Q4 2020 Imara Inc Earnings Call
Ladies and gentlemen, thank you for standing by and welcome to day in Mira, Inc. Fourth quarter earnings conference call and webcast at.
At this time all participants are in listen only mode. After the speaker presentation. There will be a question and answer session now to ask a question. During this time you will need to press star one on your telephone keypad also if you require any further assistance. Please press star zero I would now like to hand, the conference over to yours.
Today, Mr. Mike Gray. Thank you. Please go ahead Sir.
Okay. Thank you.
Good morning, everyone and welcome to <unk> 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 provision 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 on the risk factors section of our most recent annual report on form 10-K 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.
Okay with that I'll turn the call over to Omar as President and CEO Rahul ball I'll return following rules discussion to review our financial results and we'll then open the call for any questions Rahul.
Thank you Mike Good morning, everyone and thank you for joining 2020 was a productive year for Lora.
We made progress in building our business in accomplishing several of our key objectives. This momentum has carried into the early part of 2021.
We're looking for to a robust year of data readouts in both our sickle cell and beta thalassemia programs.
Startup Twenty-twenty was highlighted by our initial public offering in March which we raised gross proceeds of $86 5 billion throughout the course of 'twenty 'twenty and into the early months of 2021.
Continue to build the organization, including expanding our leadership and broader development teams with key hires during the last several months, including wind Hopkinson as our SVP of regulatory and Ken Addy is our chief medical.
Officer.
Lynn 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.
Alluding the Christopher cash nine programs in sickle cell disease and beta thalassemia.
Ken joined Tomorrow in January and brings more than 30 years of experience within academia and biotech most recently at accelerate on pharma, where he led global clinical development efforts that led to recent S. T E. N E. MAA approvals spatter Sep known as rebel is all which is a new treatment for patients with rare.
[noise] anemias, including beta thalassemia.
We've also expanded the company's head count, particularly in key development areas, such as clinical regulatory quality and technical operations.
Collectively this organizational growth has enabled our continued advancement of INR 67, including initiation of our art in phase <unk> clinical trial in sickle cell disease, and our <unk> phase <unk> clinical trial beta thalassemia.
For T trial reached an important milestone earlier in 2021.
Data monitoring committee approved opening day any of those niche.
Patients will receive doses of INR 67 up to 400 milligrams.
We anticipate that the drug monitoring committee will meet later in March to evaluate opening the higher dose arm and the artist sickle cell trial, both the Arden and for T. Phase <unk> study, we continue to expect reporting interim data in the second half of 2021.
We also completed our phase Iia clinical trial of INR 67, sickle cell disease and reported topline results from that trial in January we're continuing to study a subset of these phase III patients in an open label extension or OLED clinical trial, we increased enrollment in the oily trial from two patients in June of 2012.
<unk> to 'twenty for patients at the end of 2020 and last August we presented case narratives on the first two patients for the OLED trial that completed at least six months of INR 67 treatment today, we disclosed updated data for these two patients.
As well as a broader group of patients from the OLED trial in each case, demonstrating absolute increases in H P. F <unk> and F cells compared to baseline with patients for on a higher dose of 200 milligram <unk>.
We believe these results start to show how higher doses of INR 67.
For additional benefits to patients.
We also held what we believe to be an important type C meeting with the FDA in December of 'twenty 'twenty for.
Regarding our planned pediatric study in sickle cell disease during which the agency expressed alignment with the overall clinical trial design and indicated the study could be submitted with the adult study data in the same NDA. We believe that this is an important step forward as the pediatric population represents a significant portion of the overall simple.
Population.
In addition in 2020, we expanded the potential of INR 67 through completion of preclinical study in heart failure with preserved ejection fraction models and we are currently developing a phase two protocol for potential clinical development in this indication.
Lastly, we also expanded our efficacy and patient community efforts highlighted by our 2020 launch of the real impact grants initiatives to support local community based organizations, serving patients and families affected by rare blood disorders.
Plan to continue to expand our advocacy efforts, including the real impact grants program in 2021.
We believe that our organizational build and clinical trial execution in 2020 will result in important clinical data, including the new loans.
On the Lee data that we will discuss this morning being.
Being released during 2021.
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 our phase Iia trial in January 2021, we disclosed topline results for this program as a reminder, in the second quarter of 2019, we amended the trial protocol for the mono therapy sub study to create population a one which was comprised of patients who they are.
