Q4 2021 Regulus Therapeutics Inc Earnings Call
Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Regulus Therapeutics Q4 2021 conference call. At this time, all participants are in a listen-only mode.
Ladies and gentlemen, thank you for standing by and welcome to the Regulus Therapeutics Q1, 'twenty Q4, 2021 conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question during the session need to press star one on your telephone if you require any further assistance. Please press star zero I would now like to turn the call over to your host Chris.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you need to press star 1 on your telephone. If you require any further assistance, please press star 0. I will now return the call to your host, Chris Calsada. You may begin. Thank you, operator. Good afternoon, and thank you for joining us to discuss Regulus Therapeutics' fourth quarter and full year 2021 financial results and corporate highlights.
Cal Saudi you may begin.
Operator: With me on today's call is Jay Hagan, President and Chief Executive Officer, and Dr. Dennis Drygen, Chief Scientific Officer. Jay will provide opening remarks and share progress on our 80PKD program, and I will review the financial results before we open the line for questions. Before we begin, I would like to remind you that this call will contain forward-looking statements concerning Regulus Therapeutics' future expectations, plans, prospects, corporate strategy, and performance, which constitutes forward-looking statements for the purpose of the safe harbor provisions under the private security's litigation reform act of 1995 1995. However, actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our silence with
Thank you operator, good afternoon, and thank you for joining us to discuss regiments therapeutics fourth quarter and full year 2021 financial results and corporate highlights.
With me on today's call, Jay Hagan, President and Chief Executive Officer.
And Dr. Dennis.
Chief Scientific officer, Jay will provide opening remarks and share progress on our ADP JV program and I will review the financial results before we open the line for questions.
Before we begin I.
I would like to remind that this call.
We will contain forward looking statements concerning regulus therapeutics future expectations plans prospects corporate strategy and performance.
Which constitute forward looking statements for the purpose of the Safe Harbor provision under the private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these forward looking statements.
As a result of various important factors, including those discussed in our filings with the SEC.
In addition, any forward looking statements represent our views only as of the date of this webcast and should not be relied upon.
As representing our views as of any subsequent date, we specifically disclaim any obligations to update such statements I will now turn the call over to Jay.
Operator: In addition, any forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements.
Chris Calsada: I will now turn the call over to Jay. Thank you, Chris. Welcome everyone to our fourth quarter and full year 2021 earnings call and business updates. 2021 was a transformational year for Regulus, with the accomplishments in our ADPKD program and steady progress in our Alport Syndrome program made by our partner, Sanofi. I'll begin by mentioning the financing last November, in which we successfully closed a $34.6 million private placement on favorable terms that included several new institutional investors and support from several of our existing institutional investors.
Thank you Chris welcome everyone to our fourth quarter and full year 2021 earnings call and business update.
2021 was a transformational year for Regulus with the accomplishments of our ADP <unk> program and steady progress in our <unk> syndrome program made by our partner Sanofi.
I'll begin first by mentioning the financing last November in which we successfully closed a $34 $6 million private placement on favorable terms that included several new institutional investors and support from several of our existing institutional investors.
Chris Calsada: Given the challenging recent market conditions in the biotechnology sector and more broadly, our ability to secure this financing speaks to the promise and viability of our pipeline, which continues to move steadily forward. In December, we announced the appointment of Dr. Mohamed Amedian as Vice President, Chemistry and Pharmaceutical Development.
Given the challenging recent market conditions in the biotechnology sector and more broadly our ability to secure this financing speaks to the promise and viability of our pipeline, which continues to move steadily forward.
Jay Hagan: Moh's deep experience leading operations for life science companies and background managing various projects, including the development and manufacture of therapeutic oligonucleotides, make him a natural fit for helping to guide our programs forward. His hiring came at a particularly opportune time as we entered into discussions with the FDA regarding the IND for our RGLS-A429-A2PKD program. In January, we announced a successful completion of the pre-IND meeting for RG-LSA-429, which included minutes detailing FDA's overall agreement with the sufficiency of the non-clinical package, the overall trial design, and the length of our planned phase one study. With this feedback, we remain on track with our plan to submit an IND application in the second quarter of this year.
In December we announced the appointment of Doctor Muhammad immediate as Vice President of chemistry in pharmaceutical development, most deep experience, leading operations for life science companies and background managing various projects, including the development and manufacturer of therapeutic oligonucleotides make him a natural fit for helping to guide our pro.
Grams for it.
His hiring came at a particularly opportune time as we entered into discussions with the FDA regarding the AAD for RG LSA for two nine <unk> program.
