IMARA Inc.

Q1 earnings conference call and webcast. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone keypad. If you require any further assistance, please press star then 0. I would now like to hand the conference over to your speaker today, Mike Gray. Thank you and please go ahead, sir.

Okay, thank you. And good morning, everyone, and welcome to Amara's first quarter 2021 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 that we filed with the SEC this morning, as well as any other filings that we make with the SEC. 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 change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. With that, I'll now turn the call over to Amara's President and CEO, Rahul Bilal. I'll return following Rahul's discussion to review our first quarter financial results, and we'll then open the call for questions. Rahul?

Thanks, Mike. Good morning, everyone, and thank you for joining this morning's call. The start of 2021 has been a productive period for Amara and marks the beginning of a data-rich year for both our sickle cell and beta thalassemia clinical programs. We have made substantial enrollment progress in our Phase IIb clinical trials for patients with sickle cell disease and beta thalassemia, which are designed to test higher doses of IMR 687. We are now conducting these studies at 75 clinical trial sites across 20 countries and have fully enrolled the transfusion-dependent beta thalassemia arm of the FORTE trial. closing new screening activities for that subgroup. We remain on track to complete the protocol-driven interim analyses from the ARDIN and FORTE trials and expect to report interim data in the second half of 2021 for both these programs. We also expect to report data from the primary analyses for both these studies in the first half of 2022 and data from the final analysis in the second half of 2022. This progress is a testament to the entire company across every function, and I'm appreciative and excited by this momentum. Importantly, following the recommendation of independent data monitoring committees, we have opened the higher-dose treatment arms in both Phase IIb clinical trials and are currently testing IMR687 at daily doses of up to 400 mg. With the high dose open in both trials, three out of every four patients are being randomized to an active treatment arm, with the high-dose being enriched in a two-high-dose, one-low-dose, one-placebo schema, which is a two-to-one-to-one randomization. Both interim readouts in the second half of 2021 will have patients from the high-dose arm. In addition to our progress in the Phase 2B clinical trials, we reported top-line data from our Phase 2A clinical trial of IMR687 in sickle cell disease. in which IMR687 was well-tolerated and in which we saw promising reductions in the rate of vaso-occlusive crises, or VOCs, with variable changes in HBF and F-cells. We also reported preliminary data from our Phase IIa open-label extension trial, which showed that IMR687 at doses of 200 mg was well-tolerated and in which increases in fetal hemoglobin and F-cells were observed. We plan to present comprehensive VOC data from the larger 93-patient phase 2A parent study, as well as additional data from the ongoing open-label extension trial at the European Hematology Association, or IHA, 2021 virtual congress in June. We've also been working to explore the therapeutic potential of IMR687 in additional indications. We're pleased to have successfully completed preclinical studies of IMR687 in heart failure with preserved ejection fraction, or HFPAF, and have submitted an abstract to an upcoming cardiovascular meeting later in 2021. We continue to formulate a protocol for a proof-of-concept study with our clinical advisory board, which is made up of leading cardiologists. Lastly, in March, we launched the second annual Real Impact Grants Program, to support local community-based organizations serving patients and families affected by rare blood disorders. 2020 marked an incredibly difficult time for those living with sickle cell disease and beta thalassemia, and many of these challenges remain as we move through 2021. We expect to increase grant funding under the Real Impact program from 125,000 in 2020 to up to 150,000 in 2021 across three key areas. including social determinants of health, including COVID-19 relief, virtual support program, and community-based organization, or CBO, capacity. We continue to strive to put our patients first, and the Real Impact Grant Program is a key embodiment of our core mission. We expect awards to be made in June, and we look forward to supporting the 2021 recipients in their ongoing commitment to the patient community. I would now like to spend a few minutes with further details on our core programs before turning the call back to Mike to review financial results. I'll begin with an overview of recent progress from our Phase IIb clinical trials of IMR687, including the ARDENT trial in adult patients with sickle cell disease and the FORTE trial in adult patients with beta thalassemia. We continue to expand the global footprint for our ARDENT and FORTE studies. with 35 and 40 active clinical centers, respectively, and across 20 countries with additional near-term activation of centers. This clinical operations effort has resulted in accelerated enrollment in both the ARDIT and FORTE trials, and we now have fully enrolled the transfusion-dependent beta-thalassemia arm of the FORTE trial, having randomized over 60 patients in this arm. As mentioned earlier, we remain on track to complete the respective protocol-driven interim analyses for these Phase IIb trials in the second half of 2021, and I'm pleased to reaffirm this guidance from earlier this year. With