Arrowhead Pharmaceuticals - Earnings Call - Q3 2020
August 5, 2020
Transcript
Speaker 0
Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. Throughout today's recorded presentation, all participants will be in a listen only mode. After the presentation, there will be an opportunity to ask question. I will now hand the conference call over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.
Speaker 1
Thank you, Jeff. Good afternoon, everyone. Thank you for joining us today to discuss Arrowhead's results for fiscal third quarter ended 06/30/2020. With us today from management are President and CEO, Doctor. Christopher Anzalone, who will provide an overview of the quarter Doctor.
Javier San Martin, Chief Medical Officer, who will discuss our clinical programs and Ken Myszkowski, our Chief Financial Officer, who will give a review of the financials. In addition, James Hazard, our Chief Commercial Officer and Doctor. Kirk Bradshaw, our Chief Scientific Officer, will be available during the Q and A session of today's call. Before we begin, I would like to remind you that comments made during today's call contain certain forward looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact, including without limitation, those with respect to Arrowhead's goals, plans and strategies are forward looking statements.
These include statements regarding our expectations around the development, safety and efficacy of our drug candidates, projected cash runway and expected future development and commercialization activities. These statements represent management's current expectations and are inherently uncertain. Thus, actual results may differ materially. Arrowhead disclaims any intent and undertakes no duty to update any of the forward looking statements discussed on today's call. You should refer to the discussions under Risk Factors in Arrowhead's annual report on Form 10 ks and the company's subsequent quarterly reports on Form 10 Q for additional matters to be considered in this regard, including risks and other considerations that could cause actual results to vary from the presently expected results expressed in today's call.
With that said, I'll turn the call over to Chris Anzalone, President and CEO of the company. Chris?
Speaker 2
Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. We've already made a lot of progress this year, notwithstanding the challenges that COVID-nineteen has presented to the world broadly and particularly to those of us developing new medicines. We took decisive action and placed a voluntary pause on new patient screening and enrollment in some of our clinical studies in order to limit the risk of participants. We take very seriously our obligation to protect the health, safety the health and safety of our employees, business partners, and patients that participate in our studies.
That was the right thing
Speaker 1
to do. The good news is that we
Speaker 2
don't believe any of our development programs were affected in a material way. That is a testament to the Arrowhead drive toward innovation, speed, and precision. We find a way forward even when the way is not clear. This is a hallmark of the Arrowhead culture and something that I am very proud of. Even though COVID still presents some uncertainty, we are confident that 2020 can continue to be a highly productive, last part of the year as we work to, one, expand our pipeline, two, make progress and provide data readouts on multiple clinical programs, and three, gain clinical proof of concept for our first extrahepatic candidates.
So what have we done, and what are our plans in order to achieve these three important goals? Let's answer that by reviewing some key programs. I'll start by speaking broadly about our discovery stage programs. The partnership we signed with Janssen in 2018 included three potential new products against targets to be selected by Janssen. While I can't disclose the targets, the specific stage, or report data on these potential product candidates, we can say that we have made good progress on all three.
We previously talked about ARO J and J1 because the first target was selected early on in the partnership and work began soon after. We are now at sufficiently advanced stage of the other two potential product candidates to add them to our pipeline and designate them as ARO JNJ2 and ARO JNJ3. The partnership with Janssen has been very productive, including for ARO HBV, now called JNJ3989, which continues to progress rapidly in multiple phase 2b studies being conducted by Janssen. Staying with earlier stage development, let's move on to our preclinical programs that utilize our TRiM platform targeting the pulmonary space. Our second program after ARO ENaC is ARO Lung two, designed to treat COPD by inhibiting an undisclosed target in pulmonary epithelia.
We previously announced that it had officially been nominated as a candidate, and moved from preclinical to pre IND stage. We have continued to make good progress on the IND enabling studies, and are on track to potentially file a CTA for ARO Lung two at the end of this year. It has been our goal to gain clinical proof of concept, and then move into a rapid pipeline expansion phase for the pulmonary platform.
Speaker 3
We think we're just on
Speaker 2
the cusp of that phase now. To that end, we continue to work in parallel on multiple additional targets in the pulmonary space. We think the lung is a target rich environment with multiple opportunities for asthma, COPD, idiopathic pulmonary fibrosis, and other diseases that are not adequately treated. We've also made good progress on several potential candidates designed to treat the novel coronavirus that causes COVID nineteen. This is the first time we have disclosed that we are pursuing multiple different therapeutics at the same time, and I think it's important.
This is a difficult virus, and we believe the best way forward is to address multiple strategies. One is to close the front door, if you will, by knocking down a receptor that the virus uses to gain entry into cells. A second is a direct antiviral approach that targets the viral mRNA. And the third is to pursue anti inflammatory pathways. We are pursuing all of these in parallel and believe this broad holistic strategy gives us multiple shots on goal and a more complete approach to a poorly understood virus.
Given our experience in the lung and our work in HBV, I believe we are well positioned to play a role in addressing COVID nineteen and possibly future coronavirus outbreaks. With ARO ENaC, ARO Lung two, our suite of COVID nineteen programs, and the additional potential candidates that are progressing rapidly, we are confident in our belief that the emerging lung pipeline can be an engine that drives substantial value in the near to midterm. What we have done and continue to do in the liver, we now seek to do in the lung. Now moving on to our clinical pipeline. I'll start with ARO AAT, our phase twothree candidate against a rare genetic, liver disease associated with alpha-one antitrypsin deficiency.
We have fully enrolled, dosed, and collected six month repeat biopsies for the first cohort of the open label 2,002 study. Biopsies are now being analyzed, and we plan to present data before the end of the year. This is important progress and an important readout. It will be the first data for a therapeutic targeted at alpha-one liver disease, and it will be an important step in understanding what happens at the hepatocyte level after patients are treated. We will be looking at many measures of alpha-one liver disease, but most focused on the change from baseline in Z AAT monomer.
That is a direct measure of the drug's ability to inhibit production of the faulty mutant protein. We have a high level of confidence in our ability to show improvements here. We will also be assessing other measures that will likely require longer drug exposure to show treatment effect. That includes Z AAT polymer content and inflammation. We don't believe that six months of therapy is enough time to see changes, but we are the first company to investigate this disease in humans, so we really don't know what to expect.
Remember that in the phase two three SEQUOIA study, patients will receive around two years of treatment. If we see signs of improvement at earlier time points than expected, that would be a very exciting result and could cause us to consider working with the regulators to change the parameters of the study. I will now talk about our cardiometabolic programs. Let's start with AMG eight ninety, the candidate we licensed to Amgen, targeting Lp for the treatment of cardiovascular disease. We announced last week that Amgen started a Phase II study, and triggered a $20,000,000 milestone payment.
