Q2 2021 Imara Inc Earnings Call
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Operator: Good day. Thank you for standing by, and welcome to the Amara Inc. Q2 earnings conference call and webcast. At this time, all participants are in a 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 zero. I would now like to hand the conference over to your speaker today. Mike Gray, thank you. Please go ahead.
Good day, Thank you for standing by and welcome to the Tomorrow, Inc. Q2 earnings conference call and webcast.
At this time all participants are in a listen only mode.
And the speaker's presentation, there will be a question and answer session.
To ask a question during the session you will need to press star 1 on your telephone.
If you require any further assistance please press star zero and.
I would now like to hand, the conference over to your Speaker today, Mike Gray. Thank you. Please go ahead.
Operator: Okay, thanks, Gondra.
And thanks QUADRA.
Mike Gray: 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 Adi. 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.
Good morning, everyone and welcome to the second quarter 2021 Conference call I'm joined this morning by of Morris, President and CEO will hold the law and our Chief Medical Officer, Ken Eddie before.
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 1095.
Actual events or results could differ materially from the expressed or implied by these forward looking statements as a result of various important factors, including those set forth and 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 and the future. We specifically disclaim any obligation to do so even if our views change.
Mike Gray: 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 10Q 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.
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 <unk>, President and CEO of <unk>, who will provide an overview of our second quarter and key recent accomplishments I'll then.
And return following the rules discussion to review our second quarter financial results and we'll then open the call for questions from <unk>.
Thank you Mike Good morning, everyone and thank you for joining today's call. The second quarter in recent weeks have been and productive period from Mara and specifically <unk> 67.
We're pleased to have moved the ball downfield and have made substantial progress and our ongoing phase <unk> trials.
<unk> and sickle cell disease, we've made key progress and our ongoing <unk> phase <unk> clinical trial, we have seen accelerated study enrollment and the art and trial and as announced yesterday. We have completed patient enrollment. This is an important accomplishment from Ara and I want to thank our team for its dedication.
Mike Gray: 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.
And commitment to this trial most of which has been conducted and the backdrop of the COVID-19 pandemic.
The art and study has been a global effort as we enroll subjects from across the world, including the U S 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 and the first quarter.
Mike Gray: With that, I'll now turn the call over to Amara's president and CEO, Rahul Bilal, who will provide an overview of our second quarter and key recent accomplishments. I'll then return following his discussion to review our second quarter financial results, and we'll then open the call for questions.
Of 2022.
As part of that primary analysis, we expect to examine and safety PD, biomarkers, including fetal hemoglobin or hbf and F cells as well as the effect of INR 67 on visa occlusive crises or Voc's and approximately 99 patients at 24 weeks. We also expect to report data from.
And the interim analysis of approximately 1 third of patients enrolled in this trial at 24 weeks during the fourth quarter of 2021.
Rahul Bilal: Thank you, Mike. Good morning, everyone, and thank you for joining us on today's call. The second quarter in recent weeks has been a productive period for Mara, and specifically, IMR 687. We are pleased to have moved the ball down field and have made substantial progress in our ongoing Phase 2B trials. First, in sickle cell disease, we have made key progress in our ongoing Ardent Phase 2B clinical trial. We have seen accelerated study enrollment in the Arden trial, and, as announced yesterday, we've completed patient enrollment.
With the focus on safety dose and PD biomarkers, including HP FNF sales.
We view this interim readout as a check and ahead of the full study results and Q1.2022.
We have worked tirelessly on the conduct of the art and 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 controlled clinical trial and its open label extension of our OLED trial of INR 607, and adults with sickle cell disease at the 2021 European Hematology mythology Association or <unk>.
The annual Congress, which was held virtually in June.
We held the webcast to review these data in June.
And that webcast and presentation are both available within the events and presentations of the investors section of our website.
We view the phase III results presented at <unk> as an important proof of concept for relevant clinical outcomes with <unk> 687 and treatment.
It strengthens our expectations at the phase <unk> study at substantially higher dose levels could achieve its primary endpoint, which is and hbf response rate defined as an absolute hbf increase of at least 3% and 35% of subjects on INR 67.
Rahul Bilal: 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 U.S., Europe, the Middle East, and even Africa.
Versus 5% on placebo.
In addition, we expect to demonstrate clinical outcome improvements and the key secondary endpoint of annualized as EOC rate similar to what was seen in the phase Iia study.
At the end of the day, if we can replicate the low rates of the oce scene and the phase Iia parent and OLED studies, the phase <unk> will be of success.
Rahul Bilal: As a result of 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 vasoeclusive crises or VOCs in approximately 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.
607, and we'll have a clear path to phase III.
