Q2 2024 Arrowhead Pharmaceuticals Inc Earnings Call

May 9, 2024

<unk> the presentation, there well there will be an opportunity to ask questions to ask a question simply press star one one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one once again, we do ask that all participants limit themselves to one question.

<unk> and one follow up I will now hand, the conference call over to Vince Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead Vince.

Thank you.

Good afternoon, everyone and thank you for joining us today to discuss arrowheads results for its fiscal 2024 second quarter ended March 31, 2024 with US today from management are president and CEO, Dr. Chris Anzalone, who will provide an overview of the quarter Dr. Bruce given our interim chief medical scientists, who will provide an up.

<unk> on our cardio metabolic pipeline, Dr. James Hayward, our chief of Discovery and translational medicine will provide an update on our earlier stage programs and Ken Moskovsky, Our Chief Financial Officer, who will give a review of the financials before we begin I would like to remind you that comments made during today's call contains certain forward looking statements within.

The meaning of section 27 a of.

Of the Securities Act of $19 33, and section 21 E of the Securities Exchange Act of 934, all statements other than statements of historical fact are forward looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward looking.

For further details concerning these risks and uncertainties. Please refer to our SEC filings, including our most recent annual report on Form 10-K, and our quarterly reports on Form 10-Q, I would now like to turn the call over to Chris Anzalone, President and CEO of the company Chris.

Thanks Vince.

Good afternoon, everyone and thank you for joining us today.

As we discussed in our last conference call <unk> has reached a point, where our business requires a greater degree of focus we are in the process of building out our expertise within the cardio metabolic space and focusing more of our spend in that area.

These are wholly appropriate actions, because our cardio metabolic programs represent a substantial amount of potential near mid and long term value.

We need to ensure that they are properly resource both from a financial and human capital standpoint, and that they are at the center of Investor analysis of our business.

This is a good thing for Arrowhead, we have two late stage drugs drug candidates with data across diverse populations from ultra rare to highly prevalent spanning over 1000 human subjects.

We see a train of potential value creation with Bose ASUR, Enzo gas ran and expect to file NDA or supplements to expand those labels almost every year over the next five to six years.

This is a pipeline within just two drugs and I believe we will start unlocking value in the very near term.

Further we expect to expand our cardio metabolic reach into obesity and metabolic disease with two additional drug candidates, reaching the clinic this year.

The possessor in palisade phase III study in patients with familial <unk> syndrome, or FCS is clinically complete.

Last patient last visit occurred last week, the database should be locked over the next two weeks and I expect to disclose top line data at our cardio metabolic webinar in June with a fuller data set hopefully presented this year at an appropriate medical conference.

We believe that <unk> will become our first commercial product and we are preparing for an NDA submission for use in FCS patients by the end of the year with a potential launch in 2025.

To this end our commercial preparations are well underway, we have begun building our commercial team, including people with deep expertise in cardio metabolic marketing commercial operations and market access.

We're also in the later stages of solidifying a specialty pharma and patient hub system that will be ready to help ensure fcs patients get pedestrians soon after its anticipated approval.

Beyond our commercial infrastructure, we have begun building out our medical affairs team with a focus on field support to help clinicians better understand <unk> three inhibition.

Additionally, we have begun helping physicians, who request early access to possess or in to do so for appropriate Fcs patients prior to approval.

We are also studying <unk> in the broader severe hyperkalemia triglyceride EMEA or <unk> population toward that end, we have begun screening patients in two phase III studies chefs at three and chest before and are preparing a third phase III and justified.

It is early but our aggressive goal is to complete enrollment of those studies in 2025.

She has to three in Chester for our 52 week studies and justified and acute pancreatitis study that will follow patients until a set number of pancreatitis events is reached.

Turning to <unk>, we submitted briefing documents, including Phase III study designs for patients with homozygous familial hypercholesterolemia or HOS age to the FDA and expect an end of phase II meeting. This month, we hope to initiate phase III soon after we receive regulatory feedback.

We have also completed our analysis of how to move forward in the large mixed dyslipidemia population with a cardiovascular outcomes trial or cbot.

We have submitted our proposal to the FDA and expect feedback over the next month and then we will seek input from the EMA and other regulatory authorities. We will provide detailed information about our plans expected timing and costs. Once we know we have regulatory alignment on design.

Please ask your engines at ASUR and our important candidates for us because they offer new and expanding commercial opportunities over the next several years and because clinical data have suggested that they have a high probability of success Bruce.

Bruce will talk more specifically about results, but a lot of data have been presented recently and we've been encouraged by the safety and Tolerability target engagement and downstream changes in lipids and lipoproteins across multiple patient populations.

As I mentioned over 1000 people have enrolled in the <unk> in clinical studies.

Safety and Tolerability data have given us confidence that these could be appropriate therapeutics not only for small and medium size populations, but also importantly broad mixed dyslipidemia populations.

Please enter your dial-in pin and press pound when finished.

Target engagement measured by circulating protein knockdown of <unk> three for both <unk> and <unk> have been impressive and consistent exam.

The exact numbers will vary a bit depending on the study population duration of treatment dose level and measurement time point. However, we are consistently seeing mean, Max knockdown exceeding 75% to 90% with a long duration of effect that supports a quarterly dosing interval proposed essar and <unk>. This is what we designed the programs to achieve so.

We are very encouraged to see clinical results consistent with our expectations.

The downstream change in various lipids and lipoproteins have been favorable and consistent with published genetic data enabled <unk>, three and <unk> III deficient humans and consistent with experimental data in animals, receiving apoc III and <unk> inhibitors.

Similar to target engagement the exact changes.

Varied.

Alright, the exact changes varied a bit between different study populations, but generally speaking subjects treated with <unk> showed improvements in multiple.

<unk> lipid and lipoprotein levels, including remnant cholesterol, which is increasingly viewed as an important target for new therapies to address atherosclerotic cardiovascular disease or <unk> CBD.

Numerous.

Immunologic studies have shown an association between higher triglyceride rich proteins or <unk> and an increased risk of CBD. Despite potent LDL cholesterol lowering therapies residual ASC BD risk persists due in part to high levels of Atherogenic Trl's.

Remnant cholesterol is also believed to be a major contributor to the residual risk of atherosclerotic sclerotic cardiovascular disease. After LDL is well controlled.

We believe <unk> at Astro and represents significant opportunities to help a lot of patients for all the reasons I mentioned, we are moving as quickly as possible towards treatments and FCS HOS H.

<unk> and the very large population of patients with CBD due to mixed dyslipidemia.

We believe we can help a large number of patients and create a substantial amount of value with <unk> alone. However, it makes sense to leverage our growing cardio metabolic capabilities by expanding the vertical we expect to introduce two new candidates into the clinic in the fourth quarter aimed at obesity and metabolic disease.

These are arrow iron HPE, a liver directed candidate targeting inhibiting <unk> and an undisclosed candidate targeting adipose directly we will discuss those in more depth during a focused webinar in the summer.

We continue to make progress beyond the cardio metabolic vertical as well within pulmonary the arrow MMP seven in <unk> phase one studies continue to enroll patients in the Aero Rage Phase one study is enrolling <unk> patients with moderate to severe asthma.

Pinot cohorts have been slow to enroll because the high baseline required of the study has led to a high screen fail rate. We believe in the candidate and target engagement data has been what we had hoped for so we are not going to wait for that to read out before progressing to a phase II study.

We have designed a phase II study in asthma patients and are moving toward launching that in the fourth quarter.

Aero Rage Tolerability has been good in the phase one study we have seen clear evidence of substantial target engagement in the phase one data in animal models were very encouraging. The rage pathway has also generated a good amount of kols interest. So we are excited to move forward as quickly as we can.

Moving to our new programs during the last quarter, we began dosing in two new clinical programs <unk> for the treatment of disease diseases associated with activation of the complement pathway and <unk> one for the treatment of type one myoclonic dystrophy or <unk> one fees.

These programs put well with <unk>, three and <unk> four respectively performer is enrolling the patient portion of our phase one two study and together with <unk> provides a focused portfolio in complement mediated diseases.

<unk> four is enrolling fsh D patients in a phase one two study and together with arrow deem one creative focus skeletal muscle portfolio.

We now have 14 clinical stage programs 10 of which are wholly owned I expect we could have 18 clinical programs by the end of the year.

This is a lot and they certainly can be difficult to track and properly valued by investors.

We think of our wholly owned assets in a series of verticals.

As we have discussed the cardio metabolic vertical is our primary focus but beyond that we have at pulmonary vertical.

Implement vertical and muscular disease vertical and by the end of the year CNS vertical.

We expect to partner with we expect to partner within these four verticals in order to limit our spend and bringing capital to properly fund, our cardio metabolic vertical and our other research programs, but we believe this is the way investors should look at our pipeline.

Understanding and properly valuing these assets can still be difficult. So we recently announced the upcoming 2020 for summer series of R&D Webinars to highlight some of our work.

Starting this month and continuing each month through September we will host five webcast events. Each event will feature presentations by Arrowhead team members and external key opinion leaders, who will discuss disease areas and treatment landscapes.

We will talk about arrowheads candidates, the biological rationale and preclinical data supporting each candidate and our clinical development strategy for each pipeline program.

The series is designed to highlight important value drivers in a focused way.

The summer series schedule is as follows may.

May 'twenty three is muscle vertical day, where we will cover <unk> and aero decks for.

June 25, as cardio metabolic day, where we will give an overview of both <unk> and data to date, including phase III Palisades.

Muscular disease vertical and by the end of the year, our CNS vertical.

Data and talk about the future of the programs in the diseases, we aim to treat.

We expect to partner with we expect partner within these four verticals in order to limit our spend and bringing capital to properly fund, our cardio metabolic vertical and our other research programs, but we believe this is the way investors should look at our pipeline.

July 16 is pulmonary day, which includes arrow rage, <unk> AC and <unk> seven.

August 15 is obesity and metabolic disease day, where we will talk about <unk> and HPE and the undisclosed edibles candidate.

Understanding and properly valuing these assets can still be difficult. So we recently announced the upcoming 2020 for summer series of R&D Webinars to highlight some of our work.

On September 25 is CNS day, where we will highlight our central nervous system programs, including updates on the platform and on a specific undisclosed candidate plans to enter clinical development later this year.

In addition to the summer series, we also recently announced a busy month of presentations at medical and scientific meetings. These include presentations at tides USA. The American Thoracic Society 2024 International Conference. The International Conference on Antiviral Research European Atherosclerosis Society Congress in.

We will talk about arrowheads candidates, the biological rationale and preclinical data supporting each candidates and our clinical development strategy for each pipeline program.

The series is designed to highlight important value drivers in a focused way.

The National Lipid Association scientific sessions.

The summer series schedule is as follows.

These are all planned for May in addition, we plan to present on many of our programs at several medical meetings throughout the year, we have a lot going on including a lot of exciting results to talk about.

May 'twenty three is muscle vertical day, where we will cover <unk> and aero decks for.

June 'twenty five as cardio metabolic day, where we will give an overview of both ASUR Enzo to Essar and data to date, including phase III Palisades, FCS data and talk about the future of the programs in the diseases, we end to treat.

During the last few months, we've also strengthened our balance sheet with two inflows. The first was that in January when we announced an equity financing with gross proceeds of $450 million the.