These represent important steps forward for the AMG eight ninety program and support Arrowhead's strategy of utilizing our platform and expertise in RNAi therapeutics to build a valuable pipeline of both wholly owned and partnered drug candidates. Amgen has extensive experience in developing and commercializing innovative cardiovascular medicines, and we are excited to see the program continue to advance. Our two wholly owned cardiometabolic candidates, ARO APOC3 and ARO ANG3, are both progressing rapidly toward value inflection points, including multiple data readouts this year and advancement into the next stages of clinical development. The second half of twenty twenty is gonna be an important time for both programs. Both candidates are in phase one, two studies, and together have enrolled nearly 200 healthy volunteers and patients.
Both studies include single and multiple dose assessments, and both have various cohorts with specific patient populations. This accelerated first in human study design yields data on safety and tolerability, dose response, duration of effect, and how different types of patients respond to the therapy. It allows us to give data readouts from both programs at two or three conferences over the next few months. It also gives us enough actionable information about each candidate to engage regulators and discuss the next stages of clinical development, up to and including potential registrational studies. We have already been communicating with the FDA on ARO APOC3, and our plan is beginning to take shape.
We will have similar discussions on ARO ANG3 and also engage with European authorities to gain clarity on various study design characteristics, endpoints, and target patient populations. Importantly, both candidates provide a high level of optionality on which patient populations and disease characteristics to focus on, and how to stage the clinical studies to assess the candidate's utility. For example, for ARO APOC3, there are potential patient populations that range from ultra rare genetically defined, such as FCS, in which patients have triglycerides in thousands of milligrams per deciliter, to extremely high prevalence disease, such as patients with mildly elevated triglycerides above 150 milligrams per deciliter. There are also various levels in between these extremes that each have their own characteristics and would require a different clinical design with respect to size of study, duration of treatment, and acceptable endpoints. Taken together, this represents a very large market opportunity.
In The US alone, they are estimated to be approximately one million adults with triglycerides greater than 1,000 milligrams per deciliter, more than three million adults with triglycerides between 501,000, and more than forty one million with triglycerides between two hundred and five hundred. Of course, not all of these patients will be potential candidates for therapy, but thinking of ARO APOC3 solely as an orphan indication drug candidate is missing the larger breadth of opportunities ahead. This type of opportunity also exists for ARO ANG3 in patients with mixed dyslipidemias, specifically triglycerides, LDL C, and other measures of cardiovascular and metabolic disease. I don't think investors fully appreciate the size of the potential commercial opportunities for both ARO APOC3 and ARO ANG3. This an exciting time for these programs, as we are beginning to see potential paths to commercialization.
We will be talking about these paths and timelines in the future, which should provide a level of detail for investors to properly assess how significant the opportunity is to help very large populations of patients that could benefit from new treatment options. We have also made good progress on ARO HSD in development to treat alcohol and non alcohol related liver disease. We began dosing in a Phase onetwo study in March. We have since completed all healthy volunteer cohorts, and have activated the cohorts that enrolled patients with NASH or suspected NASH. The target, HSD17 beta-thirteen, is not a secreted protein, so we will be collecting liver biopsies to measure target engagement.
This program experienced a short pause in screening and enrollment due to
Speaker 1
the
Speaker 2
COVID-nineteen situation, but similar to other programs, we don't think this had a material effect on our anticipated timelines. As long as patient screening and enrollment continue to move forward as planned, we should be generating data through the end of twenty twenty and be in a position to present in the first half of twenty twenty one. Lastly, I wanna mention ARO ENaC, our first inhaled RNAi candidate to target the pulmonary epithelium. We anticipate dosing to start this month in our phase one two study in healthy volunteers and in patients with cystic fibrosis. The candidate is designed to reduce expression of the epithelial sodium channel or ENaC in the lungs to help rehydrate CF related dehydrated mucus and potentially help improve mucociliary clearance.
As we discussed on our ENaC webinar last week, there has been great progress in new therapies to treat CF over the last decade, but significant unmet need still exists. We estimate that there are approximately fourteen thousand patients in The US alone that are either not eligible for the most advanced therapies because of their specific genotype, or have been shown in clinical trials to be non responders or insufficient responders. This
Speaker 4
is
Speaker 2
a lot of patients who still suffer from CF and are in need of alternative treatments. We think ENaC may be that alternative, and importantly, the mechanism of action should theoretically be genotype agnostic. This is an exciting program, and we hope to generate data through the rest of 2020 that may enable us to have a data readout in the first half of twenty twenty one. Our preclinical data has been has been highly promising, and we are eager to see the translation of animal data to humans in our new pulmonary TRiM platform. With that overview, I'd now like to turn the call over to Doctor.
Javier San Martin. Javier?
Speaker 3
Thank you, Chris, and good afternoon to everybody on the call. I want to highlight a few of our clinical programs and some key progress we made since our last conference call. Just like all biotech companies, COVID had an effect on some of our programs. But I'm very pleased to say that it appears the effect has been generally minor. In fact, some programs experienced little to no delay in our anticipated timelines.
We continue to monitor the situation closely to ensure the study participants are now being exposed to additional risk, while at the same time moving forward rapidly when it's safe to do so. Even in the challenging environment of the last several months, I'm proud that Arrowhead's clinical development team has executed at a very high level. Let's start with ARO AAT, our second generation investigational RNAi therapeutic being developed as treatment for a rare genetic liver disease associated with alpha-one antitrypsin deficiency. As we announced last quarter, we voluntarily put the SEQUOIA Phase twothree study and the 2,002 open label study on a temporary pause for new screening and enrollment due to concerns around COVID-nineteen. Both studies are now back up and running and open to new patient screening and enrollment.
The pause caused a delay of approximately eight weeks for SEQUOIA and for the second cohort in 02/2002, after which sites began to reopen and resume patient screening. The first cohort in 2,002 was already fully enrolled and importantly, we did not experience any concerning protocol deviation for those already on study. Let's talk more about 2002 open level study because we plan to have data readout this year. To review, the study is designed to enroll approximately 12 participants in two sequential cohorts. Between the two cohorts, biopsy data will be assessed at baseline and after six months, twelve, eighteen, and twenty four months of treatment with ARO AAT.