And have a competitive commercial profile and approved.
As a refresher the final results from the phase Iia trial indicate a well tolerated safety profile lower boc rates and crew.
<unk> patient reported pain and severity score.
And variable biomarker results, including with respect to Hbf. The COC results for all of <unk> 93 subjects enrolled demonstrate a 40% lower mean annualized rate and the pooled INR 67 and treated groups versus the pooled placebo groups.
In addition, a significant increase and median time to first VLC of 169 days for the INR 67, and treated groups versus 87 days for the placebo groups was observed.
Regarding the annualized rate of <unk> related hospitalizations. The rate was 0.84 hospitalizations per year, and the INR 67, and treated groups compared with 136 per year and the placebo group.
And patients taking background hydroxyurea, the mean annualized rate was substantially lower and patients on INR 67, plus <unk> versus placebo plus each day.
We're also encouraged to see patients and the separate OLED clinical trial continuing to benefit from lower annualized COC rates. This is based on interim data from 18 patients treated for approximately 8 months and is a distinct data set from the phase Iia study.
Rahul Bilal: 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 art and trial and are very pleased to have important data readouts in the coming month. We also recently presented final data from the 93 patient, Phase 2A, placebo control clinical trial and its open label extension, or OLE trial, of IMR 687 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 section of our website.
Patients who are on active treatment and the parent maintained similar low <unk> rates on INR 687, and the OLED clinical trial.
For patients who were previously and the placebo groups and the parent phase Iia study.
There was a 39% decrease in the mean annualized rate when they switched to INR 67, and the OLED study with patient serving as their own control.
The continued <unk> benefits in this trial further support the findings from the 93 patient phase III study.
Finally, we believe that the VLC improvement point points.
Points to a multimodal mechanism of action of INR, 687% and sickle cell sickle cell disease, which potentially works across several categories red blood cells reduce the activation and adhesion of white blood cells, and other cell types and reduce inflammation and visa dilation and.
Poorly INR 67 was well tolerated as a monotherapy as well as in combination with HQ and each of the phase Iia and OA clinical trials opening the opportunity for both the combination therapy alongside monotherapy use.
Rahul Bilal: We view the phase 2A results presented at IHA as an important proof of concept for relevant clinical outcomes with IMR687 treatment. It strengthens our expectations that the phase 2B study at substantially higher dose levels could achieve its primary endpoint, which is an HBF response rate defined as an absolute HBF increase of at least 3% in 35% of subjects on IMR 687 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 2A study.
In addition to positive the OC data. We are also pleased at 36% or 4 of 11 patients in the OA clinical trial had absolute hps increases of more than 3% at the 8 month time point, while receiving a 200 milligram dose volume of 687.
We believe the higher doses of INR 687, and have the potential to show even more robust hbf increases remember art and phase <unk> clinical trial is currently dosing up to 400 milligram daily and is powered to show an HP of response rate of 35% on INR 687.
Versus 5% on placebo at 24 weeks, so with 200 milligram and the OLED and a 36% Hbf response rate, we are already and the right ballpark and expect higher doses to further improve on that signal.
Turning to our <unk> phase <unk> clinical trial and beta thalassemia. We've also seen accelerated enrollment in this trial, having reached full enrollment and the transfusion dependent or TDD cohort, while also seeing increased enrollment in the non transfusion dependent and TVT cohort.
Rahul Bilal: At the end of the day, if we can replicate the low rates of VOCs seen in the Phase 2A parent and OLE studies, the Phase 2B will be a success. IMR 687 will have a clear path to phase three and have a competitive commercial profile, it will be approved.
We have enrolled approximately half of the study patients we expect to report interim data from the TVT cord in the fourth quarter of 2021, and which we plan to evaluate safety transfusion burden and PD Biomarkers and approximately 30 patients at 24 weeks on the study.
Furthermore, faster enrollment rates now allow and additional readout of the full TVT cohort of 24 weeks and the first quarter of 2022 looking at similar data points data points as the interim analysis.
Rahul Bilal: As a refresher, the final results from the Phase 2A trial indicate a well-tolerated safety profile, lower VOC rates, approved 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 IMR 67 treated groups versus the placebo group. In addition, a significant increase in median time to first VOC of 169 days for the IMR 687-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 IMR-687-treated groups compared with 1.36 per year in the Loceiver Group.
We are also selectively expanding our indication footprint to areas, where PD 9 overexpression is implicated and serious disease with high unmet medical needs to that and we are developing of protocol for a phase II proof of concept study and heart failure with preserved ejection fraction or have the test.
With help from our experienced cardiology clinical advisory board and we expect to interact with the FDA cardio renal position in late 2021.