In January we announced the successful completion of the pre IDE meeting for RGA, Let's say four to nine which included minutes detailing FDA is overall agreement with the sufficiency of the non clinical package. The overall trial design and the length of our planned phase one study.
With this feedback we remain on track with our plan to submit an IND application in the second quarter of this year.
Jay Hagan: As a reminder, our Phase 1 study plan involves a single dose escalation study in healthy volunteers followed by a multiple dose escalation study in patients with ADPKD with the goal to establish a dose response around the dose level where robust clinical biomarker effects were demonstrated with RGLS 4-3-2-6, the first generation comp [inaudible] Top-line biomarker data in the first cohort of RGLS 842-9 treated patients Importantly, we are leveraging the clinical pharmacology data from the first generation molecule to better understand the relationship between dose and exposure, which we intend to use in fine-tuning the dose selection in the SAD and MADS portions of the Phase 1B program.
As a reminder, our phase one study plan involves a single dose escalation study in healthy volunteers, followed by a multiple dose escalation study in patients with ADP JD with the goal to establish a dose response around the dose level, where robust clinical biomarker effects were demonstrated with RGA last for three to six the first generation.
Compound.
Topline biomarker data in the first cohort of <unk> 8429 treated patients with ADP KD.
As anticipated in the first half of next year, and we look forward to providing updates on progress.
Importantly, we are leveraging the clinical pharmacology data from the first generation molecule to better understand the relationship between dose and exposure, which we intend to use in fine tuning the dose selection in the sad and Mad portions of the Phase <unk> program.
Jay Hagan: We plan to extrapolate the dose for the fourth and final cohort based on the PK data from the first two cohorts of the SAD in healthy volunteers and the exposure at the NOAELs in the IND-enabling talk study. This will allow us to demonstrate safety and tolerability in humans at the exposure levels from the NOAELs.
We plan to extrapolate that the dose for the fourth and final cohort based on the PK data from the first two cohorts of the Sandy in healthy volunteers and the exposure at the end of <unk> and the IND, enabling Tox studies. This will allow us to demonstrate safety and tolerability in humans at the exposure levels from the Nols.
Jay Hagan: We will also use these data, along with the learnings from the first generation PK results, to ensure that the dose levels chosen in the MAD portion of the study in patients will provide the exposure that was achieved at the one milligram per kilogram level and that produced robust increases in polycystin levels. Noted Last Year No, no, no, no, no, no, no, no, Importantly, we believe our completed IND-enabling tox studies for RGLSA-429 will allow us to dose significantly higher than the 1 mg per kg, where we saw the impressive increases in polycystins in the first-generation compound, and one other bit about the upcoming study.
We will also use these data along with learnings from the first generation PK results to ensure that the dose levels chosen in the <unk> portion of the study in patients. We will provide the exposure there was achieved at the one milligram per kilogram level and that produced the robust increases in polycystic levels.
Noted last year.
Importantly, we believe our completed IND, enabling Tox studies for our jealousy 429 will allow us to do is significantly higher than the one Meg per kg, where we saw the impressive increases in polycystic <unk> in the first generation compounds.
And one other bit about the upcoming study.
Jay Hagan: We also look at changes in GFR, total kidney volume, and cystic architecture over the three-month dosing period. Since this is a short-term dosing study, we're not likely to see meaningful improvements in these parameters. However, we may be able to correlate polycystin changes with cystic improvements, a potentially significant advancement in understanding the impact of targeting miR-17 in this disease.
We also look at changes in GFR total kidney volume in cystic architecture over the three month dosing period.
Since this is a short term dosing study, we're not likely to see meaningful improvements in these parameters. However, we may be able to correlate polycystic changes with cystic improvements and potentially significant advancement in understanding the impact of targeting Mir 17 in this disease.
Jay Hagan: Turning briefly to the Lena Mare Center RG012 program for the treatment of Alport syndrome. Last month, we announced Sanofi's completion of enrollment in the phase two global HERA clinical study evaluating ledomersin for the treatment of adult patients with Alport syndrome. Under our collaboration and license agreement, Sanofi. Alport syndrome represents a significant unmet need with no approved therapies.
Turning briefly to the letter medicine or <unk> program for the treatment of <unk> syndrome.
Last month, we announced Sanofi is completion of enrollment in the phase two global HERA clinical study evaluating let a medicine for the treatment of adult patients with <unk> syndrome under our collaboration and license agreement with Sanofi.
Outboard syndrome represents a significant unmet need with no approved therapies.
