Q2 2020 Earnings Call

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This conference call.

Throughout today's recorded presentation, all participants will be in listen only mode.

I think your presentation, there will be an opportunity to ask questions.

I'll now hand, the conference over to Vincent Angelotti, Vice President Investor Relations Sport I Okay.

Joe had been.

Thanks.

Sorry about the delay everybody, we're having some technical difficulties on the line.

Good afternoon. Thank you for joining us today to discuss arrowheads results for fiscal second quarter ended March 31st 2020.

unknown: Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. Throughout today's recorded presentation, all participants will be in a listen-only mode.

With us today from management, our President and CEO Dr., Christopher Anzalone, who will provide an overview of the quarter Dr. hobby Urson Martino, Chief Medical Officer, who will discuss our clinical programs Dr. Kerr Bradshaw, our chief Scientific officer, who will discuss our discovery platform development and manufacturing efforts and Ken Myszkowski our chief.

unknown: After the presentation, there will be an opportunity to ask questions. I will now hand the conference over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

Vincent Anzalone: Thanks Buena and sorry about the delay, everybody. We were having some technical difficulties on the line. But good afternoon.

To answer lobster, who will give a review the financials. In addition, James hazard or Chief commercial officer will be available during the Q any session of today's call.

Vincent Anzalone: Thank you for joining us today to discuss Arrowhead's results for its fiscal second quarter ended March 31st, 2020. With us today from management are President and CEO Dr. Christopher Anzalone, who will provide an overview of the quarter, Dr. Javier San Martin, Chief Medical Officer, who will discuss our clinical programs, Dr. Kurt Bradshaw, our Chief Scientific Officer, who will discuss our discovery, platform development, and manufacturing efforts, and Ken Myszkowski, our Chief Financial Officer, who will give a review of the financials. In addition, James Hazard, our Chief Commercial Officer, will be available during the Q&A session of today's call. This is the first earnings call without Dr. Bruce Given, who retired last week since he joined the company 10 years ago. I want to start by thanking Bruce for all of his contributions to Arrowhead. Bruce developed strong relationships with the investment community over the years, and I'm certain that Javier, Kurt, and Jim will do the same.

This is the first earnings call without Dr., Bruce given who retired last week since he joined the company 10 years ago I want to start by thank you Bruce for all of his contributions to Arrowhead first developed strong relationships with the investment investment community over the years and I'm certain that Javier curtain, Jim will do the same.

Before we begin that we'd like to remind you that comments made during today's call contain certain forward looking statements within the meaning of section 27 eight of the Securities active 1933 section 21, you have the Securities Exchange Act like Cdthirty four all statements other than statements of historical facts, including without limitation those.

With respect to airlift schools plans and strategies are forward looking statements. These include statements regarding our expectations around the developments safety and efficacy of our drug candidates projected cash runway and expected future development and commercialization activities. These statements represent management's current expectations and are inherently uncertain.

Vincent Anzalone: Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Therefore, all statements other than statements of historical fact, including without limitation those with respect to Arrowhead's goals, plans, and strategies, are forward-looking statements. These include statements regarding our expectations regarding the development, safety, and efficacy of our drug candidates, projected cash runway, and expected future development and commercialization activities. These statements represent management's current expectations and are inherently uncertain.

The actual results may differ materially Arrowhead disclaims any intent and and undertakes no duty to update any forward looking statements discussed on todays call you should refer to the discussions under risk factors and arrowheads annual report on form 10-K, and the company subsequent quarterly reports on form 10-Q for it.

No matter to be matters to be considered in this regard, including risks and other considerations that could cause actual results to vary from the presently expected results expressed in today's call that said I'd like to turn the call over to Christians, Lonely President and CEO The company Chris.

Vincent Anzalone: Thus, actual results may differ materially. Arrowhead disclaims any intent and undertakes no duty to update any of the forward-looking statements discussed on today's call. You should refer to the discussions under risk factors in Arrowhead's annual report on Form 10-K and the company's subsequent quarterly reports on Form 10-Q for additional matters to be considered in this regard, including risks and other considerations that could cause actual results to vary from the presently expected results expressed in today's call. With that said, I'd like to turn the call over to Chris Anzalone, President and CEO of the company. Thanks, friends. Good afternoon, everyone.

Thanks Vincent.

Good afternoon, everyone. Thank you for joining us today.

I'd like to start, but thank you Dr. Bruce given.

Fantastic job developing the R&D organization and still in the culture of innovation, there will be Alaskan legacy.

Bruce his contributions are cleared to all we know him work with them and I'm confident that we have assembled and developed rank team to enable us to continue to execute in true airline fashion.

Javier Curt and Jim are seasoned executives, who are expanding a professional life in their respective functions and I put arrowhead is a very strong position to prosper. During this next phase of growth.

2020 is the year, the we tend to make the promise of already high outside deliver a reality, we hope to gain clinical proof of concept in the long in solid tumors and then rapidly expand our pipeline much as we did with our past that targeted pipeline in 2018 29.

Christopher R. Anzalone: Thank you for joining us today. I'd like to start by thanking Dr. Bruce Given, who did a fantastic job developing the R&D organization and instilling a culture of innovation that will be a lasting legacy. Bruce's contributions are clear to all who know him or have worked with him, and I'm confident that we have assembled and developed the right team to enable us to continue to execute in true Arrowhead fashion. Javier, Kurt, and Jim are seasoned executives who are expanding and professionalizing their respective functions and have put Arrowhead in a very strong position to prosper during this next phase. 2020 is the year that we intend to make the promise of RNAi outside the We hope to gain clinical proof of concept in lung and solid tumors and then rapidly expand our pipeline, much as we did with our hepatiocyte-targeted pipeline in 2018 and 2019. This could provide new treatment options for countless patients and provide Arrowhead shareholders with continued value growth. While, of course, we're looking to expand our reach, we are also looking to squeeze as much risk out of our business as we can. We have also made good progress on this front. First, we are well capitalized.

This could provide new treatment options for catalyst patients and provide her with shareholders with continued value growth.

Well of course, we're looking to expand our region. We're also looking to squeeze as much risk.

Out of our business as we can.

We've also made good progress on this front first we are well capitalized.

Second we are developing increasingly validated platform and trim, we do totaling 273 human subjects with 570 doses across our clinical programs and keep in mind. This does not include all the people have been treated by Janssen and Amgen with our partner candidates.

Third Arnie I Im increasingly validated modality.

Fourth we are addressing gene targets. The experts generally you as well validated fifth we are addressing unmet medical needs and sticky we are the first Arnie I player in all of our clinical programs.

Christopher R. Anzalone: Second, we are developing an increasingly validated platform in TRMM. We've treated a total of 273 human subjects with 570 doses across our clinical programs. And keep in mind that this does not include all the people who have been treated by Janssen and Amgen with our partner candidates. Third, RNAi is an increasingly validated modality. Fourth, we are addressing gene targets that experts generally view as well-validated. Finally, we are addressing unmet medical needs. And sixth, we are the first RNAi player in all of our clinical programs. All this puts us on solid footing, but the greatest risk in the room is COVID-19. This has to be the lens through which you view our business, at least in the near to mid-term.

All this puts us on solid footing, but the relevant risk in the room is cobot 19. This has to be the lens through which you are business at least in the near to midterm. Therefore idling use my portion of this call to provide a high level overview more programs and how they may be affected by the outbreak.

Let's start with airway team, our investigational medicine against Alpha one liver disease.

In March and voluntarily pause to new patient screening and enrollment for at least forming period in the phase two three Sequoia study and the girl 18 2002 open label study.

We're now working sites investigators to begin the process of resuming screening and enrollment.

Any patients already involved in these days continued to be dose to per protocol and continue to come in for their follow up visits.

Christopher R. Anzalone: Therefore, I will use my portion of this call to provide a high-level overview of our programs and how they may be affected by the outbreak. I will start with Arrow AAT, our investigational medicine against alpha 1 liver disease. In March, we voluntarily paused new patient screening and enrollment for at least a four-week period in the Phase 2-3 Sequoia Study and the Arrow AAT-2002 Open Label Study. We are now working with sites and investigators to begin the process of resuming screening and enrollment. Any patients already enrolled in these studies continue to be dosed per protocol and continue to come in for their follow-up visit. Importantly, protocol deviations have not been out of the norm. Before the enrollment pause, we are already fully enrolled in the first cohort of the 2002 study, so we are still on schedule to collect six-month biopsies in the summer. We intend to report those data in the fall at an appropriate venue.

Importantly protocol deviations have not been out of the ordinary.

The 40 enrollment pause we were already fully enrolled in the first cohort of the 2002 study. So we're still on schedule to collect six month biopsies in the summer we intend to report those data in the fall at an appropriate thing.

We believe this is an important readout for this program and have the field.

While we don't expect sees the logical changes after that short amount of treatment in may provide an early indication that the drug is doing what he wasn't it is designed to do which is to reduce new production of an mutant misfolded 18 protein.

This will be assessed by measuring amount of 18 monitoring in Nevada sites.

Further it'll be interesting it'll be interesting to compare pre and post treatment levels of accumulated ABT polymer this might give us a view of the pace at which pesticides can break down in Cleveland, the polymerize protein, which is the root causes the progressive liver disease in patients performance I guess ZZ mutation.

Christopher R. Anzalone: We believe this is an important readout for the program and for the field. While we don't expect any histological changes after that short amount of treatment, it may provide an early indication that the drug is doing what it is designed to do, which is to reduce new production of the mutant misfolded AAT protein. This will be assessed by measuring the amount of AAT monomer in hepatocytes. Furthermore, it will be interesting to compare pre and post treatment levels of accumulated AAT polymer.

We believe these data are important for us in the field and we expect this read outs to be the first of its kind anywhere.

Underlying both our substantial lead and developing a treatment for alphaform liver disease, and our position as thought leaders in the field.

There are other already I based approaches but to date, none have reported data demonstrating tolerability and pharmacologic activity even in normal healthy volunteers. In addition, there other approaches to treating 18 efficiency by correcting them you HBP protein in hopes of allowing it to be more efficiently exports from the past sites, we see some serious challenges.

Christopher R. Anzalone: This might give us a view of the pace at which hepatocytes can break down and clear the polymerized protein, which is the root cause of the progressive liver disease in patients with homozygous ZZ mutations. We believe these data are important for us in the field, and we expect this readout to be the first of its kind. This underlines both our substantial lead in developing a treatment for alpha-limb liver disease and our position as thought leaders in the field. There are other RNAI-based approaches, but to date, none have reported data demonstrating tolerability and pharmacologic activity, even in normal, healthy volunteers. In addition, there are other approaches to treating AAT deficiency by correcting the mutant AAT protein in hopes of allowing it to be more efficiently exported from the path. However, we see some serious challenges for that approach to show clinical benefit for patients with liver manifestations of AAT deficiency. First, the liver produces an estimated two grams of AAT protein per day.

