Enliven Therapeutics, Inc.
Q4 2020 Earnings Call Transcript

Published: 5 Mar 2021

[Operator:]

Ladies and gentlemen, thank you for standing by, and welcome to the IMARA Inc. Fourth Quarter Earnings Conference Call and Webcast. . I would now like to hand the conference over to your speaker today, Mr. Mike Gray. Thank you. Please go ahead, sir.

[Michael Gray:]

Okay. Thank you. Good morning, everyone, and welcome to IMARA's Fourth Quarter 2020 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 annual report on Form 10-K that will be filed with the SEC this morning as well as any other filings that we make with the SEC.

[Rahul Ballal:]

Thank you, Mike. Good morning, everyone, and thank you for joining. 2020 was a productive year for IMARA, and we made progress in building our business and accomplishing several of our key objectives. This momentum is carried into the early part of 2021 and we are looking forward to a robust year of data readouts in both our sickle cell and beta-thalassemia programs. The start of 2020 is highlighted by our initial public offering in March, in which we raised gross proceeds of $86.5 million. Throughout the course of 2020 and into the early months of 2021, we've continued to build the organization, including expanding our leadership and broader development teams with key hires during the last several months, including Lyn Hopkinson as our SVP of Regulatory; and Ken Attie as our Chief Medical Officer. Lyn joined us from Vertex Pharmaceuticals where she served as Global Head of Regulatory Strategy for the Cystic Fibrosis Program as well as Head of North American Regulatory Strategy for several clinical development candidates, including the CRISPR/CAS9 program with sickle cell disease and beta-thalassemia. Ken joined IMARA in January and brings more than 30 years of experience within academia and biotech, most recently at Acceleron Pharma, where he led Global Clinical Development efforts that led to recent FDA and EMA approvals of luspatercept, known as REBLOZYL, which is a new treatment for patients with rare anemias, including beta thalassemia. We've also expanded the company's headcount, particularly in key development areas, such as clinical, regulatory, quality and technical operations. Collectively, this organizational growth has enabled our continued advancement of IMR-687, including initiation of our Ardent Phase IIb clinical trial in sickle cell disease, and our Forte Phase IIb clinical trial in beta thalassemia. The Forte trial reached an important milestone earlier in 2021. Data Monitoring Committee approved opening the higher dose arm. Patients will receive doses of IMR-687 up to 400 milligrams. We anticipate that the Drug Monitoring Committee will meet later in March to evaluate opening the higher dose arm in the Ardent sickle cell trial. Both the Ardent and Forte Phase IIb studies, we continue to expect reporting interim data in the second half of 2021.

[Michael Gray:]

Okay. Thanks, Rahul. Our fourth quarter and year-end 2020 results can be found in the press release that we issued this morning, and I'll summarize those now. More details are also included in the 10-K that we filed with the SEC also earlier this morning. R&D expenses were $32.2 million for 2020 as compared to $19 million for 2019. The increase was primarily related to the development and manufacturing of clinical materials, clinical research and oversight of our clinical trials and investigator fees related to the development of IMR-687 as well as increased personnel-related and other R&D operating costs. G&A expenses were $9.5 million for 2020 as compared to $5.1 million for 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 attributed to common stockholders was $49.2 million or $3.53 per share for 2020 as compared to a net loss of $23.5 million or $33.40 per share for 2019. We ended 2020 with cash, cash equivalents and investments of $88.2 million, and we expect that this will be sufficient to fund our planned operations into mid-2022. That concludes our prepared remarks. We'd like to open the line for questions. Operator?

[Operator:]

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

[Matthew Harrison:]

I guess, two for me. First one, as you think about the two patients where you gave sort of the patient histories and all the information, how would you think about those as being typical or atypical patients we might see in the Phase IIb? And I guess what I'm really asking is, do you think the doses that they were receiving because of the weight-based dosing and other factors represent something that you're going to see in Phase IIb? Or do you think people could get even higher doses on average than them? And then secondly, could you maybe just talk about how pace of enrollment and other factors are going on in Phase IIb?

[Rahul Ballal:]

Thanks, Matt, for asking the question. So in terms of the 2 patients, if you look at their overall weights and where they would be, if you were to put them in the Phase IIb, both of them would be at the higher doses. Of course, depending on where they're randomized to, they would ultimately be in doses that would be in the 300-milligram range. So from a mg per kg exposure, I would expect those patients very equivalent to go up in dose on the Phase IIb. In addition, again, these patients are on trial so these are monitored much more carefully in the Phase IIb to get data from them every month. So there's kind of additional data points on these patients that you get, obviously, in Phase IIb of higher dose. To answer your second question, the approach that we took for the Phase IIb studies, both in Ardent and Forte have paid off for us. And what I mean by that is we have decided that it was important to go broad in terms of the number of countries, so approximately 14 to 15 countries in each of those studies and wide in terms of the number of sites. Approximately 50 sites ultimately will be activated for those two studies, respectively. And what we've seen is in areas where COVID is not as prevalent as example, Israel, for example, we've seen increased enrollment in those areas. And in areas where COVID is prevalent, case in point of Italy, we've continued to see delays. And so I would say what's nice about our approach is that we are leaning on the countries that have patients coming in. We've organized around those patients to ensure that they have access to the centers, access to local labs, access to home health care if needed and also ensure that as those sites that are COVID contingent, as they open up, we're one of the first groups in there. As an example, the U.K. should be opening up for both sickle cell and beta thalassemia in the coming month, and we have all of our in order from approvals to site contracts, and we're ready to go.

