IMARA Inc.

Good day. Thank you for standing by, and welcome to the EMARA Inc. Q2 Earnings Conference Call and Webcast. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today. Mike Gray, thank you. Please go ahead.

Thanks, Kalandra. Good morning, everyone, and welcome to Amara's second quarter 2021 conference call. I'm joined this morning by Amara's president and CEO, Rahul Bilal, and our chief medical officer, Ken Addy. Before we begin, I'd like to remind everyone that various statements that 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 may 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 Blal, who will provide an overview of our second quarter and key recent accomplishments. I'll then return following Rahul's discussion to review our second quarter financial results, and we'll then open the call for questions. Rahul?

Thank you, Mike. Good morning, everyone, and thank you for joining today's call. The second quarter and recent weeks have been a productive period for Amara, and specifically IMR 687. We are pleased to have moved the ball downfield and have made substantial progress in our ongoing Phase IIb trials. First, in sickle cell disease, we have made key progress in our ongoing ARDENT Phase IIb clinical trial. We have seen accelerated study enrollment in the ARDENT trial and, as announced yesterday, we have completed patient enrollment. This is an important accomplishment for Mara. And I want to thank our team for its dedication and commitment to this trial, most of which has been conducted in the backdrop of the COVID-19 pandemic. The ARDEN study has been a global effort as we enrolled subjects from across the world, including the US, Europe, Middle East, and even Africa. As a result, faster enrollment across several countries, we are refining our prior guidance and now expect to report data from the primary analysis from this trial in the first quarter of 2022. As part of that primary analysis, we expect to examine safety, PD biomarkers, including fetal hemoglobin or HBF, NF cells, as well as the effect of IMR687 on vaso-occlusive crises or VOCs in approximately 99 patients at 24 weeks. We also expect to report data from an interim analysis of approximately one-third of patients enrolled in this trial at 24 weeks during the fourth quarter of 2021 with a focus on safety dose and PD biomarkers, including HBF and F cells. We view this interim readout as a check-in ahead of the full study results in Q1 2022. We have worked tirelessly on the conduct of the ARDN trial and are very pleased to have important data readouts in the coming months. We also recently presented final data from the 93-patient Phase IIa Placebo-Control Clinical Trial and its Open Label Extension, or OLE, trial of IMR687 in adults with sickle cell disease at the 2021 European Hematology Association, or EHA, Annual Congress, which was held virtually in June. We held a webcast to review these data in June, and that webcast and EHA presentation are both available within the events and presentations of the investors section of our website. We view the Phase IIa results presented at EHA as an important proof of concept for relevant clinical outcomes with IMR687 treatment. It strengthens our expectations that the Phase IIb study at substantially higher dose levels could achieve its primary endpoint, which is an HPF response rate defined as an absolute HPF increase of at least 3% in 35% of subjects on IMR687 versus 5% on placebo. In addition, we expect to demonstrate clinical outcome improvements in the key secondary endpoint of annualized VOC rate, similar to what was seen in the Phase IIa study. At the end of the day, if we can replicate the lower rates of VOCs seen in the Phase IIa and OLE studies, the Phase IIb will be a success. IMR 687 will have a clear path to Phase III and have a competitive commercial profile if approved. As a refresher, the final results from the Phase IIa trial indicate a well-tolerated safety profile, lower VOC rates, improved patient-reported pain severity scores, and variable biomarker results, including with respect to HBF. VOC results for all 93 subjects enrolled demonstrate a 40% lower mean annualized VOC rate in the pooled IMR687 treated groups versus the pooled placebo groups. In addition, a significant increase in median time to first VOC of 169 days for the IMR687 treated groups versus 87 days for the placebo groups was observed. Regarding the annualized rate of VOC-related hospitalizations, the rate was 0.84 hospitalizations per year in the IMR687 treated groups compared with 1.36 per year in the placebo group. In patients taking background hydroxyurea, the mean annualized VOC rate was substantially lower in patients on IMR687 plus HU versus placebo plus HU. We are also encouraged to see patients in the separate OLE clinical trial continuing to benefit from lower annualized VOC rates. This is based on interim data from 18 patients treated for approximately eight months and is a distinct data set from the Phase IIa study. Patients who were on active treatment in the parent maintained similar low VOC rates on IMR687 in the OLE clinical trial. For patients who were previously in the placebo groups in the parent Phase IIa study, there was a 