24 versus placebo. And the trial is powered for statistical significance for this endpoint. Patients will continue on treatment through 52 weeks to provide data for planned secondary and additional endpoints, including the evaluation of IMR-687 versus placebo on VOCs, HBF-associated biomarkers, indices of red cell hemolysis, white blood cell adhesion, quality of life measures, and antiprobian. The 4C trial is a test for immunocompromised blood and placebo protocol used in adult patients with beta thalassemia. The trial will evaluate the safety and tolerability of IMR687 in approximately 60 transfusion-dependent patients and approximately 60 non-transfusion dependent patients. Additionally, for transfusion-dependent patients, we plan to evaluate the effect of IMR-67-versus-glucasebo on the transfusion burden and the change in iron load as a result of transfusion.

Fusion dependent patients at approximately 60, not as fusion dependent patients.

Additionally for transfusion dependent patients we planners.

The Weimar success.

See about upgrading converted and the change in iron load as a result of transfusion during the trial and in comparison recorded rates in the 12 weeks prior to initiation the.

Rahul Balal: During the trial and in comparison with recorded rates in the 12 weeks prior to initiation, the 4K trial will also examine additional exploratory efficacy endpoints, as well as safety and PK endpoints. Like our ARDENT study, we plan to continue utilizing weight-based dosing with potential doses as high as 400 mg. Safety and Tolerability will be assessed after 24 weeks of treatment. As a reminder, we plan to report formal and interim analysis of Forte Phase IIb trials when 33 and 30 patients respectively have completed 24 weeks of treatment.

14 trial also examined additional exploratory efficacy pinpoint as well as safety and PK endpoints.

Like our Arden study, we plan to continue utilizing weight based dosing with potential doses as high as 400 milligram safety and Tolerability will be assessed after 24 weeks of Joseph.

As a reminder, we plan to report formal.

<unk>.

14 days to be trials with 33, and 30 patients respectively have completed 24 weeks of treatment.

Due to COVID-19 enrollment delays we are adjusting are expected report interim data on these trials from our previously estimated timeline of the first half of 2021 to the second half of 2024.

Rahul Balal: Due to COVID-19 enrollment delays, we are adjusting our expected time to report interim data on these trials from our previously estimated timeline of the first half of 2021 to the second half of 2021. I can assure you that our team has worked diligently internally as well as with our CRO and clinical sites to minimize delays as much as possible. For example, we continue to increase the global reach of the ARDENT and FORTECH studies with 16 active clinical centers across multiple countries. For the ARDENT sickle cell disease study, we have seven active clinical centers in three, Hoover, Walt Whitman, and others. In the Forte Beta Thalassemia trial, we have 9 active clinical centers in 5 countries with regulatory approval in 14 of 15 planned countries, with final approval expected later this year.

I can take care of you start to Miss work diligently internally as well as with our sorrow and clinical site to Minimise minimize delays as much as possible. For example, we continue to increase the global reach of the Arden and 40 studies with 16 active clinical centers across multiple countries for.

Rahul Balal: We are continuing to activate multiple clinical centers for each of these studies across multiple countries despite COVID-19. I will touch briefly on our pediatric development program for sickle cell disease. Most of us were able to accelerate our originally planned timeline to initiate this clinical program primarily due to advancements in our oral solution formulation of IMR-6875, which includes promising preclinical stability data and progress in scaling up third-party manufacturing. Oral solutions are generally preferred in younger patients and enable dosing to be more customized based on weight, age, and other parameters.

Mike Gray: We currently anticipate initiating the clinical program in the first half of 2021, approximately six months ahead of our previous expectations. We plan to conduct a single ascending dose trial and expand the program to a multiple dose extension study in adolescents and younger children. In summary, we believe the third quarter marked another productive period for Amara, and we look forward to working with you in the future. Thank you, and I will now turn this call back to Mike to review our third quarter financial response. Okay, thanks, Rahul. Our third quarter results can be found in the press release we issued this morning, which I'll summarize now. More details are also included in the 10-Q that we filed with the SEC earlier this morning.

And I will now turn the call back to my to review, our third quarter financial results.

Okay. Thanks for hole.

Our third quarter results can be found in the press release, we issued this morning, which I will summarize now.

More details are also included within the 10-Q that we filed with the SEC earlier this morning.

R&D expenses were $95 million for the third quarter of 2020 as compared to $5.1 million for the third quarter of 2019.

Mike Gray: R&D expenses were $9.5 million for the third quarter of 2020 as compared to $5.1 million for the third quarter of 2019. The increase of $4.4 million is primarily related to the conduct of our clinical trials and manufacturing of clinical materials related to the development of IMR687, as well as increased personnel related and other R&D operating costs. General and administrative expenses were $3 million for the third quarter of 2020 as compared to $1.7 million for the third quarter of 2019. The increase was primarily due to increased personnel related and other G&A costs as a result of operating as a public company.