We have submitted our recent preclinical work and have passed to our cardiology focused medical meeting and hope to present. These data later this year.
We have been interested and have tests has an indication for some time now and think that PD 9 is and enriched and act attractive target that may help treat this debilitating disease. Hence we are excited to begin working on the syndication and a meaningful way in the coming months with an eye towards the clinic.
During the second quarter, we also announced the grant recipients for our second annual real impact community support initiatives.
This program, which includes grant funding to support nonprofit community based organizations, serving patients and families impacted by sickle disease sickle cell disease, and beta thalassemia awarded 30 grants to CBOE and 16 states totaling $150000. The grant funding was increased by 25000 from.
Rahul Bilal: In patients taking background hydroxyurea, the mean annualized VOC rate was substantially lower in patients on IMR 687 plus HU versus placebo plus H. We are also encouraged to see patients in a 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 2A study. Patients who were on active treatment in the parent maintained similar low VOC rates on IMR 687 in the OLE clinical trial.
2020, the program's inaugural year.
We are proud of the positive effects of the real impact program has had on the health and lives of patients their families and their local communities to date.
Spanning the program for the second year reflects our continued commitment to foster innovative ideas and 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 Flora Williams <unk> 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 our significant experience leading clinical trials and guiding prop.
<unk> through commercialization.
She is a strong advocate and community, making here and Outstanding addition to our board.
And also in July we closed the $50 million public financing, which provides a more of the important capital to continue to fund the INR 687 and extends our capital run 1 way through the end of 2020 to.
Lastly in June the United.
Rahul Bilal: For patients who were previously in the placebo groups in the parent phase 2A 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 controls. The continued VOC benefits in this trial further support the findings from the 93 patient phase 2A study. Finally, we believe that the VOC improvement points to a multimodal mechanism of action of IMR-687 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.
United States adopted names council of our use and formally adopted <unk>. It's the generic generic name for INR 67, you may see INR 687 referred to as 2 of <unk> and our future communications.
In conclusion, we believe that the second quarter and first part of the zone.
Active periods from Ara, both in terms of presenting encouraging the boc data and making significant progress and our ongoing phase <unk> clinical trials, we look forward to updating you on further progress including on multiple data readouts planned and the.
And 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 the financial results.
Thanks Rahul.
Our second 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 and the 10-Q that we filed with the SEC earlier this morning.
R&D expenses were $10.1 million for the second quarter of 2021 as compared to $7.9 billion for the second quarter of 2020 the.
The increase of $2.2 million was primarily related to the development manufacturing of clinical materials clinical research and oversight of the company's clinical trials and investor day or fees related to the development of INR 607.
Rahul Bilal: Importantly, IMR687 was well tolerated as monotherapy as well as in combination with HU in each of the Phase 2A 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 4 of 11 patients in the OLA clinical trial had absolute HBF increases of more than 3% at the 8-month time point while receiving a 200 milligram dose of IMR687.
G&A expenses were $3.1 million for the second quarter of 2021 as compared to $2.4 million from the second quarter of 2020.
The increase of $700000 was primarily due to increased personnel related and other G&A operating cost as a result of operating as a public company.
Net loss attributable to common stockholders was $13.2 million or <unk> 74 per share for the second quarter of 2021 as compared to a net loss of $10.2 million or <unk> 59 per share for the second quarter 2020.
We ended the first quarter, sorry in the second quarter with cash cash equivalents and investments of $66.8 million, we believe that our cash cash equivalents and investments as of June 32021 as.
And as well as the approximately $47 million and net proceeds from our July of 2021 public offering of shares of common stock will enable us to fund our operating expenses and capital expenditure requirements through the end of 2022.
Rahul Bilal: We believe that higher doses of IMR687 have the potential to show even more robust HBF increases. Remember, the Arden Phase 2B clinical trial is currently dosing up to 400 milligrams daily, and it's powered to show an HBF response rate of 35% on IMR687 versus 5% on placebo at 24 weeks.
That concludes our prepared remarks, operator could you. Please open the line for questions.
And we would like to ask the question at this time typically close star and the number 1 on the telephone.
We will pause for just the mall.
I'll begin with the last day.
And your first question comes from the line of.
Oh, no commodity from Sandy.
Hi, This is carly on for Yigal, Thanks for taking our questions and.
Congrats on completing enrollment and the sickle cell trial, we had a couple of questions on the BSD data.
Rahul Bilal: So, with 200 milligrams in the OLE and a 36% HBF response rate, we are already in the right ballpark and expect higher doses to further improve that signal. Turning to our 4K, Phase 2B clinical trial on beta thalcemia, 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.
And so far so I guess first what.