For that approach to show clinical benefit for patients with liver manifestations of a deficiency.

First liver produces an estimated two grams of 18 protein per day, we do not believe it is feasible to administer enough small molecule corrector to address that level of protein production. So we think some portion will likely still accumulate and liver.

So the goal is to cracks, 20% to 30% of protein, which would still require very large amount of corrector that would mean, 70% to 80% of misfolded protein is still present, which is a lot deliver to handle.

Our data suggests an arrow eightys nearly completely suppressing the for production of the mute Ziad protein and we still believe that it may take two years of treatment to show meaningful change in liver histology.

So how long would you have to treat with the corrector that is leaving a large majority of 18 protein and deliver a years 10 years, we think that goes into serious challenge in a clinical trial setting and gives us confidence that we're in a strong competitive position.

Christopher R. Anzalone: We do not believe it is feasible to administer enough small molecule corrector to address that level of protein production, so we think some portion will likely still accumulate in the liver. So if the goal is to correct 20 to 30% of protein, which would still require a very large amount of corrector, that would mean 70 to 80% of the misfolded protein is still present, which is a lot for the liver to handle.

Let's now talk about the status of our Q cardiometabolic candidates apparel able to see three an arrow amsthree.

Christopher R. Anzalone: Our data suggests that Arrow AAT is nearly completely suppressing liver production of the mutant Z-AAT protein, and we still believe that it may take two years of treatment to show a meaningful change in liver histology. So how long would you have to treat with a corrector that is leaving a large majority of ZAAT protein in the liver? 8 years?

It's a C is being developed as a potential treatment for patients with severe hypertriglyceridemia and history or high risk of pancreatitis. Some of these patients have a single genetic cause for their disease, such as familial chylomicronemia syndrome, or actually yes, but a significantly larger population as polycom that causes for their hypertriglyceridemia. This is called.

Christopher R. Anzalone: Ten years? We think that presents a serious challenge in a clinical trial setting and gives us confidence that we are in a strong, competitive market. Let's now talk about the status of our two cardiometabolic candidates, Arrow A plus U3 and Arrow Ames 3. Arrowhead PC3 is being developed as a potential treatment for patients with severe hypertriglyceridemia and a history or high risk of pancreatitis. Some of these patients have a single genetic cause for their disease, such as familial chylomicronemia syndrome, or FCS, but a significantly larger population has poly This is called multifactorial chylomicronemia, or MCM, and we believe there are around 30,000 patients with this condition in the US alone. FCS and MCM have very similar clinical characteristics. There are both severe diseases that can lead to severe abdominal pain, recurrent pancreatitis, emergency room visits and hospitalizations, and even death.

Multi factorial kalamata anemia, or MCM and we believe that are around 30000 patients with this condition in the U.S. alone.

Yes, and MCM have very similar clinical manifestations. They are both severe diseases. The can lead to severe abdominal pain for current pancreatitis emerges emergency room visits and hospitalizations and even debt. These come with a very high cost with respect to both patients quality of life and economic costs to the healthcare system.

We have decided focused on the MCM population and are working on a plan for potentially pivotal study in MCM patients. We intend to request a meeting with the FDA made this year discussed impede studies on considerations for Registrational study.

We designed the phase one two site to provide sufficient data to enable him directly into phase three study.

We will know more after we speak with regulators, but our hope is that we can start a pivotal study in the first half from 2021.

Christopher R. Anzalone: These come with a very high cost with respect to both patient quality of life and economic cost of healthcare. We have decided to focus on the MCM population and are working on a plan for a potentially pivotal study in MCM patients. We intend to request a meeting with the FDA and EMA this year to discuss some key study design considerations for a registrational study. We designed the Phase 1-2 study to provide sufficient data to enable rolling directly into a Phase 3 study.

We believe that should be relatively short study. So we continue to believe that aero able season, we could be our first marketing product.

We continue to generate data in the phase one two clinical study it was nearly fully enrolled prior.

To the Cobot 19 outbreak and we have experienced a slight delay in improving their lean patients. We already have a substantial amount of data that we intend to present at various times. This year and are hopeful that we may.

Christopher R. Anzalone: We will know more after we speak with regulators, but our hope is that we can start a pivotal study in the first half of 2021. We believe that should be a relatively short study, so we continue to believe that Arrow ApoC3 could be our first marketing product. We continue to generate data in the Phase 1-2 clinical study. It was nearly fully enrolled prior to the COVID-19 outbreak, and we have experienced a slight delay in accruing the remaining... We already have a substantial amount of data that we intend to present at various times this year and are hopeful that we will be able to present a full data set later this year. With the disruptions to the traditional medical meeting cycle because of the COVID-19 outbreak, it is unclear what form these data releases will take. We're committed to finding alternative ways to present data if medical meetings continue to be canceled or postponed.

That we will be able to present full data set later this year.

With the disruptions to the traditional medical need cycle because of the Coca 19 outbreak is unclear what form. These data releases will take we're committed to finding alternative ways to present data if medical needs continue to be cancelled or postponed.

The early data have been exciting we expect that trend to continue as we report our last conference call. We have seen approximately 95% reduction of circulating triglycerides and hypertriglyceridemia patients after only a single dose of arrow and we'll see three.

This is truly stunning.

These patients have triglycerides in the thousands so we would expect a reduction of this magnitude to be quite meaningful for patients like these.

We're in a slightly more advanced position with airline industry, which is being developed as potential treatment for patients with mixed dyslipidemia.

Let's talk about that patient population for a moment.

Christopher R. Anzalone: The early data has been exciting, and we expect that trend to continue. As we reported in our last conference call, we have seen approximately 95% reduction in circulating triglycerides in hypertriglyceride-emitted patients after only a single dose of ArrowApoC3. This is truly stunning.

Mixed distillate mixed dyslipidemia mixed dyslipidemia patients have both elevated triglycerides and elevated LDL cholesterol and our heightened risk of atherosclerotic cardiovascular disease.

Theres strong evidence the bullet triglycerides and LDL contribute to that risk.

Christopher R. Anzalone: These patients have triglycerides in the thousands, so we would expect a reduction of this magnitude to be quite meaningful for patients like them. We are in a slightly more advanced position with Arrowhead H3, which is being developed as a potential treatment for patients with mixed dyslipidemia. Let's talk about that patient population for a moment. Mixed dyslipidemia patients have both elevated triglycerides and elevated LDL cholesterol and are at heightened risk for atherosclerotic cardiovascular disease.

This is very high prevalence disease with an estimated potential patient population of between 10 to 15 million people in the U.S. alone and is not adequately address with current standard of care.

Christopher R. Anzalone: There's strong evidence that both triglycerides and LDL contribute to that risk. This is a very common disease with an estimated potential patient population of between 10 to 15 million people in the U.S. alone, and it is not adequately addressed with the current standard of care. We see Arrowhands 3 potentially being able to reduce triglycerides to a far higher degree than other available treatments and also reduce LDL in a non-LDL receptor mediated manner, making LDL reduction potentially greater than with statins and PCSK9 inhibitors alone. As with ArrowApoC3, we reported early patient data at our last conference call, and I believe that was impressive. We saw approximately an 80% reduction in triglycerides and a 40% reduction in LDL after only a single dose of Arrowhands 3.

We see arrow, amsthree potentially being able to reduce triglycerides to a firefighter degree than other available treatments and also reduce LDL in a non LDL receptor mediated manner manner Beacon LDL reduction potentially greater than with status in PCSK nine inhibitors alone.

As with Arrow April C. We reported early patient data and our last conference call I believe that was impressive.

We saw approximately 80% reduction in triglycerides, and 40% reduction in LDL after only a single dose of airlines three.

Importantly, all of these patients were already on LDL lowering drugs, such as statements and Pcsknine inhibitors.

The patient population, we expect to address is quite large and a pivotal study to show reduction in cardiovascular events would also be large.

We and we think most experts in the field believe strongly that mixed dyslipidemia patients are in need of new treatment options and we believe the mechanism of NPL three reduction is very intriguing.

So we are now determining what the regulatory and development path would look like for that indications.

Because of our focus on this high prevalence population, we will likely need to run a phase Twob study instead of rural and directly into pivotal study as we maybe able to do with Airlaid, we'll see three.

Christopher R. Anzalone: Importantly, all of these patients were already on LDL-lowering drugs, such as statins and PCSK9 inhibitors. The patient population we expect to address is quite large, and a pivotal study to show a reduction in cardiovascular events would also be large. We, and we think most experts in the field, believe strongly that mixed dyslipidemia patients are in need of new treatment options, and we believe the mechanism of ANG-PTL3 reduction is very

We plan on engaging with FDA this year and hope to initiate the phase the phase to be in the first half of 2021.

The early three phase one two study is making good progress even in the Coca 19 environment.

Study is fully enrolled so we do not expect any real delays as we continue to follow patients and generate data.

Christopher R. Anzalone: So we are now determining what the regulatory and development path would look like for that indication. Because of our focus on this high-prevalence population, we will likely need to run a Phase 2b study instead of rolling directly into a pivotal study, as we may be able to do with Arrow ApoC3. We plan on engaging with FDA this year and hope to initiate the Phase 2B in the first half of 2021. The Arrowhead 3 Phase 1-2 study is making good progress, even in the COVID-19 environment. The study is fully enrolled, so we do not expect any real delays as we continue to follow patients and generate data. We believe we will have a full data set to report later in the year, and we'll also look for opportunities to share data subsets throughout the year. Just like ArrowAquacy, we will assess alternative ways to present data if medical meetings continue to be canceled or postponed.

We believe we will have a full data center report later in the year and we'll also look for opportunities to shared data subsets throughout the year.

Just like Arrow equal C. We will assess alternative ways to present data at medical meetings continue to be cancelled or postpone.

I'd now like to move.

Now, let's move onto our newest clinical candidates aero have to and development to treat the clear cell form of renal cell carcinoma for which we filed an idea in December.

Aero HST in development to treat alcohol and non alcohol related liver disease for which we filed the DTA in December.

Aero Enac in development, three cystic fibrosis for which we filed the Cts recently.

We expect the arrow have two phase one thing to begin enrolling shortly we have one site open now for screening and enrollment and we anticipate the first patients will be dose this quarter.

