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spk04: enrollment response, and it's 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 IMR687 versus placebo on VOCs, HPF-associated biomarkers, indices of red cell hemolysis. white blood cell adhesion, quality of life measures, and NT-PRO-BNP. The 4-T trial is designed to analyze the line of placebo-cold patients with beta-alcemia. The trial will evaluate the safety and tolerability of IMR-687 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 IMR67 versus placebo on transition burden 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 FORTE 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 dosing. As a reminder, we plan to report formal interim analysis for phase 2B trials when 33 and 30 patients respectively have completed 24 weeks of treatment. 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 site to minimize delays as much as possible. For example, we continue to increase the global reach of the ARDENT and FORTESH studies with 16 active clinical centers across multiple countries. For the ardent sickle cell disease study, we have seven active clinical centers in three countries and have received approval . In the Forte beta thalassemia trial, we have nine active clinical centers in five countries, with regulatory approval in 14 of 15 planned countries, with final approval expected later this month. 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 in sickle cell disease next. Most to accelerate our originally planned timeline to initiate this clinical program, primarily due to advancements in our oral solution formulation of IMR687, 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. 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 seeing progress. Thank you, and I will now turn the call back to Mike to review our third quarter financial results.
spk00: 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 within the 10Q that we filed with the SEC earlier this morning. 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 was primarily related to the conduct of our clinical trials and manufacturing of clinical materials related to the development of IMR 687, as well as increased personnel related and other R&D operating costs. General 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. Net loss attributable to common stockholders was $12.4 million or 72 cents 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 planned operations into mid-2022. That concludes our prepared remarks. Operator, if you could open the line for questions. Thank you.
spk02: If you would like to ask a question, please press star, then a number 1 on your telephone keypad. Again, press star, then a number 1 on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. You have a question from Matthew Harrison with Morgan Stanley.
spk06: Hey, good morning, everyone. This is for Matthew. I have a quick question on your Phase 2b study. I'm wondering, in case you achieve the 3% or higher in fetal hemoglobin, whether you have discussed with regulators what are the next steps towards registration For example, how much would you need to expand the study in the selected dose or maybe additional studies that will be needed? Can you please provide some clarity on that? Thank you.
spk04: Sure. 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 did. 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 measures that we've discussed, including VOCs, ACS, patient-reported outcomes, and others. And so we certainly believe that a catalyst and certainly important data set for us to go back to the agency and have a discussion with them on it.
spk06: Okay, thank you. And maybe one more quick question. Can you disclose how many patients you have those so far in the phase 2b study in sickle cell or not at this point?
spk04: Yeah, so we're not guiding on that, Kostas. I think, you know, we've dose several, and 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 multiple clinical center approach to avoid slowdowns. Okay.
spk06: Great. Thank you.
spk01: Our next question is from Joseph Schwartz with SBB.
spk05: Great. Thanks very much, and congrats 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 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?
spk04: Sure. Joe, it's nice to hear from you. 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. 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 to some of that data into the presentation as well. And that incremental data is still on its way.
spk05: 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, are you not that 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 know, you could get increasing efficacy with increasing baseline of levels of HBF up until a point and then And then maybe, you know, diminishing returns after a certain point. I'm just wondering, you know, if you've thought about this phenomenon, you know, whether or not, you know, the environment could select for any different types of patients and whether that matters at all.
spk04: It's actually a really good question. 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 from, for sake of discussion, from the U.S. And so I think we've done a good job, a priori, of balancing trials. So we'll see patients across a 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 we anticipate from the type of centers we pick, we will have enough patients on background 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 the phase two of the study. So we feel pretty good about the design of the backend analytics to enable us to see .
spk05: Thanks very much.
spk04: Thanks, Joe.
spk01: Your next question is from Yagal Melchoklis with Citi.
spk03: Great. Thanks very much. And congrats 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 HBF or might we get some more additional details on secondary endpoints like vaso-occlusive crises, the red cell hemolysis, white cell adhesion, quality of life, biomarkers, and so forth? Just 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.
spk04: 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. 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. And the third one that would be important in terms of my initial comments regarding going back to the FDA is some of the relevant clinical endpoints related to those first two buckets, specifically VOCs. We'll be looking at some of the PROs. And so 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 analysis. And since it's formal and protocol-driven, we will do the appropriate QCing and cleaning to make that a data set that we can actually have a discussion, hopefully with the FDA on it. 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 the white cell markers.
spk03: Okay, thanks. And 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 is Is that just based on the total enrollment being different, or is there another reason?
spk04: Yeah, I think it's based on enrollment. As you know, in the sickle cell study, it's approximately 99 patient studies. 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. Remember, it's a study of two different groups, transfusion-dependent patients numbering about 60, 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.
spk03: Okay, great. Thank you very much.
spk04: Thanks, Hugo.
spk01: And at this time, there are no questions.
spk04: Okay, thank you.
spk00: Sorry, I was on mute. Okay, if there are no more questions, we can wrap up the call. Thank you.
spk04: Thanks, everyone.
spk01: This concludes today's conference. You may now disconnect.
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