As I mentioned, the first cohort, which is four patients, was already fully enrolled prior to COVID-nineteen and patients have continued on study as planned. All doses were administered and the six months repeat biopsy have all been collected. Samples are being processed as we speak. And our plan is to have analysis completed in time to submit a late breaker after to the ASLD Liver Meeting later this year. This is a potentially important readout for the program and for the field, because it is the first view of what happens inside the liver in alpha-one patient after receiving therapy.
We'll be assessing reduction in the Z AAT monomers, which we would expect based on the plasma data from our Phase I healthy volunteer study. The Phase I data demonstrated that Ao AAT treatment led to reduction in serum AAT levels down to below the level of quantitation with a multi month duration of effects. This suggests that we may be achieving near complete suppression of the liver production of the mutant Z AAT protein. At this time, no other therapy has shown this type of result used in any modality. We will also be looking at whether the accumulated ZAAT polymers can start to decrease after six months, which are not expecting but would be pleasantly surprised to see.
In addition, we will look at changes in inflammation and in various histologic parameters. Again, we wouldn't expect to see these measures change after only six months of treatment, but it would be very exciting result if we were to see improvement this quickly. Let's now move to our cardiometabolic pipeline. I will start with AMG A90, an investigational siRNA therapeutic designed to lower lipoprotein A or LP for the treatment of cardiovascular disease, which is licensed to Amgen. As Chris mentioned, Amgen recently started a Phase II study, which I'm very excited about.
The study is double blind, randomized, placebo controlled Phase II study to evaluate efficacy, safety, and tolerability of AMG eight ninety in approximately two forty subjects with elevated LPA. The primary endpoint, the percent change in LPA from baseline to week thirty six. Key secondary endpoints include the percent change in LPA from baseline to week forty eight, percent change in LDL cholesterol, and APOB from baseline to week thirty six and forty eight. Now, moving to our two wholly owned cardiometabolic candidates, ARO APOC3 and ARO ANG3. Let's begin with ARO APOC3, our candidate targeting apolipoprotein C3 being developed as a potential treatment for patients with hypertriglyceridemia.
We continue to be very impressed and encouraged by results from the ongoing Phase onetwo clinical study called ARO APOC31001. I will talk about the study design and progress and let's discuss where and when we expect to present data. ARO APOC31001 is a Phase onetwo single and multiple dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effect of ARO APOC3. There is a single dose and multiple dose portion of the study in adult healthy volunteers and multiple dose portion of the study in patients with hypertriglyceridemia. The study reached full plan enrollment of 80 subjects.
We subsequently expanded the study to assist a total of up to 112 subjects. As of today, 100 subjects have been treated. The first data from a single dose healthy volunteer portion was presented at the American Heart Association in 2019. We have been accepted to present additional data at the European Society of Cardiology meeting, the National Lipid Association meeting, and we might potentially have additional data at the American Heart pending after acceptance. Between this team in the second half of twenty twenty, we plan to have multiple dose and follow-up data in both healthy volunteers and patient cohorts.
Together, this represents a rather full data set and should be a good view on the safety and activity of ARO APOC3. Data from the ARO APOC3 Phase onetwo study have indicated a very potent triglyceride reduction, frankly, more potent than anything I've seen before. Because of this, we are exploring potential designs for the next stages of clinical development to study the drug in multiple patient populations that might benefit from triglyceride reduction. We have been engaging with regulators on that topic and hope to provide some clarity later this year. We're hopeful that during the first half of twenty twenty one, we will be able to initiate a phase three study in a smaller population and a phase 2b study in a larger population.
Our other wholly owned cardiometabolic candidate is ARO ANG3 targeting angiopoietin like protein three or ANGPTL3. And it's being developed as a potential treatment for patients with mixed dyslipidemia. The current clinical study is called ARO ANGPTL3. It is a Phase onetwo single and dose study to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic effect. Both the healthy volunteer and patient portions of this study have reached full plan enrollment of 93 subjects.
Similar to ARO APOC3, we continue to be very encouraged by the clinical data and plan to present at ECS and NLA and hope to also present at the American Heart Association pending after acceptance. We're working on clinical development plan and we'll be engaging with regulators shortly to discuss this plan. Our hope is to start a Phase 2b study in the first half of twenty twenty one in appropriate patient population that might benefit from a lowering of both triglycerides and LDL cholesterol. This may affect multiple cardiovascular risk factors simultaneously, which is potentially very exciting. I will now briefly touch on progress in our earlier stage pipeline.
ARO HST is our investigational candidate for the potential treatment of alcohol and or non alcohol related liver disease. The genetic validation is strong for inhibiting the target HST17 beta 13 in NASH cirrhosis and alcoholic hepatitis and cirrhosis patients. This is an exciting program for us as it is the first candidate against this novel target using any modality to enter clinical study. We're conducting a Phase onetwo single and multiple dose escalating study to evaluate the safety collaterability, pharmacokinetic and pharmacodynamic effect of ARO HST with normal healthy volunteer as well as in patients with NASH or suspected NASH. Additional exploratory objectives include assessment of various measures of drug activity using liver biopsy.
We have completed enrollment and dosing of the healthy volunteer portion of the study, and we have initiated a multiple dose portion of the study. There was a short delay in this study due to COVID-nineteen, but it did not materially affect our anticipated timeline. We anticipate that initial data should be available to present in 2021. Our two other early stage programs, ARO HIF2 and ARO ENaC are also our first candidate targeting tissues outside the liver. ARO HIF2 is designed to treat renal cell carcinoma and we're currently screening patients to begin a Phase Ib study.
ARO ENaC designed to treat cystic fibrosis is scheduled to begin dosing in Phase onetwo study this month. We hosted a webinar last week to talk about the target, the preclinical data, and the plan for the candidate. The webinar also featured outside cystic fibrosis expert, Doctor. Marcus Moore. It was full of good information about the program and I highly recommend you watch a replay if you didn't see it live.
It is still available on the Events and Presentation page on our website. I will now turn the call over to Ken Myszkowski, Arrowhead's Chief Financial Officer. Ken?
Speaker 5
Thank you, Javier. As we reported today, our net loss for the quarter ended 06/30/2020, was $13,600,000 or $0.13 per share based on 101,800,000.0 fully diluted weighted average shares outstanding. This compares with net income of $20,300,000 or $0.21 per share based on 98,900,000.0 fully diluted weighted average shares outstanding for the quarter ended June 3039. Revenue for the quarter ended 06/30/2020 was $27,400,000 compared to $42,700,000 for the quarter ended June 3039. Revenue in the current period relates to the recognition of a portion of the upfront payments and milestones received from our license and collaboration agreements with Janssen as we continue to work toward completing our performance obligation of managing the current phase onetwo HBV clinical trial.