Christopher R. Anzalone: I would now like to move on to our newest clinical trial, Arrowhead 2, in development to treat the clear cell form of renal cell carcinoma, for which we filed an IND in December. Arrow HSD in development to treat alcohol and non-alcohol-related liver disease, for which we filed a CTA in December, and Arrow-ENAC in development to treat cystic fibrosis, for which we filed a CTA recently. We expect the Arrowhead 2 Phase 1 sites to begin enrolling shortly.

The startup process for the study has taken longer than we had hoped which is likely due in part to Cook a 19.

Many of the investigators right academic centers and the contract and initiation process may be experiencing delays due to health and safety precautions.

We expect to potentially have proof of concept into for the candidate and for the tumor targeted trimmed platform. This year.

But the timing may be too tight to report anything publicly until next year.

We should have a better idea about this as we see the pace of enrollment we are already thinking about additional targets for the tumor program and we intend to build out the pipeline. Once we have clinical proof of concept on our own potentially in collaboration with a partner.

Christopher R. Anzalone: We have one site open now for screening and enrollment, and we anticipate the first patients will be dosed this quarter. The start-up process for this study has taken longer than we had hoped, which is likely due in part to COVID-19. Many of the investigators are at academic centers, and the contracting and initiation process may be experiencing delays due to health and safety precautions. However, we expect to potentially have proof-of-concept data for the candidates and for the tumor-targeted trim platform this year. But the timing may be too tight to report anything publicly until next year. We should have a better idea about this as we see the pace of enrollment.

So what does success look like for the current phase one.

We will be taking biopsies from metastasis and if we see good hit to help and knock down we will be happy that we are on the right correct.

First because if you out because well validated targets approximately 80% of patients with clear cell RCC, we'll have about nickel lindhout mutation, we would have an expectation to arrowhead too could be helpful. For these patients.

Christopher R. Anzalone: We are already thinking about additional targets for the tumor program, and we intend to build out the pipeline once we have clinical proof, on our own and potentially in collaboration with a partner. So what does success look like for the current phase one? We will be taking biopsies from metastases.

Second because our targeted strategy is intended to work across different solid tumor types, rather than just in RCC hip 12 enough down would suggest that we might have a broad solid tumor franchise.

Once we achieve clinical proof of concept that we're knocking down here give to alpha our goal is to do quickly expand into new solid tumors against new targets. We view this as a scalable and rapid value creation strategy.

Christopher R. Anzalone: And if we see good HIP2-alpha knockdown, we will be happy that we are on the right track. First, because HIF-2 Alpha is a well-validated target for the approximately 80% of patients with clear cell RCC who have the von Hippel-Lindau mutation, we would have an expectation that Arrowhead 2 could be helpful for these patients. Second, because our targeting strategy is intended to work across different solid tumor types rather than just in RCC, HIF-12 and knockdown would suggest that we might have a broad solid tumor friendship. Once we achieve clinical proof of concept that we are knocking down HIF-2-alpha, our goal is to quickly expand into new solid tumors against new targets. We view this as a scalable and rapid value creation strategy.

Aero HSD began dosing in phase one two study in March.

We are through the first cohort and we previously received approval from safety monitoring Committee escalate. The next higher dose because of Coca 19 related restrictions and New Zealand enrollments of this second quarter was pause, but we expect it to reopen for healthy volunteer shortly patients sometime after that we are working with the site on plans to restart and.

Element and believe this is only a minor delays that we don't think will have any lasting effects program for our general guidelines.

For Aero enacted by the DTA last month, so again, a phase one two study in healthy volunteers and in patients with cystic fibrosis.

Christopher R. Anzalone: Arrow HSD began dosing in the Phase 1-2 study in March. We are through the first cohort, and we have previously received approval from the Safety Monitoring Committee to escalate to the next higher dose. Because of COVID-19-related restrictions in New Zealand, enrollment of this second cohort was paused, but we expect it to reopen for healthy volunteers shortly and patients sometime after that. We are working with the site on plans to restart enrollment and believe this is only a minor delay that we don't think will have any lasting effects on the program or our general government.

Too early to say, if there will be any kogan accumulated delays in this program that largely depends on what happens next couple of months and beyond.

Belief is that we will be able to generate data on the safety connectivity the compound and by proxy the pulmonary platform.

But we don't know we will have enough data by key abstract deadlines to present data at scientific conferences this year.

Christopher R. Anzalone: For Arrow ENAC, we filed a CTA last month to begin a Phase 1-2 study in healthy volunteers and in patients with cystic fibrosis. It's too early to say if there will be any COVID-19-related delays in this program, but that largely depends on what happens in the next couple of months and beyond.

Christopher R. Anzalone: Our belief is that we will be able to generate data on the safety and activity of the compound and, by proxy, the pulmonary platform, but we don't know if we will have enough data by key abstract deadlines to present data at scientific conferences this year. But I want to talk briefly about the CF patients we hope to help. Clearly, there has been an enormous amount of progress over the last several years in CF treatment options, but there are still opportunities to A, help those who don't respond to standard of care, and B, to make those that do respond even better. The gene target of Arrow-ENAC is the epithelial sodium channel, or ENAC.

Christopher R. Anzalone: There is good genetic validation that CF patients, who are also essentially heterozygous ENAC knockouts, have a mild form of CF or even no discernible lung complications several decades into life. We see this as an indication that therapeutic enactment inhibition in the lung may benefit all patients with CF, regardless of their genetics. The idea is that reduction of ENAC expression in the lung helps to rehydrate CF-related dehydrated mucus and may help improve mucociliary clarity.

Christopher R. Anzalone: Importantly, this first study is designed to give us a readout on both tolerability and efficacy in the target patient population. This could be a potentially important value inflection point for both Arrow ENAC and for the pulmonary platform broadly. If the data are supportive of further development, we hope to launch a Phase III study in 2021 and move rapidly to expand the pipeline with product candidates that address other underserved pulmonary diseases such as COPD, asthma, and pulmonary fibrosis. Toward that goal, I'm pleased to announce that we have completed discovery and optimization work on our second Lung Targeter program and have nominated Arrow Lung 2 as our next candidate. We are not disclosing the target at this point, but we can say that it is designed to treat COPD patients.

Christopher R. Anzalone: We have been very encouraged by the data in this program and for Arrow Lean Act and are eager to begin the expansion of our pulmonary franchise. We are now working on manufacturing and IND-enabling toxicology studies for Arrow Lung 2 and plan on filing a CTA in the first half of 2021 to begin the first human study. We had previously hoped this could happen by the end of this year, but COVID has slowed development down a bit and will delay the first human studies by probably one or two. In the past, we have discussed our excitement in establishing a rapidly expanding pulmonary franchise, and you are seeing that start to play out now. Given our studies in rodent, primate, and sheep models spanning several years, we have a high degree of confidence that our inhaled delivery will be well-tolerated and active in humans.

Christopher R. Anzalone: Further, the lung represents a target-rich environment that enables us to address a number of indications in innovative ways. So we see this as a big opportunity for patients and a significant value driver for our shareholders. In addition to CF, COPD, asthma, and IPF, people have asked us about applying inhaled trim to coronavirus.

Christopher R. Anzalone: We have not disclosed any work previously, but we are happy to report today that we have an active program to address the current novel coronavirus that causes COVID-19 and other possible future pulmonary-borne pathogens. We are not disclosing more details about this program or the strategy, but we wanted to provide this update. We are looking to bring the same ingenuity and innovative thinking to this issue that we did in revolutionizing the approach to hepatitis B. All of us who work in biopharma and drug development play a role in improving global health, and Arrowhead is proud to say that we have joined the fight. A number of factors give us confidence that we could play an important role in the current novel coronavirus, future coronaviruses, and other pulmonary-borne pathogens.

Christopher R. Anzalone: First, we are clear RNI leaders in addressing the lung and have a clinic-ready inhalation program. Second, history suggests that we are faster than any RNAi company, and arguably any other biotech company, going from concept to clinic. And third, we are the leading RNAi company in antivirals and are known as HPV thought leaders. We look forward to keeping you up to date on the progress of this program. The final program I'd like to mention is our muscle-targeted program. We have not yet disclosed the initial indication, or gene target, of our first clinical candidates, but consistent with our other programs, we view the indication as having substantial unmet medical need, the gene target is well-validated, and we expect to be the first RNAi company there.

Christopher R. Anzalone: As with the solid tumor and pulmonary franchises, we view our ability to address skeletal muscle as a sharpened spear. Once we achieve clinical proof of concept, we expect to rapidly expand our pipeline into new indications and gene targets addressable via muscle delivery. We remain on track to file a CTA by the very end of 2020. I believe we have unmatched reach into diverse indications. Unmatched speed to the clinic and unmatched depth of the pipeline for a company our size. Our partner programs continue to look good as well. Amgen stated on its recent quarterly conference call that it expects to begin a phase two study with AMG 890 in the second half of this year. Janssen continues to conduct its first two Phase IIb studies with J&J 3989 against chronic HPV, and we are actively working together on the three undisclosed additional targets.

Resourced our employees continue to be a great inspiration to me as their focus work ethic and innovative spirit have never Wayne's during these difficult times.

Without overview I now like to turn the call over stuff their hobby or 17 Javier.

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Christopher R. Anzalone: COVID-19 has introduced a new set of challenges, but Arrowhead has adapted. We believe that we have important new medicines that can potentially help countless patients, so we feel very fortunate that the current environment has only caused minor delays to our development programs and that we are well-resourced. Our employees continue to be a great inspiration to me as their focus, work ethic, and innovative spirit have never waned during these difficult times. With that introduction, I'd now like to turn the call over to Dr. Javier San Martin. Javier?

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Javier San Martin: Thank you, Chris. I'm happy to join the call and hope I can be a good resource to everyone listening. Please give a good overview of the clinical development programs, and I will provide some further details on their status and study design. Let's begin with Arrow ApoC3, our candidate targeting ApoLacrocotine C3 being developed as a potential treatment for patients with hypertrophic celiac disease. As Chris mentioned, we believe this may be a good treatment option for MCM patients that have severely elevated triglycerides, often in the thousands of milligrams per day. These patients can experience recurrent abdominal pain are at high risk for pancreatitis and, in some cases, can require frequent visits to the ER and be admitted for multiple day hospitalization. In the most severe cases of pancreatitis, these attacks can even be fatal.