And so marker data are you collecting and the phase <unk> trial that could help support INR 6.8 and Kevin and effect on DSD and then secondly, I think you mentioned that you plan to report data as part of the primary analysis and the first quarter of next year or so.
Just wanted to get your thoughts on if you anticipate 24 weeks will be enough time to see and impact on vlccs or if we should really be waiting for sort of the 52 week data to better understand.
Rahul Bilal: 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 PD9 over-expression is implicated in serious diseases with high unmet medical needs.
Yes.
And a large.
<unk> cohort of patients. Thank you.
Thank you very much currently for the questions I'm going to turn it over to our Chief Medical Officer, Ken added to cover those responses.
Hi, yes, good morning, Thanks, maybe.
And maybe I'll take your second question first.
Yes.
When we say that we're going to do an interim analysis with subjects at 24 weeks and it's actually win.
When that particular subject of weather.
And a third of the pace and so all of the patients has reached 24 weeks.
All of the other subjects have somewhere between $24.52 weeks, so they actually will be.
The large number of subjects with substantially more than 24 weeks of treatment and.
And then what you do and and the Boc analyses is annualize it and so we will use all data available so of someone who was treated with 9 months, we annualize it based on the 9 months, some patients and might even be at 12 months already so I think it'll be a pretty good approximation, but obviously youre correct when everyone reaches 50.
2 weeks that will be the most accurate reflection of the 1 of the air VLCC rates.
To your first question, we are measuring many of the same.
Rahul Bilal: To that end, we're developing a protocol for a Phase 2 proof-of-concept study in heart failure with preserved ejection fraction, or HEPPF, with help from our experienced cardiology clinical advisory board, and we expect to interact with the FDA cardiorenal position in late 2021. We've submitted our recent preclinical work in HFest to our cardiology-focused medical meeting and hope to present these data later this year. We've been interested in HEPF 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.
Biomarkers that we've been looking at.
Pre clinically and <unk>.
And clinical trials previously this includes.
Markers of hemolysis.
And because of the adhesion.
Markers of inflammation, and then and even of the cardiac stress so.
We still have all of those biomarkers being measured in the study.
Of course, it's blinded right now and.
And so those results or not.
Available and just yet but.
The primary of Biomarkers of course that we look at are related to hemoglobin asset and total hemoglobin and the red blood cells that contain hemoglobin F. R. F cells and those will be and the primary biomarkers that we look at it.
Okay. That's very helpful. Thank you so much.
Okay.
Thanks.
And your next question comes from the line of Matthew Harrison from Morgan Stanley.
Good morning, everyone. This is cost of Sean for the <unk> 2 questions from loss of 687, and the first 1 is around competition given that the.
Rahul Bilal: 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 disease, sickle cell disease, and beta-thalsemia, awarded 30 grants to CBOs in 16 states, totaling $150,000.
Several small molecules for sickle cell disease currently progressing and development and these molecules include hbf and the use of solar.
And while global modifiers.
We are wondering how are you thinking about the competition and what in your view of would be finished the 80.687 versus competitors.
And then I have the follow up.
Great. Thank you I'll start and then of turn it over to Ken to add some additional commentary first of all we're excited by the development and sickle cell, it's great to see lots of the different companies approaching this landscape and our fundamental view for INR 687 is that.
Rahul Bilal: 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 thalacines.
And.
Unlike other competitors, the drug works and a multimodal way and that it.
Potentially works on red cells white cells inflammation, and even the visa dilation and the aggregation of all of those different mechanisms of allows us to differentiate ourselves on the biosis.
And at the end of the day when you look at the approved products, both from Hydroxyurea and of DAC Theo our phase Iia results and the 93 patient study squarely hit approximately the <unk>.
Same type of EOC reductions that those 2 products saw hydroxyurea is and the mid forty's adapt <unk> and the mid <unk> in terms of reduction.
And annualized the EOC rates or fees.
<unk> results the main changes around 40% and we've seen the same type of results and the OE.
So just taking a step back when you look at our target product profile for the company I think differentiating on Voc's by taking all of the advantages of the mechanism into that readout is ultimately for us what makes us competitive.
Rahul Bilal: 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 commercialization, she is a strong advocate for the teaching community, making her an outstanding addition to our board. Also in July, we closed the $50 million public financing, which provides Amar with important capital to continue to fund IMR687 and extends our capital run one way through the end of 2022.
Anything else Ken.
Think of that in some of the other molecules are quite focused on red blood cells, and the hemoglobin changes and.
And I think.
That being the case.
And they might see very nice results, there, but maybe not as robust results in terms of the ocs and so we are.
