Q3 2021 Regulus Therapeutics Inc Earnings Call

November 10, 2021

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Operator: Good afternoon, ladies and gentlemen, and welcome to the Regulus Therapeutics Inc. Quarter 3, 2021 conference call. At this time, all participants are in only mode. Later, we will conduct a question and answer session, and instructions will follow at the time. If anyone should require assistance during the conference, please press star, then zero on your touchstone telephone. As a reminder, this conference call is being recorded. I'd like to turn the call over to your host, Ms. Chris Elsada, Chief Financial Officer. You may be kidding me.

Good afternoon, ladies and gentlemen, and welcome to do Regardless Therapeutics, Inc, quite or 320 21 conference call at.

This time, all participants I notice an oldie mode. Neither of them will conduct a question and answer session and his chance to follow at that time, if anyone should require assistance. During the conference. These breasts or is he wrote on your Touchtone telephone.

As a reminder, this conference call is being recorded.

And I'd like to turn the conference over to your host mystery, So Sarah Chief Financial Officer, you may begin.

Crispina Calsada: Thanks, Operator. Good afternoon, and thank you for joining us to discuss Regulus Therapeutics' third quarter 2021 financial results and corporate highlights. With me on today's call is Jay Hagan, President and Chief Executive Officer, and Dennis Drygin, Chief Scientific Officer. Jay will provide opening remarks and share progress on our 80 PKD program, and I will review the financial results before we open the lines for questions. Before we begin, I'd like to remind you that this call will contain forward-looking statements concerning regular therapeutics' future expectations, plans, prospects, corporate strategy, and performance, which constitute forward-looking statements for the purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995.

Thanks operated good afternoon, and thank you for joining us to discuss regular therapeutic third quarter 2021 financial results and corporate highlight with me on today's call Jay Hagan, President and Chief Executive Officer, and Dennis Dragon, Chief Scientific Officer J will.

Provide opening remarks and share progress on our 80 P. K D program.

And I will review the financial results before we open the line to the question.

Before we begin I'd like to remind you that this call will contain forward looking statements concerning regular therapy pudic future expectation plan prospects corporate strategy and performance.

Which constitute forward looking statements for the purposes of the safe Harbor provision under the private security <unk>.

Litigation Reform Act of 1995.

Crispina Calsada: 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 obligation to update such statements. I'll now turn the call over to Jay.

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.

Pacifically disclaim any obligations updates such statements.

I'll now turn the call over to Jay.

Thanks, Chris.

Joseph P. Hagan: Welcome everyone to our Q3 earnings call and business update. We're pleased to share an update on our 80 PKK program and plans for next year. Before we get into more detail on our efforts to address this important unmet medical need, I want to spend a few minutes discussing the landscape. Autosomal dominant polycystic kidney disease, or 80 PKD, is a genetic kidney disease caused by mutations in either the PKD1 or PKD2 genes. It is one of the most common human monogenetic disorders and the leading genetic cause of end-stage renal disease.

Welcome everyone to our two three earnings call his business update where.

We're pleased to share an update on our ADP could a program and plans for next year.

Before we get into more detail on our efforts to address this important unmet medical need I want to spend a few minutes discussing the landscape.

All those little dominant polycystic kidney disease or ADP J D.

Genetic kidney disease caused by mutations in either the P. P D. One or P. K two gene and is one of the most common human monogenetic disorders, and the leading genetic causes of end stage renal disease.

Joseph P. Hagan: In the United States, there are approximately 160,000 patients diagnosed with the disease, but it's believed to be significantly underdiagnosed, with closer to half a million in the US alone. The disease is characterized by slowly progressive bilateral enlargement of the kidneys due to growth and proliferation of fluid-filled cysts. Patients with ADPKD experience impacts on quality of life, including pain in their sides and back due to the enlargement.

And the United States are approximately 160000 patients diagnosed with the disease. However, it is believed to be significantly older diagnosed with closer to half a million in the U S alone.

The disease is characterized by slowly progressive bilateral enlargement of the kidney due to growth and proliferation of fluid filled cysts.

Patients with ADP give you experienced impacts on quality of life, including pain in their sides and back due to the Lord and their prognosis is a progressive loss of renal function.

Leading to kidney failure for the average patient in their fifties or seventies, depending on what type of mutation day huh.

Mutations in the P. P D one gene or the predominant form of the disease accounting for 85% of the diagnoses.

With the remaining 15% due to mutations in the <unk>.

Mutations in the peak any one gene tend to have lead to more aggressive disease and renal decline.

Current treatment options for patients are very limited with one only one approved product <unk>.

Joseph P. Hagan: Current treatment options for patients are very limited, with only one approved product, TovapD. Telvaphton is a vasopressin antagonist and has safety intolerability issues that are likely limited to its use. It has a block box warning for potential fatal liver injury and failure requiring transplant, which requires restrictive distribution in ongoing liver monitoring and patient education. Due to its mechanism, it also has significant tolerability issues leading to patient discontinuation for those who cannot tolerate the medication, which speaks to both the medical need and the opportunity for improved treatments in That said, sales are estimated to exceed $800 million in 2021, in its third year on the market.

Till that that is a visa precedent antagonists and has safety and tolerability issues that is likely limited as uptake.

It has a black box warning for potential fate of liver injury and failure required transplant, which requires restrictive distribution an ongoing liberal monitoring in patients.

Due to its mechanism. It also has significant tolerability issues, leading to patient and discontinuation for those who cannot tolerate the medication, which speaks to both the medical need and the opportunity for improved treatments in this category.

That said sales are estimated to exceed $800 million in 2021, and it's third year on the market.

Now turning to our approach to address this important disease.

Call that we are developing an antagonist to mere 17, which has been shown to be upregulate in the disease indirectly controls pick any one in PGD two expression.

In addition to the data generated by our team and that of her collaborators at U T. Southwestern.

We were excited to read the recent publication added Professor Sokolow's group at Yale in nature Genetics, where they described in mouse models of the disease. The rapid reversal of multiple aspects of the ADP K D. Phenotype. After re expression of both polycystic, one and polycystic to providing further support of targeting.

Joseph P. Hagan: Now turning to our approach to address this importance. Recall that we are developing an antagonist to Mere 17, which has been shown to be upregulated in the disease and directly controls PK1 and PKD2 expression. In addition to the data generated by our team and that of our collaborators at UT Southwestern, We were excited to read the recent publication out of Professor Somlo's group at Yale in Nature Genetics, where they described in mouse models of the disease the rapid reversal of multiple aspects of the ADPKD phenotype after re-expression of both polycystin 1 and polycystin 2, providing further support of targeting Mere 17 to treat ADPKD.