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Javier San Martin: In addition, these patients live with a very restrictive diet that becomes difficult to maintain, and even if they comply, they still have to have extremely high triglycerides levels. This has severely impacted quality of life, and these patients are desperately in need of better therapies that can achieve deep and durable reductions in triglycerides levels and therefore reduce the risk of pancreatitis and allow for a better quality of life. As Chris mentioned, we previously announced some preliminary results in the patient population, but I want to review them today because they were very encouraging. After a single dose of 50 mg of AeroApoC-3 in patients with severe hyperpiglycemia, we demonstrated a reduction of around 95% in circulating triglycerides.

In addition, efficiently with a very restrictive value that becomes difficult to maintain and even if they complied. They still had have extremely high triglycerides level.

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71, SAP should have been involved and those in the study we still have a few patient too low in order to reach the plan Goldman were working with investigator and size to ensure that we reach discipline and Goldman as soon as possible [laughter]. We'll look forward to the also to me 2% additional from South from this heavy late in the.

Javier San Martin: We would expect this type of solution to have substantial clinical benefits, particularly in patients with a history of cancer. We are currently conducting our Phase I, single and multiple dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of Arrowhead Positra. The single-dose portion of the study is in adult healthy volunteers, and the multiple-dose portion includes patients with severe hyperplasticity. Seventy-one staff chairs have been enrolled in this study. We still have a few patients to go in order to reach the planned enrollment.

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Javier San Martin: We're working with investigators to ensure that we reach this planned enrollment as soon as possible. We look forward to the opportunity to present additional results from this study later in the year. Our other cardiometabolic candidate is Arrow H3, targeting angiopoietin-like protein 3 or H-PTL2, and is being developed as a potential treatment for patients with mixed dyslipidemia. This program is also moving forward efficiently.

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Javier San Martin: HPTL-3 is the regulator of lipid and lipoprotein metabolism. Inhibiting HPTL-3 should result in lower triglycerides and LDL cholesterol and potentially provide improvement in other lipids and metabolic markers. Our data in animal models and our early clinical data strongly suggest this. For example, at doses of 200 or 300 milligrams, maximum mean triglyceride reduction in the high triglyceride cohort approaches 80%, and the maximum mean reduction in LDL cholesterol in the various high LDL cohorts is averaging around 40%, while patients who are already on maximal medical care consisting of statins plus or minus zeta my with PCSK9 inhibitors in some.

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Javier San Martin: Lowering both triglycerides and LDL to this extent was an exciting result, and we think it could serve to hit multiple cardiovascular risk factors simultaneously. The current clinical study is a Phase I-II single- and multiple-dose study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamic effects. The single-dose portion of the study is in adult healthy volunteers. The multiple-dose portion is in normal volunteers and in patients with various types of dyslipidemia. This includes patients with hypertrichlyceridemia, patients on stable LDL treatment regimens but with persistently elevated LDL cholesterol, patients with heterozygous or homozygous familial hypercholesterolemia, and patients with no alcoholic fatty liver. We have enrolled 93 subjects in this study and have reached full and planned enrollment. The data for both the Arrow ApoC3 and Arrow H3 strongly support further development, and we intend to find appropriate ways to share the data publicly. Earlier, Chris discussed some of our future plans for AeroAngel.

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The data for both the L.C.D. and ancient Greece strongly support photos development and we tend to find appropriate ways to share the data publicly this year.

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Javier San Martin: It seems likely that a Phase IIb study that assesses various dose levels and dosing intervals will be a smart addition to our data package before embarking on a Phase III cardiovascular outcome trial. This will give us more certainty on the magnitude of the treatment effect in a large data set, allow us to select the right dose in a regimen, and also build our safety data, which is developing our strategy and plan to engage with regulators this year to discuss development and regulation. Arrow HSD, our new investigational candidate targeting HSD-17 beta-13 for the potential treatment of alcohol and or non-alcohol related liver disease, is another exciting program that has made progress recently. We see this as the most intriguing target for Nash at the moment.

See this has the most intriguing target for matched at the moment.

Relation base genetic data have shown from protection against Nash cirrhosis alcoholic hepatitis uncivilized humans opposes lots of since you're mutation in the H.U.C. 17, because 13 inside.

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Javier San Martin: Population-based genetic data have shown strong protection against NASH cirrhosis, alcoholic hepatitis, and cirrhosis in humans that have a loss of function mutation in the HSD-17 beta-13 enzyme. We're eager to see how that translates therapeutically in patients that receive aero-HSD treatment. Our current clinical study is a phase one, single, and multiple dose escalating study to evaluate the safety, tolerability, decay, and pharmacodynamic effects of Arrow HSD in normal healthy volunteers, as well as in patients with NAS or suspected NAS. Additional exploratory objectives include assessment of various measures of drug activity using liver biopsies. The first cohort of volunteers received their dose, and tolerability data was collected. The DSMB reviewed those data and recommended continued dose escalation. The study will resume enrollment shortly once some of the COVID-19-related restrictions are eased in New Zealand.

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The first cohort of volunteer received a go on forever integrate that was collected.

The D.S.N.D. reviewed those data I'm recommending continue those escalation.

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Respect to begin involved in the first cohort of mass spacious multiple those portion of the after the review of a 60 parameter from the sick uncle core of healthy volunteers.

Despite all of these scientists other she makes the time to patients activities eight that far shorter than it's original sequential face one single S.M. Windows, we're faced to Multiplus in no time, it's another another the way the arrowhead.

Okay.

Lastly, I want to an update on the eight A.T.. Our second generation investigation I may I to that the L.C.D. endeavor I said three men for the real genetic liver disease.

Javier San Martin: We expect to begin enrolling the first cohort of NASH patients in the multiple dose portion of the study after the review of the safety parameters from the second cohort of healthy volunteers. This parallel design strategy makes the time to patient activity data far shorter than a traditional sequential phase one single ascending dose to a phase two multiple ascending dose design. It's another innovative way that Arrowhead operates.

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There are two ongoing clinical study they potential people does Sequoia study and the open level 2000 them to study.

<unk> voluntarily put both on it for a week goes for news cleaning and enrollment due to concerns around the Kobe 19.

Many also one patients have compromised lung function and maybe are increasingly suffered severe illness in the event of a coffee 19 infection.

Javier San Martin: Lastly, I want to do an update on ARO-AAT, our second generation investigational RNAi therapeutic being developed as a treatment for the rare genetic liver disease associated with alpha-1 antidepressant deficiency. There are two ongoing clinical studies, the potential Pivotal Sequoia study and the Open Label 2002 study. We voluntarily put both on a four-week pause for new screening and enrollment due to concerns around COVID-19. Many Alpha-1 patients have compromised lung function and may be at increased risk of severe illness in the event of a COVID-19 infection. Continuing to enroll new patients might also jeopardize the integrity of study data as patients could have difficulty completing study visits and could miss doses or relevant studies related to procedures as a result of travel restrictions or concomitant illness.

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Well not working with participant ties to restart clean and Goldman where and when his cousin to do so.

Well I still have scheduled to collect six months biopsy from color one of the 2000 them to study by the end up with someone who was then work on precision and analyzing for south on subsequently plan on sharing those data in inappropriate fan.

Maybe the first leave it by L.C. data for patients Treaty with any set up the design to other is also one leave at beaches.

What would be looking intently to learn what happens to the C.A.T. one of my flavor on accumulate C.A.T. polymers. In addition to other possible issues.

Javier San Martin: We're now working with participant sites to restart screening and enrollment where and when it's prudent to do so, and they are still on schedule to collect a six-month biopsy from cohort 1 of the 2002 study by the end of the summer, and they will then work on processing and analyzing results, and subsequently plan on sharing those data in an appropriate venue. This may be the first liver biopsy data for patients treated with any therapy designed to address alpha-1 liver disease. We will be looking intently to learn what happens to the ZAAT monomers level and accumulate ZAAT polymers in addition to other possible. I will now turn the call over to Dr. Kurt Bradshaw, Arrowhead's Chief Scientific Officer. Kurt?

I will now turned a corner over to Doctor <unk> Arrowhead, Chief scientific off curved.

Thank you Javier and good afternoon every one I'm pleased to meet you all virtually and hope to connect more when things he's up a bit.

When they give you a little color on what we're working on an early programs and how we're addressing resource needs in research in manufacturing.

From a discovery standpoint, we have a lot of programs, an actor delta and more than planning stages as Chris mentioned Arrow Arrow lung too has already been nominated and we are now in manufacturing and I and enabling study phase for that program.

We have been highly encouraged by our Nonclinical result, with arrow enact and long too. So we're moving as quickly as possible into new targets that leverage our success with the pulmonary training structure.

Kurt Bradshaw: Thank you, Javier. And good afternoon, everyone.

Kurt Bradshaw: I'm pleased to meet you all virtually and hope to connect more when things ease up a bit. I want to give you a little color on what we're working on in our early programs and how we're addressing resource needs in research and manufacturing. First, from a discovery standpoint, we have a lot of programs in active development and more in the planning stages. As Chris mentioned, Arrow Lung 2 has already been nominated, and we are now in the manufacturing and IND enabling study phase for that program. We have been highly encouraged by our non-clinical results with Arrow ENAC and LungTube, so we're moving as quickly as possible into new targets that leverage our success with the pulmonary trim structure. This includes some ideas and initial work on pulmonary infectious agents like the novel coronavirus that causes COVID-19 and other corona and non-corona viruses were knocked down of a target in the pulmonary epithelium may be helpful.

This includes some ideas and initial work on pulmonary infectious diseases like a novel Corona virus that causes Kobe 19, and other corona and non Corona viruses were knocked down of a target the pulmonary up I feel anything helpful.

The idea of a long duration intervention where are in it which are any I generally has demonstrated give some unique advantages over other approaches far inhaled delivery platform has been developed and optimized over the last several years. So we think we have a significant lake up over other potential Arnie I solutions.

We're going onto our other more advanced preclinical efforts.

Liver, we are working towards several new programs importantly days include new targets as well as possible dimer or by specific programs designed to silence to gene targets with a single drunk candidate.

Kurt Bradshaw: The idea of a long-duration intervention, which RNAI generally has demonstrated, gives some unique advantages over other programs. Our inhaled delivery platform has been developed and optimized over the last several years. So we think we have a significant leg up over other potential RNIs. Moving on to our other more advanced preclinical efforts in the liver, we are working on several new programs. Importantly, these include new targets as well as possible dimer or bispecific programs designed to silence two gene targets with a single drug and Muscle.

In muscle we have one leave program and another two that are an accepted alike, but earlier stage.

So how are we building a and allocating resources to support these plans one of the positive aspects of being accompanied built around a single mechanism and a single plot skeletal platform is that.