<unk> placebo or INR 67 at a once daily dose of 100 milligrams through for weeks and then 200 milligram for an additional 20.
For the same time, we amended the trial protocol for the combination sub study to create population do you want.
Which was comprised of patients to receive either placebo or INR 67. Once daily at 50 milligram. In addition to standard of care Hydroxyurea or H U S.
Escalation after four weeks 200 milligram volume are 67 for an additional 20 weeks.
None of the patients enrolled in part a one or B. One for included as part of the second interim analysis, which we previously reported in August of 2019.
Overall, the phase Iia demonstrated that INR 67 was well tolerated as a monotherapy and in combination with each you know dose levels, a 30% lower rate of basal occlusive crises for sickle cell pain crises as part of the safety analysis was observed in the population age group when compare.
For it to placebo.
Furthermore, the rate of Boc related hospitalizations was lower than the population a one group when compared to placebo.
There were no meaningful differences in boc's or boc related hospitalizations between the population be one group.
Placebo.
Biomarker results for population a one showed minimal changes in F cells hbf levels in total H b from baseline through week 20 for biomarker results and Pete in population be one treated patients showed an overall increase in <unk> cells and hbf levels from baseline at week 24, while HP levels did not meaningfully change.
I'll now move to the open label extension study.
This is data that we released today.
We believe that this new data reestablish as H B F and F cell activity treatment with 200 milligram of INR 67, after seeing variable results for these biomarkers in the phase Iia trial.
As a reminder that for year OLED trial allows patients from the phase III program to enroll in a long term safety and Tolerability study of INR 67, following completion of the phase III.
The oily trial was initially designed for patients for administered a daily dose of 100 milligram or 67.
And in the second quarter of 2020, a protocol amendment increased the daily dose 200 milligram pay.
Patients from the combination sub study continued to receive the same dose of <unk> that they received while they're on the phase Iia and throughout the duration of the OLED trial base.
Based on the Tolerability profile of INR 687 observed thus far the safety Review Committee has approved a dose escalation in the <unk> trial to a minimum daily dose of 300 milligram up from 200 milligram with certain patients being eligible for a daily dose of 400 milligram based on their way.
This weight based approach similar to our ongoing phase <unk> clinical trial in sickle cell disease.
Safety Review Committee approved these dose adjustments contingent on the independent data monitoring committee opening up the higher dose arm for the Arctic phase two B trial is itself, we expect the Arden phase <unk> to make a decision on opening this higher dose March 2021 paving.
The way for the OLED dose adjustment via protocols.
And the <unk>, we conducted a preliminary review of 'twenty for patients as of December 31, 2020 overall data from the 24 patients enrolled in the <unk> trial demonstrated that <unk> was well tolerated and had a safety profile similar to that observed.
On the phase III clinical trial.
As of December 31, 2020, approximately 12 of these patients evaluable for.
Biomarkers for at least four months from Q.
On the homes.
We're organized for patients with valuable PD biomarkers into two subgroups.
First subgroup, which are treatment interrupted patients which comprise of approximately eight patients who initiated treatment on the OLED trial after substantial break from the phase Iia, specifically more than 12 months after completing.
Second subgroup, which are direct rollover patients is comprised of approximately for patients who initiated treatment on the OLED trial right. After the phase two day, specifically within 12 weeks to complete.
Biomarker results demonstrated absolute increases.
On Hbf and F cells after four months of treatment in both the treatment interrupted sogou.
And the direct to rollover.
Specifically, there was a mean absolute increases hbf for one 7% and the treatment interrupted so group and a mean absolute increase of F cells, a five 9% in.
In their direct rollover subgroup there is a mean absolute increase in <unk> of two 3% and.
And a mean absolute increase in <unk> of 10, 2%.
There were minimal changes in total HB in both subgroups.
<unk> in the treatment interrupted Sogou also demonstrated improvements in markers of hemolysis. After four months of treatment, whereas the direct rollover subgroup should variable changes in these metrics further details on biomarker results from the early trial are described in our annual report on form 10-K, which we filed this morning with the SEC.
Yeah.
Looking ahead, we on the process of analyzing outcomes with respect to the Ocs from the early trial and expect to reported this information at future medical meetings.