Revenue from the Janssen agreement is recognized based on our estimate of the proportion of effort expended towards fulfilling our performance obligations, primarily overseeing the completion of the current phase onetwo HBV clinical trial. We expect the remaining $26,300,000 of deferred revenue to be recognized in this calendar year. In addition, period revenue also included the $20,000,000 milestone payment we accrued due to Amgen initiating their phase two clinical trial for AMG eight ninety. Revenue in the prior period related to the recognition of a portion of the upfront payments and milestones received through our license and collaboration agreements with Janssen. Total operating expenses for the quarter ended 06/30/2020 were $43,300,000 compared to $24,100,000 for the quarter ended June 3039.
This increase is primarily due to increased noncash stock compensation expense. Stock compensation expense has increased because the valuation of new stock option and restricted stock awards granted has increased with the growth in our stock price. Additionally, stock compensation expense increased due to the timing of achievement of certain performance based awards in each period. The increase in our total operating expenses was also driven by the increased clinical trial costs as our pipeline of clinical candidates has increased and increased personnel costs in both R and D and G and A as our headcount continues to grow. Net cash used by operating activities during the quarter ended 06/30/2020 was $33,400,000 compared with net cash provided by operating activities of $10,500,000 during the quarter ended June 3039.
The increase in cash used by operating expenses during the quarter is consistent with the increase in our cash operating expenses. The cash provided by operating activities in the prior period was driven by the receipt of a $25,000,000 milestone payment from Janssen due to the initiation of the triple combination cohort in the HBV phase one two clinical study. We estimate our near term cash burn to average 30 to 35,000,000 per quarter. Turning to our balance sheet. Our cash and investments totaled 464,600,000.0 at 06/30/2020 compared to 302,900,000.0 at 09/30/2019.
The increase in our cash and investments is primarily due to the December 2019 equity financing we completed, which generated $250,500,000 in net cash proceeds for the company. Our common shares outstanding at 06/30/2020, were 102,300,000.0. With that brief overview, I will now turn the call back to Chris.
Speaker 2
Thanks, Ken. As we discussed, Arrowhead has a lot going on in all of the following stages. One, platform development and expansion into new extrahepatic tissues, such as lung, tumor, muscle, and other cell types. Two, early discovery, as evidenced by several COVID related programs, ARO J and J one, two, and three, and other undisclosed programs. Three, early development, such as ARO Lung two, ARO HIF2, ARO ENaC, and ARO HSD.
And four, emerging mid to later stage developments such as Aero AAT, Aero APOC3, Aero ANG3, and partner programs J and J 3,989 and AMG eight ninety. This is a very large pipeline with enormous opportunity for a company of only 200 people that currently only burns between $30,000,000 to $35,000,000 per quarter and has a market cap less than $5,000,000,000 This again speaks to the Arrowhead culture of finding a way forward and not allowing bureaucracy or legacy processes to block innovation. It is also a testament to our commitment to capital efficiency and being good, responsible stewards of the capital that we have been entrusted with. Even as we continue to grow, these attributes will be important parts of the Arrowhead culture. The rest of 2020 is going to be very busy.
We anticipate multiple data readouts, important clarity on the future paths and timelines for some of our programs, and new announcements about previously undisclosed targets and candidates. Our existing, programs continue to advance, and the reach of our technology platform continues to expand. This is a very exciting place to be. Thanks again for joining us today. I would now like to open the call to your questions.
Operator?
Speaker 0
Thank you. Our first question from the line of Alethia Young. Your line is now open.
Speaker 6
Hi. Thank you. This is Alberto on for Alethia from Cantor Fitzgerald. Congratulations on the quarter. And I have two quick questions.
So first is the HIF-two program, which you started in December, if I recall correctly. We were just curious about how you're thinking regarding updating the street on that. Would you do an interim readout later this year, or are you waiting for all patients to be treated?
Speaker 2
Yeah. Thanks for that question. We're we're not planning an interim readout this year. I'll tell you, that has progressed a bit more slowly than we had hoped. As you mentioned, we filed that IND in December.
And frankly, I expected us to dosing that by June. COVID really slowed us down on that. Are because it's a biopsy study, we are we are focused not entirely, but largely in academic, institutions. And so that's just taking a long time to get to get contracting done to start that study. We we are hopeful that we that we'll start to dose that shortly.
And look. It's our anticipation to to to report that, you know, once that study is complete. And so so by the end of of this year, it is unlikely, you know, maybe maybe the middle of next year, but we'll we'll see how that goes. We'll we'll give you better guidance once we start dosing that.
Speaker 6
Thank you for that. And then just on the a h AHD asset, do you have a view on potential differentiation that different RNAi approaches can have in liver disease? And along those lines, is it still your goal to find a partner for this program, or are you considering going at it alone? And if so or either way, I guess, what gives you the confidence to continue investing in this given the challenging space?
Speaker 2
Say sorry. Which program? HSD did
Speaker 3
you did you say? Yes.
Speaker 2
Okay. Yeah. So look. So I'll tell you. Our our our our initial and differentiator is our is our speed.
You know, we are we are the first as I understand it, I think we're the first company of any modality, you know, to, to to bring an HSD, based therapeutic to the clinic. And so so, you know, that's gonna be interesting. So that's first. Second, look. You know, I I expect that to be a good a good, therapeutic.
I I expect that to be to be potent, and I expect, you know, good deep knockdown. And so and so, you know, I think we've got a very good shot at having something that's gonna knock down that that, that protein. So here are the challenges. Challenge one is that is that it's not a secreted protein. And so at least right now, there's no secreted biomarkers.
So it's gonna have to be, at least in the near term, a biopsy study. We are okay with that. And and as you know, the current study enables that, and and I think that we can enroll that. No problem. But that's gonna
Speaker 6
be that's gonna be a bit of
Speaker 2
a challenge. The second challenge is that is that the, you know, the mechanisms of this of this target are not well understood. The genetic validation is clear. You know, it appears that that that knocking HSD down should be very beneficial for NASH and even more beneficial potentially for alcohol related, hepatitis. But the but the the biology of that still is a bit lagging, and so and so we'll see where that goes.
We're we are we are excited about the program. You know, at some point, you know, could that be something that we target? Sure. But at least right now, it's you know, we are happy to push that forward as it is. We can handle it as it is.
NASH is a is a is a complicated space, but at least in this the state at this early stage of this program, we're happy to to continue moving forward. And then we'll, know, we'll just be opportunistic. You know, should a should a good deal at some point happen, we're happy to listen. But right now, we're happy to, you know, to continue to to treat patients.