Things from one program tend to inform the development of others. It's absolutely true for L. had research team, we've not needed to drastically increase head count and our only selectively adding one specialized expertise is needed.

For example, we are adding a few folks to support the growing pulmonary area.

Kurt Bradshaw: We have one lead program and another two that are in active development but at an earlier stage. So how are we building and allocating resources to support these plans? One of the positive aspects of being a company built around a single mechanism and a single scalable platform is that learnings from one program tend to inform the development of others. This is absolutely true for Arrowhead Research.

There will be some additional means for some <unk> some of the new cell types, who are working on this is partly why we venues San Diego R. and D. facility, which we open last month is helpful.

I was just to tap into additional skill sets in one of their countries premier biotech hubs.

It has also expanded our capacity for preclinical model. So we are able to do more that early early work in parallel.

Kurt Bradshaw: We've not needed to drastically increase headcount and are only selectively adding when specialized expertise is needed. For example, we are adding a few folks to support the growing Pullman area. There will be some additional needs for some of the new cell types we're working on. This is partly why the new San Diego R&D facility, which we opened last month, is helpful. It allows us to tap into additional skill sets in one of the country's premier biotech hubs and has also expanded our capacity for preclinical models, so we are able to do more of that early work in parallel. Lastly, I want to touch on our manufacturing capabilities and what we are seeing in this COVID-19 environment. We are monitoring this situation very closely because we never want drug manufacturing to delay a clinical study. So far, we have not seen any supply disruption. We have not encountered any material delay in receiving raw materials needed for the manufacturing processes, and we have not seen any contract manufacturer delays either.

Lastly, I want to touch on our manufacturing capabilities and what we are seeing in this cobin 19 environment.

We are monitoring the situation very closely because we never won drug manufacturing to delay a clinical study. So far we have not seeing any supply disruptions, we've not encounter any material delay and receiving raw materials needed for the manufacturing processes and we've not seen any contract manufacturer to lazy either.

We utilized a combination of internal champion manufacturing and extra L.C.M. house. So we typically manufacture all material for.

Preclinical talk study than face on clinical studies and house and then you see a mouse for phase two M.P. odd.

We maintain redundancies, both internally and with various yellows and different geography in order to guard against the risk of supply disruptions. So to summarize we think we are probably in a good position to supply the needs of our clinical development team now in into the future even with the uncertainty of coping 19.

I will now turn Nepal over Academy, Skalsky Arrowheads, Chief Financial Officer, Okay.

Kurt Bradshaw: We utilize a combination of internal GMP manufacturing and external CMOs. So we typically manufacture all material for preclinical toxicology studies and phase one clinical studies in-house and then use TMOs for phase two and beyond. We maintain redundancies both internally and with various CMOs in different geographies in order to guard against the risk of supply disruption.

Thank you Kirk.

46 or is that off a quarter I didn't mark 31st 2020, with 19, corn 8 million or 20 cents per share based on 101.7 million or diluted weighted average or is outstanding.

<unk>, who I didn't come of 23.9 or 24 cents per share based on 98.1 law enforcement diverted weighted average yourself standing for the quarter ended March 31st 2019.

Kenneth A. Myszkowski: So to summarize, we think we are probably in a good position to supply the needs of our clinical development team now and into the future, even with the uncertainty of COVID. I will now turn the call over to Ken Myszkowski, Arrowhead's Chief Financial Officer. Thank you, Kurt.

Revenue for the quarter end of March 31st 2020, or 23.5 million compared to 48.1 million for the quarter ended March 31st <unk>.

Kenneth A. Myszkowski: As we reported today, our net loss for the quarter ended March 31st, 2020, with $19.8 million, or $0.20 per share, based on $101.7 million fully diluted weighted average shares outstanding. This compares with net income of $23.9 million, or $0.24 per share, based on 98.1 million fully diluted weighted average shares outstanding for the quarter ended March 31, 2019. Revenue for the quarter ended March 31st, 2020 was $23.5 million compared to $48.1 million for the quarter ended March 31st, 2019. Revenue in both periods relates to the recognition of a portion of the upfront payments and milestones received from our license and collaboration agreements with JAMF. So we continue to work toward completing our performance obligation of managing the current Phase I-II HPV clinical trial. Revenue from the Janssen Agreement is recognized based on our estimate of the proportion of effort expended toward fulfilling our performance obligations, primarily overseeing the completion of the current Phase I-II clinical program. We expect the remaining $33.2 million of deferred revenue to be recognized in this calendar year.

Periods related relates to the recognition of a portion of the <unk>.

I also receive from our life within collaboration agreements Janson.

Continue to work toward complete completing our performance obligation of managing the current pays more into H.T.V. clinical trial.

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Nice based on our estimate a proportion of effort expended toward fulfilling our performance obligation.

Kenneth A. Myszkowski: Any additional milestones achieved with Janssen or Amgen will be added to this list. Total operating expenses for the quarter ended March 31, 2020, were $45.8 million, compared to $26.1 million for the quarter ended March 31st, 2019. This increase is primarily due to increased non-cash stock compensation. Stock compensation expense has increased because the valuation of our new stock options and restricted stock awards granted has increased with the growth of our stock price. Additionally, stock compensation expense increased due to the timing of the achievement of certain performance-based awards in each period. The increase in total operating expenses was also driven by increased clinical trial costs, as our pipeline of clinical candidates has increased, and increased personnel costs in both R&D and G&A as our headcount continues to grow. Net cash used by operating activities during the quarter ended March 31, 2020, was $27.6 million, compared with net cash used by operating activities of $19.6 million during the quarter ended March 31, 2019. The increase in cash use by operating expenses during the quarter is consistent with the increase in our cash operating expenses.

Early overseeing the completion of the current phase one two critical program.

We expect a remaining 33.2 million or deferred revenue three recognized in this calendar here any additional milestones, but she is with janson orange would be additive this objection.

Total operating expenses for the quarter ended March 31st 2020 or 45.8 million.

26.1 million for the quarter added March 31st you'd have low team.

Increases primarily due to increased niqash stock compensation expense.

Stock company fashion experience has increased because evaluation of our new.

Stock options and restricted stock awards granted has increased with the girl for our Cyprus.

Additionally, it start compensation express increase to the timing of the achievement certain performance space or it's in each period.

Increasing total operating expenses was also driven by increased clinical trial costs.

As our pipeline of political candidates has increased and increase personal costs, both in both r. and D.N.G.N.A. because our headcount continues to grow.

Not cashiers by operating activities during the quarter headed March 31st 2020 was 27.6 million compared with not cash used by operating activities I'm 19.6 million during the quarter ended March 31st 2019.

Increasing trash used by operating expenses.

During a quarter is consistent with the increase in our cash operating expenses.

We estimate or near term cash for to average 30 to 35 million per quarter.

Turning to our balance sheet, our cash flow vessels total <unk> excuse me 498.2 million at March 31st 2020, compared to 302.9 million at September 30th 2000 in 19.

The increase our cash and invest were primarily due to the December 2019 equity financing, we completed which generated.

250.5, more net cash proceeds for the company.

Kenneth A. Myszkowski: We estimate our near-term cash burn to average $30 to $35 million per quarter. Turning to our balance sheet, our cash and investments totaled $498.2 million at March 31, 2020, compared to $302.9 million at September 30, 2019. The increase in our cash and investments is primarily due to the December 2019 equity financing we completed, which generated $250.5 million in net cash proceeds for the company. Our common shares outstanding at March 31, 2020 were $101.7 million.

Are common shares outstanding March 31st 2020, or 101.7 million.

With that brief overview or we're all during a call back to Chris.

Thanksgiving.

<unk> 19 is caused everyone to rethink how they operate in their personal and professional lives.

Arrowhead or not immune to that we are committed to protect our employees business partners and patients to participate in our studies.

Decisive action toward that cool.

I'm an investment standpoint, we're in for into the outbreak has not so far cause wide scale disruptions to our business and worse, we have seen some minor extensions two are anticipated all the time lines.

Unfortunately, we're excited to be leveraging our leading inhalation franchise and actively working on treatments for the current novel Corona virus as well as future pulmonary viruses. This is directly in our wheel house and we are confident that we have much to offer.

Kenneth A. Myszkowski: With that brief overview, I will now turn the call back to Chris. Thanks, Ken. COVID-19 has caused everyone to rethink how they operate in their personal and professional lives. We at Arrowhead are not immune.

Christopher R. Anzalone: We are committed to protecting our employees, business partners, and patients that participate in our studies and have taken decisive action toward that goal. From an investment standpoint, we are encouraged that the outbreak has not, so far, caused wide-scale disruptions to our business, and, at worst, we have seen some minor extensions to our anticipated development timelines. Importantly, we are excited to be leveraging our leading inhalation franchise and actively working on treatments for the current novel coronavirus, as well as future pulmonary viruses. This is directly in our wheelhouse, and we are confident that we have much to offer.

In addition, we believe 2020 holds great potential to be an important here for the company in terms of expanding our reach engine do indications and continuing to validate the trim platform infanticides solid tumors, the lawn and skeleton muscle.

We intend never read house across most of our programs and we expect needs to be important data. We also expect starts to gain clinical from concept for our extra Patrick platforms again, the pipeline expansion phase of our growing pulmonary platform expand the trim flat for him to new opportunities and gained regulators to gain clarity on our plans to move our Cardiometabolic Canada.

Christopher R. Anzalone: In addition, we believe 2020 holds great potential to be an important year for the company in terms of expanding our reach into new indications and continuing to validate the trim platform in hepatocytes, solid tumors, the lung, and skeletal. We intend to have readouts across most of our programs, and we expect these to be important data. We also expect to start to gain clinical approval for our extra hepatic platforms, begin the pipeline expansion phase of our growing pulmonary platform, and expand the TRMM platform into new opportunities. Engaging the regulators to gain clarity on our plans to move our cardiometabolic candidates into pivotal... and maybe even have a breakthrough or two. We've had equally ambitious plans in the past, and we think we have a pretty good track record of meeting or exceeding those expectations.

Just use a pivotal studies and maybe even hampering through June to discuss.

We've had equally ambitious plans and asked we think we have a pretty good track record a meeting or exceeding those expectations.

And again for joining us today, Oh now like to open a call your questions operator.

[laughter] actually reminder inch T. ask questions, he really depressed Taiwan on your time or something.

So they try your question <unk>.

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Yeah first question comes from the line, where you May cross.

Line is how often.

Hi, everyone. Thanks for taking my question and just want an adequate congratulated Bruce investment shows the next steps in retirement.