July 16 is pulmonary day, which includes arrow rage, <unk> AC and <unk> seven.

The second was just announced last week that was a $50 million milestone payment that we received from royalty pharma. Following the completion of enrollment of the phase III Ocean, a outcomes trial of El Paso and being conducted by Amgen We originally.

August 15 is obesity and metabolic disease day, where we will talk about <unk> and the undisclosed adipose candidates.

The license we originally licensed will pass or improve previously called Arrow LTA to Amgen in 2016, and then monetize our future royalty stream in a transaction with royalty pharma in 2022.

Arrowhead is further as further eligible to receive up to an additional $375 million from Amgen and $110 million from royalty pharma in aggregate development regulatory and sales milestone payments associated with El Paso Ram.

This is a this is a good example of how we use partnering and creative financing structures as important parts of our long term financing strategy. We are always working on potential future deals and now is no exception. We are confident that we can complete additional transactions. This year to further strengthen our balance sheet to support future clinical development and commercialization of our wholly owned programs with that.

National Lipid Association scientific sessions.

These are all planned to make in.

In addition, we plan to present on many of our programs at several medical meetings throughout the year.

<unk> not including a lot of exciting results to talk about.

During the last few months, we've also strengthened our balance sheet with two inflows. The first was that in January when we announced an equity financing with gross proceeds of $450 million.

Overview I'd now like to turn the call over to Bruce Bruce.

Thank you Chris good afternoon, everyone.

Chris discussed possess <unk> at a high level, but I want to spend some time going over a few specific things.

The data on the <unk> two study of <unk> that we presented at ACC and simultaneously published in Jama cardiology.

We originally licensed El Pen, we originally license will pass or improve previously called Aro LTA to Amgen in 2016, and then monetize our future royalty stream transaction with royalty pharma in 2022.

The design and status of chefs.

345 third expectations for our upcoming Eas and MLA presentations and lastly, a review of the soon to report palisade study of <unk> in familial Chylomicron nemea syndrome or Fcs.

<unk> is further as further eligible to receive up to an additional $375 million from Amgen and $110 million from royalty pharma in aggregate development regulatory and sales milestone payments associated with El Paso ran.

Let's jump right in with chefs to two study of <unk>.

To review <unk> is designed to reduce production of April lipoproteins C three or apoc III, a component of triglyceride rich lipoproteins trl's.

This is a this is a good example of how we use partnering and creative financing structures as important parts of our long term financing strategy. We are always working on potential future deals and now is no exception. We are confident that we can complete additional transactions. This year to further strengthen our balance sheet support future clinical development and commercialization of our wholly owned programs.

A key regulator of triglyceride metabolism.

Apoc III increases plasma triglyceride levels by inhibiting breakdown of <unk> by lipoproteins lipase. It also inhibits uptake of remnant cholesterol <unk> derived from Trl's by hepatic receptors in the liver.

With that overview I'd now like to turn the call over to Bruce Bruce.

The <unk> study was a double blind placebo controlled phase II <unk> study in adults with severe hyper triglycerides EMEA, our SAP <unk>.

Thank you Chris good afternoon, everyone.

Chris discussed possess <unk> at a high level, but I wanted to spend some time going over a few specific things.

Three dose levels of possessor at 10 milligrams 25 milligrams 50 milligrams were evaluated against placebo in 229 participants with fast and triglycerides of greater than or equal to 500 milligrams per deciliter at screening.

First the data on the <unk> two study of <unk> that we presented at ACC and simultaneously published in Jama cardiology.

Second the design and status of chefs to 345.

Each participant received subcutaneous injections on day, one and at week 12 with subjects, followed all the way out to week 48.

<unk> expectations for our upcoming Eas and MLA presentations and lastly, a review of the soon to report palisade study of <unk> in familial Chylomicron nemea syndrome or Fcs.

The primary objective of this study was to evaluate the safety and efficacy of <unk> in adults with <unk> and to select a dosing regimen for later stage clinical studies in this patient population.

Let's jump right in with chefs to two study plus Ashford.

To review <unk> is designed to reduce production of April lipoproteins C three or apoc III, a component of triglyceride rich lipoproteins.

<unk> is characterized by triglyceride levels greater than 500 milligrams per deciliter and is known to significantly increase the risk of CBD and acute pancreatitis, often with recurrent attacks requiring repeat hospital admissions and worst need outcomes.

And a key regulator of triglyceride metabolism.

Apoc III increases plasma triglyceride levels by inhibiting breakdown of <unk> by Lipoproteins light base. It also inhibits uptake of remnant cholesterol derived from trl's by hepatic receptors in the liver.

Pancreatitis risk is proportional to the number characteristics.

<unk> and increases as triglycerides increase.

The <unk> study was a double blind placebo controlled phase II study in adults with severe hybrid triglycerides EMEA or <unk>.

Currently available drug therapies, generally don't sustainably reduce triglycerides below the pancreatitis risk threshold.

In addition to chefs to two there is also an open label extension study that is ongoing.

So final data from the double blind treatment period of <unk> were presented at ACC and published in Jama cardiology.

Each participant received subcutaneous injections on day, one and at week 12 with subjects, followed all the way out to week 48.

These were exciting data, which received a lot of attention and were well received at ACC and a subsequent discussions with physicians.

With respect to pharmacologic activity treatment with possess round led to dose dependent placebo adjusted reduction in triglycerides at 24 weeks, which was the primary endpoint.

The primary objective of this study was to evaluate the safety and efficacy of <unk> in adults with S. H T G and to select a dosing regimen for later stage clinical studies in this patient population.

The reductions observed were minus 49% minus 53% and minus 57% for the 10, 25% and 50 milligram doses respectively.

<unk> is characterized by triglyceride levels greater than 500 milligrams per deciliter.

It is known to significantly increase the risk of CBD and acute pancreatitis, often with recurrent attacks requiring repeat hospital admissions and worsening outcomes.

For perspective currently available drugs, usually would be expected to produce reductions of maybe 20% or so.

As expected these triglyceride reductions were driven by corresponding placebo adjusted reduction in Apoc III of minus 68% minus 72% and minus 70% at week 24 all.

Pancreatitis risk is proportional to the number characteristics and concentrations of <unk> and increases as triglycerides increase.

Currently available drug therapies, generally don't sustainably reduce triglycerides below the pancreatitis risk threshold.

All of these measures were highly statistically significant.

With 24 measurements represent the point of minimal efficacy.

In addition to Shasta too. There is also an open label extension study that is ongoing.

<unk> two is trough measurements just prior to the next planned quarterly dose.

Mean maximum non placebo adjusted reduction from baseline in triglycerides, Apoc III, we're up to 86, and 90%, respectively and typically occurred Rod week 16 or week 20.

So final data from the double blind treatment period of <unk> were presented at ACC and published in Jama Cardiology. These were exciting data, which received a lot of attention and were well received at ACC in subsequent discussions with physicians.

Importantly, we also looked at the percentage of patients who met the goal of reducing triglyceride levels below 500 milligrams per deciliter, a level above which the risk of acute pancreatitis meaningfully increases.

With respect to pharmacologic activity treatment with possess round led to dose dependent placebo adjusted reduction in triglycerides at 24 weeks, which was the primary endpoint.

Amongst subjects treated with <unk> at the week 24 trough time point greater than 90%, receiving the fit 25, or 50 milligram doses achieved a triglyceride level less than 500 milligrams per deciliter.

Reductions observed were minus 49% minus 53% and minus 57% for the 10, 25% and 50 milligram doses respectively.

For perspective currently available drugs, usually would be expected to produced reductions of maybe 20% or so.

In addition around half of the subjects at these doses achieved normal tragus triglyceride levels of less than 150 milligrams per deciliter at week 24, which is surprising given the mean.

As expected these triglyceride reductions were driven by corresponding placebo adjusted reduction in <unk> of minus 68% minus 72% minus 70% at week 24.

Starting levels of almost 900 milligrams per deciliter.

In addition to reductions in triglycerides subjects treated with <unk> also showed improvements in multiple atherogenic lipids and lipoproteins levels, including remnant cholesterol HDL cholesterol and non HDL cholesterol.

All of these measures were highly statistically significant.

We 24 measurements represent the point of minimal efficacy.

<unk> two is trough measurements just prior to the next planned quarterly dose.

Mean maximum non placebo adjusted reduction from baseline in triglycerides, Apoc, III, we're up to 86 and 90% respectively.

So SaaS for a demonstrated a favorable safety profile in Chester to.

Observed adverse events generally reflected the comorbidities and underlying conditions of the study population.

Typically occurred Rod week, 16 or week 20.

The adverse events and serious adverse event profiles were generally similar across treatment groups. Although we're seeing a diabetes did appear more frequently in the 50 milligram dose.

All serious treatment emergent adverse effects were deemed not related to <unk>.

Overall than the deep consistent and sustained reductions in <unk> III in triglycerides and improvement in multiple atherogenic lipoproteins levels gives us a level of confidence as we initiate phase III studies in patients with <unk>.

In addition around half of the subjects at these doses achieved normal triglyceride levels of less than 150 milligrams per deciliter at week 24, which is surprising given the mean.

These three.

Phase III studies are called Shasta, three Shasta, four and chefs to five.

Starting levels of almost 900 milligrams per deciliter.

I will start with descriptions of chess is three or four since they are very similar to each other and are being initiated now.

Both studies are global randomized double blind placebo controlled phase III studies to evaluate the efficacy and safety of <unk> in adult subjects with SAP <unk>.

Please ask for a demonstrated a favorable safety profile of chest to chew.

Eligible subjects will be randomized to receive either possess ran at 25 milligrams or placebo.

Observed adverse events generally reflected the comorbidities and underlying conditions of the study population.

A double blind treatment period duration will be one year.

The adverse events and serious adverse event profiles were generally similar across treatment groups. Although we're seeing of diabetes did appear more frequently in the 50 milligram dose.

Where subjects receive a total of four quarterly doses.

After month 12 eligible subjects will be referred.

Sorry will be offered an opportunity to continue and an optional open label extension.

All serious treatment emergent adverse effects were deemed not related to <unk>.

The primary endpoint for the study is placebo adjusted per cent change in fasting triglyceride levels at month 12.

Overall than the deep consistent and sustained reductions in April three in triglycerides and improvement in multiple atherogenic Viper protein levels gives us a level of confidence as we initiate phase III studies in patients with <unk>.

<unk> three is planned to include approximately 400 subjects with chefs to four is planned to include approximately 300 subjects.

We have begun activating sites for these studies it will activate others as quickly as possible there are already patients in screening. So we expect that the first patients dosed soon.

These three phase III studies are called Shasta, three Shasta four and shafts at five.

This has moved very rapidly and I am proud of the work done by all of the Arrowhead teams involved our CRO and the investigators institutions that are participating in the studies.

I will start with descriptions of shafts three and four since they are very similar to each other and are being initiated now.

Both studies are global randomized double blind placebo controlled phase III studies to evaluate the efficacy and safety of <unk> in adult subjects with S. H T G.

I also wanted to give a quick update our chefs to five we're still finalizing some details about the study but as currently planned is a multicenter randomized double blind placebo controlled phase III study to evaluate <unk> versus placebo in approximately 140 adult subjects with S. H T G at high risk of <unk>.