The increase of $4.4 million is primarily related to the conduct of our clinical trials and manufacturing a clinical materials related to the development of Weimar 687.

As well as increased personnel related another R&D operating costs.

General and administrative expenses for $3 million for the third quarter of 2020.

As compared to $1.7 million for the third quarter of 2019. The increase was primarily due to increased personnel related and other G&A costs as a result of operating as a public company.

That loss attributed attributable to common stockholders was $12.4 million or 72% per share for the third quarter of 2020 as compared to a net loss of six $6 million or $9.43 per share for the third quarter.

2019.

Operator: The net loss attributable to common stockholders was $12.4 million, or $0.72 per share, for the third quarter of 2020 as compared to a net loss of $6.6 million, or $9.43 per share, for the third quarter of 2019. We ended the third quarter with cash, cash equivalents, and investments of $96.1 million, and we expect that this will be sufficient to fund our plant operations into mid-2020. That concludes our prepared remarks. I would pray if you could open the line for questions. Thank you. If you would like to ask a question, please press star then the number 1 on your telephone keypad. Again, press star then the number 1 on your telephone keypad.

We ended the third quarter with cash cash equivalents in investments of $96 $1 million and we expect that this will be sufficient to fund our plant operations into mid 2022 that concludes our prepared remarks, operator, if you could open the line for questions. Thank you.

[laughter].

Question. Please pass by then and number one on your telephone keypad again, that's five one on your telephone keypad approximately.

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Operator: We'll pause for just a moment to compile the Q&A roster. You have a question from Matthew Harrison with Morgan's family. Hey, good morning, everyone. This is Kostas Son on behalf of Matthew.

Kostas Son: I have a quick question about your phase 2b study. I'm wondering, in case you achieve a 3% or higher rise in fetal hemoglobin, whether you have discussed with regulators what the next steps are towards registration. For example, how much would you need to expand the study at the selected dose, or maybe additional studies that will be needed? Can you please provide some clarification on that? Sure. It's nice to hear from you, Costas. Yes, we at our Type B meeting with the FDA on the interim data, and they actually suggested that we should put in a formal interim analysis, and we certainly believe, depending on the data, that we would go back to them with that interim analysis and have a discussion about a number of the different parameters you talked about, both on the fetal hemoglobin surrogate discussion, which we had started that discussion in January, as well as some of those clinical outcome And so we certainly believe that.

Rahul Balal: [inaudible] Okay, thank you. And maybe one more quick question. Can you disclose how many patients you have dosed so far in the phase 2b study in sickle cell so far or not at this point? Yes, so we're not guiding on that, Costas.

Rahul Balal: I think, you know, we've, I think it's important for us to kind of continue using the ability to increase the global footprint of the study so that in places where COVID-19 has caused shutdowns, we can leverage sites that are in other less intense COVID-19 areas to actually increase enrollment. And so what we've really tried to convey on this call is our multiple clinical center approach to avoid. Great. Your next question is from Joseph Schwartz with SBB. We're in. Great

Joseph Schwartz: Thanks very much and congratulations on all the progress. I was just wondering if you could talk a little bit about the data that we'll be seeing at ASH from the first two patients to come through the Open Label Extension. And will there be any data beyond what you've reported on your second quarter call and what's in the abstract that's available now that we should be looking for? Sure, Joe. It's nice to hear from you.

Data that will be seen at ash on the first two patients to come through the open label extension.

And will there be any data beyond what you've reported on your second quarter call and what's in the abstract.

That's available now.

That we should be looking for.

Sure Joe. Thanks. This here for you.

Rahul Balal: Number one, the ASH abstract has a little bit more color on opioid use and a little bit more color on how patients are feeling anecdotally. We were obviously very careful in some of our commentary on the second quarter conference call on this. The ASH data already has some new bits of data. Number two, certainly, our plan is to, if we have incremental data on these patients, when that abstract is actually presented, pull some of that data into the presentation as well. And that incremental data is still on its way.

Remember, what the ash abstract has a little bit more color on the opioid use.

And a little bit more color on how patients are feeling anecdotally, we were obviously very careful in some of our commentary.

In the second quarter conference call as CFO.

Yes.

Due to fits that number.

Rahul Balal: Okay, great, thanks. And then... Do you think that the current pandemic environment could select for any particular types of patient profiles that could result in ardent enrollment and baseline criteria being meaningfully different than how you've already studied IMR 687 and monotherapy in combination with hydroxyurea? Or, you know, aren't you?

Rahul Balal: sensitive to, you know, the types of patients coming in. I'm just wondering because it seems like there is a baseline effect that you could get increasing efficacy with increasing baseline levels of HBF up until a point and then maybe, you know, diminishing returns after a certain point. I'm just wondering, you know, if you've thought about this phenomenon, whether or not, you know, the environment could select for any different types of patients and whether that matters at all. It's actually a really good question.