Christopher R. Anzalone: Thanks again for joining us today. I would now like to open the call to your questions. Yes, sir. As a reminder to ask questions, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Maurice Raycroft. Your line is now open. Hi everyone. Thanks for taking my questions. And I just wanted to add a quick congratulations to Bruce and best wishes and next steps in retirement. For AAP, you mentioned you don't expect to see histological changes at six months. I'm just wondering if that's based on preclinical data, modeling estimates, or something else.

For a T.V. you mentioned you don't expect to see it's a logical changes that six months I'm. Just wondering if that's based on preclinical data modeling estimates or something else.

Yeah sure so.

Oh sure why not the thing that we've been doing is looking at all the practical data. This is a huge opportunity for translation go development. So what a linear lot above that whenever they to measure, but <unk> <unk> <unk> <unk> the amount of one of us and putting them.

<unk> focus on those too, but I'm not too is the L.D.A. possible response say that you know look at other D.C.C. that maybe he see you've only known to see if anything unless you can change it but <unk> around five noticed he may take longer.

unknown: Sure. So, Bo, one of the things that we've been doing is looking at all the preclinical data, and this is a huge opportunity for translational drug development. So we're learning a lot about that, and what I would say are the two major parameters that we aim to see results for earlier: one is the amount of monomers and polymers, and second, inflammation. So we're focused on those two parameters at the earliest possible response rate. But as you know, looking at other diseases that may behave similarly, in order to see definitive histological changes, particularly around fibrosis, it might take longer. This initial biopsy that we may present later this year was only six-month treatment for the first four patients in cohort one in study 2002.

You sound biopsies, though we hopefully made this n. later this year only see Smith feeding and for the first four bases from coal one study 2000 and too.

Yeah and for you you mentioned the inflammation are there are you going to be looking at specific inflammatory biomarker data and also for this serum Biomarkers do you plan on reporting those and or I guess can you remind what kind of <unk> biomarkers, you're going to report on.

And do you expect those to correlate to deliver data.

So so they keep <unk> eight A.T. of course. These didn't you send an <unk>. We one of these close that late though when we have is so that's number one inflammation what are working on the US we speak we were trying to be finding ways to quantify summation.

unknown: And for, um...

unknown: You mentioned inflammation. Are you gonna be looking at specific inflammatory biomarker data? And also, for the serum biomarkers, do you plan on reporting those? And, or can you remind me what kind of serum biomarkers you're going to report on? And do you expect those to correlate to the liver data?

In the way that we can barely they <unk>.

Approach to to compare the baseline to endpoint and compare between three men group. So this is working progress and what I can tell you. If that were were planning to go to the F.D.A., we know what but both opposed to the family endpoint that would be Mandy focus as I said.

unknown: Sure, so the key serum biomarker is AAT, of course; it's the mutant and total protein, and we're working on that. We are going to disclose that data when we have it, so that's number one. And with regard to inflammation, we're working on that. As we speak, we're trying to define a way to quantify inflammation in a way that we can validate that and be a reliable indicator. So a number of things are going into that. I can go into a lot more detail now. But as I said, later in the year, we will disclose more specifics around the inflammation component of this core system that will be used as the primary endpoint.

Protein accumulation and inflammation, so and number of the instead of going into that I kind of going to a lot more detain of as I said they didn't they yeah, we will disclose more specific sat around the inflammation component of fiscal system that will be use but I money and.

Got it that's very helpful and I may have missed this but for the updated development plans per industry in April see three can you say if these updates are are based on preliminary feedback from F.D.A.

<unk> going to the F.D.A. or sending D.F.D.A. briefing document for eight to see you in about three weeks to a month from now we're really request. The meeting wasn't it have any international would name I know your face to face meetings, but it would be see that it call or we can discussion within.

So that if we decided to hate to see <unk> ancient <unk> going to go to the F.D.A.F. gross I mean, although September of D.C.S. <unk> Roach piece already mentioned it to the since last week April C. one going.

unknown: Got it. That's very helpful. And I may have missed this, but for the updated development plans for ANG3 and APOC3, can you say if these updates are based on preliminary feedback from FDA?

No with the C.I.M.D. proposed seen it face to three study we'd be out of <unk> too.

unknown: We're going to the FDA or sending the FDA briefing document for ApoC in about three weeks to a month from now. We're going to request a meeting. We're going to have an interaction with them. It might not be a face-to-face meeting, but it would be either a call or a written discussion with them.

She patient study and then seeing population we'd age you know are going to propose to face to be studied to be find the those there's no space you men and be able to study design for the sign out.

I was going to evaluate that'd be less the outcomes.

unknown: So that is with regard to ApoC. For H, we're going to go to the FDA in approximately August and September of this year with a similar approach. Chris already mentioned the two different plans. With ApoC, we're going now with a pre-IND proposing a phase 2, 3 study with the objective to have a registration study in the MCM population. With H, as you know, we're going to propose a phase 2B study to define the dose, the dose regimen, and the overall study design for a final clinical outcome study or cardiovascular outcome study. So both interactions this year, about two months apart.

<unk> about two months.

Got it that's helpful. In as you're preparing was breaking documents you have any initial thoughts on the trial sizes. It in time wines or any other details in trials or you can provide.

Yeah. So for April see we think of it's going to read that first study about C. conversation you know, we don't need to have the patience asked me to show it <unk> I guess it actually have all by any face, but we want us to unless they study you could have sufficient safety data fast so the.

Agency will be hopefully okay with this one face to face to study for these first indication.

unknown: Got it. That's helpful. And as you're preparing those briefing documents, do you have any initial thoughts on the...

For <unk>, we see needs to see like South Korea's looking at the study more than one regimen and definitely more than one both level you know see waiting for the final state that from the current study you know that could be find that the size you buy it you know a face to be study.

unknown: and Timelines, or any other details of the trials that you can provide.

unknown: Yeah, so for ApoC, we think it's going to be the first study with about 300 patients. You know, we don't need 300 patients actually to show a statistically significant difference in progression actually evolving by any stretch. But we wanted to enlarge the study to have a sufficient safety data set, so the agency will hopefully be okay with this one phase two, phase three study for this first indication. For H, you know, it's a Phase IIb study; we still need to figure out exactly if we're going to have to study more than one regimen and definitely more than one dose level. We're still waiting for the final data from the current study in order to define that precisely, but, you know, a Phase IIb study is going to be in that same range, as I said for H.

In that same dangerous I said for the L.C.D.

Great. Okay. Thank you very much and I'll <unk>.

<unk>.

Okay next question <unk> no. Thanks.

Great. Thank you very much because it's hard <unk> well.

One of the current color sense for what could be Mac ducks.

In terms of eight per C., you know it says something where you really do you think you could move rapidly to a pivotal study for.

unknown: Great. Okay. Thank you very much. And I'll go back in the queue. Your next question is from the line of Ted Tenthoff.

<unk> patients, so I think kind of balance sort of the development plans between.

More targeted orphan diseases was higher Kurt levels for says broader population. Thanks, so much.

unknown: Your line is now open. Great. Thank you very much, guys. And thanks for taking the time to update us. I'm glad everyone's doing well. I wanted to kind of get a sense for what the next steps could be. In terms of APOC, you know, is this something where you really do think you could move rapidly to a pivotal study for, you know, targeted patients? And how do you kind of balance the development plans between more targeted orphan diseases with higher trig levels versus a broader population?

Well, that's a great question, what I can say what are working on that right. Now I think we had a good case because they go to keep men for these <unk> you fleets of it used to be useful function <unk>, which says you know he said.

unknown: Thanks so much.

Condition and yet they're facing in that way very similar F.T.A. population very <unk> and those patients so that N.C.N. and <unk> also have very significantly.

So some of those facing have various seem levels of of two guys today's levels. So well working together with the agencies to be fine well if that life patient population that will benefit from this intervention that again they go to fade happy if they do use the research <unk>. So what what are they find it population that it's <unk>.

unknown: Well, that's a great question, and what I can say is we're working on that right now. I think we have a good case because the goal of treatment for this patient is really to reduce the risk of pancreatitis, which as you know, is a very severe condition, and yes, the patient in the rare, very severe FCS population had a very high risk of pancreatitis, but those patients that are MCM and have past history of pancreatitis also have a very significant risk. Also, some of those patients have very extreme levels of triglycerides. So we're working together with the agency to define the right patient population that will benefit from this intervention. And again, the goal of treatment is to reduce the risk of pancreatitis. So we're going to define a population that is at risk of that condition.

Legion, but but your point.

Question.

There's a lot of things that are really interesting about this drunk to.

<unk>, Yeah, <unk> appears to be very important drunk candidate and I'm talking about it.

We were seen allergist single knows 50 milligrams per c., 95% reduction triglycerides hypertriglyceridemia patients.

That is truly just coming to us and so that's that's all that's seconds you know, we really like the the Optionality illness. You know there is very is an orphan population within these M.C.M. stations aren't working population, but it's not an altar or when you have 30000 patients that they're they have.

unknown: But to your point, though Ted, and I appreciate that question, there are a lot of things that are really interesting about this drug candidate for us.

unknown: [inaudible]

<unk> and in our in our you know relatively expensive jewelry health care systems.

unknown: Factor one is that it appears to be a very potent drug candidate. As we talked about in the data, we saw after just a single dose of 50 milligrams, we saw a 95% reduction in triglycerides in hypertriglyceride patients.

We can do a lot of good for them. We think that's that's a relatively short criminals studying maybe relatively small as well, but beyond that I think as work as we're treating huh and as we are we are we are increasing our data set but we can always you know decide to do a follow on studying in in much larger populations.

unknown: That is truly just stunning to us. And so that's helpful. But second, we really like the optionality of this. There is an orphan population within, these MCM patients are an orphan population, but it's not an ultra-orphan. You have 30,000 patients that have severely impaired quality of life and are relatively expensive to the healthcare system. We think we can do a lot of good for them.

You know, we we we we're pretty confident that the elevator I must rise or in Indiana risk factor and the back and we can't really wax reckless arrives you know when able to see three you know we think is a is a pretty powerful tool. So so you know while we are focusing on M.C.M. in the near term look I wouldn't be surprised if we if we if we do.

unknown: We think that's a relatively short, pivotal study, maybe relatively small as well. But look, beyond that, I think as we're treating them and as we are increasing our data set, we can always decide to do a follow-on study in much larger populations. We're pretty confident that elevated triglycerides are an independent risk factor, and the fact that we can really whack triglycerides with ApoC3, we think is a pretty powerful tool. And so while we are focused on MCM in the near term, look, I wouldn't be surprised if we do follow up longer studies to expand that a bit.