Eligible subjects will be randomized to receive either possess ran at 25 milligrams or placebo.

The double blind treatment period duration will be one year.

Itis.

Where subjects receive a total of four quarterly doses.

Subjects must have triglyceride levels greater than 880 milligrams per deciliter, and a history of acute pancreatitis events, there will be randomized in a one to one ratio to receive either <unk> 25 milligrams or placebo dose quarterly.

After month 12 eligible subjects will be referred.

Sorry will be offered an opportunity to continue in an optional open label extension.

The primary endpoint for the study is placebo adjusted per cent change in fasting triglyceride levels at month 12.

The primary endpoint of the study as incidents of adjudicated acute pancreatitis events compared with placebo.

SaaS to three is planned to include approximately 400 subjects with chefs to four is planned to include approximately 300 subjects.

Now the chefs to three ish has to four have been initiated the <unk> clinical development team is finalizing the chefs to five design.

We have begun activating sites for these studies it will activate others as quickly as possible there are already patients in screening. So we expect that the first patient dose soon.

Working to initiate the study as soon as possible.

We think performing a dedicated study in this high risk population if successful will be useful for payers on a global basis.

This has moved very rapidly and I am proud of the work done by all of the Arrowhead teams involved our CRO and the investigators institutions that are participating in the studies.

Next I want to highlight some upcoming presentations on <unk> III.

At the European Atherosclerosis, Atherosclerosis Society or Eas on May 28, and 29, we will be presenting final results from the mirror study of <unk> and the <unk> two study of <unk> or in <unk>.

Both of these studies are a mixed hyperlipidaemia populations recruited with identical enrollment criteria.

Dennis.

For clarity this field is moving away from the term mixed dyslipidemia to the term mixed hyperlipidemia, so expect to see and hear the two terms used synonymously in the short term, but in the longer term expect to hear mixed hyperlipidemia used more frequently.

Subjects must have triglyceride levels greater than 880 milligrams per deciliter, and a history of acute pancreatitis events that will be randomized in a one to one ratio to receive either <unk> 25 milligrams or placebo dose quarterly.

The primary endpoint of the study as incidents of adjudicated acute pancreatitis events compared to placebo.

I already described possessed mechanistically, but to review <unk> is designed to reduce production of agile appointment protein three or <unk>, three which like <unk> is a parasite expressed regulator of triglyceride metabolism.

Now the shafts three and she has to four have been initiated to possess around clinical development team is finalizing the chefs to five design where we.

Looking to initiate the study as soon as possible.

However, <unk> III, while similar to April three and having an effect on lipoprotein lipase also impacts endothelial light pays and non LDL receptor mediated uptake of LDL.

We think performing a dedicated study in this high risk population if successful will be useful for payers on a global basis.

Next I want to highlight some upcoming presentations on <unk>.

As such by reducing <unk> III, so to answer and causes some downstream changes in atherogenic lipids and lipoproteins that are different than those produced by <unk>.

At the European Atherosclerosis, Atherosclerosis Society, or Eas on May 28, and 29th we will be presenting final results from the mirror study of <unk> and the <unk> two study of soda ash or at <unk>.

These include additional reductions in Ldlc and April lipoproteins, B, while also driving similar reductions in triglycerides remnant cholesterol and non HDL cholesterol associated with <unk>.

Both of these studies are a mixed hyperlipidemia populations recruited with identical enrollment criteria.

This is why we are taking a very close look at the various options for phase III clinical development and an <unk> population with mixed hyperlipidemia.

Population of patients estimated to be around $20 million in the U S alone.

We've engaged with external advisors and have completed exhaustive analysis of potential designs and studies.

I already described pizzazz mechanistically, but to review <unk> is designed to reduce production of agile appointment like protein three or <unk>, three which like <unk>. Three is a parasite expressed regulator of triglyceride metabolism.

We have recently completed submit.

Submission to the FDA on a potential study designed and will have additional interactions on the specifics over the coming 30 to 60 days, we will talk more about our plans after we receive feedback from FDA and other key agencies.

However, <unk> III, while similar to April three and having an effect on lipoprotein lipase.

Upstream of that becoming Eas presentations will be a good way for folks outside the company to see some of the data that have gone into our thinking.

Also impacts endothelial light pays and non LDL receptor mediated uptake of LDL.

As such by reducing <unk>, so to answer and causes some downstream changes in atherogenic lipids and lipoproteins that are different than those produced by <unk>.

And our KOL advisers believe that there really is not a bad choice between the two as you will see results from both your and are just too look compelling.

These include additional reductions in Ldlc and April lipoproteins, B, while also driving similar reductions in triglycerides remnant cholesterol and non HDL cholesterol associated with <unk>.

Now moving to the palisade study of <unk> in patients with Fcs.

I'll say it included FCS patients, who are genetically confirmed and somewhere around half who are clinically diagnosed.

This is why we are taking a very close look at the various options for phase III clinical development in an ASC. The depopulation with mixed Hyperlipidemia a population of patients estimated to be around $20 million in the U S alone.

FCS FCS is a severe and ultra rare genetic condition often caused by various monogenic mutations.

FCS leads to extremely high triglyceride levels, which can lead to various serious signs and symptoms, most notably including acute and potentially fatal pancreatitis.

We've engaged with external advisors and have completed an exhaustive analysis of the potential designs and studies.

Currently the available therapeutic options, we've most FCS patients persistently vulnerable to pancreatitis.

We have recently completed a submission.

Submission to the FDA on a potential study design and we will have additional interactions on the specifics over the coming 30 to 60 days we.

The palisade study is a phase III placebo controlled study to evaluate the efficacy and safety of <unk> in adults with FCS. The primary endpoint of the study is percent change from baseline in fasting triglycerides at months 10.

We will talk more about our plans after we receive feedback from FDA and other key agencies.

Upstream of that.

Coming Eas presentations will be a good way for folks outside the company to see some of the data that have gone into our thinking.

A total of 75 subjects were randomized to receive 25 milligrams of <unk> 50 milligrams of <unk> or matching placebo. Once every three months.

And our KOL advisers believe that there really is not a bad choice between the two as you will see results from both your and arduous to look compelling.

Participants who completed the randomized period are eligible to continue in a two part extension period, where all participants receiving <unk>.

Now moving to the palisade study of <unk> in patients with Fcs.

The last study visit for the last patient enrolled implicit palisade occurred about a week ago.

I'll say it included FCS patients, who are genetically confirmed and somewhere around half who are clinically diagnosed.

This will be arrowheads first completed phase III study and represents a significant milestone for the company.

FCS FCS is a severe and ultra rare genetic condition often caused by various monogenic mutations.

Importantly, it brings possess around potentially closer to the FCS patients that may benefit.

FCS leads to extremely high triglyceride levels, which can lead to various serious signs and symptoms, most notably including acute and potentially fatal pancreatitis.

Our goal now is to work efficiently to generate initial study results and provide a topline data readout.

As soon as our cardio metabolic webinar next month.

Currently the available therapeutic options, we've most FCS patients persistently vulnerable to pancreatitis.

And subsequently present, a fuller data set at an appropriate medical meeting.

This is an exciting time at arrowhead as we eagerly await these results I will now turn the call over to James.

Thank you Bruce the discovery and early development teams made some notable progress over the last quarter and.

And we also have a busy several months ahead with the summer series of R&D Webinars that Chris mentioned earlier.

A total of 75 subjects were randomized to receive 25 milligrams of <unk> 50 milligrams of <unk> or matching placebo. Once every three months.

We do an enormous amount of work and seeking to innovate new medicines that is often only recognized once there is a clinical candidate.

Participants who completed the randomized period are eligible to continue in a two part extension period, where all participants receiving <unk>.

I wanted to talk for a moment about how we see our priorities and the goals of the team.

The last study visit for the last patient enrolled implicit palisade occurred about a week ago.

Number one is to push trim the trim platform to new cell types and continually seek to optimize the safety and activity of each construct.

This will be arrowheads first completed phase III study and represents a significant milestone for the company.

Number two is to develop new candidates against attractive gene targets, we're using RNA interference is the only or best method to inhibit the target.

Importantly.

It brings possess SRAM potentially closer to the FCS patients that may benefit.

Our goal now is to work efficiently to generate initial study results and provide a topline data readout.

Number three is to conduct IND, enabling non clinical studies and first in human clinical studies in the most efficient manner possible to get meaningful readouts that accelerate mid and late stage development.

As soon as our cardio metabolic webinar next month.

And subsequently present, a fuller data set at an appropriate medical meeting.

And number four is to develop assets, which can be readily partnered and support business development activities, which remains a key strategic focus is our pipeline has continued to grow.

This is an exciting time at arrowhead as we eagerly await these results I'll now turn the call over to James.

Thank you Bruce the discovery and early development teams made some notable progress over the last quarter and.

I think we've made good strides in these areas recently, so let's talk about a few examples.

And we also have a busy several months ahead with the summer series of R&D Webinars that Chris mentioned earlier.

We've continued to expand the reach of the trim platform.

We now have clinical programs in three different tissue types, including liver lung and muscle.

We do an enormous amount of work and seeking to innovate new medicines that is often only recognized once there is a clinical candidate.

We also expect in the very near future to have clinical programs in two additional tissues, specifically CNS in adipose.

I wanted to talk for a moment about how we see our priorities and the goals of the team.

Each one of these expands the universe of diseases, we can address and the number of patients that we can potentially help.

Number one is to push trim the trim platform to new cell types and continually seek to optimize the safety and activity of each construct.

During the CNS R&D webinar scheduled for September we plan on giving an update on a specific candidate that is currently undisclosed and highlight the significant progress we're making on our subcutaneously administered construct designed to deliver <unk> across the blood brain barrier to the <unk>.

Number two is to develop new candidates against attractive gene targets, we're using RNA interference is the only or best method to inhibit the target.

Yes, without the need for interest equal administration.

This is a much more patient friendly mode of administration and may be able to access tissues in the deep brain that have been difficult to access with <unk> injections.

And number four is to develop assets, which can be readily partnered and support business development activities, which remains a key strategic focus is our pipeline is continuing to grow.

This is potentially a big step forward for us in the field overall and we are excited about the progress.

I think we've made good strides in these areas recently, so let's talk about a few examples.

During the obesity and metabolic R&D webinar currently scheduled for August we will also talk about platform advancements and pipeline expansion.

We've continued to expand the reach of the trim platform.

We now have clinical programs in three different tissue types, including liver lung and muscle.

The pipeline is expanding by two programs and we will talk about the addition of adipose sites as a new cell type we can access with the trim platform.

We also expect in the very near future to have clinical programs in two additional tissues, specifically CNS in adipose.

As you all know the obesity space has recently gained a lot of attention with the success of GOP. One agents. However, we see clear areas that remain underserved.

Each one of these expands the universe of diseases, we can address and the number of patients that we can potentially help.

We have not disclosed much publicly about the development of our two obesity programs. So this event will be a good opportunity to get people up to speed on where we are and where we see the clinical development programs going.

Moving on to current clinical development programs during the last quarter, we brought two new agents into the clinic.

Ines without the need for <unk> administration.

First <unk> is designed to reduce hepatic expression complement factor B, which plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target.

This is a much more patient friendly mode of administration and may be able to access tissues in the deep brain that have been difficult to access with IP injections.

This is potentially a big step forward for us in the field overall and we're excited about the progress.