<unk> 17 to treat ADP D.

As we disclose earlier this year, we have been able to demonstrate statistically significant increases in these two proteins polycystic one in polycystic too through treatment with an antagonist Amir 17 in patients with ADP candy.

Now I would like to update you on a recent progress with our program.

In October we announced our plans to prioritize the advancement of our next generation compounds are.

<unk> 8429, and discontinued the development of our first generation compounds are jealous 4326.

This prioritization was driven by our business objective of allocating our resources and efforts towards the development of the more promising next generation compound.

8429 has been shown to have all the favorable properties of the first generation compound without the limitations.

We are excited by this progression as we believe Rgs 8429 holds greater promise, including a superior pharmacologic profile with the absence of the off target CNS effects that we're seeing with argue is 4326.

Joseph P. Hagan: As we disclosed earlier this year, we have been able to demonstrate a statistically significant increase in these two proteins, Polysystem 1 and Polysystem 2, through treatment with an antagonist ameer 17 in patients with ADPKD. Now I'd like to update you on recent progress with our program. In October, we announced our plans to prioritize the advancement of our next generation compound, RGLS 8429, and to discontinue development of our first generation compound, RGLS 4326. This prioritization was driven by our business objective of allocating our resources and efforts towards the development of the more promising next generation compound.

In chronic preclinical toxicology studies at the top doses tested.

Additionally, RG LSA 429 has shown equal potency to its molecular target mirror 17, and both in vitro and in vivo efficacy studies.

We have also demonstrated additive efficacy in preclinical models when combined with <unk>, an important political and commercial considerations.

We are scheduled to have a pre <unk> meeting with FDA for Rgs 8429 in December and are on track for 90 submission and initiation of clinical development in the second quarter of 2022 subject to FTA clearance of the Indy.

Looking ahead to our plan phase one study.

These plans include a single ascending dose study in healthy volunteers to enable a multiple dose escalation study in patients with ADP K D. Around the dose levels were robust clinical biomarker effects, meaning changes in polycystic one in polycystic too were demonstrated with the first generation compound.

We anticipate reporting topline biomarker data in the first cohort of arduous 8429 treated patients.

In early 2023.

Joseph P. Hagan: 8429 has been shown to have all the favorable properties of the first generation compound without the limitation. We're excited by this progression as we believe RGLS 8429 holds greater promise, including a superior pharmacologic profile and the absence of the off-target CNS effect that we're seeing with RGOS 4326, in chronic preclinical toxicology studies at the top doses test. Additionally, RGLS 8429 has shown equal potency to its molecular target, MIR 17. In both in vitro and in vivo efficacy studies, we have also demonstrated additive efficacy in preclinical models when combined with Tovaptan, an important clinical and commercial consideration.

Although we decided to discontinue are jealous 4326 in favor of the next generation compound 8429, the work to date.

On that compound directly informs development of our jealousy 429.

A number on November 4th at the American Society of Nephrology kidney week meeting and yesterday at the Biomarkers for rare disease Summit, we presented additional data from the first cohort of patients in the phase one b clinical trial of argue lists 4326.

Which reinforces our prior updates from earlier this year.

In the first cohort nine patients were enrolled in received one milligram per kilogram of argue that 4326 subcutaneously every other week for four doses.

The main increase in polycystic, one and two at the end of study compared to baseline levels.

For all nine patients in the first cohort were 58% and 38% respectively.

The trajectory of changes in these biomarkers suggests that would continue dosing higher levels of polycystic may be attainable.

Recall, the polycystic levels are depressed in patients with the disease correlating inversely with disease severity and are believed to be directly linked to the key underlying genetic drivers of the disease.

These data demonstrate further clinical proof of mechanism by showing target engagement in the kidneys.

Through these statistically significant increases and Urinated Biomarkers piece, you wanted PC to validating mirror 17 as potential target for <unk> treatment.

Joseph P. Hagan: We are scheduled to have a pre-I&D meeting with FDA for RGLS 8429 in December and are on track for an I&D submission and initiation of clinical development in the second quarter of 2022, subject to FDA clearance of the I&D. Looking ahead to our planned phase one study, these plans include a single ascending dose study in healthy volunteers to enable a multiple dose escalation study in patients with ADPKD around the dose levels where robust clinical biomarker effects, meaning changes in polycystin 1 and polyscystin 2, were demonstrated with the first generation compound.

I am proud of the work our team at Regulus and continue to advance our understanding of the role of micro and a an important disease areas, particularly diseases of the kidney we remain steadfast in our mission to help patients suffering from <unk>.

I will now turn the call back over Chris for discussion of our financial results Chris.

Turning to our financial results as of September 30th 2021, or cash and cash equivalents totaled approximately $35.8 million.

As previously disclosed we anticipate our current cash balance if the patient.

Planned operation into the fourth quarter of 2022.

Research and development expenses for the third quarter of 2021 totaled $5.9 million compared to $4 million in the same period of 2023.

Joseph P. Hagan: We anticipate reporting top-line biomarker data in the first cohort of RGLS 849 treated patients in early 2023. Although we decided to discontinue RGLS 4326 in favor of the next generation compound 8429, the work to date on that compound directly informs the development of RGLS 8429. On November 4th, at the American Society of Nephrology Kidney Week meeting, and yesterday at the Biomarkers for Rare Disease Summit, we presented additional data from the first cohort of patients in the Phase 1B clinical trial of RGLS 4326, which reinforces our prior updates from earlier this year.

These amounts reflect the internal and external costs associated with advancing.

Clinical and clinical pipeline.

General and administrative expenses for the third quarter of 2021 totaled $2.5 million compared to $2.1 million for the same period in 2020.

These amounts reflect personnel related and ongoing general business operating costs.

Net loss for the third quarter of 2021 was $8.6 million compared to a net loss of $1.5 million for the same period in 2020.

Basic and diluted net loss per share for the third quarter of 2021.

Per share compared to basic and diluted net loss per share a four cents per share for the same period in 2020.

With that I will turn the call back over again.

Thank you Chris.

Operated we're happy to take questions now please open the legs.

Ladies and gentlemen, if we have a question at this time, please fastest star and then a number one on your Touchtone telephone is that question has been asked trying to do wish to move yourself funded you. Please press spanky.

