IMARA Inc.
Q1 2021 Earnings Call Transcript

Published: 11 May 2021

[Operator:]

Ladies and gentlemen, thank you for standing by, and welcome to the 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. I would now like to hand the conference over to your speaker today, Mike Gray. Thank you, and please go ahead, sir.

[Michael Gray:]

Okay. Thank you, and good morning, everyone, and welcome to Imara'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.

[Rahul Ballal:]

Thanks, Mike. Good morning, everyone, and thank you for joining this morning's call. The start of 2021 has been a productive period for Imara. It marks 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 a 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 analysis for the Ardent 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 analysis 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 very 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 IMR-687 at daily doses of up to 400 milligram. 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, and a two high dose, one low dose, one placebo schema, which is a two-to-one-to-one randomization. Both interim readout in the second half of 2021 will have patients from the high dose arm. In addition to our progress in the Phase IIb clinical trials, we reported top-line data from our Phase IIa clinical trial of IMR-687 in sickle cell disease, in which IMR-687 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 IMR-687 at doses of 200-milligram was well tolerated and in which increases in fetal hemoglobin and F-cells we're observed. We plan to present comprehensive VOC data from the larger 93 patient Phase IIa parent study, as well as additional data from the ongoing open label extension trial at the European Hematology Association or EHA 2021 Virtual Congress in June.

[Michael Gray:]

Thank you, Rahul. Our first 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 10-Q that we filed with the SEC also earlier this morning. R&D expenses were $7.1 million for the first quarter of 2021 as compared to $5.8 million for the first quarter of 2020.

[Operator:]

Your first question comes from the line of Yigal Nochomovitz with Citigroup.

[Yigal Nochomovitz:]

Hi, Rahul and Mike. Thanks very much for taking the questions. I had a few on the interim analysis for Ardent and Forte. At first, Rahul I thought, I heard you say that the interim analysis will include patients that have enrolled on the higher dose arms, so, could you confirm that. Second, what aspect of the protocol triggers the timing of the interim analysis for Ardent and Fote? And finally, what in your view would constitute a positive outcome for the interim analysis for both of these trials? Thanks.

[Rahul Ballal:]

Thanks, Yigal. I appreciate the questions. Number one. Yes, I can confirm for both interim analysis for the Ardent and Forte trial that they will include higher doses and the higher dose arm of IMR-687. Number two; the pre-specified protocol driven analysis for those trials to report out are the following

[Yigal Nochomovitz:]

Okay, great. That's super helpful. I actually had a question on the additional indications for IMR-687. Could you just summarize quickly the conclusions from the preclinical heart failure studies and what specifically about the mechanism for 687 suggests an opportunity in HFpEF, but not in HFrEF or is HFrEF just a potential avenue that you would consider down the road, when you have more information?

[Rahul Ballal:]

Yes. Sure. So, we run three preclinical studies in the heart failure with preserved EF phenotype. Two of them are preventative as they require -- they have an insult of an agent that creates the HFpEF phenotype through an angiotensin II and aldosterone II treated mouse model. Those two are preventative models. So, you treat the patient -- the mouse with a caustic agent and ultimately on top at IMR-687 and IMR-687 has been protective of those specifically in three areas. The first one in hypertrophy, the second one in fibrosis, and the third one in inflammation. So, works in a multimodal approach in a preventative model. Then we took it one step further into a therapeutic model we treated a DB mice that had generated the phenotype after 20 weeks of eating and getting bigger and those mice have phenotype for HFpEF, then you treat those mice who have the phenotype in a treatment approach for eight weeks of IMR-687 and we saw the similar reductions in hyper -- cardiac hypertrophy, reductions in inflammation and reduction in fibrosis. Across all three models, the key takeaway finding as we see a reduction in anti-pro BNP as a biomarker of cardiac stress and as you asked a question about mechanistically why that could be relevant PDE9 uniquely works in the in neprolysin cyclic GMP pathway and so it is a uniquely configured for HFpEF versus HFrEF and specifically we found preclinically that PDE9 is over-expressed in a number of models in HFpEF and our three model showed an increase in PDE9 expression when that phenotype developed and we were able to reduce that PDE9 expression with our PDE9 inhibitor. So, there is a mechanistic, direct mechanistic relevance of PDE9 overexpression in that HFpEF model. And so that's why we believe it's uniquely positioned for this indication versus HFrEF. And we will be -- as I said on the call will be that whole package in the fall of 2021 at a cardiovascular meeting.

[Yigal Nochomovitz:]

Got it. Thank you, Rahul.

[Operator:]

Your next question comes from the line of Matthew Harrison with Morgan Stanley.

[Unidentified Analyst:]

Hi, good morning to everyone. This is on for Matthew. A question from us on sickle cell disease. You have commented that your preclinical work suggested that the driver of the 687 efficacy is that time that the PK remains above IC90. We are wondering whether you have validated these in the Phase IIa data and how your expectations would change in case other PK parameters, such as the Cmax or AUC turn out to be the efficacy drivers? Thank you.