Rahul Balal: Thanks for asking it. And the short answer is we thought a priori to COVID-19 about some of the selection bias. So pre-built into the protocol, we have two important components. Number one, patients will be stratified by HU and stratified by region. So no one arm will get patients with too many background HU patients, or no one arm will get too many patients, for sake of discussion, from the U.S. And so I think we've done a good job, a priori, of balancing the trials. So we'll see patients across the spectrum of disease in sickle cell going into the different arms of the study. And so thus far, I'd say there's no selection bias. The only other comment I'd make is that, you know, certainly from the type of centers we pick, we will have enough patients on saccharine HU to look at the combination effects of IMR687 and HU and look at the monotherapy effects of IMR687, which we've done mostly through phase two of our study. So I feel pretty good about the design of the backend analytics to enable us. Hi.

No one arm will get patients with too many background H U patience or no one arm will get too many patients from for sake of discussion from the U S and so I think we've done a good job a prior to that I was thinking files. So we'll see patients.

The spectrum of disease, and sickle cell are going into the different arms of the study and so thus far I'd say, there's still selection bias.

Only other comment I'd make is that certainly we anticipate from the type of centers. We pick we will have enough patience on background H U to look at the combination effects volume or 687, and H U and look at the mono therapy affects Weimar 67, which we've done mostly through.

Joseph Schwartz: Thanks very much. Thanks, Joe. Your next question is from Yagel Melchokewicz with Citi. Good.

Yagel Melchokewicz: Thanks very much and congratulations on all the progress. I just had a question in terms of the interim analysis for ARDENT and for FORTE. Could you just talk in a little bit more detail as to what will be conveyed in that interim analysis? Are we just going to get HPF, or might we get some more additional details on secondary endpoints like vaso-occlusive crises, red cell hemolysis, white cell adhesion, quality of life, biomarkers, and so forth? Could you just provide a little bit more perspective on how much we're going to learn at the interim analysis for both trials? Thanks. The answer is we plan, because they're formal interim analyses, we'll be doing substantial database cleaning, so we'll be providing three buckets of information.

Yagel Melchokewicz: The first one, as you noted, HBF, F-cells, markers of hemolysis. The second one, as you noted already, the selectins and related white cell adhesion markers in the second bucket. The third, which would be important in terms of my initial comments regarding going back to the FDA, are some of the relevant clinical endpoints related to those first two buckets, specifically VOCs. We'll be looking at some of the PROs

Rahul Balal: And we, as you look at those three different buckets, would say that it would be a broad range of different markers and clinical outcome measures related to that interim analysis. And since it's formal and protocol-driven, we will do the appropriate marking and cleaning to make that a data set that we can actually have a discussion, hopefully, with the FDA on. That would be the same case with the Forte trials, just to extend your question. We'd be looking, obviously, carefully at transfusion burden, markers of hemolysis, including hemoglobin, in this case, as well as white cell markers.

Rahul Balal: Okay, thanks. I'm assuming I know the answer to this question, but just to confirm, the reason that the interim analysis is triggered for 33 for the sickle cell study and 30 for the beta cell study. Is that based on the total enrollment being different, or is there another reason? Yeah, I think it's based on enrollment. As you know, in the sickle cell study, there are approximately 99 patients in the study, so we wanted to look at approximately a third of the patients, which we hope will be patients both in the lower dose group as well as potentially in the higher dose group. The same goes for the thalassemia study. That study is 120 patients, but remember, it's a study of two different groups, transfusion-dependent patients numbering about 60, and non-transfusion-dependent patients numbering about 60, so the 30 number would be to look at approximately half of each of those subgroups for the 120 total patients.

For another reason.

Yeah, I think it's pretty fun enrolment as you know in the the sickle cell study. It's approximately 99 patient study. So we wanted to look at approximately a third of the patients which will be.

Both in the lower dose group as well as potentially in the higher dose group. The same goes for the Thalassemia study that study is 120 patients remember it's a study of two different groups transfusion dependent patients Ah numbering about 60, non transfusion dependent patients bring about 60. So the 30 numbers would be to look.

Approximately half of each of those subgroups.

For the 120 total on patients.

Okay, great. Thank you very much.

Rahul Balal: Okay, great. Thank you very much. Thank you all. And at this time, there are no questions. Okay, thank you. Sorry, I was on mute. Okay, if there are no more questions, we can wrap up the call. Thank you. Thank you everyone. This concludes today's conference. You may now disconnect.

Thanks ago.

And at this time or no question.

Okay. Thank you.

Sorry, I was on mute okay. If there's no more questions. We can wrap up the call. Thank you.

Thanks, everyone.

Okay.

Disconnect.

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