Speaker 6
Thanks again for that, and congratulations.
Speaker 2
Sure. Thank you.
Speaker 0
We'll take your next question from the line of Salveen Richter of Goldman Sachs. Your line is now open.
Speaker 6
Great. Thank you for taking the question. What levels of the pulmonary reduction, do you expect to see in the six month, AAT liver biopsies? And what do you think is necessary in order to you guys approach the FDA on changing the primary endpoint and or shortening the Phase twothree trial? And then I just have a a follow-up on the, ENaC program.
Speaker 2
Sure. So I'm glad you asked that question, because I wanna be clear on this. We don't expect changes in polymer content after just six months. We do expect substantial monomer reduction, you know, and and that would be that would be reflective of, you know, of of of our expected activity, of this drug as we saw in the healthy volunteer study. Although those are plasma levels, we saw good deep reduction as as as Javier mentioned.
And so we expect good reduction in monomer, at this point. Polymer is a hard is a is a different story. Look. It's not it's not clear how that's metabolized. You know, one of the, you know, the good news, bad news of being pioneers here is that, yes, we're first, but bad news is we're first.
And so there's a lot of things we have to learn here. One of the things is how this polymer is metabolized. It could be that we are relying on the hepatocytes to turn over to decrease that polymer because because we don't know. And, you know, it's possible that metabolism is is very slow if if if it if they can metabolize at all. So so our take home message is, look.
We do expect good deep reduction of monomer. We expect we expect virtually no or no reduction in polymer, and probably no changes in inflammation at this early point at six months. You know, I think it's there's a there's a better likelihood that we would see some of those changes starting after maybe a year of therapy.
Speaker 6
Got it. That's that's helpful. And then on the, the ARO ENAP program, at what dose level would you penetrate the the tissue? And and how do you see your asset differentiate from the competitors in the space?
Speaker 2
Javier?
Speaker 3
So this is how we're dosing patients healthy volunteers first and then patients, and this is coming from the experiments in the preclinical lab. When you see the total dose that we will dose patient, approximately twenty five percent of that dose is expected to be delivered to the lab. And that is an efficiency related to the nebulization process. So that's an estimation. But right now, we don't know for sure, but that's what we've seen in the preclinical work and expected to see in the clinical work.
However, in clinic, it's very difficult to know, of course. What was the second question?
Speaker 2
Yeah. And regarding competition, look, I think I think we've said favorably, from a competitive standpoint. You know, it's a well validated target. People have gone after ENaC, the small molecules in the past, but have generally not been able to, you know, to reduce it enough, in the lung but spare in the kidneys. We are confident that we that that we will not reduce in the kidneys.
You know, we've done exhaustive studies in animals, to suggest that that that we don't expect reduction in kidneys. And so, look, I I think we're I think that we are we are virtually alone, at least with this target right now, in cystic fibrosis. You know, there there have been, some antisense programs, but but but I think that that, that those will likely have the same issues that other AnySense programs have had, which has been related to talks.
Speaker 6
Great. Thank you.
Speaker 0
Thank you. Next question is from the line of Ted Dantoff from Piper Sandler. Your line is now open.
Speaker 7
Great. Thank you very much for taking the question. I wanted to ask a little bit more in terms of COVID program. With so much going on in the space, what are the benefits of RNAi mechanism potentially for COVID? And can you tell us a little bit more about sort of maybe how that clinical program looks?
Thanks.
Speaker 2
Sure. It's so there's not much we can tell you on that because we're still early there, and and we you know, we're still really exploring a
Speaker 0
lot of things. But as
Speaker 2
I mentioned in the prepared remarks, there are three there are three broad areas that we are that we are interrogating simultaneously. One is, is knocking out or knocking down, receptors, in the lung that that enable the virus to get in. That biology is reasonably clear or as clear as as it can be in this you know, for this virus. So we're going so we will be going after that. I think we have I think we we have a role to play there.
And look. We we've got we've got a clinic ready lung program. You know, we've been leaders in HBV. You know, we were the first ones to show a good potent antiviral effect in hepatitis B, and so I think we're well positioned, you know, to play here. So we feel good about that.
Second, is is direct antivirals. Again, you know, we showed with HBV that we're pretty good at that. And I think the opportunity here is not just to look at the current coronavirus, but to think of this more broadly. If one were to expect there will be coronavirus outbreaks in the future and and and if past is is is prelude, that's probably a good assumption. We we would hope to find some well conserved regions among known coronaviruses, that we could knock down and have antiviral effects.
We are interrogating that right now. We think we can play we think we can play in that space. And third, with anti inflammatory. This this this, jives well with with our other lung programs. You know, we think that there are that there are good good indications, you know, for anti for anti inflammatories.
And so we are we're developing that right now, and we think that that might play a role in, in a therapeutic for for, for coronavirus.
Speaker 7
Cool. Sounds interesting. I look forward to hearing more.
Speaker 2
Yes. Thanks, Ted.
Speaker 0
Next question from the line of Luca of RBC Capital. Your line is now open.
Speaker 8
Terrific. For taking my question. Luca Aci from RBC Capital. Two questions. Maybe one for Javier on A1AT and maybe one bigger picture question for you, Chris.
So on A1AT, it sounds to me that you're saying that there is somewhat of a time lag between the reduction in the monomer versus the reduction in the polymer. However, when I see the preclinical data published at JCI, I don't see that much of a lag there as actually it appears that the monomer and the polymer gets reduced concurrently there. So just curious about what am I missing there? That's the first question. And then the second question, Chris, on the strategy.
You obviously have a very impressive pipeline at this point. Can you just maybe dichotomize the world for us between assets that you feel you have generated enough data that you would consider a partnership now versus assets that you want to further derisk before entertaining any type of partnership? Thank you.
Speaker 3
All right. So the first part of the question related to how the preclinical work correlates to the clinical. I think the first difference is that we haven't looked at very early standpoint in the preclinical work. It's more like on the longer term. So I don't think we have a way to see the dynamic inhibition or reduction of different component of the mutant protein in the liver.
So that's one component that I think we need to understand. The second, I think we are now getting more and more information from the natural history study that we've done and we're collaborating with others that this is clearly a dynamic progressive chronic diseases and it happens in different stages as we are learning. So the main problem is the production of this abnormal misfold protein that gets accumulated in the liver initially as monomers, but then eventually get organized as polymers as the time goes back become these globals. This is the reason why then patient develop inflammation, and as this continue develop fibrosis and finish with late stage liver disease. So we see this as a very dynamic process that start with something that can be addressed immediately which is inhibit production of this mutant protein And that over time will be associated with a decrease in the monomers in the liver and then polymers.