39% decrease in the mean annualized VOC rate when they switched to IMR687 in the OLE study, with patients serving as their own control. The continued VOC benefits in this trial further support the findings from the 93-patient Phase IIa study. Finally, we believe that the VOC improvement point points to a multimodal mechanism of action of IMR687 in sickle cell disease, which potentially works across several categories, red blood cells, reduced activation and adhesion of white blood cells and other cell types, reduced inflammation, and vasodilation. Importantly, IMR687 was well-tolerated as a monotherapy as well as in combination with HU, in each of the Phase IIa and OLE clinical trials, opening the opportunity for both combination therapy alongside monotherapy use. In addition to positive VOC data, we are also pleased that 36% or four of 11 patients in the OLE clinical trial had absolute HPF increases of more than 3% at the eight-month time point while receiving a 200-milligram dose of IMR687. We believe that higher doses of IMR687 have the potential to show even more robust HBF increases. Remember, ARDIN Phase 2B clinical trial is currently dosing up to 400 milligram daily, and it's powered to show an HBF response rate of 35% on IMR687 versus 5% on placebo at 24 weeks. So, with 200 milligram in the OLE, and a 36 percent HPF response rate. We are already in the right ballpark and expect higher doses to further improve on that signal. Turning to our FORTE Phase 2B clinical trial in beta-thalassemia, we've also seen accelerated enrollment in this trial, having reached full enrollment in the transfusion-dependent, or TDT, cohort while also seeing increased enrollment in the non-transfusion dependent or NTDT cohort where we have enrolled approximately half of the study patients. We expect to report interim data from the TDT cohort in the fourth quarter of 2021 in which we plan to evaluate safety, transfusion burden, and PD biomarkers in approximately 30 patients at 24 weeks on the study. Furthermore, faster enrollment rates now allow an additional readout of the full TDT cohort at 24 weeks in the first quarter of 2022, looking at similar data points as the interim analysis. We are also selectively expanding our indication footprint to areas where PD-9 overexpression is implicated in serious disease with high unmet medical needs. To that end, We're developing a protocol for a phase two proof of concept study in heart failure with preserved ejection fraction, or HFPEF, with help from our experienced cardiology clinical advisory board. And we expect to interact with the FDA cardiorenal division in late 2021. We've submitted our recent preclinical work in HFPEF to our cardiology-focused medical meeting and hope to present these data later this year. We've been interested in HFPEF as an indication for some time now and think that PD-9 is an enriched and attractive target that may help treat this debilitating disease. Hence, we are excited to begin working on this indication in a meaningful way in the coming months with an eye toward the clinic. During the second quarter, we also announced the grant recipients for our second annual Real Impact Community Support Initiative. This program, which includes grant funding to support nonprofit, community-based organizations serving patients and families impacted by sickle cell disease and beta thalassemia, awarded 30 grants to CBOs in 16 states, totaling $150,000. The grant funding was increased by $25,000 from 2020, the program's inaugural year. We are proud of the positive effects the Real Impact program has had on the health and lives of patients. their families, and their local communities to date. Expanding the program for its second year reflects our continued commitment to foster innovative ideas and let local community organizations further accomplish their goals of supporting people affected by sickle cell disease and beta thalassemia. We also mark key highlights on the corporate front, including the appointment of Laura Williams, MD, MPH to our Board of Directors. Laura brings 25 years of early to late stage drug development experience across multiple therapeutic areas. And in addition to her significant experience leading clinical trials and guiding products through commercializations, she is a strong advocate for the community, making her an outstanding addition to our board. Also in July, we closed a $50 million public financing, which provides Amara the important capital to continue to fund IMR 687, and extends our capital runway through the end of 2022. Lastly, in June, United States Adopted Names Council, or USAN, formally adopted Tovinitrine as a generic name for IMR 687. You may see IMR 687 referred to as Tovinitrine in our future communications. In conclusion, we believe that the second quarter and first part of the three productive periods for AMARA both in terms of presenting encouraging VOC data and making significant progress in our ongoing Phase 2B clinical trials. We look forward to updating you on further progress, including on multiple data readouts planned in the beginning in the fourth quarter of 2021 and the first quarter of 2022. Thank you, and I will now turn the call back to Mike to review financial results.