Joseph P. Hagan: In the first cohort, nine patients were enrolled and received one milligram per kilogram of RGLF4-326 subcutaneously every other week for four doses. The mean increase in polysystems 1 and 2 at the end of study compared to baseline levels for all nine patients in the first cohort was 58% and 38%, respectively. The trajectory of changes in these biomarkers suggests that with continued dosing, higher levels of polycystin may Recall that polycystin levels are depressed in patients with the disease, correlating inversely with disease severity, and are believed to be directly linked to the key underlying genetic drivers of the disease.

Ladies and gentlemen, if you have a question at this time. Please press star and then a number one key on your Touchtone telephone.

Okay. First question comes from the line of Brian Cheng from Cantor Fitzgerald. Your line is open.

Hey, guys. Thanks for taking my question.

Since you are preparing to file the Indy 529 in the second quarter.

Are there any specific items that you will need to discuss what the FDA next month at the Pim Timp meeting.

And can you also talk about how much of the work that you had done in the past 443, 26th off my lap.

Joseph P. Hagan: These data demonstrate further clinical proof of mechanism by showing target engagement in the kidneys, through these statistically significant increases in urinary biomarkers, PC1 and PC2, validating MIR 17 as a potential target for ADPKD treatment. I'm proud of the work of our team at Regulus and continue to advance our understanding of the role of microRNA in important disease areas, particularly diseases of the kidney. We remain steadfast in our mission to help patients suffering from ADPKD. I'll now turn the call back to Chris for a discussion of our financial results. Chris? Thanks, Jay.

Filing that you anticipate too.

Second quarter.

Sure Yeah. So so the the work that we're wrapping up here for for the filing.

Filing includes but below pulled the tent so to speak is receipt of the the final reports from the toxicology studies and incorporation into the documents of the team is busy at work and as we disclosed earlier, we had completed the in life portion.

The dosing of the toxicology studies. So it's just a matter of of completion of the analytical work there and in terms of what we've learned.

From the first program.

We've got a sense, obviously of where we see changes in biomarkers, which informs that dose selection here with a 429 and so our proposal FDA includes.

Moving quickly two dose levels, where we have seen those changes in biomarkers, which speeds up development, we will spend as much time in a sub therapeutic level dosing.

Crispina Calsada: Turning to our financial results, as of September 30th, 2021, our cash and cash equivalents totaled approximately $35.8 million. As previously disclosed, we anticipate our current cash balance will be sufficient to fund planned operations into the fourth quarter of 2022.

Dosing are much lower levels and.

Obviously, we have very significant presume margins based on the lack of any overt toxicity observed in the idea, enabling talk studies, which enables those sorts of starting doses. So so those are some of the elements that will speed development. Additionally, as we've outlined our proposal includes going from the.

Single, sending dose into patients with the multiple sending dose and skipping over.

Study in healthy volunteers, which further speed the development.

Crispina Calsada: Research and Development expenses for the third quarter of 2021 totaled $5.9 million compared to $4 million in the same period of 2020. These amounts reflect the internal and external costs associated with advancing our preclinical and clinical pipeline. General and administrative expenses for the third quarter of 2021 total $2.5 million, compared to $2.1 million for the same period in 2020. These amounts reflect personnel-related and ongoing general business operating costs. The net loss for the third quarter of 2021 was $8.6 million, compared to a net loss of $1.5 million for the same period in 2020.

The.

This next generation compound and in terms of the so that will all be part of the discussion was FDA in the briefing book, which teams just wrapping for a meeting December includes the proposed starting doses in clinical design supported by the results of the Tux call.

<unk> studies as well as what we've seen previously.

In terms of biomarker changes in so that's the.

The aim of the <unk> meeting in addition to more.

Typical things like the CMC package and elements like that right.

And then.

On the child data. So we expect top line from the first cohort.

In early 2023.

I am just curious whether you'll be able to do in the interim data.

Healthy war on terror.

Single dose partial to get a sense of <unk> profile and fled there and also whether there will be any data between now and Youre short patient core Qaeda in 2023.

Yeah. So we'll obviously have updates as we progress through the single sending dose study in healthy volunteers and when we wrap it be able to articulate topline results in terms of safety and pique, we're not planning to look for any PD signal because mere 17 is not up.

Crispina Calsada: Basic and diluted net loss per share for the third quarter of 2021 was 10 cents per share compared to basic and diluted net loss per share of 4 cents per share for the same period in 2020.

Regulated in in healthy volunteers, so we wouldn't expect to see.

<unk> ability to test statistically significant increases with the single dose.

Joseph P. Hagan: With that, I will turn the call back over to Jay.

So it will just be seeking PK out of the out of.

Operator: Operator, we're happy to take questions now. Please open the lives.

Healthy volunteer study.

Okay, and if I may just one more on the final.

Operator: Ladies and gentlemen, if we have a question at this time, please press the star and then the number one key on your Touchstone Telephone. If your question has been answered or you wish to remove yourself from the queue, please press the Brown key. Again, ladies and gentlemen, if you have a question at this time, please press star and then the number one key on your Touchstone Telephone. Your first question comes from the line of Brian Chang from Cantor Fitzgerald. Your line is open.

It seems that there is a slight increase in the R&D expand quarter over quarter.

Christy Anthony guidance on how we should think about your expense moving forward and.

And also on the BB fine what's your latest thoughts on potential partnerships of collaboration near term. Thanks.

So on the first piece of that Brian. So the increase in R&D expenses was primarily attributed to the GMP manufacturing campaign.

That occurred this quarter in support of our upcoming phase one so that was kind of a one time expense. So we anticipate are expensive.

Expenses to kind of go back to.

Brian Chang: Hey guys, thanks for taking my question. So as you're preparing to file the I&D for 8429 in the second quarter, are there any specific items that you will need to discuss with the FDA next month at the pre-IND meeting? And can you also talk about, you know, how much of the work that you have done in the past for 4326 overlaps with the filing that you anticipate doing in the second quarter?

What we damaged in the prior two quarters, yeah to think about it as we had two two programs, where we're spending money on 4326 clinical work and then the lumpy spend associated with manufacturer of your your clinical material for a 429.

And then with respect to beady, we have ongoing discussions with folks and I think that.

It certainly appears that would know regulatory clarity on how we're planning to move forward from a programmatic standpoint.

Has.

Fostered renewed interest in the program.

And we have ongoing discussions.

I'm not going to guide to if and whether we will do anything but our business development.

Group is active.

Alright, thanks, guys.

Okay, ladies and gentlemen, if we have question at this time. Please press star and then the number one key on your cash stone telephone.