increasing enrollment, we now expect data from the primary analysis from each of these trials in the first half of 2022 and data from the final analysis from each of these trials in the second half of 2022. This is a significant accomplishment. and demonstrates our team's ability to effectively conduct these studies in the backdrop of a global pandemic. And I'd like to take this opportunity to thank them for their tireless commitment to these studies. During the first quarter, separate independent data monitoring committees for the ARDEN and FORTE trials recommended opening of the higher-dose IMR687 treatment arm in each of these studies following review of available safety and tolerability data. These additional arms were pre-specified in the two protocols, and enrollment is proceeding in each study at the IMR687 higher dose, which is once daily dosing of 300 mg or 400 mg based on patient weight, IMR687 lower dose, which is once daily dose of 200 mg or 300 mg based on patient weight, or placebo. As a reference point, Our recently completed Phase 2A clinical trial in sickle cell disease started as low as 50 mg per day and escalated sequentially to 100 mg or 200 mg per day over 16 to 24 weeks. Dosing in the Phase 2B clinical trials is substantially higher, both at the starting dose and through the treatment period, starting as high as 400 mg on day one and without a dose titration. As a reminder... The ARDENT Phase IIb trial will enroll approximately 99 adult patients with sickle cell disease and is a double-blind, randomized trial where patients will be stratified by use of hydroxyurea as well as by region. The planned primary efficacy objective is to evaluate the proportion of patients with fetal hemoglobin response defined as an increase of HPF 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 key secondary endpoint evaluating IMR687 versus placebo on annualized VOCs. Other secondary endpoints include time till first VOC, HBF-associated biomarkers, indices of red cell hemolysis, white blood cell adhesion, and quality of life measures. The fourth day trial will evaluate safety and tolerability of IMR687 in approximately 60 transfusion-dependent patients and approximately 60 non-transfusion-dependent patients. For transfusion-dependent patients, we plan to evaluate the effects of IMR687 versus placebo on transfusion burden, pre-transfusion hemoglobin, and the change in iron load as a result of transfusion during the trial and in comparison to historical rates in the 12 weeks prior to study start. The Forte trial will also examine additional exploratory endpoints as well as safety and PK endpoints. Safety and tolerability of IMR687 will be assessed after 24 weeks of dosing. I'll next turn very briefly to our Phase IIa clinical trial. We disclosed top-line results in January, in which IMR687 was well-tolerated and in which promising reductions in the rates of vaso-occlusive crises and variable changes in certain biomarkers, including HPF and F cells, were observed. We look forward to presenting comprehensive VOC data from this completed 93-patient placebo-controlled Phase IIa clinical trial at EHA next month, as VOCs remain an important clinical outcome for this program. I'll now turn to our Phase IIa open-label extension trial, or OLE trial, for which we reported new data in March. We believe this new data helped reestablish HBF and EFSA activity from treatment with 200 mg of IMR687 after seeing variable results from these biomarkers in the Phase IIa trial. As a reminder, the four-year OLE trial allows patients from the Phase IIa program to enroll in a long-term safety, and tolerability study of IMR 687 following completion of the Phase II-A trial. The OLE trial was initially designed so patients were administered a daily dose of 100 mg of IMR 687, and in the second quarter of 2020, a protocol amendment increased the daily dose to 200 mg. A preliminary review of 24 patients enrolled in the OLE program as of December 31, 2020, demonstrate that IMR687 was well tolerated and had a safety profile similar to that observed in the Phase 2A clinical trial. Approximately 12 of these patients had evaluable PD biomarker data for at least four months of treatment on the OLE trial. Biomarker results demonstrated absolute increases in both HBF and F cells after four months of treatment. In addition to this four-month data, In March, we also provided an update on two case narratives that we most recently reported at the American Society of Hematology Annual Meeting, December 2020. Both patients continued to see increased HPF from baseline of greater or equal to 4.5% and increases from baseline in F cell measurements. Falling in line with our higher dose arm in the Phase IIb studies, A separate safety review committee has approved dose escalation in the OLE trial to a minimum daily dose of 300 mg, with certain patients being eligible for a daily dose of 400 mg based upon their weight. This same weight gate-driven approach is employed in both of our Phase IIb programs and is an efficient way to maximize exposure and maintain safety. We have submitted a revised protocol to the FDA and MHRA and expect to start transitioning patients to higher doses of IMR-687 in mid-2021 on the OLE study. We also expect to present additional data from the OLE, including eight-month PD biomarker and VOC data at the upcoming EHA Congress. In conclusion, we believe that the first quarter marked another productive period for AMARA in both enrollment gains and the important transition to administering higher doses of IMR 687. We look forward to updating on our further progress, including multiple data readouts planned in 2021. Thank you, and I will now turn the call back to Mike to review our financial results.