Jay Hagan: Final data from this Phase 2 study is expected in the first half of 2023. Under the terms of the agreement, the company is eligible to receive $25 million upon successful completion of the ongoing hair study or initiation of the next phase of development for let Emerson. And more importantly, potentially provide further validation of our platform technology designed to address genetic disorders. This potential additional cash infusion would further our cash runway into 2024.
Final data from this phase II study is expected in the first half of 2023.
Under the terms of the agreement the company is eligible to receive $25 million. Upon successful completion of the ongoing HERA study or initiation of the next phase of development for <unk> and more importantly, potentially provide further validation of our platform technology designed to address genetic kidney diseases.
This potential additional cash infusion, which further our cash runway into 2024.
Jay Hagan: We have an ambitious but achievable year ahead of us, and I look forward to continuing our work to further understand the role of Micronane Disease, where we can leverage our technology to ultimately improve the lives of the patients. I'll now turn the call back over to Chris for a discussion of our financial results.
We have an ambitious but achievable year ahead of us and I look forward to continuing our work to further understand the role of micro named disease, where we can leverage our technology to ultimately improve the lives of patients.
I'll now turn the call back over to Chris for a discussion of our financial results Chris. Thank you Jay.
Chris Calsada: Thank you, Jay. Turning to our financial results as of December 31, 2021, our cash and cash equivalence totaled approximately $60.4 million. We expect that our existing cash will fund planned activities through 2023. This guidance does not include the potential Sanofi milestone.
Turning to our financial results as of December 31, 2021, our cash and cash equivalents totaled approximately $64 million.
We expect that our existing cash will fund planned activities through 2023.
This guidance does not include the potential Sanofi milestone.
Chris Calsada: Research and development expenses for the fourth quarter of 2021 totaled $4.4 million, compared to $4 million in the same period for 2020. For the full year 2021, R&D expenses were $17.8 million, compared to $15.3 million for the prior year. These amounts reflect the internal and external costs associated with advancing our ADPKD program and our other research efforts in our pipeline. General and administrative expenses for the fourth quarter of 2021. Total $2.6 million compared to $2.1 million for the same period in 2020. General and administrative expenses for the full year 2021 were $10 million, compared to $8.8 million for the same period in the prior year. These amounts reflect personnel-related and ongoing general business operating costs.
Research and development expenses for the fourth quarter of 2021 totaled $4 4 million compared to $4 million.
Same period for 2020.
For the full year 2021, R&D expenses were $17 $8 million.
Compared to $15 3 million for the prior year. These amounts reflect the internal and external costs associated with advancing our ADP JV program and our other research effort in our pipeline.
General and administrative expenses for the fourth quarter of 2021.
<unk> totaled $2 $6 million compared to $2 1 million for the same period in 2020.
General and administrative expenses for the full year 2021 were $10 million compared to $8 $8 million for the same for the prior year.
These amounts reflect reflect personnel related and ongoing general business operating costs.
Chris Calsada: Net loss for the fourth quarter of 2021 was $7.1 million compared to a net loss of $1.3 million for the same period in 2020, which included an interim enrollment milestone of $5 million from our ongoing collaboration with Sanofi for Vladimir's. Basic and diluted net loss per share for the fourth quarter of 2021 was $0.07 per share compared to basic and diluted net loss per share of $0.03 per share for the same period in 2020. The net loss for 2021 was $27.8 million compared to $15.7 million for the previous year. Basic and diluted net loss per share for 2021 was $0.32 per share compared to $0.45 per share for the prior year.
Net loss for the fourth quarter of 2021 was $7 1 million compared to a net loss of $1 3 million for the same period in 2020, which included an interim enrollment milestone of $5 million from our ongoing collaboration with Sanofi for nanometers.
Basic and diluted net loss per share for the fourth quarter of 2021 was <unk> <unk> per share compared to basic and diluted net loss per share <unk> <unk> per share for the same period in 2020.
Net loss for 2021 was $27 8 million compared to $15 $7 million for the previous year basic and diluted net loss per share for 2021 was <unk> 32 per share compared to 45 per share for the prior year.
Jay Hagan: With that, I will turn the call back over to Jane. Thanks, Chris. We're happy to take any questions now. Operator, please open the line.
With that I will turn the call back over to Jay.
Thanks, Chris we're happy to take any questions now operator, please open the lines.
Operator: Ladies and gentlemen, if you have a question or a comment at this time, please press the star and then the one key on your touchtone teleph. Your question has been answered. If you wish to move yourself from the queue, please press the pound.