Certainly focus now on the ability of our drug to reduce not only not only of the number of painful crises with the number of hospitalizations and the number of and.
And the severity of the pain crisis as well.
Thank you very helpful and the follow up.
Out of hearings.
The impact from the <unk> for sickle cell patients remains significantly below the pre pandemic levels, mostly because the vaccination in this so you can sell digital population of the vaccination of rate is lower than the total population.
We are on that and keep features or potentially get ahead of any impact on the sampling of PK PD measurements from the sickle cell disease patients and your study. Thank you.
Rahul Bilal: Lastly, in June, the United States, the United States adopted names council or USAN formally adopted tovinotrine as a generic name for IMR687. You may see IMR687 referred to as tovinotrine in our future communication. In conclusion, we believe that the second quarter and first part of the third were 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 of the fourth quarter of 2021 and the first quarter of 2022. Thank you, and I will now turn the call back to Mike for a review of financial resources.
I think that's a good question.
I can say that.
We've seen a turning point and many countries.
Net.
They're making sure that patients are coming in for per.
Our all office visits well visits as well as.
And our clinic visits for studies, so we've been averaging something like 10, new patients the week for the last few weeks, that's a really robust.
Recruitment rate.
And part due to bringing more sites on board, but I think theres also some enthusiasm and.
Getting a drug like this and.
And trying it out and patients.
So we haven't seen too many missed visits and.
And we've simplified our PK collection and based on some of our PK modeling, we decided we didn't need to have them stay overnight for PK sampling, so thats being done and.
The 1 day visit so and I think our our PK data is going to be.
Pretty robust we've also.
And the middle of and extensive PK study in healthy volunteers. So we have a lot of.
PK and PD data coming in.
Yes.
And you very much very helpful.
Thank you ex us.
Your next question comes from the line of Joseph Schwartz of SBB Leerink.
Mike Gray: Our second 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 earlier this morning. R&D expenses were $10.1 million for the second quarter of 2021 as compared to $7.9 million for the second quarter of 2020. The increase of $2.2 million was primarily related to the development and manufacturing of clinical materials, clinical research, and oversight of the company's clinical trials and investigator fees related to the development of IMR-687.
Good morning, Thanks very much.
And your last comments on PK and are of good segue to 1 of my questions, which is.
Basically have you done.
And any response exposure analysis for the phase Iia and.
And data that supports the hypothesis that higher doses of INR 607, and produce better responses that are increases and hbf or decreases and vlccs and <unk>.
Are there any implications on the phase 2 b trial were some higher doses are being evaluated.
Yes, hi, and thanks for that question.
We have indeed done those analyses not in the formal way that we hope to do it when we have a bit more data from from these new studies, but ill give you. An example of what we've looked at so.
For the subjects in the Phase Iia study, where we are able to do full PK evaluation at the end of the study.
Mike Gray: GNA expenses were $3.1 million for the second quarter of 2021 as compared to $2.4 million for the second quarter of 2020. The increase of $700,000 was primarily due to an increase in personnel related and other GNA operating costs as a result of operating as a public company.
And when you compare the annualized VLCC rate versus the.
Area under the curve floor for the PK profile, and we saw a nice negative correlation and so thats. The we want right. So as the as the exposure increases, we see fewer and fewer of the ocs.
That didn't have a very high R P value, but that trend was the there and.
Mike Gray: The net loss attributable to common stockholders was $13.2 million, or 74 cents per share, for the second quarter of 2021 as compared to a net loss of $10.2 million, or 59 cents per share, for the second quarter of 2020. We ended the first quarter, sorry, the second quarter with cash, cash equivalence, cash equivalence, and investments of $66.8 million. We believe that our cash, cash equivalence, and investments as of June 30, 2021, as well as the approximately $47 million in net proceeds from our July 2021 public offering of shares of common stock will enable us to fund our operating expenses and capital expenditure requirements through the end of 2022. That concludes our prepared remarks. Operator, could you please open the line for questions?
And really.
Really at the higher exposures and we're talking about on the 200 milligrams per day.
And we saw fairly low.
VLCC rates less than 2 per year. So as we go up now to 3 and 400 milligrams and our phase 2 B trial, we know that we're going to be approximately doubling the AUC and some patients.
That will extend that curve out to again really low POC.
The level that relationship was even stronger for hemoglobin F and for F cells and particular so.
And the absolute change and upsell percentage and.
Increased with increasing exposure.
And the area and our of 4.
4.3 and of P of <unk> <unk> so.
That was saying that we're going to see this 10 to 15% to 20% increase.
And F cells and our current dose levels, even at 200, and then as we go to 3 and 400, we could see that go even dramatically higher so we're going to start seeing subjects with 40% 50% of there.