Joseph P. Hagan: Sure, yeah, so the work that we're wrapping up here for the I&D filing includes the long poll in the tent, so to speak, is receipt of the final reports from the toxicology studies and incorporation into the document. The team is busy at work, and as we disclosed earlier, we had completed the in-life portion of the dosing of the toxicology studies, so it's just a matter of completion of the analytical work there.

Next question comes from the line of the Chen from H U. We night your line is open.

Yeah.

Thank you for taking my question.

80, 429 has <unk> has a similar potency compared to 40 could 26.

Should we expect to see a similar percentage level increase.

Joseph P. Hagan: In terms of what we've learned from the first program, you know, we've got a sense, obviously, of where we see changes in biomarkers, which informs dose selection here with 8429. And so our proposal with FDA includes moving quickly to dose levels where we have seen those changes in biomarkers, which speeds up development. We won't spend as much time at a sub-therapeutic level dosing at much lower levels. And, you know, obviously, we have very significant, presumed margins based on the lack of any overt toxicity observed in the I&D enabling toxic studies, which enables those sorts of starting doses. So those are some of the elements that will speed development.

Sorry, <unk>, a similar percentage level of increase in <unk> polycystic wanted to.

Or there are some other factors that could affect.

<unk>. Thank you.

Yeah. So so in terms of what we would anticipate potentially seeing I think the way we think about it.

Is that based on everything we've seen to date in like the and this is all in our updated investor deck in the PK D. One flux R. C model the kidney of the 8429 treated animal looks a heck of a lot like the kidney or the 4326 treated animal which looks much better.

Meeting not filled with cysts the way the PBS or control treated animals are similarly, and all these vitro testing.

Joseph P. Hagan: Additionally, you know, as we've outlined, our proposal includes going from the single ascending dose into patients with the multiple ascending dose and skipping over the MAD study and healthy volunteers, which further speeds the development of this next generation compound. And in terms of the, so that'll all be part of the discussion with FDA in the briefing book, which the team is just wrapping up for our meeting in December, including, you know, the proposed starting doses and clinical design supported by the results of the toxicology studies as well as what we've seen previously in terms of biomarker changes. And so that's the aim of the pre-undee meeting. in addition to more typical things like the CMC package and elements like that, right?

In terms of the potency.

To the target.

An engagement as well as the.

PK profiled the molecule it.

It looks like it behaves very much like.

8429, behaves very much like 4326, and when we put it through Pan lab screens. It doesn't have any other off target unwanted off target effects that we discovered.

4326 possessed and we've shown that as well and are updated investor deck that it has no activity on the Amp a receptor which was we believe underlying the CNS side effects that were observed and that has been confirmed in our robust toxicology studies, where we have essentially.

Does the same amount of compound that would be dose in a chronic talk study now so really quite robust for 90, and so with all those important points that leads us to believe we should have a similar type of activity now turning to the phase one study as.

We've discussed in the past.

Brian Chang: Okay, and then on the trial data, so we expect top line from the first cohort in early 2023. I'm just curious, you know, whether you'll be able to do an interim data cut in the healthy volunteer single dose portion to get a sense of the TKPD profile and, you know, whether and also whether there will be any data between now and your first patient cohort data in 2023.

Higher changes from baseline have been shown to be achievable with lower levels of baseline polycystic, meaning the more severe patients demonstrate higher changes than those with less severe disease. So there are important nuances to two comparing it.

Cross studies, because patients could be different from one study to the next so I just want to have that important caveat, but I think if I were to rephrase. Your question long term would we expect to see a similar effect in a robust sample said I'd say absolutely.

Joseph P. Hagan: Yeah, so we'll, you know, obviously have updates as we progress through the single ascending dose study in healthy volunteers and when we wrap it up, be able to articulate top-line results in terms of safety and PK. We are not planning to look for any PD signal because MIR 17 is not upregulated in healthy volunteers, so we wouldn't expect to see, you know, an ability to detect statistically significant increases with a single dose. So it'll just be safety and P.K. out of the healthy volunteer study.

Does that mean the previous animal model you build four was 43.

26 or safety margin is.

Is due to Kabul was 80 429.

The PK profile the population PK model.

Well, we'd have to confirm that and get and get PK data, but based on the PK did we have right now with from animals. It does look like a similar P. K.

Okay, great. Thank you.

You're welcome.

I am showing no further question at this time I would like to turn the conference back to <unk> Hakan.

Great well. Thank you very much for the opportunity to provide this update to you and we appreciate your continued support of regulars.

Brian Chang: Okay, and if I may, just one more on the finance side. It seems that there is a slight increase in the R&D expense quarter over quarter. Chris, do you have any guidance on how we should think about your expense moving forward? And also, on the BD front, what are your latest thoughts on your potential partnerships or collaborations during your term? Thanks.

Thank you.

Ladies and gentlemen. This concludes today's conference call. Thank you for your participation and have a wonderful day can we all disconnect.

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Okay.

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Crispina Calsada: So on the first piece of that, Brian, the increase in R&D expenses was primarily attributed to the GMP manufacturing campaign that occurred this quarter in support of our upcoming phase one. So that was a kind of a one-time expense. So we anticipate our expenses to kind of go back to what we've averaged in the prior Yeah, and think about it as we're

Joseph P. Hagan: Yeah, think about it is we had two programs; we were spending money on the 436 clinical work and then the lumpy spend associated with the manufacture of, you know, your clinical material for 849. And then with respect to BD, yeah, we have ongoing discussions with folks, and I think that now regulatory clarity on how we're planning to move forward from a programmatic standpoint has fostered renewed interest in the program, and we have ongoing discussions about it. I'm not going to guide you to if and whether we'll do anything, but our business development group is active. Great, thanks, guys.

Operator: Again, ladies and gentlemen, if you have questions at this time, please press star and then the number one key on your dashstone telephone. The next question comes from the line of Yi Chen from H.R. Wynenwright. Your line is open.

Yi Chen: Thank you for taking Michael.

Joseph P. Hagan: Since 8429 has a similar potency compared to 4326, should we expect to see a similar percentage level increase in the biomarker polysystem 1 and 2, or are there some other factors that could affect the biomarker readout? Thank you. Yeah, so in terms of what we would anticipate potentially seeing, I think the way we think about it, Ye is that based on everything we've seen today in the, and this is all on our updated investor deck, in the PKD-1-Flox RC model, the kidney of the 849 treated animal looks a heck of a lot like the kidney of the 4326 treated animal, which looks much better, meaning not filled with cysts the way the Animals are.

[music].