Ladies and gentlemen, if you have a question or comment at this time. Please press. The Star then the one key on your Touchtone telephone mix. Your question has been answered you were seeing with yourself from the queue. Please press the pound key our.
Jay Hagan: Our first question comes from Brian Changwakan. Hey guys, thanks for taking my questions. So my first question is on your phase one study. I'm just curious how you view COVID as a factor in meeting the timeline that you have laid out for data from the phase one set portion and also phase one deep in patient portion as well. And I won't follow up.
Our first question comes from Brian Cheng with Cantor.
Yes.
Hey, guys. Thanks for taking my questions.
So first question is on your <unk> study I'm just curious how you view copay, that's a factor in meeting the timelines that you have laid out for.
Data from the phase one sad portion and also phase one beep in patient portion as well and I have one follow up.
Jay Hagan: Sure, thanks, Brian. Yeah, with respect to the sad part, we're planning to conduct the study at the same site we used before where, you know, a couple of years ago, COVID had a much more significant impact. It happened to be in a state that tends to be a little more liberal with respect to COVID restrictions and didn't really encounter any significant issues in terms of recruiting healthy volunteers at a single phase one unit.
Sure. Thanks, Brian Yeah with respect to the sad.
We're planning to conduct.
The study at the same site, we used before where.
Couple of years ago, Covid was much more significant impact.
It happened to be in a state that tend to be a little more.
Liberal with respect to Covid restrictions and didn't really encounter any significant issues in terms of recruiting healthy volunteers at a single phase one unit. So we don't we don't anticipate any impact.
On that of course these are forward looking statements and things can change with respect to the pandemic.
Then with respect to.
The phase one b in patients we're targeting about double the number of sites we had in the first.
In the study with a first generation molecule, which.
Should alleviate concerns about hitting timelines with respect to that.
The time to getting data here.
Jay Hagan: And to follow up on your comments about some of the efficacy measures for the second-generation molecule, you know, in phase one B, you will be looking at GFR and total kidney volume. Based on what you've seen in preclinical data, what are your thoughts about how long patients will need to be on the study and on treatment to see a meaningful response in GFR or total kidney volume?
Okay.
To follow up on your comment about some of the efficacy measure it for.
The second Gen molecule.
In the phase one b, you'll be looking at GFR entitled Kidney volume.
Based on what you're seeing in preclinical data.
What's your thoughts about how long we will need to for the patients to be on the study to be on treatment to see a meaningful risk bonds on CFR, alright, total kidney volume.
Jay Hagan: Yeah, so, you know, obviously, we've only studied treatment for six weeks thus far in patients with the disease. So I'm basing our commentary, you know, primarily on what has been required for other compounds in development. And of course, though, our mechanism is quite unique, and I think the impact on cystic architecture we've seen with targeting miR-17, to our knowledge, we haven't seen that with any other mechanism.
Yes, so we obviously all in patients with the disease. We've only studied treatment for six weeks, thus far so.
So I'm basing our commentary.
Primarily based on what is.
What has been required for other compounds in development and of course, though our mechanism is quite unique I think the impact on cystic architecture, we seen with targeting Mir 17.
To our knowledge, we haven't seen that with any other mechanisms. So we're hopeful that we can see something in a short period of time, but that's why we guided that.
Jay Hagan: So we're hopeful that we can see something in a short period of time, but that's why we said that, you know, we're cautiously optimistic with respect to seeing something in under three months. In terms of where we think it would take, you know, ultimately, in the trial design we've discussed before, in a phase two study of one year in duration to see an impact on TKB, we may see something in GFR in that timeframe, but it may take a bit longer. And that's, again, based on historical precedent.
We're cautiously optimistic with respect to seeing something in short of three months.
Or where we think it would take ultimately.
The trial design, we've discussed before in a phase II study of one year in duration to see an impact on Teekay <unk>, we may see something in GFR and that timeframe, but it may take a bit longer and that's again based on historical precedent, but importantly, there are advancements in MRI imaging that enable one to look at what we're describing assistant.
Jay Hagan: But importantly, there are advancements in MRI imaging that enable one to look at what we're describing as cystic architecture, cyst count, and cyst volume. And that's where we're particularly intrigued to see if we can correlate a change in polycystin levels from baseline with changes in that architecture, which would be quite interesting. And that, you know, that's where we might be able to see something in the shorter term duration study. Got it. Thank you, Chairperson. Sure. Our next question comes from me, Chen, with Italy Wayne.
Architecture <unk> count in <unk> volume.
