IMARA Inc.

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 third quarter and key recent accomplishments. I'll then return following Rahul's discussion to review our third quarter financial results, and we'll then open the call for any questions. Rahul?

Thank you, Mike. Good morning, everyone, and thank you for joining today's call. The third quarter and recent weeks have been productive periods for AMARA, and specifically on IMR687, which we'll also refer to in its generic name, to Vinotrin. We are pleased to have made substantial progress in our ongoing Phase IIb trials, and we expect to report interim data from both our ARTID trial in sickle cell disease and FORTE trial in beta-valcemia this quarter. Furthermore, we have taken concrete steps to expand our development pipeline by continuing to work with tuvinitrine in heart failure with preserved ejection fraction, or HFPS, and announcing a new clinic-ready program in IMR261, an oral nerve 2 activator. Beginning with sickle cell disease, and as we reported earlier this quarter, we have completed patient enrollment in our ongoing ARDENT Phase 2B clinical trial of tuvinitrine. We expect to report data from an interim analysis of this trial in approximately one-third of patients at 24 weeks during this quarter. The interim analysis will have a focus on safety dose and PD biomarkers, specifically HBF and F cells. In addition to this readout, we expect the primary analysis dataset in the first quarter of 2022. The primary analysis will focus on HBF and F cells as well as the effect of tivinitrine on the rate of vaso-occlusive crises, or VOCs, at 24 weeks. The ARDN study has been a global effort, as we have enrolled approximately 115 subjects from across the world, including Europe, U.S., Middle East, and Africa. Our team has worked tirelessly on the conduct of this trial and are pleased to have important data readouts in the coming months. In addition to the ARDN trial readout this quarter, We look forward to reporting updated 12-month safety and VOC data from our Phase IIa Open Label Extension, or OLE, trial of tavinitrine in adults with sickle cell disease at the American Society of Hematology annual meeting to be held December 11th through the 14th of this year. As a refresher, we reported final results from the Phase IIa parent trial, as well as eight-month data from the OLE in June at the European Hematology Hematology Association Annual Congress. The parent study results indicate a well-tolerated safety profile, lower VOC rates, improved patient-reported severity score, and variable biomarker results, including with respect to HPF. Importantly, VOC results for all 93 subjects enrolled in the Phase II trial demonstrated a 40 percent lower mean annualized VOC rate in the pooled-to-vinitrine-treated groups versus the pooled placebo groups. In addition, data from the parent study demonstrated a significant increase in the median time to first VOC, as well as reduced rate of annualized VOC-related hospitalizations in each case when pooled tovinetrine groups were compared to pooled placebo groups. We're also encouraged to see patients in the OLE clinical trial continue to benefit from lower annualized VOC rates. We believe that these continued VOC benefits in the OLE trial further support the findings from the 93-patient Phase 2A study. Lastly, in addition to the positive VOC data in the OLE study, we're also pleased that 36%, or 4 of 11 patients in the OLE trial, had absolute HPF increases of more than 3% at the 8-month time point, while receiving 200 mg of tovinetrine. We believe that higher doses of tivinitrine have the potential to show even more robust HPF increases. Remember that the ARDENT Phase IIb trial is currently dosing at up to 400 milligram daily and is powered to show an HPF response rate of 35% in tivinitrine versus 5% on placebo at 24 weeks. We expect higher doses may further improve on that signal, which is why we're looking forward to reporting the interim data from the ARDENT trial later this quarter. Turning to our Forte Phase 2B clinical trial in beta thalassemia, we also reached full enrollment in the transfusion-dependent or TDT cohort, while also seeing continued enrollment in the non-transfusion-dependent or NTDT cohort. We expect interim data from the TDT cohort this quarter, in which we plan to evaluate safety, transfusion burden, and PD biomarkers in approximately 30 patients at 24 weeks on stage. Furthermore, we plan to conduct additional readouts for the full TDT cohort at 24 weeks in the first quarter of 2022, looking at similar data points at the interim analysis. In addition to this important upcoming clinical data, we plan to present preclinical data in beta thalassemia at the upcoming ASH annual meeting in December, and we are looking forward to providing both of these updates in the coming weeks. We are also selectively expanding our indication footprint to areas where PD9 overexpression is implicated in serious diseases with high unmet needs. To that end, we expanded our internal team and developed a protocol for a phase two proof of concept study in heart failure, the preserved rejection fraction, or HEPPF, with the help of our experienced cardiology clinical advisory board. We also expect to interact with the FDA Division of Cardiology and Nephrology this quarter So collectively, we've made substantial progress in enabling the HF-PEF program with an eye towards the clinic