Joseph P. Hagan: Similarly, in all the in vitro testing in terms of potency for the target and engagement, as well as the PK profile of the molecule, it looks like it behaves very much like 4326. And when we put it through PanLab screens, it doesn't have any other unwanted off-target effects that we discovered 4326 possessed. And we've shown that as well in our updated investor deck that it has no activity on the AMPA receptor, which is, we believe, underlying the CNS side effects that were observed.

Joseph P. Hagan: And that's been confirmed in our robust toxicology studies where we have essentially dosed the same amount of compound that would be dosed in a chronic talk study now, so really quite robust for an I&D study. And so with all those important points, that leads us to believe we should have a similar type of activity. Now, turning to the phase one study, as we've discussed in the past, higher changes from baseline have been shown to be achievable with lower levels of baseline polycystid, meaning the more severe patients demonstrate higher changes than those with less severe disease. So there are important nuances to comparing across studies because patients could be different from one study to the next. So I just want to have that important caveat.

Joseph P. Hagan: But I think if I were to rephrase your question, you know, long term, would we expect to see a similar effect in a robust sample set? I'd say absolutely. Does that mean the previous animal model you built for, with 4326 for a safety margin, is still applicable with 8429? The PK profile? The population PK model? Yeah. Well, we'd have to confirm that and get PK data, but based on the PK that we have right now from animals, it does look like it has similar PK. Okay, great. Thank you.

Operator: I am showing another question at this time. I would like to turn the conference back to Jay Hagen.

Joseph P. Hagan: Great, well, thanks very much for the opportunity to provide this update to you, and I appreciate your continued support of Regulose. Thank you.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation and have a wonderful day. You may all disconnect.

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Operator: Good afternoon, ladies and gentlemen, and welcome to the Regulus Therapeutics Inc. Quarter 3, 2021 conference call. At this time, all participants are in an ill-s in only mode. Later, we will conduct a question-and-answer session, and instructions will follow at the time. If anyone should require assistance during the conference, please press star, then zero on your touch-down telephone. As a reminder, this conference call is being recorded. I'd like to turn the call over to your host, Ms. Chris Elsada, Chief Financial Officer. You may be...

[music].

Joseph P. Hagan: Welcome everyone to our Q3 earnings call and business update. We're pleased to share an update on our 80 PKK program and plans for next year. Before we get into more detail on our efforts to address this important unmet medical need, I want to spend a few minutes discussing the landscape. Autosomal dominant polycystic kidney disease, or ADPKD, is a genetic kidney disease caused by mutations in either the PKD1 or PKD2 genes. It is one of the most common human monogenetic disorders and the leading genetic cause of end-stage renal disease.

Joseph P. Hagan: In the United States, there are approximately 160,000 patients diagnosed with this, but it's believed to be significantly underdiagnosed, with closer to half a million in the US alone. The disease is characterized by slowly progressive bilateral enlargement of the kidneys due to growth and proliferation of fluid-filled cysts. Patients with ADPKD experience impacts on quality of life, including pain in their sides and back due to the enlargement.

Joseph P. Hagan: Their prognosis is a progressive loss of renal function, leading to kidney failure for the average patient in their 50s or 70s, depending on what type of mutation they have. Mutations in the PKD1 gene are the predominant form of the disease, accounting for 85% of the diagnosis, with the remaining 15% due to mutations in the PKD2 gene. Mutations in the peak 81 gene tend to lead to more aggressive disease and renal decline. Current treatment options for patients are very limited, with only one approved product, Tolvadad. Telvapden is a vasopressin antagonist and has safety intolerability issues that likely limit its uptake.

Joseph P. Hagan: It has a block box warning for potential fatal liver injury and failure requiring transplant, which requires restrictive distribution in ongoing liver monitoring in patients. Due to its mechanism, it also has significant tolerability issues leading to patient discontinuation for those who cannot tolerate the medication, which speaks to both the medical need and the opportunity for improved treatments in this category. That said, sales are estimated to exceed $800 million in 2021 in its third year on the market. Now, turning to our approach to address this importance, we are developing an antagonist to Mere 17, which has been shown to be upregulated in the disease and directly controls PKD1 and PKD2 expression.

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Joseph P. Hagan: In addition to the data generated by our team and that of our collaborators at UT Southwestern, we were excited to read the recent publication out of Professor Somlo's group at Yale in Nature Genetics, where they described in mouse models of the disease the rapid reversal of multiple aspects of the ADPKD phenotype after re-expression of both polycystin 1 and polycystin 2, providing further support of targeting As we disclosed earlier this year, we have been able to demonstrate a statistically significant increase in these two proteins, Polysystem 1 and Polysystem 2, through treatment with an antagonist, ameer 17, in patients with ADPKD.

Good afternoon, ladies and gentlemen, and welcome to the Regardless Therapeutics, Inc. Quarter 320, 21 conference call. At this time all participants are in Edison only mode. Later, we will conduct a question and answer session and instructions so.

At that time, if anyone should require assistance during the conference. Please press Star then zero on your Touchtone telephone as a reminder, this conference call is being recorded.

But I'd like to turn the conference over to your host MS. Grace Tostada Chief Financial Officer, you may begin.

Thanks, operator, good afternoon, and thank you for joining us to discuss Regulus Therapeutics third quarter 2021 financial results and corporate highlights.

Joseph P. Hagan: Now I'd like to update you on recent progress with our program. In October, we announced our plans to prioritize the advancement of our next generation compound, RGLS 8429, and discontinued development of our first generation compound, RGLS 4326. This prioritization was driven by our business objective of allocating our resources and efforts towards the development of the more promising next generation compound.

With me on today's call is Jay Hagan, President and Chief Executive Officer, and Dennis <unk>, Chief Scientific Officer, Jay will provide opening remarks and share progress on our 80 P. J D program.

And I will review the financial results before we open the lines for questions.

Before we begin I'd like to remind you that this call will contain forward looking statements concerning regulus therapeutics pudic future expectations plans prospects corporate strategy and performance, which constitute forward looking statements for the purposes of the safe Harbor provision under the private securities.

Joseph P. Hagan: 8429 has been shown to have all the favorable properties of the first generation compound without the limitation. We are excited by this progression as we believe RGLS 8429 holds greater promise, including a superior pharmacologic profile and the absence of the off-target CNS effect that we're seeing with Arjus 4326 in chronic preclinical toxicology studies at the top doses test. Additionally, RGLS 8429 has shown equal potency to its molecular target, MIR 17. In both in vitro and in vivo efficacy studies, we have also demonstrated additive efficacy in preclinical models when combined with Tovaptan, an important clinical and commercial consideration.

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'll now turn the call over to Jay.

Thanks, Chris and welcome everyone to our Q3 earnings call and business update we're pleased to share an update on our ADP <unk> program and plans for next year.