And that's where we're particularly intrigued to see if we can't correlate a change in policy system levels from baseline with changes in that architecture, which can be quite interesting.
That's where we might be able to see something in the shorter term duration study.
Got it thank you Jay.
Sure.
Our next question comes from <unk>, Chen with H C Wainwright.
Jay Hagan: Thank you for taking my question. My first question is, could you clarify what exactly needs to happen for the company to receive the additional 25 million milestone payments from Sentinel? Yeah, so some of this is obviously confidential with respect to the negotiated agreement. We tried to describe it here, Yi, and that is, you know, success in phase two, meaning hitting the primary endpoint, or their decision to advance further into clinical development.
Thank you for taking my question. My first question is could.
Could you clarify what exactly.
What exactly needs to happen.
For the company to pursue the additional 25 million milestone payments from Sanofi.
Yes. So some of this is obviously confidential with respect to negotiated agreement we tried to describe it here and that is <unk>.
Success success in the phase II meeting hitting the primary endpoint or their decision to advance further into clinical development because often when you. When you prospectively designed study youre not quite sure of the treatment effect and so you might see trends that don't quite reached statistical significance and you still may decide to move forward into clinical development. So in our view that.
Jay Hagan: Because often, you know, when you prospectively design a study, you're not quite sure of the treatment effect. And so you might see trends that don't quite reach statistical significance, and you still may decide to move forward into clinical development. So in our view, there are sort of two ways to win.
Sort of two ways to win here.
Got it got it.
Jay Hagan: Got it, got it. So my next question is, recently, we had to receive a complete response letter for paroxysilone. So how does that affect the field for Alport syndrome and for ADPKD as well? Yeah, I don't know any more than what's been disclosed by RIATA, but obviously, they've indicated they plan to work with FDA to find what additional information they can provide to address the complete response letter with respect to the CRL for Alport syndrome.
So my next question is.
Recently, we have to receive the complete response letter.
Four products alone. So how do you see that affects the <unk>.
For al procedure for ADP kidney as well thank you.
Yes, I don't know any more than what's been disclosed by by reorder, but obviously they've indicated they plan to work with FDA to find what additional information they can.
Provide to address the.
<unk>.
A complete response letter with respect to.
The CRM for.
For <unk> syndrome. So.
Jay Hagan: So I do know that in discussions with our partner, we still have the potential here to be the first approved therapy, which is a very significant unmet need. You know, as was discussed at the ad common is what we know from our work with the Alport community. And given the pharmacology that was described in that advisory committee, I don't expect there to be much of a difference in the ADPKD setting, where you do have an improved therapy and it is an older patient population who might be at greater risk for potential cardiovascular events. So we shall see. They have made a number of adjustments to the trial design, including the amount of follow-up. I think they extended it from four weeks to eight weeks, and they increased the sample size.
I do know that in discussions with our partner that that we still have the potential here to be potentially.
First approved therapy, which is a very significant unmet need.
As was as was discussed at the I'd comment is what we know.
With our work with the with the output community.
And given the pharmacology that was described in that Advisory Committee I don't I don't expect there to be much of a difference in the ADP <unk> setting where you do have an approved therapy and it is an older patient population who might be at a greater risk for potential cardiovascular events. So we shall see they have made.
A number of adjustments to the trial design, including the amount of follow up.
The extended from four weeks to eight weeks and increase the sample size. So that's ongoing and we will see.
Okay got it thank you.
Operator: So that's ongoing, and we'll see. Okay, I got it. Thank you. Again, ladies and gentlemen, if you have a question or a comment at this time, please press the star and then the one key on your touchtone telephone. And I'm not showing any further questions at this time. I'd like to turn the call back to Jay for any closing. Great, thanks everyone for joining us today. We appreciate your interest and support of Regulus and look forward to providing updates as we move forward with our progress. Thank you. Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have music.
Again, ladies and gentlemen, if you have a question of our comp time. Please press. The Star then the one key on your Touchtone telephone.
And I'm not showing any further questions at this time I'd like to turn the call back to Jay for any closing remarks.
Great. Thanks, everyone for joining us today, we appreciate your interest and support of Regulus and look forward to providing updates as we move forward with our progress. Thank you.
Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.
Yeah.
Okay.
[music].
Okay.
[music].
Jay Hagan: So we don't anticipate any impact on that. But, of course, these are forward-looking statements, you know, and things could change with respect to the pandemic. And then with respect to phase one B in patients, we're targeting about double the number of sites we had in the first study with the first generation molecule, which should alleviate concerns about hitting timelines with respect to the time beginning data here. Okay.