I'll briefly now provide an update on two case narratives that we previously reported in third quarter of 2020.
As well as at the American Society of Hematology annual meeting in December of 2020.
Both patients in these case narratives have continued to see absolute increases in hbf from baseline of greater or equal to four 5% as well as absolute increases in Arizona.
Patient one was part of the pop a monotherapy sub study of the phase Iia trial and enrolled in the OLED is in direct rollover patient.
As of December 31, 2020 patient one had been on the early trial for approximately 18 months.
And on INR 67 for approximately 24 months.
And as shown in continued increasing levels of hbf with an absolute increase over baseline of four 8%. After 18 months on the early trial for.
Furthermore, this patient has seen increased <unk> sales compared to baseline as well as improvements in several at TD disease Biomarkers.
In addition, a comparison of Boc data for the 24 month period that the patient has been on INR 687.
At six months on the phase Iia in 18 months on the OLED.
Versus data from a retrospective gross.
Retrospective review of the patients' Medical records for the 24 months prior to initiation of INR 60 per.
Indicate additional boc benefits and the 24 months.
For months period on INR 67 for patient reported 20 Boc as.
As compared to <unk> 50 reported 55 reported POC and the 24 month period prior to INR.
670 administration.
A 60 for reduction in the rate.
Yes.
Patient two was part of the <unk> combination sub study and the phase Iia trial was randomized to the placebo dose and therefore never received INR 60 Senator in Phase Iia.
The patient started the OLED trial for 14 months after completing the phase Iia trial and as a treatment interrupted patient.
The patient is remain on stable dose of EQ. During this interim period and while on the OA trial.
As of December 31, 2020, we had data on this patient through eight months to treat reflecting the most recent OLED visit.
Patient number two as shown on a sustained increase in levels of hbf with an absolute increase over baseline of four 5%. After eight months on the <unk> trial and an increase over based on an F. Sales. However, this patient has also shown increasing variability other SCD biomarkers versus.
The original case.
In addition, a comparison of Boc data for patient number two for the eight months OLED trial period versus data from a retrospective review of the patients' Medical records for the eight month period prior to the initiation of the OA trial indicates potential benefits of INR 67 minutes.
<unk> in combination with <unk>.
And the eight month period on INR 67 patient had a 69% reduction in the rate of reported Voc's 16 to five events as compared to the eight month period prior to INR 67, and while on <unk>.
We caution that the case narratives reflect data from only two patients at specified enrolls in the Yodlee trial and reported Boc comparisons involve retrospective reviews of the patients' Medical records. As a result, we cannot assure you that future data on these patients will continue to be favorable for the data on other patients for the oil.
The trial will demonstrate <unk>.
<unk> benefit environments.
I would now like to turn to our phase two phase II clinical trials of INR 67, including our ardent trial in adult patients with sickle cell disease and for T trial in adult patients with beta thalassemia.
We expended significant effort last year and initiating these trials and we continue to expect.
We reported interim data in the second half of 2021.
We continue to expand the global footprint for both studies with 22% and 36 active clinical centers for <unk> and <unk>, respectively.
Across multiple countries and with continued near term activation of additional centers.
The art in phase two B trial will enroll approximately 99 patients with sickle cell disease is a double blind randomized trial, where patients will be stratified by use of hydroxyurea as well as by region.
We are utilizing weight based dosing to maximize exposures across a wide range of patient weighted with the initial lower dose being administered at either 200 or 300 milligrams.
We currently anticipate that the data monitoring committee will make a decision later this month on whether to open the higher dose arm of the study, which would provide for doses of up to 400 milligrams for 52 weeks.
Recall that we utilized doses of 50 to 200 milligram and our phase Iia clinical trial in a titrated manner through 24 weeks. So this phase <unk> trial is being run at both higher doses and longer duration of treatment with <unk>.
The planned primary efficacy objective is to evaluate the proportion of patients with fetal hemoglobin response defined as.
As an increase of <unk>, 3% or greater from baseline to week 24 versus placebo and the trial is powered for statistical significance at this endpoint.
Patients will continue on treatment for 52 weeks to provide data for planned secondary and additional endpoints, including the evaluation of <unk> 67 versus placebo on Boc's Hbf associated Biomarkers indices of Red cell hemolysis white blood cell adhesion markers and quality of life measures.