Joseph P. Hagan: We are scheduled to have a pre-I&D meeting with FDA for RGLS 8429 in December and are on track for an I&D submission and initiation of clinical development in the second quarter of 2022, subject to FDA clearance of the I&D. Looking ahead to our planned phase one study, these plans include a single ascending dose study in healthy volunteers to enable a multiple dose escalation study in patients with ADPKD around the dose levels where robust clinical biomarker effects, meaning changes in Polyscystin 1 and Polyscystin 2, were demonstrated with the first generation compounds.

Before we get into more detail on our efforts to address this important unmet medical need I want to spend a few minutes discussing the landscape.

I was almost dominant polycystic kidney disease or ADP J D.

Genetic kidney disease caused by mutations in either the PD, one or <unk> gene.

And as one of the most common human monogenetic disorders, and the leading genetic cause of end stage renal disease.

In the United States. There are approximately 160000 patients diagnosed with the disease. However, it is believed to be significantly under diagnosed with closer to half a million dollars in the U S alone.

The disease is characterized by slowly progressive bilateral enlargement of the kidney due to growth in proliferation of fluid filled cysts.

Patients with ADP <unk> experienced impacts on quality of life, including pain in their size and back due to the enlargement and their prognosis is a progressive loss of renal function.

Leading the kidney failure for the average patient in their <unk> or <unk>, depending on what type of mutation data.

Mutations in the PD, one gene are the predominant form the disease accounting for 85% of the diagnosis.

With the remaining 15% due to mutations in the <unk>.

Mutations in the PD, one gene tend to have lead to more aggressive disease and renal decline.

Current treatment options for patients are very limited with one only one approved product talk about that.

So that then is a vasopressin antagonist and has safety and tolerability issues that is likely limited its uptake.

Joseph P. Hagan: On November 4th at the American Society of Nephrology Kidney Week meeting, and yesterday at the Biomarkers for Rare Disease Summit, we presented additional data from the first cohort of patients in the Phase 1B clinical trial of RGLS 4326, which reinforces our prior updates from earlier this year. In the first cohort, nine patients were enrolled and received one milligram per kilogram of RGLF 4-326 subcutaneously every other week for four doses, The mean increase in polycystins 1 and 2 at the end of study compared to baseline levels for all nine patients in the first cohort were 58% and 38% respectively, The trajectory of changes in these biomarkers suggest that with continued dosing, higher levels of polycystin may be attainable.

It has a black box warning for potential failure, liver injury, and failure, requiring transplant, which requires restricted distribution and ongoing liver monitoring and patient.

Due to its mechanism. It also has significant tolerability issues, leading to patient discontinuation for those who cannot tolerate the medication, which speaks to both the medical need and the opportunity for improved treatments in this category.

That said sales are estimated to exceed $800 million in 2021, and its third year on the market.

Now turning to our approach to address this important disease recall that we are developing an antagonist to mere 17, which has been shown to be up regulated in the disease and directly controls PD, one and <unk> two expression.

In addition to the data generated by our team and that of our collaborators at Ut southwestern.

We were excited to read the recent publication at a professor <unk> group at Yale in nature Genetics, where they described in mouse models of the disease. The rapid reversal of multiple aspects of the ADP <unk> phenotype. After re expression of both polycystic, one and polycystic two providing further support of targeting.

<unk> <unk> to treat <unk>.

Joseph P. Hagan: Recall that polycystine levels are depressed in patients with the disease, correlating inversely with disease severity and are believed to be directly linked to the key underlying genetic drivers of the disease. These data demonstrate further clinical proof of mechanism by showing target engagement in the kidneys, through these statistically significant increases in urinary biomarkers, PC1 and PC2, validating MIR 17 as a potential target for ADPKD treatment. I'm proud of the work by our team at Regulus and continue to advance our understanding of the role of microRNA in important disease areas, particularly kidney diseases. We remain steadfast in our mission to help patients suffering from ADPKD. I'll now turn the call back over to Chris for a discussion of our financial results. Chris? Thanks, Jay.

As we disclosed earlier this year, we have been able to demonstrate statistically significant increases in these two proteins polycystic one in polycystic too through treatment with an antagonist a mere 17 in patients with ADP.

Now I'd like to update you on our recent progress with our program.

In October we announced our plans to prioritize the advancement of our next generation compounds.

<unk> eight <unk> hundred two nine and discontinued development of our first generation compound RG less for three to six.

This prioritization was driven by our business objective of allocating our resources and efforts towards the development of the more promising next generation compounds.

8429, it's been shown to have all the favorable properties of the first generation compounds without the limitations.

We are excited by this progression as we believe RJ, let's say four to nine holds greater promise, including a superior pharmacologic profile with the absence of the off target CNS effects that we're seeing with argues for three to six.

And chronic preclinical toxicology studies at the top doses tested.

Additionally, our Ngls 8429 has shown equal potency to its molecular target mere 17 in both in vitro and in vivo efficacy studies.

We have also demonstrated additive efficacy in preclinical models when combined with <unk>, an important clinical and commercial considerations.

We are scheduled to have a pre IND meeting with FDA for RG unless 8429 in December and are on track for 90 submission and initiation of clinical development in the second quarter of 2022 subject to FDA clearance of the IND.

Looking ahead to our planned phase one study.

These plans include a single ascending dose study in healthy volunteers to enable a multiple dose escalation study in patients with ADP.

Around the dose levels were robust clinical biomarker effects, meaning changes in policy and one in polycystic two were demonstrated with the first generation compound.

We anticipate reporting topline biomarker data in the first cohort of <unk> hundred nine treated patients.

In early 2023.

Although we decided to discontinue argue list for three to six in favor of the next generation compound <unk> hundred two nine the work to date on that compound directly informs development of larger let's say for Tonight.

On November 4th at the American Society of Nephrology kidney week meeting and yesterday at the Biomarkers for rare disease Summit, we presented additional data from the first cohort of patients in the phase one b clinical trial of our Dallas for three to six.

Which reinforces our prior updates from earlier this year.

In the first cohort nine patients were enrolled and received one milligram per kilogram of <unk> Subcutaneously every other week for four doses.

The main increase in polycystic, one and two at the end of study compared to baseline levels for.

For all nine patients in the first cohort were 58% and 38% respectively.

The trajectory of changes in these biomarkers suggests that with continued dosing higher levels of polycystic may be attainable.

Recall, the polycystic levels are depressed and patients with the disease correlating inversely with disease severity and are believed to be directly linked to the key underlying genetic drivers of the disease.