in 2022. Yesterday, we announced an oral presentation at the American Heart Association Scientific Sessions, which is scheduled to take place later this week. Our abstract includes data in three preclinical mouse models of HF-PEF, in which selective inhibition of PD-9 with taminitrine was shown to reduce the median size of cardiomyocytes and lower plasma B-type and atrial natriuretic peptide levels. In addition, markers of renal dysfunction, including blood urea nitrogen and urine albumin to creatinine ratio, were lower in mice treated with tovinutrine compared to vehicle-treated mice in all models. Importantly, tovinutrine did not significantly change heart rate or blood pressure. In summary, alongside independent literature on the potential value of PD9 inhibition of half-death, as well as our own internally generated data, we believe tovinitrine may be a promising treatment option for patients with half-death. To lead clinical development of tovinitrine as a treatment for half-death, I'm also pleased to announce that Amara has appointed Tony Bransford, MD, as Vice President of Clinical Development. A seasoned cardiologist, Toni comes to Amara with 15 years of clinical development expertise within global pharmaceuticals, biotech, and clinical research organizations. Toni comes to Amara from Kaleido, where she led clinical research programs for multiple projects and oversaw translation of discovery programs. Prior to her roles at Amara and Kaleido, Tony accumulated deep experience in the cardiovascular therapeutic area, including at Novartis, where she was a clinical lead for the HF-PATH program, conducting the Paramount and Paragon trials, was also responsible for leading regulatory authority interactions. We're delighted to have Dr. Bansford join our team to lead our HF-PATH development efforts, working closely with our Chief Medical Officer, Ken Addy. In addition to the progress we've made with Suvinitrine, We are excited to announce IMR261 as a new asset in our development pipeline. Briefly, IMR261 is a clinic-ready oral activator of nuclear factor erythroid 2-related factor 2, or Nrf2. In vitro and in vivo studies show that Nrf2 coordinates the expression of antioxidant genes in response to oxidative stress, regulates inflammation, inhibits the NSKB pathway, and reactivates fetal hemoglobin, or HBF. IMR261 was formerly known as CXA10 and was previously evaluated by Complexa Inc. in Phase II clinical trials for focal segmental glomular sclerosis, FSGS, and pulmonary arterial hypertension, PAH. Independent medical literature suggests that Nrf2 activation could be relevant in a number of red blood cell diseases and disorders of hemoglobin, And as a proof of principle, there's substantial preclinical data in sickle cell models with dimethylfumarate, a known Nrf2 activator. Amara ran its own preclinical sickle cell disease models and found IMR261 significantly increased HBF and F cells, improved hemolytic markers, and decreased VOCs. In a preclinical beta thalassemia model, IMR261 increased hemoglobin, and enabled red blood cell maturation. The IMR261 data and submitted abstract was selected for an oral presentation at the upcoming ASH meeting, and Dr. Betty Pace, a leader in sickle cell research with DMF and Nrf2, is an author on this abstract. Since IMR261 is a clinic-ready asset, we've initiated work toward drug product manufacturing as we explore potential clinical development paths. We look forward to providing updates on IMR 261 in 2022. In conclusion, we believe that the third quarter and first part of the fourth quarter have been productive periods for AMARA on our core programs, expanding our indication opportunities, and developing a clinic-ready pipeline. We look forward to updating you on our further progress, including expected data readouts beginning later this quarter and in the first quarter of 2022. Thank you and I'll turn the call back to Mike to review our financial results.

Mike. Thanks Rahul. Our third quarter 2021 results can be found in the press release that we issued this morning, which I'll summarize now. More details are also included in the 10Q that we filed with the SEC earlier this morning. Research and development expenses were $10.4 million for the third quarter of 2021 as compared to $9.5 million for the third quarter of 2020. The increase of $900,000 was primarily related to the development, manufacturing of clinical materials, clinical research and oversight of the company's clinical trials, and investigator fees related to the development of divinitrine, as well as increased personnel related and other R&D operating costs. General administrative expenses were $3.3 million for the third quarter of 2021 as compared to $3 million for the third quarter of 2020. The increase of $300,000 was primarily due to increased personnel-related and other G&A operating costs. Net loss attributable to common stockholders was $13.6 million, or $0.55 per share, for the third quarter of 2021, as compared to a net loss of $12.4 million, or $0.72 per share, for the third quarter of 2020. Cash equivalents and investments were $102.8 million as of September 30th, 2021, as compared to $88.2 million as of December 31st, 2020. We believe this capital provides AMARA with sufficient funds to enable us to fund our plant operations into the first quarter of 2023. And that concludes our prepared remarks. Operator, could you please open the line for questions?