Net sales of themselves and may be even more and that in turn will drive update and government.
Percentage.
Interesting and then how much of the reduction and Voc's.
Was explained by.
Hbf factors versus.
Other things if you looked at those correlations.
Operator: If you would like to ask a question at this time, simply press star or send the number one on your telephone keypad. We will pause for just a moment to compile the Q&A RASC. And your first question comes from the line of Yigal Nocomotovich on City.
Awesome.
We would have to say that.
It would not be fully explained by the hemoglobin F or the change and ourselves.
We did look at it.
Or any specific other.
Biomarkers and we saw we saw some directional improvement and adhesion molecules and and in particular sites et cetera, but no single biomarkers seem to be and driving this and Thats why.
Carly-Anfreyagal: Hi, this is Carly-Anfreyagal. Thanks for taking our questions and congrats on completing enrollment in the single cell trial. We had a couple questions on the VOC data that you've reported so far. So I guess first, what biomarker data are you collecting in the phase 2B trial that could help support IMR 687's effect on VOCs? And then secondly, I think you mentioned that you plan to report DOC data as part of the primary analysis in the first quarter of next year.
We're going to take the data and face value and say, it's a combination of these factors right now.
Sure It would be great to have a single surrogate marker for when we go down but I'm not sure we're going to get there but.
But as we go up on the dose I think the signals will get stronger.
Right and it's probably in the complex multifactor equation.
Maybe another question on the phase Iia versus the trials can you tell us how were the vlccs and the phase Iia adjudicated and will it differ in any way and the phase <unk>.
Carly-Anfreyagal: So just wanted to get your thoughts on if you anticipate 24 weeks will be enough time to see an impact on VOCs or if we should really be waiting for sort of the 52-week data to better understand VOCs in a larger cohort of patients. Thank you.
The sickle cell trial, and how extensively distributed or the sites in the phase <unk> and <unk>.
As youre, calling ops organize too.
And ensure the highest.
Quality conduct and results.
So.
I would say and the phase Iia trial that our collection of the Vlccs.
Rahul Bilal: Thank you very much, Carly, for the questions. I'm going to turn it over to our chief medical officer, Ken Addy, to cover those responses. Hi, yeah, good morning, thanks.
Was refined over the course of the study to reflect some feedback from the FDA I don't think it changed the behavior of the sites and the UK and the U S. They know how to recognize the ocs.
Crustacean Priapism 2 test syndrome.
Ken Adi: Maybe I'll take your second question first. When we say that we're going to do an interim analysis with subjects at 24 weeks, it's actually when that particular subject, whether it's, you know, a third of the patients or all the patients, has reached 24 weeks. That means all of the other subjects have somewhere between 24 and 52 weeks. So there actually will be a large number of subjects with substantially more than 24 weeks of treatment. And then what you do in the VOC analyses is annualize it. So we will use all the data available.
And the need for analgesia and all the other parameters that you look at 2 to characterize the boc is of Aoc.
We've done most of the adjudicating through the safety review committees, which include the investigators and outside experts as well as.
Our current internal.
<unk> of the data we now have 2 Mds that are reviewing and the POC data coming in on our side as well as 2 Mds at the.
The CRO.
So I think the vlccs are being carefully.
And looked at and not with an independent Adjudication Committee.
And if that's your question.
We are capturing the <unk> on a on the unique.
This report form for the Ocs and of course, we capture even more information if they are hospitalized with the serious adverse event information.
And I think going forward that we're going to.
Continue to have careful.
Mostly to make sure that we have of standard way of characterizing the the doses as far as the <unk>.
Ken Adi: So if someone was treated for nine months, we annualize it based on the nine months. Some patients might even be at 12 months already, so I think it'll be a pretty good approximation. But obviously, you're correct when everyone reaches 52 weeks. That'll be the most accurate reflection of the one-year BOC rate.
Study and where its being conducted we are in.
10% to 15 countries.
And over 40 sites. So it is it is a challenge, but I would say the sites are performing extremely well like I said, we're not having missed visits for or labs.
And the physicians of really.
Responding to queries.
Quite rapidly and quite.
Ken Adi: To answer your first question, we are measuring many of the same biomarkers that we've been looking at pre-clinically and in clinical trials previously. This includes markers of hemolysis, markers of adhesion, markers of inflammation, and even markers of cardiac stress. So we still have all of those biomarkers being measured in this study. Of course, it's blinded right now, and so those results are not available just yet. But the primary biomarkers, of course, that we look at are related to hemoglobin F and total hemoglobin. The red blood cells that contain hemoglobin F or F cells? Those will be the primary biomarkers that we look at.