The <unk> trial is a randomized double blind placebo controlled phase two b trial in adult patients with beta thalassemia.
The trial will evaluate the safety and Tolerability of INR 67 in approximately 60 transfusion dependent patients and approximately 60 non transfusion dependent patients for transfusion dependent patients. We plan to evaluate the effects of INR 67 versus placebo on transfusion burden and the change in iron load there.
For transfusion during the trial and in comparison to historical rates in the 12 weeks prior to initiation of.
For T trial will also examine additional exploratory efficacy endpoints as well as safety and PK endpoints like Arctic phase two b trial for sickle cell, we plan to utilize weight based dosing this potential doses as high as 400 milligrams per day.
I am pleased to announce that the independent data monitoring Committee recently opened the higher dose arm for this trial, providing for doses of up to 400 milligram.
We have already enrolled several patients since the scoop was opened safety and Tolerability of INR 67 will be assessed after 24 weeks in dose.
We currently anticipate initiating our pediatric clinical program of IMS data in sickle cell disease in the first half of 2021.
These ones too.
On the adolescents between 12 to 17 years old comprised of the single ascending dose phase followed by a 36 week multiple dose expansion phase.
In December of 2020, we held a type C meeting with the FDA during which the agency expressed in alignment with this overall clinical trial design and the indicators. The study could be submitted with the adult study data in the same and D. A.
Do you view this as an important advancement for our pediatric development program.
In summary, we believe the fourth quarter margin another productive period for them on.
Do you want on.
So on the apartments multiple data readouts planned in 2021.
And I will now turn the call back to Mike to review, our financial results, Mike Great. Thanks for all.
Our fourth quarter and year end 2020 results can be found in the press release that we issued this morning and ill 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 for biomarker 687, as well as increased personnel related and other R&D operating costs.
G&A excuse me 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 for $3 53 per share for 2020 as compared to a net loss of $23 $5 million for $33 40 per share for 2019.
We ended 2020 with cash cash equivalents from 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.
At this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad.
Again that star one on your telephone keypad, we'll pause for just a moment to compile the Q&A roster.
Yes.
Your first question comes from the line of Matthew Harrison from Morgan Stanley. Your line is open.
Great. Good morning, Thanks for taking my questions I guess at two for me.
First one as you think about the two patients where you gave for the patient history and all the information.
How would you think about those as being typical or atypical patients we might see in the phase two b and I guess, what I'm really asking is do you think that doses a day, receiving because of the weight based dosing and other factors represent something that youre going to see in phase two b or do you think people forget even even higher doses on average than them.
Then secondly could you maybe just talk about how pace of enrollment and other factors are going on.
Okay. Thanks.
Yeah. Thanks, Thanks, Matt for asking the question. So in terms of the two patients. If you look at their overall weight and where they would be if you were to put them in the phase <unk> both of them will be at the higher doses.
Of course, depending on where they are randomized to.
They would ultimately be in doses debt would be in the 300 milligram range. So from a Meg per kg exposure I would expect those patients theory equivalent to go up.
And dose on the <unk>.
In addition, again.
These patients are on on OA trials for the demand.
Cash flow carefully.
These are data from them every month. So there is kind of additional data points on these patients that you get obviously on the ACB.
It's higher dose.
To answer your second question.
The approach that we took for the phase <unk> studies, both an art and for Te have paid off for us on what I mean by that is we.
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 would be activated.
For those two studies respectively.
And what we've seen is in areas, where COVID-19 is not as prevalent as example, Israel. For example, we've seen increase enrollment in those areas and areas, where COVID-19 is prevalent cases 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 ensured that as those sites that are COVID-19.
Impinged 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 coming months.
And we have all of our ducks in order from approvals to signed contracts and we're ready to go.
Great. Thanks very much.
Thanks.
Your next question comes from the line of Eagle in the channel from Citi. Your line is open.
Great. Good morning. This is currently on for Yigal, Thanks, very much for taking a question on.
On.
On your presenters from the O N E. R. You want to comment on how many of the 12 patients for Ritchie bank background.
Background, Hydroxyurea and understanding it's small numbers, but where there any chance you observed with respect to debt increases in each of the asset.
Interest on.
687, along with our sales on top of that background.
Thank you for the question. So we have 24 patients enrolled 22 ongoing.
The breakdown between <unk> and non <unk> is 17 at seven 7% on HQ.