Follow on longer settings, you to expand that.

Okay. So I finally definitely come up you know Oh, sorry.

To the to the company and one thing that it really impressive allowed Dave when you look at the April see study they say number of different population from <unk> all the way sufficient we say there <unk> and the money so that <unk> and then this phone slate if I'm with the same so you don't see that.

A very frequently and so that I think supported the idea that weekend from populations of population because the underlying problem with the same.

unknown: Tracie, if I may ask you a question. So, I'm a newcomer, you know, to the... Oh, sorry, to the company.

<unk> salsa vacancy.

That's crazy and one of the real quick follow up you know we've seen certainly the potent see <unk> then well you know not looking to <unk> have you guys consider developing a priority has the <unk>.

unknown: And one thing that is really impressive about this, when you look at the ApoC study, there are a number of different populations, from normal all the way to patients with severe hypertriglyceridinia, and the magnitude of the treatment effect is consistent. And the response rate... 100%. So you don't see that very, very frequently. And so I think that supports the idea that we can expand from population to population because the underlying problem is the same. And the magnitude of the three-minute period is also very consistent.

Sars Coby too these are partnership for what's the government or anything or girls harks Craig's too much.

Yeah, well, we have an action program that we discussed <unk> against against the the the current novel current virus as well potentially you know future current virus outbreaks. We think we have a real real and player. You know eight we we think we are we are <unk> anti viral.

unknown: That's great. And one real quick follow-up. You know, we've certainly seen the potency of siRNA as an antiviral mechanism. And well, you know, I'm not looking to jump on the bandwagon here. Have you guys considered developing siRNAs against SARS-CoV-2, either in partnership or with the government or anything along those lines? Thanks so much.

Got a lot of experience when H.P.V. I think we revolutionized that field with way and we were treating it a second look we've been working on online delivery for for several years now it's taken an awful lot of work but.

Part of my time, there so no I expect it and then we'll have something that should be active and and well tolerated that could give us a longer ability of of action and so we're excited about the program. It's it's ongoing.

unknown: We have an active program that we discuss against the current novel coronavirus, as well as potentially future coronavirus outbreaks. We think that we have a real role to play here. A. We think that we are the best in the field, in the RNAI field, for antivirals. I've got a lot of good experience with HPV. I think we have revolutionized that field with the way that we... Second, look, we've been working on lung delivery for several years. It's taken an awful lot of work, but we are now in a new lifetime. I expect that we'll have something that should be active and well tolerated that could give us a long durability of action, so we're excited about the program it's ongoing, and so you know, we expect to have more to tell you about that you know throughout the Great. Excellent.

And so you know we expect to have more Italian not only you know throughout the year.

Great.

Thanks, so much for her time in a stick tape say well.

Thanks.

Your next question <unk> money for a higher Caroline how often.

Good afternoon, everyone. This is Eric on the line for money Congrats on all the progress.

Of course, I wanted to discuss a that your neck program. So.

You compare this to the phase on trials <unk>, three and an arrow here for three.

Oh, you were able to assess target knocked down in healthy volunteers in their studies given that you know those are proteins that are expressing this year.

unknown: Thanks so much.

unknown: for the time, and...

unknown: Stay safe, stay well.

Will there be an opportunity or anything analogous to they spoke into their clinical studies at the next season cage target engagement <unk> and the healthy volunteers for is the first read out of potential ethics, you can it'd be the F.T.V. read out same cystic fibrosis paychecks.

unknown: Your next question is from the line of Mani Foroohar. Your line is now open. Good afternoon, everyone. This is Rick on the line for Mani.

unknown: Congratulations on all the progress. First, I wanted to discuss the ENAC program. So if you compare this to the phase one trials of Arrow ANG3 and Arrow APO3, you were able to assess target knockdown in healthy volunteers in those studies, given that those are proteins that are expressed in the serum. Will there be an opportunity or anything analogous to this built into the clinical studies of ENAC so you can gauge target engagement in healthy volunteers? Or is the first readout of potential efficacy going to be FEV readouts in Cystic Fibrosis patients?

Yeah. So for <unk>. So so dances I play soon is no what are going to have in the same style the patient with 65 <unk>.

Slides, so we'd have a sizable Saudi I was hoping to all these studies that up to the.

And you see down in South Korea sounds on Hong Kong.

So so that the third part of the question I didn't get to <unk>.

Alright. Thanks.

unknown: Yeah, so for aero ENAG, we're not going to look at that in normal healthy volunteers, so the answer to that question is no, but we're going to have, in this same study, a patient with cystic fibrosis, and we're measuring pharmacodynamic parameters, F1, quality of life. So we have a sizable study, and we hope to enroll this study relatively quickly.

I did have a follow up question so it sounds like for.

Darwin's theory program easier gonna be conducting a safe to trial. In addition to a larger cardiovascular outcome studies. So can you couldn't make sure you're most current thoughts on potentially partner English has said first developing it alone and if that is something that's on the table at what stage of development would it make sense to start looking for a partner.

unknown: but seeing who are doing this in New Zealand, South Korea, for example, and Hong Kong. So that's the first part of the question. I didn't understand the second one.

Yeah. So so here's what we think about all the nearest about both Errol able to see Threem, an arrow and three we just think those are those are really exciting targets and we see we have really good drug candidates against both of them.

unknown: All right, thanks. But I did have a follow-up question. So it sounds like for The Arrowhands free program, you're going to be conducting a phase two trial in addition to a larger cardiovascular outcome study. So could you maybe share your most current thoughts on potentially partnering this asset versus developing it alone? And if that is something that's on the table, at what stage of development would it make sense to start looking for a partner?

The first one second point is well Capitalised now and and we can we can certainly for it to you know do to push those programs you know deep in the clinic and so so look you know we will we're happy to talk to people, but there's not forcing function at least right now for us to to jump into a partnership if the right one should.

unknown: Yeah, so here's what we think about both Arrowhead with C3 and Arrowhead. We just think those are really exciting targets, and we think we have really good drug candidates against both of them. First point. The second point is that we're well capitalized now. We can certainly afford it. And so, look, we're happy to talk to people. But there's not a forcing function, at least right now, for us to jump into a partnership.

Should present itself, we're happy to talk but we're also happy to what's going on right now.

And these assets are just too valuable I think you know to to to junk enjoy partnership is not quite right.

Oh, great. Thanks for taking our questions.

Thank you.

Your next question as friends to line up I.D.T.A. Your line of some open.

Hey, guys. Thanks for taking my question and have you guys are doing well what on the West Coast. A couple of for me. One I mean, you guys tend to have a problem number britches, which as many pipeline item, but I just wonder in light of what's going on with like all the variables kind of clinical trial delayed <unk> does this change your prioritization of your.

unknown: If the right one should apply, well, great. Thanks for taking our questions. Yeah, thanks. Your next question is from the line of Alethea Young. Your line is now open. Hey guys, thanks for taking my questions and I hope you guys are doing well.

Fine anyway. The second question, when you're thinking about A.T. and the by update it sounded like you were quite competent around the summer is there are spectral grace period, perhaps the timeline to where to slip or anything that would come to be kind of buffer at that point in the third point as I'm just curious about hearing about more your competence around.

You know going after P.L.P.D. and light up what you are seeing with Enac or maybe not just I just kind of why discuss another <unk> kind of increase confidence in the long pardon me have there that's emerging thanks.

unknown: I have a problem of britches, which is many pipeline items. And I just wonder, in light of what's going on with all the variable clinical trial delays and adjustments, does this change your prioritization of your pipeline anyway? The second question is, when you think about AAT and the biopsies, it sounded like you were quite confident around the summer. Is there a potential grace period, perhaps, if timelines were to

Okay. So let's see might get at all so first with respect to has cast coded cause has to read prioritize our our.

Hi, bite the answer yeah. Finally, it'd be the answer is no <unk> as point you know we have not seen any.

unknown: or anything that would kind of be kind of buffered.

unknown: The third point is I'm just curious about hearing about more of your confidence around.

Any impact on coming in really drastically and second of our time aim or timeline, you're not affected all of our time line to you know too too you know to it to some extent, but generally do not not in material ways, we don't think and so.

unknown: COPD

unknown: www.youtube.com.au Okay, so let's see if I can get it all. So first, with respect to whether COVID has caused us to reprioritize our, The answer is no at this point. We have not seen any effect on COVID that has really drastically affected any of our timelines. It has affected all of our timelines to some extent, but generally not in material ways we don't think.

We were still business as usual at least right now pushing them all forward. The one thing I guess it has done is is it has opened up a new opportunity for us to be totally honest, maybe we should've been thinking about this you know in December or November last year, but we just weren't just had opened up an opportunity to go after corona viruses.

Is more broadly and a novel current virus across coven 19, specifically when things that we've gotten a lot to offer there got good experience long got good experience in Antivirals you know when when we started out we were we we were excited to be part of that fight on so.

unknown: And so it's still business as usual, at least right now, pushing them all forward. The one thing I guess it has done is it has opened up a new opportunity for us, to be totally honest, and maybe we should have been thinking about this in December or November of last year, but we just weren't. This has opened up an opportunity to go after coronaviruses more broadly and the novel coronavirus that causes COVID-19 specifically. We think that we've got a lot to offer.

And adding some some work to you know to our our our Nonclinical teams, but look at one is is is on board with this and so so that's not slowed down the other the other programs. So so there's a long way of saying no <unk> not reprioritized anymore pipeline second.

You mentioned H.C. laughs. These you know in the in the summer and and you know could you know could be.

unknown: We've got good experience in lung cancer, and we've got good experience in antivirals. When we started that, we were excited to be part of that fight, and so that has added some work to our non-clinical teams, but look, everyone is on board with this, and so that has not slowed down the other. So it's a long way of saying no, COVID has not reprioritized any of our pipelines. Second, you mentioned AAT biopsies in the summer, and could that timeline slip? The answer is sure it could. We feel pretty good about it, though. That cohort is fully enrolled, and they are due for biopsies, I think, in the August or so timeframe. Look, it is possible that one or two of them may be delayed a little bit.

Couldn't a timeline slip an answer is true good when you are pretty good about the look of you know we that that <unk>. They are due for a biopsy into I think in the longest or so timeframe. You know it is possible that that this one or two of them you know maybe delayed a little bit I joined.

And it's possible, but what's here, what's great about <unk>, frankly overthrows isn't it.

And then if somebody came in a week or two or three weeks later or even more I don't think it really affects our data because because it's not like we would expect a big drop off and you can activities. You know just wrong I expect I expect many months, maybe six months activity. After one <unk>. So so we we don't expect.