And eventually that will reduce the insult that caused the inflammation, the progression of the liver disease. So that's how we're thinking. And actually the 2002 study likely will answer this question more precisely because we're looking at biopsies at four time points post initiation of therapy six, twelve, eighteen, and twenty four months. So probably we'll be able to map out how this dynamic sequence of events happen and how we can intervene by inhibiting the insult and allowing the liver to heal.
Speaker 2
Yeah. Thanks. So with regard to your more strategic question, that's a that's a key question for our strategy. As you know, you know, we have we have been really focused on building this large pipeline and and not slowing down. You know, you've heard me say it before, look.
I think we're gonna have 10 clinical programs, you know, pretty soon, and I think we double that to 20 in the next few years. And so what that gives us is a is an awful lot of currency, you know, to do some partnerships, because, look, you know, we are, frankly, no company, don't think, nearly our size, even double our size, even triple our size, know, could commercialize all those for goodness' sakes. And so we we have you know, we've we've got the ability to go through that and and and find, you know, clusters of assets that we can commercialize ourselves, you know, to bring us to that next, you know, next level of growth, and then and then partner other ones out. With respect to which ones we can partner right now, so if you look at the current clinical programs where we have data, AAT, APOC3, and Ang3, I'd be willing to suggest that we have enough data to partner any of You know, the data have been have been quite good on all of them. You know, AAT, as Javier showed, in health volunteers, we were showing, you know, decreasing levels of plasma down below the level of quantitation.
And we'll have biopsy data shortly to, you know, see what that looks like intrahepatically. But I think that we have already, from my perspective, we have already achieved clinical proof of concept there that we are doing what we expect to do in a well tolerated manner. APOC3, we're seeing 95% reduction of triglycerides in patients, also lowering you know, a a lowering of LDL also in these patients. So far, it's been well tolerated. I think I think enough data have been have been generated there.
What we I think we've dosed 100 patients so far or or human subjects between patients and healthy volunteers. Think I there's an update there to, you know, to part of that should we want to. ARO ANG3, you know, we're seeing 85% reduction of triglycerides, 40% reduction of LDL in non LDL receptor mediated fashion, well tolerated. Same thing there. We've dosed what's ninety three patients, I guess, so far and been well tolerated and and been active.
And so I think that we've we've we've, you know, hurdled that bar as well. So the point is I think I think those are all partnerable now. And I think it's now incumbent upon us to continue to move these other programs forward and then to figure out which ones and at what time, we're gonna wanna partner.
Speaker 8
Super. Thank you. Thank you, Ken, and congrats on all the progress.
Speaker 2
Thank you.
Speaker 0
Next question from the line of, Murray Raycroft of Jefferies. Your line is open.
Speaker 9
Hi, everyone. Congrats on the progress and thanks for taking my questions. First question was on ARO AAT. Just wondering if you validated an inflammatory biomarker assay yet for that program?
Speaker 3
We haven't validated ourselves, but there is a very validated way to look at inflammation. We're likely going to do an early look at the same way we look at in the preclinical work, which is quantify forces of inflammation by field and by portal areas. So the first renal inflammation will be very standard, I think, well described, quantifiable, and that you can really is reliable and you can compare baseline to post baseline.
Speaker 9
Got it. And wondering for that program too, if you can provide any details on the baseline characteristics of the patients that you've got in the open label study? And how do those baseline characteristics compare to some of the patients that you've enrolled in pivotal Phase twothree?
Speaker 3
Well, so I don't have any detail right now. We can follow-up if you want offline. So I don't recall exactly, but we can get back to you. Yeah.
Speaker 2
Of course. Yeah. As you you know, the goal there was was to was to be treating similar patients. And so and so what what we see in the open label study, you know, our our anticipation is that is that that will read on what is what is likely happening within the blinded study. So the question is, you know, are they different slugs of patients?
The answer is they really shouldn't be.
Speaker 3
Because the inclusion criteria is similar. And so I was about to repeat that, but essentially, you know, the age groups is 18 to 50 or 55. Of course, they have to have an FEV1 higher than 65. So the inclusion criteria are very, very similar. So we state that this result will be applicable to understand what happened on the larger Phase twothree study.
Speaker 9
Got it. And I think in the prepared remarks, you said you've been having discussions with regulators for APOCIII and ANG3. Can you provide more clarity on when you're going to finalize plans and disclose some more of the details from your discussions with the regulators in The U. S. And The EU?
Speaker 2
I don't think we're ready to provide guidance on that yet. We did have interactions with the FDA, over the summer. And so we're still formulating our strategies there.
Speaker 9
Got it. Okay. Thanks for taking my questions.
Speaker 2
You're welcome.
Speaker 0
And the next question from the line of Madhu Kumar. Your line is open.
Speaker 10
Hey, everyone. Thanks for taking our questions. So my first one is on AAT. So kind of following up on Luca's question. So you can imagine there are two schools of thought around clinical benefit in the alpha-one in atripsin liver disease related to either reversal of polymer and globule formation versus liver cell turnover.
So based on your belief that six months will not be enough for AAT knock to translate to clinical benefit. Do you put yourself in the kind of liver turnover school of thought, or do you think you're kind of spread between the two? Or, like, how do you think about it in terms of which realm do you think you'll get benefit in terms of the alpha one antitrypsin liver disease?
Speaker 2
I'll let I'll I'll let Javier expand this. I don't think we know. You know? We we look. We we know that we can that that polymer should be reduced via the liver or via hepatocyte turnover.
That's what we think we know, and that's about it. I don't think we have a good idea about metabolism but beyond that. Javier?
Speaker 3
Yeah. I think as I said before, this is one of those liver diseases that start with an insult, such as hepatitis, such as NASH. And as you know, when you remove insult, more likely liver improve and that's been shown in many different circumstances like this. So this is a treatment that will remove the insult that is new. And with time, the remodeling will get rid of the polymers and globules and that will hopefully allow the cells, the hepatocytes, to heal and prevent the complication and the progression of the disease to to a stage cirrhosis.
So that's how we're thinking about it.
Speaker 10
Interesting. So y'all don't think the preclinical data suggests there's a back reaction that occurs where polymer or monomer converts back to a state. If you don't have a, like, nascent AAT forming, you don't think there's a back reaction that happens?
Speaker 2
A back reaction mean, like, you know, an unpolymerization, if you will?
Speaker 10
Exactly.