And we have not done the analysis to see if patients.
On the HQ background are benefiting more but we do plan to do.
Medical meeting in the future, including covering some of the patient journey experiences from the phase Iia study into the OLED and.
Typically looking at that comparison, whether or not they're on <unk> to your question, but also what dose of INR 607 day, we're on.
Okay, Great and assuming you get the green light to dose escalate up to 300 or 400 milligrams in the alley.
Just wondering when we might expect to see updated data on that one.
It was higher.
Yeah, like specifically trying to figure out.
Potentially before the interim data from the phase <unk> or would it likely be.
Yeah.
That's a good question. So if we get that approval, obviously contingent on the DMC from the phase <unk> will immediately amend the protocol.
80% of our patients are in the U K and if you just follow the timelines for the protocol amendment to implementation.
Probably starting to look at data at the end of this year.
Around those OLED patients at a higher dose. So are planned interim analysis for the phase <unk> study is also the second half of this year.
And so.
C data around the same time, both patients as well as the artists HCV patients.
Okay, perfect and last question from losses.
Great.
I know you faced some challenges due to COVID-19 with with net.
In the placebo arm. So I'm wondering if you could talk a little bit about how you've accounted for.
For a potential.
On the impact in Europe powering assumptions.
Okay.
With that cash.
Good day.
Yeah. It's a great question. So we've taken a different approach for the phase <unk> that allows us to avoid those issues that we encountered in the phase Iia and with.
All kind of on.
All things being equal the phase Iia.
We enrolled the one population between November of 2019 through August of 2020. So it was kind of an acute phase of Covid, where the UK was locked out on a number of times and certainly in the U K in that particularly to a trial was really driving our patient enrollment and patient dataset.
As I said earlier I think what we've done in the phase <unk> accounted for some of that risk by having number of sites across the world.
Up to 50 that'll 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.
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 it distributed approach across the world versus necessarily relying just on the U K, which in some ways has been hit the hardest with the.
The COVID-19 waves as well as the variance.
So in conclusion, we feel pretty confident that we won't have those missing visits in the same way we did it to us.
Great. Thanks very much.
Thank you for your questions.
Your next question comes from the line of Joseph Schwartz from SBB Leerink. Your line is open.
Hi, Greg This is Kelly on for Joe.
We are hoping you might be able to provide additional color on that on the 12 patients reported today, how many of those were able to clear that three per cent percent threshold.
On H B.
So we are providing all the spaghetti plots on 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 debt will provide to spaghetti pluses each individual patient.
But there was certainly a few.
Correct Me, we'll definitely look at those slides and maybe given the phase Iia data on.
Good day.
And what's known about Red blood cell turnover, what gives you confidence that their six months for all of it you'll be looking at for art.
There will be enough time to see INR 687, and tacked on to be asking yourselves.
Yes, it's a good question Theres, a number of things that give me confidence that our data readout number one the OA patients at 200 milligram.
We're already seeing it month for almost a 2% increase in the treatment interrupted patients 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 INR 687 are going to confer additional benefit that remember the phase Iia was titrated dose design, where patients are on <unk>.
On an H you started at doses as low as 50 milligram.
In our phase two b design, a patient on a shoe will start at as low as 200 milligram. So four times higher than where the two way started and potentially as high as 400 milligram eightfold higher than where they started in the phase Iia.
Similarly for the monotherapy patients that started at 100 milligram in the phase Iia there'll be starting at doses of two three or potentially 400 milligram phase two b four fold higher than the phase Iia. So there is a multiple fold increase in dose.
And that six month time point.
Allows those patients to stay on the same dose for the full six months as opposed to be titrated into phase III.
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 concentrations of INR 67 that gives us confidence that we're inhibiting PD nine degradation mechanism.
For the full 24 hour period at the 400 milligram dose and so when we kind of juxtapose both debt increased dose.
Certainly the time over the IC 90 or concentration trough levels as well as the fact that the studies for one year study in addition to that six percentage point.
Confidence level across all of those changes for the phase two b.
Makes us feel that debt and point of view debt.
Yes.
Excellent. Thanks, so much.
Yeah.
There are no more questions at this time for centers. Please continue.
Great. Thank you so much for your time and attention. This morning, and we look forward to our additional data readouts in 2021 for Brad.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
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