<unk> is being developed as a potential treatment for complement mediated kidney diseases, such as Iga nephropathy, which is the most common in glomerular disease worldwide and carries a higher lifetime risk of progression to end stage renal disease.

During the obesity and metabolic R&D webinar currently scheduled for August we will also talk about platform advancements and pipeline expansion.

The pipeline is expanding by two programs and we will talk about the addition of adipose sites as a new cell type we can access with the trim platform.

Additionally, Aero CFB may have clinical applications in non renal diseases involving complement activation.

As you all know the obesity space has recently gained a lot of attention with the success of GOP one agents.

Last month, we announced that we dosed the first subjects in a phase one two clinical trial of arrows CFB designed to enroll up to 66 healthy volunteers and patients with complement mediated kidney disease.

Whenever we see clear areas that remain underserved.

We've not disclosed much publicly about the development of our two obesity programs. So this event will be a good opportunity to get people up to speed on where we are and where we see the clinical development programs going.

Our second new clinical program <unk> is designed to reduce expression of the Dis Trophy and my Intonaco protein kinase or <unk> PK Jean in the muscle as a potential treatment for patients with type one my atonic dystrophy or <unk>.

Moving on to current clinical development programs during the last quarter, we brought two new agents into the clinic.

First <unk> is designed to reduce hepatic expression complement factor b, which plays an important regulatory role in amplifying complement alternative pathway activation.

Pathogenesis of DM, one is driven by an abnormal <unk> PK transcripts, because misread related splicing known as the place apathy for certain messenger Rnas, which are directly linked to the clinical manifestations of DMR.

Has been identified as a promising therapeutic target.

In March we announced that we had initiated and dose the first subjects in a phase one to a double blinded placebo controlled dose escalating study to evaluate single and multiple ascending doses of <unk> one in up to 48 subjects with <unk>.

Additionally, arrows CFB may have clinical applications in non renal diseases involving complement activation.

Moving on to our clinical stage pulmonary programs era rage Aero Mach five AC and <unk> seven.

Last month, we announced that we dosed the first subjects in our phase one two clinical trial of arrows CFB designed to enroll up to 66 healthy volunteers and patients with complement mediated kidney disease.

We continue to enroll patients across all three programs and are confident that we will have multiple opportunities for clinical readouts. This year.

The first of these will occur at Ats later this month.

We are scheduled to present, a poster on ERO rage, which will include data from mild to moderate asthma patient cohorts that we have not reported on previously.

Our second new clinical program <unk> is designed to reduce expression of the this trophy and my atonic, a protein kinase or <unk> gene in the muscle as a potential treatment for patients with type one my atonic dystrophy or <unk>.

To review Arrow Rage is designed to reduce expression of the receptor for advanced location and products or rage as a potential treatment for inflammatory pulmonary diseases.

We are currently enrolling asthma patients with high baseline levels of fractional exhaled nitric oxide for Pheno, which as a biomarker of IL <unk> 13, driven type two inflammation in the lung.

We are expecting to have high fino cohorts enrolled and dosed late this year.

Next programs are <unk>, which is designed to reduce production of Houston, five AC or five AC as a potential treatment for mutual obstructive pulmonary diseases.

Aero MMP, seven which is designed.

Moving on to our clinical stage pulmonary programs era rage Aero Mach five AC and <unk> seven.

To reduce the expression of matrix <unk> protein 87, or <unk> seven as a potential treatment for idiopathic pulmonary fibrosis or IPF.

We continue to enroll patients across all three programs. We are confident that we will have multiple opportunities for clinical readouts. This year.

Both <unk> and Aero MMP seven have already enrolled and dosed healthy volunteers and we anticipate the patient cohorts will be enrolled and dosed in time to enable initial clinical readouts in the second half of this year.

The first of these will occur at Ats later this month.

We are scheduled to present, a poster on ERO rage, which will include data from mild to moderate asthma patient cohorts that we have not reported on previously.

Our pulmonary R&D webinar scheduled for July will review these programs in more detail.

To review ore range is designed to reduce expression of the receptor for advanced communication end products or rage, as a potential treatment for inflammatory pulmonary diseases.

I will now turn the call over to Ken.

Thank you James and good afternoon, everyone.

As we reported today, our net loss for the quarter ended March 31, 2024 was $125 3 million or.

We are currently enrolling asthma patients with high baseline levels of fractional exhaled nitric oxide for Pheno.

Or $1 <unk> per share based on a $123 3 million fully diluted weighted average shares outstanding.

Which is a biomarker of IL <unk> 13, driven type two inflammation in the lung.

We are expecting to have high fino cohorts enrolled and dosed late this year.

This compares with net income of $48 7 million or <unk> 45 per share based on $108 1 million fully diluted weighted average shares outstanding for the quarter ended March 31 2023.

Next programs, our apparel more fiber, which is designed to reduce production of Houston five AC or are they see as a potential treatment for mutual obstructive pulmonary diseases.

No revenue was recorded in the quarter and in the quarter ended March 31, 2020 for revenue of $146 3 million was recorded in the quarter ended March 31 2023.

In Aero MMP, seven which is designed.

To reduce the expression of matrix <unk>, seven or <unk>, seven as a potential treatment for idiopathic pulmonary fibrosis or IPF.

Revenues recognized as we complete our performance obligations or key developmental milestones are reached.

Both aramark, where they see an arrow MMP seven have already enrolled and dosed healthy volunteers and we anticipate the patient cohorts will be enrolled and dosed in time to enable initial clinical readouts in the second half of this year.

Revenue in the prior period, primarily related to the recognition of payments received from our license and collaboration agreements with Takeda and GSK.

Total operating expenses for the quarter ended March 31, 2024 were $126 2 million compared to $98 1 million for the quarter ended March 31 2023.

Our pulmonary R&D webinar scheduled for July will review these programs in more detail.

I will now turn the call over to Ken.

Ken: Thank you James and good afternoon, everyone.

The key drivers of this change were increased research and development costs, primarily compensation cost and candidate costs as the Companys pipeline of clinical candidates has increased.

Ken: As we reported today, our net loss for the quarter ended March 31, 2024 was $125 3 million or.

Ken: Or one dollar and <unk> <unk> per share based on a $123 3 million fully diluted weighted average shares outstanding.

And advanced into later stages of development.

Net cash used in operating activities during the quarter ended March 31 2024.

Ken: This compares with net income of $48 7 million or <unk> 45 per share based on $108 1 million fully diluted weighted average shares outstanding for the quarter ended March 31 2023.

It was $92 4 million compared with $31 7 million during the quarter ended March 31 2023.

The increase in cash used in operating activities was primarily driven by higher R&D expenses as well as the prior period, including $40 million cash receipt of revenue milestones.

Ken: No revenue was recorded in the quarter and in the quarter ended March 31, 2020 for revenue of $146 3 million was recorded in the quarter ended March 31 2023.

Ken: Revenue is recognized as we complete our performance obligations or key developmental milestones are reached.

Construction of our Verona facility is effectively complete.

We are currently undertaking commissioning and qualification activities.

Ken: Revenue in the prior period, primarily related to the recognition of payments received from our license and collaboration agreements with Takeda and GSK.

Which puts us on track for manufacturing drug material to support our clinical trials later this year.

We expect final payments to be made over the next several months totaling $50 million after which we expect capital expenditures to be nominal.

Ken: Total operating expenses for the quarter ended March 31, 2024 were $126 2 million compared to $98 1 million for the quarter ended March 31 2023.

Turning to our balance sheet, our cash and investments totaled $523 1 million at March 31, two.

Ken: The key drivers of this change were increased research and development costs, primarily compensation cost and candidate costs as the Companys pipeline of clinical candidates has increased.

2024.

Compared to $403 6 million at September 32023.

Ken: And advanced into later stages of development.

The increase in our cash and cash or excuse me the increase in our cash and investments was primarily related to the $450 million equity issuance.

Ken: Net cash used in operating activities during the quarter ended March 31 2024 was.

Partially offset by our ongoing cash burn.

Ken: It was $92 4 million compared with $31 7 million during the quarter ended March 31 2023.

Our common shares outstanding at March 31, 2024.

$124 1 million.

Ken: The increase in cash used in operating activities is primarily driven by higher R&D expenses as well as the prior period, including $40 million cash receipt of revenue milestones.

With that brief overview I will now turn the call back to Chris.

Thanks, Ken this has been another quarter of solid execution for Arrowhead.

Our phase III palisade study of <unk> clinically complete which sets us up to take the next step in growth for Arrowhead as we make the transition into a commercial organization provided we received regulatory approval.

Ken: Construction of our Verona facility is effectively complete.

Ken: We are currently undertaking commissioning and qualification activities with which puts us on track for manufacturing drug material to support our clinical trials later this year.

We also initiated the shafts three and four phase III studies of <unk> in patients with SAP hcg and are finalizing the design and preparations to initiate chest of five in patients with <unk> at high risk of acute pancreatitis.

Ken: We expect final payments to be made over the next several months totaling $50 million after which we expect capital expenditures to be nominal.

Waiting for FDA feedback on our phase III program to address ASC, CBD, which we will discuss after we reach regulatory alignment.

Ken: Turning to our balance sheet, our cash and investments totaled $523 1 million at March 31, two.

In addition to progress in cardiomyopathy, <unk>, we have been very productive and platform development and pipeline expansion. Our trim platform can now deliver to CNS in adipose tissue and we will soon have new clinical programs targeting those tissues. We also initiated clinical studies during the quarter for two new candidates <unk> and <unk>.

Ken: 2024.

Ken: Compared to $403 6 million at September 32023.

Ken: The increase in our cash and cash or excuse me the increase in our cash and investments was primarily related to the $450 million equity issuance.

Thank you for joining us today, and I would now like to open the call to your questions operator.

Ken: We offset by our ongoing cash burn.

Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question you will need to press star one one on your telephone and wait for your name to be announced.

Ken: Our common shares outstanding at March 31, 2024.

Ken: $124 1 million.

Ken: With that brief overview I will now turn the call back to Chris.

Draw. Your question. Please press Star one one again, we do ask that all participants limit themselves to one question and one follow up please standby, while we compile the Q&A roster.

Chris: Thanks, Ken this.

Chris: This has been another quarter of solid execution for Arrowhead.

Chris: Our phase III palisade study of Lovaza, and clinically complete which sets us up to take the next step in growth for Arrowhead as we make the transition into a commercial organization provided we received regulatory approval.

Chris: We also initiated the shafts three and four phase III studies of <unk> in patients with SAP hcg and are finalizing the design and preparations to initiate shasta five in patients with <unk> at high risk of acute pancreatitis.

Our first question comes from the line of Luca IC or VC capital. Your line is now open.

Oh, great. Thanks, so much for taking my question congrats on the progress maybe.

Chris: We are waiting for FDA feedback on our phase III program to address a CBD, which we will discuss after we reach regulatory alignment and.

It sounds like the highest cohorts will reach has been slow to enroll can you maybe just expand on it.

Chris: In addition to progress in cardio metabolic we have been very productive and platform development and pipeline expansion. Our trim platform can now deliver the CNS in adipose tissue and we will soon have new clinical programs targeting those tissues. We also initiated clinical studies during the quarter for two new candidates <unk> and <unk>.