Speaker 2
Yeah. I I have stuff that we we just don't know.
Speaker 10
And then on Arrow Enac, so you obviously have kind of gone into the long, and that's really exciting as an opportunity. What data do you need to see from Arrow ENAT to kind of more broadly pursue the lung, including the COPD indication, the other kind of pulmonary petroleum directed lung indications? Like, what do you need to see? Do you need to see FEV one benefit, or do need to see something more proximal to that that will give you kind of confidence that you can hit targets in the lung?
Speaker 3
Yes. Also this is a Phase I study of course, but we're doing two assessment in patients, which is FEV1, so spirometry well established, and then LCI or Land Clearance Index. And we think that that is particularly sensitive methodology to assess early changes and somehow probably related or correlated to the NCCL and conciliary So we did a webinar about a week ago and there are a number of details in webinar that you may want to if you haven't seen it you can take a look because it's in our webpage. But I think the LCI, we have enough patients in this Phase I study to likely see difference in LCI or changes. And also if you put all the patients together, because LCI will be done in a subset of patients with FEV1 greater than seventy percent because the methodology is precise in that kind of patient population.
But we're doing FEV1 in all patients, all three cohorts of patients with cystic fibrosis. So we think that we are in a good situation to look at change from baseline and perhaps see an initial difference assuming a significant change. So we do believe that we will have proof of concept data, at least the study is designed to achieve that goal in the phase one.
Speaker 10
Okay, so then following that logic, lung clearance index as a measure for ENaC inhibition, like a surrogate measure for ENaC inhibition, that's the kind of key barometer for you to kind of broadly pursue the lung?
Speaker 3
Well, no. It will give us information that it's a pharmacodynamic effect, not necessarily only the inhibition. That will tell us that there is an improvement in respiratory ventilation homogeneity which is related to NCC and eventually clinical benefit. So it's actually a pharmacodynamic. It's not just a level of knockout.
We won't be able to measure that, of course, clinically with this target because you have to have a lung biopsy. So it's going to be really a pharmacodynamic result, and the study is designed to be able to see those changes definitely with LCI and then hopefully also with FEV1.
Speaker 10
Gotcha. Awesome. So then stepping back and thinking I know previously, we've all talked about this idea of kind of the the fancy term, I guess, is bispecific audio, like, hitting multiple targets at the same time. Like, where is your progress on that, and where are you thinking about pursuing that considering you've got this whole kind of basket of cardiometabolic targets where I think a not unreasonable expectation would be, well, why not go after multiple targets at the same time? So how are you thinking about that?
What do you need to do to kind of really pursue that in in gusto?
Speaker 2
Yeah. It's a that's a very smart it's a very smart, question, I think. That and it's something we think about a lot because you because you're right. You're cardiometabolic. You know, we've got we've got the data we've seen so far with April and Ang are so intriguing that if if, you know, if you would combine those, that's even more intriguing.
But you can also imagine that within the lung, there there are several targets that that could be very interesting by combining those. You can also look you know, think of this in NASH as well. There there are there are multiple, pathways you could address if you could go after what they call it by bispecific or dimer. So so you so, yes, we are on the same page, you know, with the the the, the great possibility of the bispecific or dimers. We are we're still working on that.
You know, there there are challenges there associated with potency and and such, and we're still working there. We can I think we can see it, but we're but we're not there yet? So so, you know, stay tuned. We'll have we'll we'll have additional, updates, as we as we we can approach the clinic with with with one of these. But it's still it's still, you know, early ish days, on this concept.
Speaker 10
Okay, great. Thanks very much,
Speaker 2
guys. Next
Speaker 0
question from the line of Mani Foroohar of SVB Leerink. Your line is open.
Speaker 11
Hey. Thank you very much. So I don't think I can match the elegance of Madhu's question around law of mass action as a one a t. So thinking about it in perhaps a more, well, we'll say a little bit more of a crass way going back going back up 10,000 feet. When you think about the time horizon to see a polymer benefit, and, clearly, it's not gonna be six months, at least some longer period, versus the time horizon to see histology improvement, should we expect polymer benefit to lead histology improvement by a year, two years, some some some very long period of time, or should it be very quick, one striking after the other, given what we know about, from the preclinical data date and natural history?
And then I have one quick follow-up on a boring finance question.
Speaker 3
Well, we really don't know. The good news, I think we're gonna answer the question as we go along. And the phase two, three study, the post baseline biopsy is right now two years post initiation of the study. So we're taking right now a relatively conservative approach to do the post baseline biopsy two year after initiation of therapy to allow enough time to be able to see what we've seen in the preclinical work. Now, how that would look like, I don't know.
But 02/2002, as a sequence of biopsy at different time points, different patient population might help us fine tune the timeframe of changes, monomer, polymers, globules, and the consequence liver damage associated with that. So more to come, please. Yeah.
Speaker 2
And just to reiterate our time expectations here, As as we mentioned, we are, we are processing the, and analyzing the the, the biopsies right now. It is our anticipation that we'll have data in time to submit a late breaker abstract, to AASLD. You know, my hope is that we get accepted there. And so so I think we can have we can have more, educated conversations about about what we're seeing and what we could be seeing in the future sometime around around then. So, it's just it's just too early to tell.
Look. But, you know, our the preclinical data were interesting. You know, we we saw improvements in in all of these measures. We just don't know how the kinetics of those are gonna translate from from, from roads to humans.
Speaker 11
That's really helpful. So and on the more boring finance question, you you spoke a little bit about the impact of, of stock based compensation, etcetera. So clearly, your stock has been has been volatile over the last couple of years, but it's not surprising given the amount of data that you've produced and the milestones that you've hit, etcetera. So when we think about modeling stock based comp, we think about it in terms of total of shares issued as opposed to dollars, which takes that event that impact out a little bit. Should we expect shares issued or options issued in a notional sense to be about flat versus this year, up materially, down slightly.
How should we think about that as we model that going forward on a stock issuance perspective as opposed to trying to use a dollar amount for a pretty volatile equity security like yours?
Speaker 2
Yes. I would expect that to be pretty flat on a stock basis. Again, to use your differentiation, right, not on a dollar basis, but on a number of share basis.
Speaker 11
Great. That's really helpful. Thanks, guys.
Speaker 2
You're welcome.
Speaker 0
Thank you. Next question from the line of Maha Mamtani of B. Riley. Your line is open.