[Operator:]

Your next question comes from the line of Yigal Nochomovitz from Citi.

[Unidentified Analyst:]

This is Carly on for Yigal. In the data you presented from the OLE, are you able to comment on how many of the 12 patients were receiving background hydroxyurea? And understanding it's small numbers, but were there any trends you observed with respect to the increases in HbF and F-cells in patients on 687 alone versus on top of background HU?

[Rahul Ballal:]

Thank you for the question. So we have 24 patients enrolled, 22 ongoing. The breakdown between HU and non-HU is 17 and 7. 7 on HU. And we have not done the analysis to see if patients on the HU background are benefiting more, but we do plan to keep monitoring this part in our medical meeting in the future including covering some of the patient journey experiences from Phase IIa study into the OLE and specifically looking at that comparison, whether or not they're on HU, to your question, but also what dose of IMR-687 they were on.

[Unidentified Analyst:]

Okay. Great. And assuming you get the green light to dose escalate up to 300 or 400 milligrams in the OLE, just wondering when we might expect to see updated data that would include those higher doses, specifically trying to figure out if that would be potentially before the interim data from the Phase IIb or would it likely be after that?

[Rahul Ballal:]

That's a good question. So if we get that approval, obviously, contingent on the DMC from the Phase IIb, we'll immediately amend the protocol. 80% of our patients are in the U.K. and if you just follow the timelines from protocol and then into implementation, you're probably starting to look at data at the end of this year around those OLE patients at a higher dose. So our planned interim analysis for the Ardent Phase IIb studies also in the second half of this year, and so we see data around the same time, both the OLE patients as well as the Ardent Phase II patients.

[Unidentified Analyst:]

Okay. Perfect. And last question from us is, just in Phase IIa, I know you've faced some challenges due to COVID with missed visits specifically in the placebo arm. So wondering if you could talk a little bit about how you've accounted for potential COVID impact in your powering assumptions for the Phase IIbs or just anything you're seeing with respect to missed visits?

[Rahul Ballal:]

Yes. It's a great question. So we've taken a different approach for the Phase IIb that allows us to avoid those issues that we encountered in Phase IIa. And with all kind of -- all things being equal, the Phase IIa enrolled the A1 population between November of 2019 through August of 2020. So it was kind of an acute phase of COVID, where U.K. was locked down a number of times and certainly in the U.K., in that particularly IIa trial was really driving our patient enrollment in patient dataset. As I said earlier, I think what we've done in the Phase IIb is accounted for some of that risk by having a number of sites across the world, up to 50, that will be activated sickle cell trial. And allowing the sites that are open and having patients come in, taking extra precautions with those patients by enabling home health visits, local lab analysis as well as tracking those patients very carefully. And so that just from an organizing principle is a completely different approach. And more importantly, is a distributed approach across the world versus necessarily relying just on the U.K., which in some ways has been hit the hardest with the COVID waves as well as the variants. And so in conclusion, we feel pretty confident that we won't have those missing visits in the same way we did in the IIa.

[Operator:]

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

[Kelly Girskis:]

This is Kelly Girskis on for Joe. We were hoping you might be able to provide additional color on the 12 OLE patients reported today. How many of those were able to clear that 3% threshold on HbF?

[Rahul Ballal:]

So we are providing all the spaghetti plots in our corporate deck. There were a number of patients that cleared that bar and instead of kind of giving you color over the phone, happy -- corporate deck will provide the spaghetti plus of each individual patient, but there is certainly a few.

[Kelly Girskis:]

Great. We will definitely look at those slides. And maybe given the Phase IIa data and OLE data, they -- and what's known about red blood cell turnover, what gets you confidence that the 6-month interval you'll be looking at for Ardent will be enough time to see IMR-687's impact on HbF and F-cells?

[Rahul Ballal:]

Yes it's a good question. There's a number of things that give me confidence in that data readout. Number one, in the OLE patients at 200-milligram, we're already seeing at month 4, almost a 2% increase in the treatment-interrupted patients and over a 2% increase in the patients that are continuing on. And so for us, I think, fundamentally, as we think about both the PK/PD modeling, we're doing internally as well as where we think the exposure response data will ultimately lie, higher doses of IMR-687 are going to confer additional benefit. And remember, the Phase IIa was a titrated dose design where patients on background HU started at doses as low as 50 milligram. In our Phase IIb design, a patient on HU will start at as low as 200 milligram, so 4x higher than where the IIa started and potentially as high as 400 milligram, 8-fold higher than where they started in Phase IIa. Similarly, for the monotherapy patients that started at 100-milligram in the Phase IIa, they'll be starting at doses of 200, 300 or potentially 400-milligram Phase IIb, 4-fold higher than the Phase IIa. So there is a multiple fold increase in dose. And that 6-month time point allows those patients to stay on the same dose for the full 6 months as opposed to be titrated into Phase IIA. And so our confidence level, when you just think about the dose paradigm is high. And if you think about the PK/PD modeling, as you get to those higher doses, you get trough concentration from IMR-687 that gives us confidence that we're inhibiting the PDE9 degradation mechanism for the full 24-hour period at the 400-milligram dose. And so when we kind of juxtapose both the increased dose, certainly, the time over the IC90 or concentration trough levels as well as the fact that the study is of 1 year study in addition to that 6 different endpoints, confidence level across all of those changes in the Phase IIb makes us feel that that endpoint will be hit.

[Operator:]

There are no more questions at this time. Presenters, please continue.

[Rahul Ballal:]

Great. Thank you so much for your time and attention this morning. We look forward to our additional data readouts in 2021. And have a very good day.

[Operator:]

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.