The earliest we can actually see that data and maybe what are the bogeys in term of seen a reduction that are below on par or above your expectations and then maybe second on <unk>. What was your reaction to merely starting <unk> cardiovascular outcome trial that is way bigger than your trial in <unk>.

Speaker Change: Thank you for joining us today and I'd now like to open the call to your questions operator.

Speaker Change: Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question you will need to press star one one on your telephone and wait for your name to be announced.

Arnie. This is trial I think Novartis has a 7000 patient trial, we have an 8000 patient trial versus really starting at 30000 patient trial here for <unk>.

Does that mean that your trial is underpowered.

Chris: <unk>. Your question. Please press star one one again, we do ask that all participants limit themselves to one question and one follow up please standby, while we compile the Q&A roster.

It's also very much appreciate it thanks so much.

Thank you Luca.

I can address the cleanup question.

Look it's.

It's just been slow to enroll because because we are requiring high <unk> in these patients with <unk>.

Sure.

With moderate to severe asthma. So so so I don't have good visibility on when that could be complete I think our take home message. There was that was that we were sick of waiting around we think this is a good drug and we want to move.

Chris: Our first question comes from the line of Luca I C or D. C capital. Your line is now open.

Luca: Great. Thanks, so much for taking my question congrats on the progress maybe on <unk>.

Expeditiously into a phase II and so we're going we've got a phase II design and we are moving towards that I think we'll start that in the fourth quarter and so we are looking forward to seeing the pheno data of course.

Luca: It sounds like the highest cohort for reach has been slow to enroll can you maybe just expand on it.

Luca: The earliest we can actually see that data and maybe wondering if the whole easy term have seen a reduction that are below on par or above your expectations and then maybe second on <unk>. What was your reaction to middle East starting your cardiovascular outcome trials. It is way bigger than your try on in Nevada.

But it is not rate limiting I think the drug has two important till two O to wafer that Bruce you have anything to add about the <unk>.

I don't think Theres a problem with the Novartis are the.

Or the Amgen study has been underpowered I don't really know.

Chris: This is trial I think Novartis has a 7000 patient trial do you have an 8000 patient trial versus really starting a 30000 patient trial here for <unk> does that mean that your trial is underpowered.

No what what's driving that very large.

Study size for for Eli Lilly.

The Devil may be in the details there but.

But I don't I don't worry about the.

The power of either the Novartis are the Amgen studies.

Speaker Change: Much appreciate it thanks, so much.

Speaker Change: I think Luca.

Got it thanks, so much.

Speaker Change: I can address the cleanup question.

Thank you.

Speaker Change: It's.

Speaker Change: It's just been slow to enroll because because we are requiring <unk> in these patients with <unk>.

Thank you for your question. Please standby for our next question.

Chris: With moderate to severe asthma. So so.

Speaker Change: So I don't have good visibility on when that could be complete I think our take home message. There was that was that we were sick of waiting around we think this is a good drug and we want to move.

Our next question comes from the line of Edward <unk> of Piper Sandler Your line. Thank you Allison.

Chris: Expeditiously into a phase II and so we're going we've got a phase II design and we are moving towards that I think we'll start that in the fourth quarter and so we are looking forward to seeing that data of course.

Great. Thank you very much so many things going on the tougher the popular science, but with a phase III palisade data coming out topline data to a cardiovascular event.

Chris: But it is not rate limiting I think the drug has two important till two O to wait for that.

Again, what kind of expectations should we look for in the trig lowering.

Chris: Bruce do you have anything to add about the <unk>.

Especially with data already out.

Bruce: I don't think Theres a problem with the Novartis are the.

Earlier studies and how will this really compare do you think with.

Bruce: Or the Amgen study has been underpowered.

With the <unk> program.

Which is.

Bruce: Really.

A little bit ahead of you guys. How do you expect to compete for the small patient population.

Bruce: No what what's driving that very large.

Bruce: Study size for for Eli Lilly.

Well.

Bruce: The Devil may be in the details there, but but I don't I don't worry about the power of either the novartis are or the Amgen studies.

As far as.

Expectations go.

Youre asking me for a crystal ball.

I think that.

Our indications so far is that.

Plus <unk>.

Speaker Change: Got it thanks, so much.

Very powerful drug when it comes to knocking down Apoc, III and <unk> seems to be very important for this patient population.

Speaker Change: Thank you.

Speaker Change: Thank you for your questions. Please standby for our next question.

But that said I mean.

I don't have any.

Insight into at this point what the.

Speaker Change: Our next question comes from the line of Edward <unk> of Piper Sandler Your line. Thank you Allison.

Good.

The palisade data will show so.

Hopes our hopes but in reality you guys see the data.

Edward: Great. Thank you very much so many things going on the tougher the popular sun, but with the phase III palisade data coming out topline data to a cardiovascular event.

That said I don't I don't have any reason to believe that.

We won't expect a good outcome, but but.

Edward: What kind of expectations should we look for in the trig lowering.

These trials are 75 patient trial, so we'll have to see.

Speaker Change: Especially with data already out.

You'll see how the trial goes how the placebo group has performed because that oftentimes has a lot to do with happens what happens in these trials.

Edward: From our earlier study and how will this really compare do you think with.

Edward: With the <unk> program.

Edward: Which is a little bit ahead of you guys. How do you expect to compete for the small patient population.

So I can't really give you a forecast on that Ted I mean, we're we're excited to see the.

Clara Bruce Im sorry, the tough alpha since declaring yes go ahead.

Edward: Well.

Edward: As far as.

Edward: Expectations Scott.

With kind of the reductions that you've seen with the prior prior Craig reductions.

Scott: Youre asking me for a crystal ball.

Speaker Change: I think that.

The other study.

Speaker Change: Our indications so far is that.

Severe hypercholesterolemia patients et cetera.

Speaker Change: Plus <unk>.

Speaker Change: Very powerful drug when it comes to knocking down in April three in April <unk>, three seems to be a very important for this patient population.

Piper Triglyceride places, where do you think how do you think that will play into these FCS patients sorry, if that was more my question.

Speaker Change: But that said I mean.

Yes, I guess.

Speaker Change: I don't have any.

What I can say is we've had a smattering of FCS patients and in the <unk>.

Speaker Change: Insight into at this point what the.

Speaker Change: Good.

Speaker Change: The palisade data will show.

Speaker Change: So.

Study, we've had a few patients in phase one.

Speaker Change: Hopes our hopes but in reality you guys see the data.

Speaker Change: That said I don't have any reason to believe that that.

So far.

And that's in that small number of patients.

Speaker Change: We won't expect a good outcome, but but.

We've seen essentially similar results.

From the perspective of percent reductions in triglycerides between the FCS patients and the <unk>.

Speaker Change: These trials are 75 patient trial, so we'll have to see.

Speaker Change: You'll see how the trial goes how the placebo group has performed because that oftentimes has a lot to do with happens what happens in these trials.

And Chris as what we saw in the regular <unk> patients.

If that holds in this larger patient population, so we should be in good shape, but.

Speaker Change: So I can't really give you a forecast on that Ted I mean, we're we're excited to see that.

As I said each clinical study has its own clinical study, but we don't have reason from what we've seen so far to go in expecting.

Speaker Change: Sure.

Speaker Change: So just wanted to touch on the.

Speaker Change: This is a clear yes go ahead.

Speaker Change: With kind of the reduction.

Speaker Change: Even with the prior prior Craig reductions.

A different result, but but we will have a much larger patient population here to look at.

Speaker Change: The other study.

Speaker Change: Javier hypercholesterolemia patients et cetera.

And again, how do you guys expect Thats helpful. How do you guys expect to compete with <unk>. Thank you.

Speaker Change: Hyper Triglyceride places, where do you think how do you think that will play into these FCS patients sorry that was more my question.

Yeah Yeah.

Speaker Change: Yes, I guess.

Of course, that's going to Pan out if that's going to depend upon our data here's here's what I believe.

Speaker Change: What I can say is we've had a smattering of FCS patients in in the H T G.

I believe that we will have an advantage in.

And dosing intervals, I think we'll be dosing once a quarter and rather than once a month and then and then as Bruce says, we'll see if the data holds with what we've seen in the past My my hope is that is that we will.

Speaker Change: Study, we've had a few patients in phase one.

Speaker Change: So far.

Speaker Change: And that's in that small number of patients.

Speaker Change: We've seen essentially similar results.

We continue to have a.

Speaker Change: From the perspective of percent reductions in triglycerides between the FCS patients and the <unk>.

A more powerful drug that is better tolerated, but we'll have to wait and see what these data look like in this in this relatively small study I'll also say one more thing you mentioned, a very small population of FCS Ted and of course genetic FCS is not a very large population, but the population that we studied was was genetic Fcs and phenotypic FCS if you will so.

Speaker Change: And Chris that's what we saw in the regular SHT G patients.

Speaker Change: If that holds in this larger patient population, we should be in good shape, but.

Are those patients with <unk>.

Speaker Change: As I said you know each clinical study has its own clinical study, but we don't have reason from what we've seen so far to go in expecting.

With <unk> above 80% history of pancreatitis.

And it turned out to be about half and half in our study and so we'll see what what what.

What makes it to the label, but that's but that's the population that we studied and that is a substantially larger population than simply genetic Fcs.

Speaker Change: A different result, but but we will have a much larger patient population here to look at.

Speaker Change: And again, how do you guys expect Thats helpful. How do you guys expect to compete with <unk>. Thank you.

Yes.

Appreciate it.

Sure.

Thank you for your question. Please standby for our next question.

Speaker Change: Yeah Yeah.

Speaker Change: Of course, that's going to Pan out if that's going to depend upon our data here's here's what I believe.

Our next question comes from the line of Ellie Merle of UBS. Your line is now open.

Speaker Change: I believe that we will have an advantage in.

Speaker Change: And dosing intervals, and I think we'll be dosing once a quarter and rather than once a month and then and then as Bruce says, we'll see we'll get the data holds with what we've seen in the past My my hope is that is that we will.

Hi, This is jasmine on for Elliot. Thanks, so much for taking our question. So when we get updates from patient cohorts from Mark PVC and MMP. Seven later in the year can you give any color on the number of patients that we might see and anything on specifically what endpoints will get thank you.

Speaker Change: We continue to have a.

Speaker Change: A more powerful drug that is better tolerated, but we'll have to wait to see what these data look like in this in this relatively small study I'll also say one more thing you mentioned, a very small population of FCS and of course genetic FCS is not a very large population, but a population that we studied was was genetic Fcs and phenotypic FCS if you will.

Yes sure so the.

The number of patients.

It depends on enrollment we're doing about we're doing seven per cohort in the IPF patient cohort so.

Speaker Change: So those patients with <unk>.

Single digit number of patients call it less than 10.

Speaker Change: With <unk> above 80 and history of pancreatitis.

Assuming we report maybe the first dose of IPF patients.

Speaker Change: And it turned out to be about half and half in our study and so we will see what we what.

Speaker Change: What makes it to the label, but that's but that's the population that we studied and that is a substantially larger population than simply genetic Fcs.

And then.

And then the endpoint for that would be Mark Butler MMP seven levels in in the balance that we're measuring and all IPF patients.

Speaker Change: Yes, I appreciate it.

Speaker Change: Sure.

Speaker Change: Thank you for your question. Please standby for our next question.