These data demonstrate further clinical proof of mechanism by showing target engagement in the kidneys through these statistically significant increases in urinary Biomarkers PC wanted PCT validating mere 17 as potential target for ADP <unk> treatment.

Joseph P. Hagan: With that, I will turn the call back over to Jay.

Operator: Operator, we're happy to take questions now. Please open the lines.

I'm proud of the work our team at Regulus and continue to advance our understanding of the role of Microrna in important disease areas, particularly diseases of the kidney we remain steadfast in our mission to help patients suffering from <unk>.

Operator: Ladies and gentlemen, if we have a question at this time, please press the star and then the number one key on your touchstone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the brown key. Again, ladies and gentlemen, if you have a question at this time, please press star and then the number one key on your touchstone telephone. Your first question comes from the line of Brian Chang from Cantor Fitzgerald. Your line is open.

I'll now turn the call back over to Chris for a discussion of our financial results Chris Thanks, Jay.

Turning to our financial results as of September 32021, our cash and cash equivalents totaled approximately $35 million.

As previously disclosed we anticipate our current cash balance is sufficient to fund planned operations into the fourth quarter of 2022.

Research and development expenses for the third quarter of 2021 totaled $5 9 million compared to $4 million in the same period of 2020. Please.

These amounts reflect the internal and external costs associated with advancing our preclinical and clinical pipeline.

General and administrative expenses for the third quarter of 2021 totaled $2 $5 million compared to $2 1 million for the same period in 2020.

These amounts reflect personnel related and ongoing general business operating costs.

Net loss for the third quarter of 2021 was $8 6 million compared to a net loss of $1 5 million for the same period in 2020.

Basic and diluted net loss per share for the third quarter of 2021 was <unk> <unk> per share compared to basic and diluted net loss per share of <unk> <unk> per share for the same period in 2020.

Joseph P. Hagan: Sure, yeah, so the work that we're wrapping up here for the I&E filing includes, but the long game in the tent, so to speak, is receipt of the final reports from the toxicology studies and incorporation into the document. The team is busy at work, and as we disclosed earlier, we had completed the in-life portion of the dosing of the toxicology studies, so it's just a matter of completion of the analytical work there.

With that I will turn the call back over to Jay.

Thank you Chris.

Operator, we're happy to take questions now please open the lines.

Ladies and gentlemen, if you have a question at this time. Please press. The Star then the number one key on your Touchtone telephone. If a question has been answered with Louise Chen move yourself from the queue. Please press the pound key again, ladies and gentlemen, if you have a question at this time. Please press Star then the number one key on your <unk>.

Joseph P. Hagan: In terms of what we've learned from the first program, you know, we've got a sense, obviously, of where we see changes in biomarkers, which informs dose selection here with 8429. And so our proposal with FDA includes moving quickly to dose levels where we have seen those changes in biomarkers, which speeds up development. We won't spend as much time at sub-therapeutic levels dosing at much lower levels. And, you know, obviously, we have very significant presumed margins based on the lack of any overt toxicity observed in the I&D enabling toxic studies, which enables those sorts of starting doses. So those are some of the elements that will speed development.

Josh Stone telephone.

Okay.

Your first question comes from the line of Brian Cheng from Cantor Fitzgerald. Your line is open.

Hey, guys. Thanks for taking my question.

Youre preparing to file the IND for <unk> hundred 29 in the second quarter.

Are there any specific items that you will need to discuss with the FDA next month at the Pim pre IMD meeting.

And can you also talk about how much of the work that you have done in the past 443, 20, <unk> overlap with the filing that you anticipate to do that.

Second quarter.

Sure Yes.

The work that we're wrapping up here for the IDE filing includes but the long pole in the tent. So to speak is receipt of the final reports from the toxicology studies and incorporation into the document of the team is busy at work and as we disclosed earlier, we have completed the in life portion of.

The dosing of the toxicology studies, so its just a matter of.

Completion of the analytical work there.

And in terms of what we've learned.

Joseph P. Hagan: Additionally, you know, as we've outlined, our proposal includes going from the single ascending dose into patients with the multiple ascending dose and skipping over the M&E study and healthy volunteers, which further speeds the development of this next generation compound. And in terms of the, so that'll all be part of the discussion with FDA, you know, in the briefing book, which the team is just wrapping up for our meeting in December, which includes, you know, the proposed starting doses and clinical design supported by the results of the toxicology studies as well as what we've seen previously in terms of biomarker changes. And so that's the aim of the pre-undee meeting. in addition to more typical things like the CMC package and elements like that, right?

The first program.

We've got a sense, obviously of where we see changes in biomarkers, which informs that dose selection here with a 429.

So our proposal to the FDA includes mood.

Moving quickly to dose levels, where we have seen those changes in biomarkers, which speeds up development, we won't spend as much time in a sub therapeutic level dosing at much lower levels.

And.

Obviously, we have very significant presume margins based on the lack of any overt toxicity observed in the IND, enabling tox studies, which enables those sorts of starting doses. So so those are some of the elements that will speed development. Additionally, as we've outlined our proposal includes going from the.

Single ascending dose into patients with the multiple ascending dose and skipping over.

<unk> study in healthy volunteers, which further speak to development.

The.

This next generation compound and in terms of the so that'll all be part of the discussion with FDA in the briefing book, which teams just wrapping for a meeting in December.

<unk> the proposed starting doses and clinical design.

<unk> bye.

The results of the toxicology studies as well as what we've seen previously.

In terms of biomarker changes and so that's the DAA.

The aim of the pre NDA meeting in addition to more.

Typical things like the CMC package and elements like that Brian.

Okay and then.

On the trial data so we expect top line from the first cohort.

In early 2023, I'm, just curious whether you'll be able to do an interim data cut in a healthy volunteer.

Single dose portion to get a sense of the PK PD profile and whether and also whether there will be any data between now and your first patient cohort data in 2023.

Yes, so we'll obviously have updates as we progress through the single ascending dose study in healthy volunteers and when we wrap it be able to articulate topline results in terms of safety and PK, we're not planning to look for any PD signal because mere 17 is not up.

Regulated in in healthy volunteers, so we wouldn't expect to see.

And the ability to detect statistically significant increases with a single dose.

So it will just be safety and PK out of the.

The healthy volunteer study.

Brian Chang: Okay, and if I may, just one more on the finance side. You know, on the expense side, it seems that there is a slight increase in the R&D expense quarter over quarter. Chris, do you have any guidance on how we should think about your expense moving forward? And also, on the BD front, what are your latest thoughts on your potential partnerships or collaborations during your term? Thanks.