Speaker 4
Congrats team on the progress. Just no more a one eighty question. I I just wanna drill down on the cardiometabolic portfolio. Starting
Speaker 7
with the
Speaker 4
eight nine zero, the the Amgen compound, could could you just comment on what data they have presented or they will present? And and, you know, in context of another agent that is already in outcome study, just just kind of, anything that is out there, you know, you can talk about the data, that they have so far.
Speaker 2
Right. Yeah. So so, as far as I know, they have not they've not presented any data. I'm not in any jeopardy of of telling you something I shouldn't tell you because I don't because they haven't told us anything. My expectation is that is that is that they would they would present some data, by the end of this year.
At what venue, you know, what time, I don't know. And and and what are they gonna see, I don't know. You know, we're we're we are optimistic that they should be good data because, look, we thought that was a really good trigger. You know, we we expected it to be potent. We expected it to lead to to good, deep, and durable LP little a knockdown knockdown.
But that's but that was speculation based on the, animal models. So, you know, we'll be looking forward to seeing that side by side with you.
Speaker 4
Okay. And and then on APOC three, I I I'm sensing there's a little bit of a change, relative to, I I think, what you were talking about earlier, you know, with Ang3 maybe positioned for the broader population, but it seems like you you wanna do APOC3 also in in the broader hypertriglyceridemia space. So just curious, is it is it more to do with how the landscape there is evolving or with the, you know, the regulatory dialogue you're having, in in real time? Like, just or or is it, like, the data that, you know you know, we'll get to see more at NLA and and other conferences? Could could you just maybe give more color there?
Speaker 2
Yeah. Thanks for asking that question because because I think it's important. You know, part of part of this may be, that we could have messaged this better, but another part is that is that our thinking really has evolved. You know, we've talked a lot about about addressing smaller populations because that looked like a near term, path commercialization. And so we've always thought that we that that's how we approach this asset.
You know, we we we get into these these smaller populations relatively quickly, and then expand the label by essentially walking down, the the triglyceride levels. And so if you think of this just in in broad terms of, say, above a thousand and then, say, 500 to a thousand and then, say, 200 to 500 as we talked about in the prepared remarks. I think Vascepa I think I think their first their first, tranche, if you will, was was two was 500 to a thousand, I think, was their first the first group they got approved on. In any event, you know, we so so so our our so a, we we we we are trying to message this a bit better that we see this as a as a whole, as a spectrum of of patients that we can address, you know, from small market to larger market. So I I wanna talk about that a bit more.
But, also, as I mentioned, you know, I think our I think that our our thinking has changed here a bit in part because the data have just been so good. You know, as we look at at the at the, the the safety profile and as we look at at the the depth of of triglyceride knockdown we're seeing, and, frankly, the increase in HDL, we have not talked very much about, but we think still could be important. You know, as we look at all that, we just say to ourselves, we've got something here that that really should be brought to larger populations. And so, again, our goal here is to maybe start with small populations because we can get to that commercial opportunity most rapidly. But then to expand this out and look, I think this is at least, as large a market opportunity as ANH3.
Maybe larger, but at least as large as that, given the type of patients that we can address. Look, the numbers we talked about, forty one million adults are estimated to have triglycerides between two hundred and five hundred in The US alone. That's a pretty big swap for us to potentially treat some subset of that.
Speaker 4
Okay. Great. And and then, on the ANG3, just, can you confirm if, you still have some fatty liver disease patient, subjects being enrolled there? And you'll still are are you still planning to do PDSS on some of these subjects?
Speaker 2
Yeah. So so it's, Javier, couldn't understand what you said. So, you're talking about the various patient cohorts, and are we still enrolling?
Speaker 3
Well, IH3 is completely enrolled. So we complete that study. We're starting to look at the data that comes. So no, we complete that study together. And as Chris said, we're planning on the first interaction with the regulatory agency here with the FDA to plan the Phase 2b study to start hopefully the beginning of the first half of twenty twenty one.
So the study is complete in terms of enrollment, and very soon we'll have completed one hundred and thirteen days final data for all patients, all subjects and patients in the study.
Speaker 2
And we've talked about lipid panels for all these patients. And what has always excited us about this pathway and this target has been the possibility of lowering LDL a non LDL receptor mediated fashion and lowering triglycerides. That's been the core of our interest. Now if you go a bit beyond that and you look at the possibility of insulin sensitivity, and liver fat, the data that we and others have seen, in animal models have been interesting. And so that was nice to have but not a need to have, if you will.
And we were looking forward to seeing whether or not we see that translate into humans. Given the data from antisense candidates, we are we we are not expecting to see, to see that translate. We're not expecting to see changes in or improvement in insulin sensitivity. We're not expecting to see changes in liver fat now that, you know, we haven't seen the data yet, so so maybe we're wrong there. But just given given what we've seen from antisense, we're not we're not expecting to see that.
We think that's that's fine because it's the triglycerides and LDL that make this a really powerful, asset. But we but we do we do have those those cohorts enrolled, and so we'll find that out, and we'll be reporting on those as well.
Speaker 4
Excellent. Look forward to those updates. Thanks for taking my questions.
Speaker 2
You're welcome.
Speaker 0
Thank you. And the last question from Robert Fogacciki of biobiostat.com. Sir, your line is open.
Speaker 12
Hi. Thank you so much for taking my questions. First off, congrats on your progress and continued growth. I only have a couple of quick matters as you cover my other questions. I'm sorry if I missed it, but did Sequoia Part B start dosing yet?
Speaker 2
No, it has not.
Speaker 12
Okay. And I know that you mentioned before that Arrowhead is comfortable in rolling out its own orphan drugs. Would you consider partnering or selling any of your orphan drugs, especially ENaC or AAT? Or are your orphan drugs off the table when it comes to these kinds of deals? No, I wouldn't say they're off
Speaker 2
the table. So don't think of us as an orphan indication company. But also don't think of us you know, as as holding on to everything that we have in those spaces. I think that that, you know, if you fast forward, you know, five or ten years from now, I think you'll see you'll see, you know, a portfolio of drugs. You know,
Speaker 11
some of
Speaker 2
which are small indications, some are large indications, some could be very large indication. So no, there's nothing about smaller indications that would indicate that we are absolutely going to hold on to those, you know, come hell or high water.
Speaker 12
Okay. That's all I have. Thank you so much.
Speaker 2
All right. Thank you.
Speaker 0
Thank you. And there are no further questions at this time. I would like to turn it over to Chris Andaloni for closing remarks.
Speaker 2
Thanks, everyone, for joining our call today. I hope everyone stays safe, and enjoy the rest of your summer to the extent that you can.
Speaker 0
Thank you. And that concludes today's conference. Thank you, everyone, for participating. You may know all this tonight.