And then for Mark five AC it would probably have a little bit more in terms of number of patients.

Or so.

You have available to report on and that would be marked by basi protein levels from from Sputum. That's the primary biomarker that we're looking at.

Speaker Change: Our next question comes from the line of Ellie Merle of UBS. Your line is now open.

Speaker Change: Hi, This is jasmine on for Elliot. Thanks, so much for taking our question. So when we get updates from.

Okay, Great and just a quick follow up if I could at Ats.

Jasmine: <unk> patient cohort and Mark PVC and NSC seven later in the year can you give any color on the number of patients that we might see and anything on specifically what endpoints will get thank you.

On <unk> can you give any specifics on what we can expect there.

Thank you Dan.

Yes, sure. So we will be presenting the healthy volunteer rage data and then the.

Speaker Change: Yes sure.

The rage to serum <unk> knockdown data in the patient goals that we have available.

Speaker Change: The number of patients.

Speaker Change: It depends on enrollment we're doing about we're doing seven per cohort in the IPF patient cohort so.

Okay.

Great. Thank you.

Thank you for your question. Please standby for our next question.

Speaker Change: Single digit number of patients call it less than 10.

Speaker Change: Assuming we report maybe the first dose of IPF patients.

Speaker Change: And then.

Our next question comes from the line of Jason <unk> of Bank of America. Your line is now open.

Speaker Change: And then the endpoint for that would be a.

Speaker Change: Mark Butler MMP seven levels in in the balance that we're measuring in an all IPF patients.

Hi, good evening Dana on for Jason.

Congrats on the progress this quarter and thank you so much for taking our question.

Speaker Change: And then for Mark five AC will probably have a little bit more in terms of number of patients.

Just had a quick one.

Pleasant Darin just in terms of thinking about the palisade data.

Speaker Change: <unk>.

Speaker Change: So that we have available to report on and that would be marked <unk> protein levels from from sputum. That's the primary biomarker that we're looking at.

I believe your data will include.

FCS patients and high TG patients with functional LDL activity.

Just curious how you see the inclusion of the patients with the LPL activity enriching your data set.

Speaker Change: Okay, Great and just a quick follow up if I could add etfs.

Speaker Change: On <unk> can you give any specifics on what we can expect there.

You plan to break out clinical activity of these two subgroups to maybe inform comparisons with ion at Olive garden.

Speaker Change: When you do that.

Speaker Change: Yes, sure. So we will be presenting the healthy volunteer rage data and then the.

Well as Chris said it means that the patients that are not.

Speaker Change: The rage serum <unk> knockdown data in the patient goals that we have available.

Genetically.

Proven Fcs at the point they enroll are fine are typically FCS patients. So they're not just high triglyceride patients their patients really look and feel like Fcs.

Speaker Change: Great. Thank you.

Speaker Change: Thank you for your question. Please standby for our next question.

But they just have not had the generic <unk>.

<unk> done at the time of enrollment.

Speaker Change: Our next question comes from the line of Jason <unk> of Bank of America. Your line is now open.

As Chris said that that's a fairly large population and they they tend to be.

Jason: Hi, good evening.

Jason: On for Jason.

Some of them are on diagnosed Fcs patients, but but oftentimes there.

Jason: Congrats on the progress this quarter and thank you so much for taking our question.

Speaker Change: Just had a quick one.

Compound heterozygous.

Speaker Change: Pleasant Darin just in terms of thinking about the palisade data.

Which may or may not include LPL.

Speaker Change: I believe your data will include.

But then have other.

Pleasant Darin: <unk> patients and high TG patients with functional LPL activity and just curious how you see inclusion of the patients with LPL activity.

Other genetic abnormalities as well.

And the compound effect winds up having seen a typically look like they have FCS. So it's a heterogeneous sets a heterogeneous group and.

Pleasant Darin: Rich in your data set.

Pleasant Darin: We plan to break out clinical activity of these two subgroups to maybe inform comparisons with eye on it.

And at this point again, you know when we haven't seen the data everything's blinded can't really say how that might play into the results.

Speaker Change: Thank you.

That's going to be one of the really interesting things to see in the data is.

Rich: Well as.

Rich: As Chris said it means that the patients that are not.

Do the <unk>.

<unk> Fcs patients.

Rich: Genetically.

Rich: Proven Fcs at the point, they enroll our pheno typically FCS patients so they're not just high triglyceride patients or their patients that really look and feel like Fcs.

Look and behave the same.

I'll see we'll we'll know more.

Once we once we have all the data in our hands.

Okay.

Thank you.

Quick follow up.

Rich: But they just have not had the generic.

Pardon me if I missed this in your prepared remarks.

Rich: Genetics done at the time of enrollment.

For the Aero Rage to asthma trial that you are planning to initiate later this year is that an all comers population or is that going to be.

Rich: And as Chris said that that's a fairly large population and they.

Rich: They tend to be you know some of them are on diagnosed fcs patients, but but oftentimes their car.

And just the Selic.

Hi type two patients. Thank you.

Yeah.

Yes, we're still waiting on.

Rich: Compound heterozygous.

Feedback from.

Rich: Which may or May not include LPL, but then have other.

And our regulatory agencies. So we'll talk more about the design later once it's <unk>.

Rich: Other genetic abnormalities as well.

Year to us.

Yes.

Rich: And the compound effect winds up having a fee and a typically look like they have Fcs.

Got it thank you so much.

Sure.

Thank you for your question. Please standby for our next question.

Rich: So it's a heterogeneous sets a heterogeneous group and.

Rich: And at this point again, you know when we haven't seen the data everything's blinded.

Our next question comes from the line of Maury Raycroft of Jefferies. Your line is now open.

Rich: Can't really say how that might play into the results.

Rich: That's going to be one of the really interesting things to see in the data is.

Hi, Congrats on the progress and thanks for taking my question.

Rich: Do the.

I was going to ask one on FCS use follow up some of the others.

Rich: Genetic Fcs patients.

Rich: Look and behave the same.

Rich: We'll see we'll we'll know more.

Assuming the genetic and clinical patients performed the same.

Rich: Once we once we have all the data in our hands.

The Palisades Fcs study.

And that study is successful what are your expectations for a label what the label would look like and how could that play into the commercial opportunity and then as a follow up can you comment on baseline pancreatitis in this study and what you expect to see on that measure.

Speaker Change: Thank you.

Speaker Change: Quick follow up.

Speaker Change: Pardon me if I missed this in your prepared remarks.

Speaker Change: For the Aero Rage to asthma trial that you are planning to initiate later this year is that an all comers population or is that going to be.

Speaker Change: And just the NFL Ache, hi type two patient thank you.

Okay.

Speaker Change: Okay.

Well, let me.

Speaker Change: Yes, we're still waiting on.

Take the pancreatitis question first.

There there was a significant history of pancreatitis in the in the patient population.

Speaker Change: Feedback from.

Speaker Change: And our regulatory agencies. So we will talk more about the design later once it's clear to us.

And we have had some events.

There is still.

Speaker Change: Got it thank you so much.

A few events to be adjudicated.

Speaker Change: Sure.

Our I think are being adjudicated, maybe this week or next.

Speaker Change: Thank you for your question. Please standby for our next question.

I don't know what the total number of pancreatitis events in the study.

It will be.

Speaker Change: Our next question comes from the line of Maury Raycroft of Jefferies. Your line is now open.

In the end.

But it's.

A number.

Maurice Thomas Raycroft: Hi, Congrats on the progress and thanks for taking my question.

It's.

Enough that it will be able to to hopefully see something but we don't know at this point.

Maurice Thomas Raycroft: I was going to ask one on FCS use follow up some of the others.

So that's on pancreatitis with respect to labeling and of course, we don't make that decision the agency does but the.

Maurice Thomas Raycroft: Assuming the genetic and clinical patients performed the same in the palisade study.

Maurice Thomas Raycroft: And that study is successful what are your expectations for a label what the label would look like and how could that play into the commercial opportunity and then as a follow up can you comment on baseline pancreatitis in this study and what you expect to see on that measure.

The decision to to look at.

Yes.

Either genetic Fcs patients or if you will phenotypic FCS patients is something that.

That the agency.

Bought into.

Speaker Change: Okay well.

Certainly historically.

Speaker Change: Let me.

Speaker Change: Take the pancreatitis question first.

Yeah.

Speaker Change: There there was a significant history of pancreatitis in the in the patient population.

When theres been agreement between the agency and a company historically the agency tends to give you.

Speaker Change: And we have had some events.

Speaker Change: There is still.

Labeling that reflects the population that you studied.

Speaker Change: A few events to be adjudicated that are I think are being adjudicated, maybe this week or next.

Obviously.

Any individual situation can can vary but.

Speaker Change: So I don't I don't know what the total number of pancreatitis events in the study.

Our our.

Speaker Change: We will be.

Certainly.

Speaker Change: In the end.

Expectation going in would be that the labeling would reflect the patient population studied.

Speaker Change: But it's.

Speaker Change:

Speaker Change: You know a.

Speaker Change: A number.

Speaker Change: It's.

And that would have an impact obviously with respect to potentially a different there could be a differential label.

Speaker Change: Enough that it will be able to to hopefully see something but we don't know at this point.

Speaker Change: So that's on pancreatitis with respect to labeling of course, we don't make that decision the agency does.

Between between Us and.

Sure.

<unk>.

We won't know until we get there, but it could we could see a distinction.

Speaker Change: But the.

Speaker Change: The the decision to to look at.

Got it that's really helpful and maybe one last follow up for a number of patients out there that would be clinically defined with Fcs.

Speaker Change: Either genetic Fcs patients or if you will phenotypic FCS patients is something that.

Guys have any any book ends on that.

What that could look like.

Speaker Change: You know that the agency.

Speaker Change: Bought into.

So we've got it we've gone at that.

Speaker Change:

Speaker Change: Certainly historically.

Bye.

From a number of ways and it's.

Speaker Change: When theres been agreement between the agency and a company you know historically the agency tends to to give you.

It's in the thousands we haven't we haven't set on it on it on an exact number but it feels like it's in the thousands beyond that it's hard it's hard to tell at this point.

Speaker Change: Labeling that reflects the population that you studied.

Okay. Okay understood. Thanks for taking my questions.

Thank you Amit.

Speaker Change: Obviously.

Our next question please standby.

Speaker Change: Any individual situation can can vary but.

Speaker Change: R R.

Our next question comes from the line.

Speaker Change: Certainly.

Speaker Change: Expectation going in would be that the labeling would reflect the patient population studied.

My Young man Tommy from B Riley Your line is now open.

Speaker Change: And that would have an impact obviously out with respect to potentially a different there could be a differential label.

Hello.

This is Kevin.

On my end.

From B Riley Thanks for taking our question.

Speaker Change: Between between Us and.

I have a question about the future strategy in terms of you have those.

Speaker Change: <unk>.

Speaker Change: We won't know until we get there, but it could we could see a distinction.

<unk> drugs.

And so that's <unk>.

Speaker Change: Got it that's really helpful and maybe one last follow up for a number of patients out there that would be clinically defined with Fcs.

Elaborate.

How you would go.

The target population given that they're split.

Speaker Change: Do you guys have any any book ends on that.

Speaker Change: What that could look like.

That's a distinction.

Mick can be even more clinical.

Speaker Change: So we've got it we've gone at that.