[Rahul Ballal:]

Thank you. So couple of answers to that question, and I appreciate you asking it, we will be presenting some additional data that we had that look at exposure response and help start determining that concept around time above the IC90 or trough levels in addition to looking at Cmax and AUC. So, that data is in front of us and certainly we'll be presenting part of that at EHA. Number two, the advantage of going up on dose of up to 400-milligram is you check the box across a number of these different PK parameters. Number one, you increase AUC exposure by going up to 400-milligram. You certainly increase Cmax and you increased trough levels past the, the IC90 for 24 hours. And so part of the reason that we like going up on dose and this is not just for the Phase IIb program, but for the open label extension is we get to see the advantages of those PK parameters play out across the exposure response curve. And so as you think about the Phase IIb data coming in the interim analysis we'll be doing additional work on the PK side of things, specifically for beta thalassemia to help us understand and continue to realize the potential of higher dose treatment, including AUC, C24 as you noted in Cmax.

[Unidentified Analyst:]

Thank you. Very useful. Looking forward to the data.

[Rahul Ballal:]

Thank you.

[Operator:]

Your next question comes from the line of Joseph Schwartz with SVP Leerink.

[Joseph Schwartz:]

Hi, thanks very much. I have a -- my first question is similar to Yigal's first question on when he asked about the interim analysis and what that entails. I was hoping you could do the same and walk us through what the primary analysis will entail? Is that a new look I only recall interim and final analysis before? But maybe I missed something. And so in addition to what primary entails, will you be able to make any course corrections based on what you're seeing in each of these analysis? And is the regulatory agencies okay with you unblinding and each of these looks and keeping the trial intact?

[Rahul Ballal:]

Yes. It's a good question. Let me walk you through. So, we've always had a primary -- an interim a primary in the final Joe and that's in part due to the fact that the studies are quite long as you know. Let me walk you through both studies both sickle and beta-thalassemia to give you at least a snapshot of what we expect to see in report out. The interim analysis as we've guided to in the second half of this year, we'll look at 33 patients at 24 weeks and I really look at that as a, as a check the box on exposure safety, tolerability, and initial understanding of PD biomarker. The primary analysis, which is the statistically powered time point, which is 99 patients at 24 weeks will be a rigorous and statistically powered analysis of HbF at in 99 patients and looking for that response of 3% or greater. It will also step down in a hierarchical fashion to look at annualized VOCs at their primary analysis as well as looking at time till first VOC and then a litany of other secondary and exploratory biomarkers that will be done in an hierarchical fashion to maintain power and preserve alpha. And as you know, the study is a 52-week treatment paradigm. So, patients will be read out at week 24, but those 99 patients are the ones that continue. We'll go through a treatment link. And so that 52-week period will be part of the final analysis and of course we'll look at annualized VOC. The primary analysis as we've guided will be in the first half of 2022. That final analysis which look at the 52-week time point specifically focused on VOCs will be in the second half of 2022. The beta-thalassemia program is slightly different. It's shorter in length. It's a nine-month treatment paradigm and a six-month primary. And so for the interim analysis will be again looking at a subset of patients, 30 patients at 24 weeks in the second half of this year. In the first half of 2022 we'll be looking at 60 patients in the TDT arm and a subset of those in the NTDT arm at 24 weeks. And in the second half of 2022, we will be looking at that nine months or 36-week time point in beta-thalassemia. So, just taking a step back, that will be the 420 patients in both the NTD and TD subgroup in those final analysis. And so the difference overall between primary and final in beta-thalassemia is 24 weeks versus 36 weeks, the difference in sickle between primary and final is 24 weeks versus 52 weeks, and I've already delineated the timeframe for that. Does that help?

[Joseph Schwartz:]

That makes a lot of sense. Absolutely. Thank you. That's helpful again. And then in your queue highlights that you're planning to perform a stat MAD study looking at what appears to be up to twice the doses that are being studied currently. Can you talk about that decision, is that based on anything that you've seen so far from a response exposure analysis?

[Rahul Ballal:]

Yes. Sure. So, when we opened up the higher dose arms for the Phase IIb studies for both beta-thalassemia in January and sickle cell in March, we open those dose arms and wanted to see how higher doses we're doing and if they're well-tolerated. Those doses are proceeding. We believe obviously we're blinded. We believe that the safety signals from those higher doses points to tolerability. And so part of the rationale to start a SAD MD study is continue to explore higher doses beyond 400-milligrams as you noted and so certainly we believe that this SAD MD study will allow us to potentially expand the dose range for IMR-687 and we just wanted to have that optionality as we had and are going through the Phase IIb programs. Will we implement higher doses of IMR-687 potentially? That is data dependent upon that SAD MD study but we wanted to make sure that we had an opportunity to do that, which is why we started the study now versus later.

[Joseph Schwartz:]

Very helpful. Thanks again for taking my question.

[Rahul Ballal:]

Thanks, Joe.

[Operator:]

And there are no further questions at this time, I would now like to turn the call back over to the speakers for any closing remarks.

[Rahul Ballal:]

Thank you, everyone. We'll appreciate you joining us this morning. We look forward to future updates as a data-rich year and we're excited to have enrollment to have that data later this year, and see you at EHA. Thank you.

[Operator:]

This concludes today's conference call. You may now disconnect.