And of Concertedly, theyre, making an effort to not only recruit patients, but keep them and the study when logistical challenges come up.
So we're really noticing that.
So we have our own group of trial managers and the group at <unk>.
Tray icon that are now quite experienced at it just to give you. An example, we're trying to collect and send.
And some of these biomarker data from Africa to Europe, and Thats and Thats the challenge sometimes.
In terms of the transport of the samples and so we've done a number of creative things to make sure of the samples arrive and good condition and can still be analyzed and.
Ken Adi: Okay, that's very helpful. Thank you so much. Thank you. Thank you. And your next question comes from the line of Matthew Harrison from Morgan Stanley.
The timely manner. So these things are being looked at carefully throughout the study.
That's really helpful color. Thanks for all of the insights.
Thanks, Joe.
And again, if you would like to ask the question simply press Star then the number of wine.
Matthew Harrison: Good morning, everyone. This is Costa-S-on for Matthew.
And there are no further questions at this time Mr. Greg.
Costa-S-on: Two questions from us on 6-8-7. The first one is around competition, given that several small molecules for sickle-cell disease are currently progressing in development, and these molecules include HBF-indusers or hemoglobin modifiers. We are wondering, how are you thinking about competition and what, in your view, would differentiate 687 versus competition? Thank you. And then I have a follow-up.
Thank you very much operator of.
Again, we wanted to thank you for joining today's call and were excited of our momentum going into the fall and look forward to upcoming data readouts across our programs later this year stay safe and healthy and speaks it thanks Ken.
This does conclude today's conference call. Thank you for your participation you may now disconnect.
Okay.
[music].
Rahul Bilal: Great, thank you. I'll start, and then I'll actually turn it over to Ken to add some additional commentary.
Rahul Bilal: First of all, we're excited by the development of sickle cell. It's great to see lots of different companies approaching this space. Our fundamental view for IMR 687 is that, unlike other competitors, the drug works in a multimodal way in that it potentially works on red cells, white cells, inflammation, and even vasodilation, and the aggregation of all those different mechanisms allows us to differentiate ourselves in VOCs. And at the end of the day, when you look at the approved products, both from hydroxioria and Adacteo, our phase 2A results in the 93 patient study squarely hit approximately the same type of VOC reductions that those two products saw. Hydroxureas in the mid-40s, Adaxiorea, and the mid-40s
Ken Adi: VOs in the mid-40s in terms of reduction in annualized VOC rates are phase 2A results; the mean changes around 40%, and we've seen the same type of results in the OLE. So just taking a step back, when you look at a target product profile for the company, I think differentiating on VOCs by taking all the advantages of the mechanism into that readout is, ultimately, for us, what makes us competitive. Anything else, Ken?
Ken Adi: No, I just think that some of the other molecules are quite focused on red blood cells and hemoglobin changes. And I think, if that being the case, they might see very nice results there, but maybe not as robust results in terms of the OCs. So we are certainly focused now on the ability of our drug to reduce not only the number of painful crises but the number of hospitalizations and the number and severity of the pain crises as well.
Ken Adi: Thank you. Very helpful. As a follow-up, we are hearing that in-person physician visits for sickle cell patients remain significantly below pre-pandemic levels, mostly because in this sickle cell disease population, the vaccination rate is lower than the total population. We are wondering if this has or potentially can have any impact on the sampling of PK-PD measurements from the sickle cell disease patients in your study.
[music].
Ken Adi: I think that's a good question. I could say that we've seen a turning point in many countries where they're making sure that patients are coming in for all office visits, well visits, as well as, you know, clinic visits for studies. So, you know, we've been averaging something like 10 new patients a week for the last few weeks. That's a really robust recruitment rate, you know, in part due to bringing more sites on board, but I think there's also some enthusiasm about getting a drug like this and trying it out in patients.
Ken Adi: So we haven't seen too many missed visits. We've simplified our PK collection based on some of our PK modeling. We decided we didn't need to have them stay overnight for PK sampling, so that's being done in a one-day visit. So I think our PK data is going to be pretty robust. We're also in the middle of an extensive P.K. study and healthy volunteers. So we have a lot of PK and PD data coming in. Thank you very much.
Costa-S-on: Thank you very much. It was very helpful.
Joseph Swartz: Your next question comes from the line of Joseph Swartz of SVB Lering.
Joseph Swartz: Good morning, thanks very much. Your last comments on P.K. are a good segue to one of my questions, which is, basically, you know, have you done any response exposure analyses for phase 2A and found data that supports the hypothesis that higher doses of IMR 687 can produce better responses, better increases in HBF or decreases in VOCs? And are there any implications for the phase 2b trial where some higher doses are being evaluated? Yeah, hi, thanks for that question.