These two compounds.

Speaker Change: Bye.

Speaker Change: From a number of.

Thanks.

Speaker Change: And it's.

Sure.

Speaker Change: It's in the thousands we haven't we haven't set on a on an exact number but it feels like it's in the thousands beyond that it's hard it's hard to tell at this point.

So Kevin the way I tend to think of it if you if you think of.

<unk> sort of lipids and lipoproteins as a bit of a continuum and on one end you.

Speaker Change: Okay. Okay understood. Thanks for taking my questions.

Speaker Change: Thank you Amit.

Speaker Change: Our next question please standby.

Have.

Familial hypercholesterolemia Barry LDL dominated.

Speaker Change: Our next question comes from the line of.

Sort of disease, if you will which then it comes down.

Amit: <unk> <unk> from B Riley Your line is now open.

Into F <unk> and patient set for other reasons just have very high cholesterol.

Amit: Hello.

Kevin: This is Kevin.

Kevin: For my end from B Riley Thanks for taking our question.

But maybe normal triglycerides, and then you come into the middle of where you have a mix what used to be called mixed dyslipidemia now called mixed hyperlipidemia.

Speaker Change: Sure.

Kevin: I have a question about the future and strategy in terms of you have.

Speaker Change: Potent.

Speaker Change: Drugs so <unk>.

And an untreated stage patients or maybe a combination of all.

Speaker Change: Elaborate.

Speaker Change: How you would go.

LDL and triglycerides, often with a lot of metabolic syndrome, obesity diabetes et cetera.

Speaker Change: The target population given that there.

Speaker Change: The distinction in terms of mechanism more clinical effect by at least two compounds.

About 20 million patients.

In the U S and a lot of those patients are already on statin and already have.

Speaker Change: Okay. Thanks.

Speaker Change: Sure.

Some level of control of their LDL.

Speaker Change: So Kevin the way I tend to think of it if you.

So from a from what's left untreated it's largely in this.

Speaker Change: If you think of.

Glyceride rich lipoproteins slash.

Speaker Change: Sort of lipids and lipoproteins as sort of a continuum and on one end.

<unk>.

Sure.

Speaker Change: You have.

Remnant.

No.

Speaker Change: Familial hypercholesterolemia are very LDL dominated.

So type if you will and then going further up that side you get into the severe hypertrophy Glyceride EMEA is and yet at the outer end of that when you have SCS. So if you think of it that way almost I almost think of it like a U shape with one one into the U is familial hypercholesterolemia and the <unk>.

Speaker Change: Sure.

Speaker Change: <unk> disease, if you will which then it comes down.

Speaker Change: Yo into F <unk> and patient set for other reasons just have very high cholesterol.

Speaker Change: But maybe normal triglycerides.

Other ended the U as FCS and you come down and in the Middle you have this 20 million patients with mixed hyperlipidemia.

Speaker Change: And then you come into the middle of where you have a mix what used to be called mixed dyslipidemia now called mixed hyperlipidemia.

So on that on the one end that's cholesterol.

Speaker Change: And an untreated state pace.

Speaker Change: Patients or maybe a combination of of LDL and triglycerides, often with a lot of metabolic syndrome obesity diabetes et cetera.

That's a very healthy place for hedge <unk> III.

And we've already seen that to an extent for us.

With.

Regeneron Maas full antibody.

Speaker Change: About 20 million patients.

<unk> works well on that side of the spectrum and then on the far side of the other spectrum with FCS and <unk>.

Speaker Change: In the U S and a lot of those patients are already on statin and already have some level of control of their LDL.

<unk> and <unk>.

Speaker Change: So from a from what's left untreated it's largely in this.

In a typical FCS you have plus ASUR at.

So the real question is in the middle where you've got a mix of LDL and.

Speaker Change: Triglyceride rich lipoproteins slash.

Speaker Change: You know.

And triglycerides.

Speaker Change: Remnant.

In the in the phenotype.

Speaker Change: No.

Speaker Change: Type if you will and then going further up that side you get into the severe hyper triglycerides <unk> and yet at the outer end of that when you have SCS. So if you think of it that way almost I almost think of it like a U shape, where one one into the U is familial hypercholesterolemia and the <unk>.

Both drugs.

Look to be very interesting drugs in that debt that mixed dyslipidemia or mixed hyperlipidemia population.

So what it means to us is that.

On the two ends of the spectrum.

Drugs have target markets that make a lot of sense and in the middle.

Speaker Change: Other ended the U as FCS and you come down and in the Middle you have this 20 million patients with mixed hyperlipidemia.

Both both drugs look like they could be.

Yes.

A major improvement over what's been available to practicing physicians for the last 30 years. So that's that's kind of how we see it I hope Kevin that that makes some sense to you.

Speaker Change: So on.

Speaker Change: On that on the one end that's cholesterol.

Speaker Change: That's a very healthy place for edge <unk> III.

Yes. It does thank you so much.

Speaker Change: And we've already seen that to an extent for us.

Thank you for your question. Please standby for our next question.

Speaker Change: With.

Speaker Change: With Regeneron <unk> Atlantique body.

Speaker Change: It works well on that side of the spectrum and then on the far side of the other spectrum with Fcs and.

Our next question comes from the line of Brendan Smith of Cowen. Your line is now open.

Speaker Change: <unk> and <unk>.

Speaker Change: In a typical FCS you have plus ASUR at.

Great. Thanks, very much for taking the question.

Maybe just another quick one on pulmonary and then I have a broader follow up.

Speaker Change: So the real question is in the middle where you've got a mix of LDL and.

First I actually just wanted to see if theres anything else specifically that you are seeing in the asthma patient data, that's giving you more confidence to move into phase III.

Speaker Change: And triglycerides.

Speaker Change: In the in the phenotype and both drugs.

Maybe more to the point, if you've seen any of the high patient data yet like if you're saying gets you know knock down or anything like that.

Speaker Change: Look to be very interesting drugs in that debt that mixed dyslipidemia or mixed hyperlipidemia population.

And then more broadly I just wanted to check and see if there's any update on potential licensing our commercialization partnerships or maybe when we might get an update there and what that is looking like thanks very much.

Speaker Change: So what it means to us is that.

Speaker Change: On the two ends of the spectrum.

Speaker Change: <unk> have target markets that make a lot of sense and in the middle.

Sure.

Yes.

I think the biggest driver in moving.

Speaker Change: Both both drugs look like they could be.

And not waiting and moving.

Towards the phase two is is the safety and Tolerability that we've seen so far in the end the target engagement, we're seeing good rage knockdown.

Speaker Change: Yes.

Speaker Change: A major improvement over what's been available to practicing physicians for the last 30 years. So that's kind of how we see it I hope Kevin that make some sense to you.

We have seen.

You've seen a lot of excitement from Kols.

Kevin: Yes. It does thank you so much.

For the <unk> pathway and so it just makes sense just makes sense.

Speaker Change: Thank you for your question. Please standby for our next question.

So we're moving as quickly as we can there.

On the on the partnering side.

We have.

We are always are virtually always in discussions as you can imagine we have no control over timing and so I have nothing to report at this point other than the fact that this is an important part of our business and we do expect to execute additional transactions.

Kevin: Our next question comes from the line of Brendan Smith of TD Cowen. Your line is now open.

Brendan Smith: Great. Thanks, very much for taking the question.

Brendan Smith: Maybe just another quick one on pulmonary and then I have a broader follow up.

Brendan Smith: So first I actually just wanted to see if theres anything else specifically that you are seeing in the asthma patient data, that's giving you more confidence to move into phase III.

Okay. Thanks very much.

Youre welcome thank.

Thank you for your question. Please standby for our next question.

Brendan Smith: Maybe more to the point, if you've seen any of the high patient data yet like if you're seeing good knockdown or anything like that.

Our next question comes from the line of Cana.

Brendan Smith: And then more broadly I just wanted to check if there's any update on potential licensing our commercialization partnerships or maybe when we might get an update there and what that's looking like thanks very much.

From Chardan. Your line is now open.

Thank you.

Last question.

Is there a rationale for the different sample size is between three.

Brendan Smith: Sure.

Brendan Smith: I think the biggest driver in moving and.

<unk> III and floor is one deliberately over sampled.

Brendan Smith: And not waiting and moving.

Brendan Smith: Towards the phase two is is the safety and Tolerability that we've seen so far in the end the target engagement, we're seeing good bridge knockdown.

Not really.

Yes, so the the design of the <unk> program.

Brendan Smith: We've seen.

Brendan Smith: You've seen a lot of excitement from Kols.

Was.

In many ways, a result of our discussions with FDA about their overall.

Brendan Smith: For the <unk> pathway and so it just makes sense just makes sense.

Brendan Smith: So we're moving as quickly as we can there.

Brendan Smith: On the on the partnering side.

Expectations for what they wanted to see and efficacy database safety database et cetera.

Brendan Smith: We have.

Brendan Smith: We are we were always are virtually always in discussions as you can imagine we have no control over time and so I have nothing to report at this point other than the fact that this is an important part of our business and we do expect to execute additional transactions.

And it just turned out that.

Sure.

It could have been 350 in both.

In the end it practically it made sense to have one before 101 300, but it was really largely just driven by the practicalities.

Speaker Change: Okay. Thanks very much.

Speaker Change: Youre welcome.

Speaker Change: Thank you for your question. Please standby for our next question.

Two to get the patient population that.

The agency was requesting so it really is.

Speaker Change: Our next question comes from the line of key not gay from Chardan. Your line is now open.

<unk> is accidental you might say that they are different size.

Okay, and then in terms of the approach.

Yes, they're both way over powered for efficacy.

Speaker Change: Thank you.

Key: Last question.

If you saw that if you saw the results from <unk> two they're both way over powered for efficacy.

Key: Is there a rationale for the different sample size is between three.

Key: Three and four as one deliberately over sampled.

Okay.

Good to hear.

In terms of the mix evolved.

Key: Not really.

Since you have a design ready.

Key: Yeah. So the the design of the <unk> program.

To submit for review.

Have you selected one of the two and then based on the feedback.

Key:

Key: It was.

You're still I guess have the option to switch or how should we be thinking about where you're at with that.

Key: And in many ways, a result of our discussions with FDA about their overall.

Yes.

Till we get until we have feedback in alignment with what the regulators. It makes sense for us just to choose to stand Pat on this will give you of course, all the information that we can once we once we have confirmation from the regulators that we're all aligned on what the study looks like so so stay tuned on that we're still working.

Key: Expectations for what they wanted to see and efficacy database safety database et cetera.

Key: And it just turned out that.

Key:

Key: Sure.

Key: It could have been 350 in both you know.

Key: In the end it practically it made sense to have one bid 401 300, but it was really largely just driven by practicalities.

Okay.

Thank you for your question. Please standby for our next question.

Key: To get the patient population that.

Key: The agency has requested.

Our next question comes from the line of William Pickering of Bernstein. Your line is now open.

Key: So it really it really is accidental and you might say that there are different size.

Hi, good evening and congrats on the progress and thank you for taking my question.

Speaker Change: Okay, and then in terms of the approach.

Speaker Change: Yes, they're both way over powered for efficacy.

S. Hcg in constitute you had a fairly sizeable placebo effect of 17% at 24 weeks could you comment on whether you think that's a reasonable proxy for what to expect in the pivotal and if there any strategies essentially limit that.