Okay, and if I may.

One more on the finance side.

On the expense it seems that there is a slight increase in the R&D expense quarter over quarter.

Chris do you have any guidance on how we should think about your expense moving forward and.

And also on the BD front, what's your latest thoughts on potential partnerships or collaborations near term. Thanks.

Crispina Calsada: So on the first piece of that, Brian, the increase in R&D expenses was primarily attributed to the GMP manufacturing campaign that occurred this quarter in support of our upcoming phase one. So that was a kind of a one-time expense. We anticipate our expenses to kind of go back to what we've averaged in the prior quarter. Yeah, and think about it as we're

So on the first.

A piece of that Brian So the increase in R&D expenses was primarily attributed to the GMP manufacturing campaigns.

That occurred this quarter and in support of our upcoming phase one so that was a kind of a one time expense. So we anticipate our.

Expenses to kind of go back to.

What we've averaged in the prior two quarters, Yes think about it is we had two programs, where we're spending money on for three to six clinical work and then the lumpy spend associated with manufacturer of.

Joseph P. Hagan: Yeah, to think about it is we had two programs; we were spending money on the 436 clinical work and then the lumpy spend associated with the manufacture of your clinical material for 849. And then with respect to BD, yeah, we have ongoing discussions with folks, and I think that now regulatory clarity on how we're planning to move forward from a programmatic standpoint has fostered renewed interest in the program, and we have ongoing discussions on that. I'm not going to guide you to if and whether we'll do anything, but our business development group is active. Great, thanks, guys.

Your your clinical material for <unk> nine.

And then with respect to BD, yes, we have ongoing discussions with folks and I think that.

It certainly appears that with now regulatory clarity on how we're planning to move forward from a programmatic standpoint.

Has.

Fostered renewed interest in the program.

And we have ongoing discussions on that.

I'm not going to guide to if and whether we'll do anything but our business development.

Group is active.

Alright, thanks, guys.

Operator: Again, ladies and gentlemen, if you have questions at this time, please press Star and then the number one key on your touchstone telephone. The next question comes from the line of Yi Chen from H.E. Wingright; her line is open.

Again, ladies and gentlemen, if you have question at this time. Please press Star then the number one key on your guys' stone telephone.

Next question comes from the line of <unk> Chen from HC Wainwright. Your line is open.

Yi Chen: Thank you for taking my question.

Thank you for taking my question.

Yi Chen: Since 8429 has a similar potency compared to 4026, should we expect to see a similar percentage level increase in biomarker policy systems 1 and 2, or are there some other factors that could affect the biomarker readout? Thank you.

<unk> 80 for 2009 has does has a similar potency compared to 426.

Should we expect to see a.

<unk> percentage level of increase.

Im sorry, a similar percentage level increase in the bond market polycystic wanted too.

Or there are some other factors that could affect the pump.

Biomarker readout. Thank you.

Joseph P. Hagan: Yeah, so in terms of what we would anticipate potentially seeing, I think the way we think about it, Ye is that based on everything we've seen today in the, and this is all in our updated investor deck, in the PKD1-Flox RC model, the kidney of the 849 treated animal looks a heck of a lot like the kidney of the 4326 treated animal, which looks much better, meaning not filled with cysts the way the Animals are similarly in all the in vitro testing in terms of the potency for the target and engagement as well as the PK profile of the molecule. It looks like it behaves very much like a49 behaves very much like 4326, And when we put it through PanLab screens, it doesn't have any other unwanted off-target effects that we discovered 436 possessed. And we've shown that as well in our updated investor deck that it has no activity on the AMPA receptor, which is, we believe, underlying the CNS side effects that were observed.

Yes, so so in terms of what we would anticipate potentially seeing I think the way we think about it is that based on everything we've seen to date in like the and this is all in our updated investor deck and the PK PD. One flocks are C model the kidney of the eight 4% to nine treated animals looks at.

Heck of a lot like the kidney of the $43 six treated animals, which looks much better.

Meeting not filled with <unk> the way the PBS are controlled treated animals are similarly in all of the in vitro testing.

In terms of the potency.

To the target.

And engagement as well as the.

The PK profile of the molecule.

Looks like it behaves very much like.

April Tonight behaves very much like for three to six.

And when we put it through Pan lab screens. It doesn't have any other off target unwanted off target effects that we discovered.

<unk> hundred 86 possessed and we've shown that as well in our updated investor deck that it has no activity on the alpha receptor, which was we believe underlying the CNS side effects that were observed.

And Thats been confirmed in our robust toxicology studies, where we have essentially.

Dose the same amount of compound that would be dosed in a chronic tox study now so really quite robust for an IND.

And so with all of those.

<unk> points that leads us to believe we should have a similar type of activity now turning to the phase one study as we've discussed in the past.

Higher changes from baseline has been shown to be achievable with lower levels of baseline polycystic, meaning the more severe patients demonstrate higher changes than those with less severe disease. So there are important nuances to two comparing.

<unk> across studies, because patients could be different from one study to the next so I just want to have that important caveat, but I think if I were to re.

Joseph P. Hagan: So I just want to have that important caveat, but I think if I were to rephrase your question, you know, long term, would we expect to see a similar effect in a robust sample set? I'd say, absolutely. Does that mean the previous animal model you built for, with 4326 for the safety margin, is still applicable with 8429? The PK profile? The population PK model? Yeah. Well, we'd have to confirm that and get PK data, but based on the PK that we have right now from animals, it does look like it has similar PK. Okay, great. Thank you.

Rephrase. Your question long term would we expect to see a similar effect in a robust sample set I would say absolutely.

So does that mean the previous animal model you've built for.

<unk> 43.

2006 for safety margin.

Applicable.

For 2009.

The PK profile that population PK model, yes, well, we'd have to confirm that and get and get PK data, but based on the PK that we have right now with from animals. It does look like a similar PK.

Okay, great. Thank you.

Welcome.

Operator: I am showing another question at this time. I would like to turn the conference back to Jay Hagen.

I am showing no further question at this time I would like to turn the conference back to Jay Hagan.

Joseph P. Hagan: Great, well, thanks very much for the opportunity to provide this update to you, and I appreciate your continued support.

Great well. Thank you very much for the opportunity to provide this update to you and we appreciate your continued support of Regulus.

Okay.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation and have a wonderful day. You may all disconnect.

Ladies and gentlemen. This concludes today's conference call. Thank you for your participation and have a wonderful day you may all disconnect.

Q3 2021 Regulus Therapeutics Inc Earnings Call

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