Ken Adi: We have indeed done those analyses, not in the formal way that we hope to do it when we have a bit more data from these new studies, but I'll give you an example of what we looked at. So for the subjects in the phase 2A study, where we were able to do full PK evaluation at the end of the study, we compared the annualized VOC rate versus the area under the curve for their PK profile.
Ken Adi: And we saw a nice negative correlation, so that's what we want, right? So as the exposure increases, we see fewer and fewer VOCs. You know, that didn't have a very high R or P value, but that trend was there. And really, at the higher exposures, and we're talking about only 200 milligrams per day, we saw fairly low VOC rates, you know, less than two per year. So as we go up now to 3 and 400 milligrams in our phase 2b trials, we know that we're going to be approximately doubling the AUC in some patients, and that will extend that curve out to, again, really low VOC levels. That relationship was even stronger for hemoglobin F and for F cells in particular.
Ken Adi: So the absolute change in F-cell percentage increased with increasing exposure. And there we had an R of.43 and a P of.043. So that was saying that we're going to see this 10, 15, 20 percent increase in F cells at our current levels, even at 200, and then as we go to 300 and 400, we could see that go even dramatically higher. So we're going to start seeing subjects with 40, 50%, red cells or Zep cells and maybe even more. And that, in turn, will drive up the Hymn Glemen F percentage.
Ken Adi: Interesting. But how much of the reduction in VOCs was explained by HBF factors versus other things? Have you looked at those correlations also? We would have to say that, We, it would not be fully explained by human global and F or the change in F cells. Um, we did look at it or any specific other biomarkers. We saw some directional improvement in adhesion molecules and in reticulocytes, et cetera. But no single biomarker seemed to be driving this, and that's why we're going to take the data at face value and say it's a combination of these factors right now. Sure, it would be great to have a single surrogate marker for when VOCs go down, but I'm not sure we're going to get. I will get there.
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Ken Adi: But as we go up on the dose, I think these signals will get stronger. Right, it's probably a complex multi-factor equation. Maybe another question on the phase 2A versus B trials. Can you tell us how the VOCs were?
Joseph Swartz: in the phase 2A adjudication, and will it differ in any way?
Joseph Swartz: in the phase 2B sickle cell trial, and how extensively distributed are the sites in phase 2B, and is your Clinops organized to ensure the highest quality?
Ken Adi: quality conducted results.
Ken Adi: So I would say in the phase 2A trial that our collection of VOCs was refined over the course of the study to reflect some feedback from the FDA. But I don't think it changed the behavior of the sites in the UK and the U.S.
Ken Adi: They know how to recognize VOCs, sequestration, the Priapism, Q-Chess syndrome, you know, the need for analgesia, and all the other parameters that you look at to characterize. We've done most of the adjudication through safety review committees, which include investigators and outside experts as well as our own internal review of the data. We now have two MDs that are reviewing the VOC data coming in on our side, as well as two MDs at the CRO. So I think the VOCs are being carefully looked at, not with an independent independent adjudication committee. If that's your question,
[music].
Ken Adi: We are capturing BOCs on a unique case report form for VOCs, and, of course, we capture even more information if they're hospitalized with serious adverse event information. So I think going forward that we're going to continue to have careful, mostly to make sure that we have a standard way of characterizing the BOCs. As far as the study and where it's being conducted, you know, we are in 10 to 15 countries and over 40 sites. So it is a challenge, but I would say the sites are performing extremely well.
Ken Adi: Like I said, we're not having missed visits or labs. The physicians are really responding to our queries quite rapidly and quite concertedly. They're making an effort to not only recruit patients but keep them in the study when logistical challenges come up. So we're really noticing that.
Ken Adi: So we have our own group of trial managers and the group at PRA ICOM that are now quite experienced at it. Just to give you an example, we're trying to collect and send some of this biomarker data. You know, from Africa to Europe and that's sometimes a challenge in terms of the transport of the samples. So we've done a number of creative things to make sure the samples arrive in good condition and can still be analyzed in a timely manner. So these things are being looked at carefully throughout the study.
Joseph Swartz: That's really helpful, Color. Thanks for all the insights. Thanks, Joe.
Operator: Again, if you would like to ask a question, simply press star, then number one. And there are no further questions at this time, Mr. Gray?
Mike Gray: Thank you very much, operator. Again, we wanted to thank you for joining today's call, and we're excited by our momentum going into the fall and look forward to upcoming data readouts across our programs later this year. Stay safe and healthy, and speak to you later. Thanks again.
Operator: This does conclude today's conference call. Thank you for your participation. You may now disconnect.
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