Speaker Change: If you saw that if you saw the results from <unk> two they're both way over powered for efficacy.

Speaker Change: Okay, well that's good.

Speaker Change: Good to hear.

Speaker Change: Just in terms of the mix evolves.

Speaker Change: If you have a design ready to submit for review.

Yeah, well, it's kind of interesting because if you actually look at the data placebo was essentially plugging along at or right around zero change and then.

Speaker Change: Have you selected one of the two and then based on the feedback.

Speaker Change: You're still I guess have the option to switch or how should we be thinking about where you're at with us.

<unk>.

At week 20, it was like zero and then at week 24 dips down to go.

Speaker Change: Yes until we get until we have feedback in alignment with the regulators. It makes sense for us just to choose to stand Pat on this will give you of course, all the information that we can once we once we have confirmation from the regulators that we're all aligned on what the study looks like so so stay tuned on.

Whatever minus 17 I guess.

And then.

And then it was halfway back up to up to zero.

Four weeks later and then eight weeks later it was right back to where it had been for the first 20 weeks. So it's just one of those were deals that.

Speaker Change: That we're still working.

Speaker Change: Okay. Thanks.

This is what makes it hard to do placebo controlled studies Youll placebo, just behave strangely it at unpredictable times and.

Speaker Change: Thank you for your question. Please standby for our next question.

Speaker Change: Our next question comes from the line of William Pickering of Bernstein. Your line is now open.

All of us.

Just have to put up with that.

We did things in the trial to try to minimize placebo.

William Pickering: Hi, good evening and congrats on the progress and thank you for taking my question.

William Pickering: S. Hcg in constitute you had a fairly sizeable placebo effect of 17% at 24 weeks could you comment on whether you think that's a reasonable proxy for what to expect in the pivotal and if there any strategies essentially limit that.

Changes in placebo, but.

But in the end.

It's always difficult to.

To really manage that.

And if I could just squeeze in a very quick follow up.

Speaker Change: Yeah, well, it's kind of interesting because if you actually look at the data placebo was essentially plugging along.

Thank you to take the 25 milligram instead of the 50 and do you think that youll be able to demonstrate a more compelling efficacy profile versus <unk> at that dose.

Speaker Change: Right around zero change and then.

Yes were 50 and 25 were very similar with respect to.

Speaker Change: At week 20, it was like zero and then at week 24 dips down to go.

Speaker Change: Whatever minus 17, I guess and.

With respect to activity with respect to efficacy.

Speaker Change: And then.

And that was not only in Chester too, but that was also in mirror.

Speaker Change: Then it was halfway back up to up to zero.

Speaker Change: Four weeks later and then eight weeks later it was right back to where it had been for the first 20 weeks. So it's just one of those weird deals that.

They just look really close and yet there was a difference.

Tolerability and so it really was a benefit risk decision in the in the parlance.

Speaker Change: You know this is what makes it hard to do placebo controlled studies Youll placebo, just behaved strangely it at unpredictable times.

Of.

The regulatory parlance, but in our parlance as well you know you look for.

Speaker Change: And.

Speaker Change: You know all of us are.

We put up with side effects in this in this business when we have to.

Speaker Change: Just have to put up with that.

Speaker Change: So we did things in the trial to try to minimize placebo.

But if in fact, there's a dose available. They essentially gives you full efficacy and has a better safety and Tolerability you take that one.

Speaker Change: Changes in placebo, but.

Speaker Change: But in the end.

The.

Speaker Change: It's always difficult to.

Our overall assessment of the 25 milligram dose.

Speaker Change: To really manage that.

In both of those two large phase twos, and which was in is that it's kind of indistinguishable from placebo differ.

Speaker Change: And if I could just squeeze in a very quick follow up.

Speaker Change: Thank you to pick the 25 milligram instead of the 50 and do you think that you'll be able to demonstrate a more compelling efficacy profile versus <unk> at that dose.

Difference between active and placebo is so small as to be.

Not convincingly different.

Speaker Change: Yes were 50 and 25 were very similar with respect to.

At the 25 milligram dose in terms in terms of safety in terms of safety and Tolerability right.

And that that.

Speaker Change: With respect to activity with respect to efficacy.

That mattered a lot.

When the efficacy look basically at the same at 50 milligrams looked a little different from placebo. So we took advantage of of the fact that we are at the top of the dose response curve for efficacy and we had we had.

Speaker Change: And that was not only in Chester too, but that was also in Nir.

Speaker Change: They just looked really close.

Speaker Change: And yet there was a difference in tolerability and so it really was a benefit risk decision in the in the <unk>.

<unk>.

Better safety and Tolerability profile.

Makes sense. Thank you very much.

You bet.

Speaker Change: Of the.

Thank you for your question. Please standby for our next question.

Speaker Change: Tori parlance, but in our <unk> as well you know you look for.

Speaker Change: We put up with side effects in this in this business when we have to but.

Our next question comes from the line of William Pickering.

Speaker Change: But if in fact, there's a dose available. They essentially gives you full efficacy and has better safety and Tolerability you take that one.

Im sorry, our next question comes from the line of Patrick Tricky how of H C. Wainwright and company. Your line is now open.

Thanks, Good evening.

Speaker Change: They are.

Speaker Change: Our overall assessment of the 25 milligram dose.

A couple of follow up questions on the complement programs.

Speaker Change: In both of those two large phase twos, and which was in is that it's kind of indistinguishable from placebo. The difference between active and placebo is so small as to be.

Firstly I appreciate that dosing in the phase one trial began last month I'm wondering if you can talk about potential timing of the initial data on this and this trial evaluating <unk>.

Kind of what you'd be looking for in that initial data later, David give confidence in advancing this program and then secondly, if you can talk more broadly about the potential advantages of CFB relative to existing treatments for various complement mediated disease and how you envision CFT extending the different treatment paradigms and then lastly, how should we think about this.

Speaker Change: Not convincingly different.

Speaker Change: At the 25 milligram dose in terms of safety in terms of safety and Tolerability right.

Speaker Change: And that.

Speaker Change: That mattered a lot.

Speaker Change: When the efficacy look basically the same at 50 milligrams looked a little different from placebo. So we took advantage of of the fact that we are at the top of the dose response curve for efficacy and we had we had.

Complement program relative to <unk> can you talk in more detail. How these programs may progressing in parallel.

Speaker Change: <unk>.

Speaker Change: Better safety and Tolerability profile.

Yes, sure maybe I'll take the last one first thanks for the question.

Speaker Change: Makes sense. Thank you very much.

Speaker Change: You bet. Thank you for your question. Please standby for our next question.

I think we will make a data driven decision for <unk> three versus Cfd. We think there are maybe some indications.

Indications, where C III might work better something like <unk>, where the disease is really driven by.

Speaker Change: Our next question comes from the line of William Pickering, I'm Sorry. Our next question comes from the line of Patrick Jerky, how of H C. Wainwright and company. Your line is now open.

The accumulation of.

Excessive C. Three and then others, where CFB might work better, but I think that'll be really data driven.

Patrick Ralph Trucchio: Thanks, Good evening.

Patrick Ralph Trucchio: A couple of follow up questions on the complement programs. So firstly and I appreciate that dosing in the phase <unk> trial began last month I'm wondering if you can talk about potential timing of initial data in the in this trial evaluating <unk>.

And then in terms of.

Advantages over some of the other therapeutics out there.

I think the the dosing advantage is really significant.

Patrick Ralph Trucchio: What you'd be looking for in that initial data on later, David give confidence in advancing this program and then secondly, if you can talk more broadly about the potential advantages of cfd relative to existing treatments for various complement mediated diseases and how you envision.

Would have or both of these in terms of duration of effect for <unk> three.

We're getting.

8% knockdown that can be essentially maintained for three to four months. After a single dose. So I think if you again looking at dosing quarterly versus other therapies that require.

Patrick Ralph Trucchio: Sitting with me.

Patrick Ralph Trucchio: A different treatment paradigms and then lastly, how should we think about this complement program relative to <unk>.

Either daily oral dosing.

Patrick Ralph Trucchio: Can you talk in more detail how these programs may progressing in parallel.

Frequent subcutaneous dosing I think there is a big advantage there we will see what the dose the dosing regimen looks like for <unk>, but based on our preclinical data that is a very potent.

Speaker Change: Sure maybe I'll take the last one first thanks for the question.

David: So I think we will make a data driven decision.

Speaker Change: Q3 versus Cfd, we think there are maybe some.

Molecule and so I would expect.

Speaker Change: Indications, where C III might work better something like <unk>, where the disease is really driven by.

Something similar in terms of duration of effect.

And then data timing.

The <unk> study just got started its a healthy volunteer study and so is the biomarker knockdown of circulating plasma CFP.

Speaker Change: So the accumulation of.

Speaker Change: Excessive C. Three and then others, where CFB might work better, but I think that'll be really data driven.

I mean efficacy or activity biomarker of interest and we could potentially have something.

Speaker Change: And then in terms of.

Speaker Change: Advantages over some of the other therapeutics out there.

<unk> year end for that.

Okay.

Speaker Change: I think the the dosing advantage is really significant.

Great. Thanks, so much.

Thank you for your question. This does cause our question and answer session I would now like to turn the call back over to Chris Anzalone for some closing remarks.

Speaker Change: Would have for both of these in terms of duration of effect for <unk> three.

Speaker Change: We're getting.

Speaker Change: The 8% knockdown that can be essentially maintained for three to four months. After a single dose. So I think if you again looking at dosing quarterly versus other therapies that require either daily oral dosing.

Thanks, everyone for joining today and we look forward to seeing you at the summer series starting later this month.

This does conclude today's conference you may now disconnect.

Speaker Change: Frequent subcutaneous dosing I think there is a big advantage there we will see what the dose the dosing regimen looks like for the CFP, but based on our preclinical data that's a very potent molecule and so I would expect.

Speaker Change: Something similar in terms of duration of effect.

Speaker Change: And then data timing.

Speaker Change: The <unk> study just got started its a healthy volunteer study and so is the biomarker knockdown of circulating plasma CFP.

Speaker Change: I mean.

Speaker Change: Efficacy or activity biomarker of interest and we could potentially have something by year end for that.

Speaker Change: Okay.

Speaker Change: Great. Thanks, so much.

Speaker Change: Thank you for your question this does come.

Speaker Change: <unk> and answer session I would now like to turn the call back over to Chris Anzalone for some closing remarks.

Christopher R. Anzalone: Thanks, everyone for joining today and we look forward to seeing you at the summer series starting later this month.

Speaker Change: This does conclude today's conference you may now disconnect.

Speaker Change: Goodbye.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: Mhm.

Speaker Change: Hum.

Speaker Change: [music].

Speaker Change: Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call throughout today's recorded presentation, all participants will be in a listen only mode.

Speaker Change: After the presentation, there well there will be an opportunity to ask questions to ask a question simply press star one one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one once again, we do ask that all participants limit themselves to one.

Speaker Change: Question and one follow up I will now hand, the conference call over to Vince Anzalone, Vice President of Investor Relations for <unk>.

Vincent Anzalone: Arrowhead. Please go ahead Bert.

Vincent Anzalone: Thank you.

Q2 2024 Arrowhead Pharmaceuticals Inc Earnings Call

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