Expressed any problem, there and and again if you if there are some minor problems, we don't expect it to to to change the integrity of the of the data and look I think <unk>. These are important then no one's ever seen what the liberal looks like after after you know some period of reducing production of A.T. I think it's I think it's important and.

unknown: I don't expect that, but it's possible. But what's great about this drug and, frankly, all of our drugs is that the durability is such that if somebody came in a week or two or three weeks later or even more, I don't think it really affects our data because it's not like we would expect a big drop-off in activity. With this drug, I expect many months, maybe six months of activity after one dose

I think that we don't want more exciting to see what the models language <unk> when information looks like I understand at my prepared remarks, I think this underlines you're not only are are substantial lead in this in this space, but also our position as a thought leader in the field in third you meant.

unknown: So we don't expect any problem there. And again, if there are some minor problems, we don't expect them to change the integrity of the data. And look, I think these are important data. No one's ever seen what the liver looks like after some period of reducing the production of AAT.

<unk> <unk>.

Give us confidence can into this new program Arrow long too.

I think one and this is this look our our our nonclinical data with the with upon our platform have been had been quite good and it's not good in one or two animals, but it's been good in Rhode model nonhuman primate models and shoot models and so.

unknown: I think it's important, and I think that we're excited to see what the monomer looks like, what the polymer looks like, and we're excited to see what inflammation looks like. And, as I said in my prepared remarks, I think this underlines not only our substantial lead in this space but also our position as a thought leader in the field. So a couple of things give us confidence in this new program, Arrow 1-2. Thing one is that, look, our non-clinical data with the pulmonary platform have been quite good. And it's not good in one or two animals, but it's been good in rodent models, in non-human primate models, and in sheep models.

Wasn't like we just started this a year ago. It is something we'd been working on for quite some time and we think we we think we think we're there and second you do look as I mentioned that very mark the longest is interesting because it's a target rich environment. There's there's a lot of good validated gene targets to go after and also applies to C.O.P.D. So.

You know we feel like the biology is is in our favor here in our in our our data are quite good use the word look we're excited about that you know we think this is a big year for pulmonary which set up before that we think the pulmonary franchise is a big Valiant driver for us going forward and and we are taking the first steps now and really blowing out that franchise I think.

unknown: And so it wasn't like we just started this a year ago. This is something we've been working on for quite some time, and we think we're there. And second, look, as I mentioned in the prepared remarks, the lung is interesting because it's a target-rich environment. There are a lot of good, validated gene targets to go after, and that also applies to COPD. So we feel like the biology is in our favor here, and our data are quite good too. So look, we're excited about that. We think this is a big year for Pulse. We've said it before that the Pulse franchise is a big value driver for us going forward, and we are taking the first steps now in really blowing out that franchise, I think.

Oh, Thank you very much.

Sure that can we get.

<unk>.

Thanks for taking my questions in a great to have Javier incurred on the call and then we should be efforts navigating the kind of environment Yep, just quit quit follow up on the.

To sort of what we have heard from you before maybe could you just go all out or the the book enough scenarios that you think and I've been assuming this is still the list deliver that that'd be a working rather than the open or they would study and and that is the optionality to go higher under those lives with the with the along with them study. So could you just.

unknown: Thank you very much.

unknown: Your next question is from the line of Mayank Mamtani. Your line is now open.

Layout, what what do you expect to see that in the different outcomes.

unknown: Thanks for taking my questions, and it's great to have Javier and Kurt on the call, and I appreciate the effort in navigating the current environment. Just a quick follow-up on the AAD relative to sort of what we've heard from you before. Maybe you could just call out the bookend of scenarios that you think, and again, assuming this is still the lowest dose that you're working with in the open-label study and there is the optionality to go higher on the doses with the longer-term study, could you just lay out what you expect to see in the different outcomes?

<unk> just to understand so you're asking what we expect to see in the in a six month biopsy data for the open. They will study yeah. Just a book enough to know is the expectation because obviously the <unk> you have to see them protein data and then you have the the biopsy data, but I I was.

Just curious like <unk> instead of Lord <unk> studying right and you have the option to go to hide your setting in <unk>. So this could you just lay out how you'd think about being back to the Big Garden study.

Yeah.

So I'll I'll leave that out here, but but just to clarify so they open able study is not doing desolation studying.

unknown: Sorry, so Mayank, just so I understand you're asking what we expect to see in the six-month biopsy data for the open-label study.

All the patients are receiving 200 milligrams a doses.

unknown: Yeah, just the bookend of scenarios, the expectation, because obviously you have the serum protein data and then you have the biopsy data, but I was just curious, like, it's still a lower dose you're studying, right, and you have the option to go to a higher, you're studying in parallel a higher dose, so just, could you just lay out how you think about the impact of the broader study?

Yeah. So what have you seen could happen before that what we're doing as you probably know is the 2001 study the basic potential recitation study to pause just thought hey, you say, one way or whatever 15, C.D.'s and doses first tendency station. The you know stuff by with evaluating the P.D. they spawn.

And safety and the D.S.N.D. will have to say the right those to the rest of this study will be and grow when we get for the five d., which would be will I would call. The safety of the vegetation parts of the study that we'd go along we chest.

unknown: Yeah, so I'll leave that, Javier, but just to clarify, the open-label study is not a dose escalation study. All the patients are receiving 200 milligram doses.

unknown: Yes, so we're not using 2002 for that. What we're doing, as you probably know, is the 2001 study, the potential registration study, has two parts. Part A is the one where we're assessing three different doses in the first 36 patients. At the end of that part, we're evaluating the PD response and safety, and the DSMB will help to select the right dose, so the rest of the study will be enrolled, and when we get to Part B, which will be what I would call the phase three of the registration part of that study, that will go on with just the decided or the But, you know, based on the phase one study, you know...

Decided or that'd be fine fine outdoors, but you know based on the face. One study you know all of those to cut it very profound supervision of A.T.. So I'm really interesting to see how a whole see those is from the 2001 study will look like <unk> again the enough those first 76.

And we're going to look at the data and made the call to continue on the final say 352001 study.

In mind, the the data that we're talking about a report in public just from the over labels study, we we won't be recording any of the pivotal study data probably until it's complete.

I understood and then on I see open I did see patients how many <unk> patients and and <unk> just no I just would not be what is a medium follow up you'd have a in the in the next update you may have.

unknown: All doses have a very profound suppression of AAT, so I'm really interested to see how all three doses from the 2001 study will look. But again, at the end of those first 36 patients, we're going to look at the data and make the call to continue on the final phase three part of the 2001 study.

Did now facing about eight patients approximately.

One or two.

unknown: And Mike, the data that we're talking about, reporting publicly, or just from the Open Label Study, we won't be reporting any of the Pivotal Study data publicly until it's

By when we're gonna have that data over here. The you know see she has you know that that's I think I'd say he population were also on top of the <unk> profile wasn't M.I.

unknown: Understandable. And then on ANS3, of the 93 patients, how many are NAFLD patients? And not just for NAFLD, what is the median follow-up you'd have in the next update you may have? I did now have about eight patients, approximately, give or take one or two.

The the data maybe I'd be able to yeah, yeah, maybe he'll wine.

Okay. So so as we owned a mixed in the B.B.S. study would go only focus on the <unk> the metabolic syndrome disease that right that they used to be study [noise].

Yeah.

The well, we're thinking about for the for the phase to be starting next year and again this meal a thousand County US you know nothing you can we just we have not discuss this would be up here, yet, but we're thinking of.

unknown: By when we're gonna have the data, probably at the end of this year. You know, in that particular patient population, we're also on top of the metabolic profile while doing MRI. Okay, so assume the mixed lipidemia study would only focus on the lipid part of the metabolic syndrome disease. Is that right? The phase two study?

Is is the <unk>, we're not we're we're not right now contemplating you know more metabolic syndrome or.

Type patients you know just because we we don't have we don't have insulin sensitivity dating yet and we don't have never about dating yet that's still a little bit up in the air what we do know isn't isn't it pissed drunk as a great job of producing triglycerides and does a great job producing the L.D.L. in a non you'll be able to stop immediately fashion. So we're running with that anything else can be greedy, but.

unknown: Yeah so the what we're thinking about for the for the phase 2b study next year and again there's you know a thousand caveats you know nothing which is we have not discussed this with the FDA yet but what we're thinking of you know is is is the mixed dyslipidemia we're not we're not right now contemplating you know more metabolic syndrome type patients you know just because look we don't have we don't have insulin sensitivity data yet we don't have liver fat data yet that's still a little bit up in the air what we do know is that

But but that's published for right now.

Like it without no palatial something we haven't seen it of course.

Create a big hit the gratification <unk>, if do I would go program understand either Oh, the see <unk> may not be as in fact, it just curious India guiding square the update by the end of the as proof of concept what what do you expect in terms of number.

<unk> <unk> <unk>, maybe you.

You could have then.

Yeah, Yeah, when am I speculate on now because because you know it's it's just to just a bit early right. You know we only have one side open we haven't dose patients yet so so give us some time to start enrolling patients and see how this has this goes you know I think but and let me just be clear I'm on on on the on the proof of concept do you mention I think that we're going to know.

unknown: Likely to die from ovulation, but some of them will have. Great, appreciate the clarification. And last question on the HIF-2 Alpha program. I understand these are obviously cancer patients, so enrollment may not be as impacted. Just curious in your guidance for the update by the end of the year as proof of concept, what do you expect in terms of the number of patients or median follow-up you could have then?

This is working at least internally by the enemy or will we have enough data you know bye bye key abstract headlines just submit an abstract then presented to present these probably I don't know yet.

I can certainly be tight and it's and and who knows what's going to happen with without controversy anyway. So so we feel good about where we are now it's been a bit slower than we expected because co. It has has slowed our our opening them sites, but but you know I expect them to start joking patients as quarter and then we'll see how this guy.

unknown: Yeah we don't want to speculate on that now because because you know it's just it's just a bit early right you know we only have one site open we haven't dosed patients yet so so give us some time to start enrolling patients and see how this as this goes you know I think that and let me just be clear on the proof of concept you mentioned I think that we're going to know if this is working at least internally by the end of the year will we have enough data you know by by key abstract deadlines to submit an abstract and then present it to present these probably I don't know yet you know that that could certainly be tight and it's and and who knows what's going to happen with with those conferences anyway so so look we feel good about where we are now it's been a bit slower than we expected because COVID has has slowed our our opening of sites but but you know I expect we'll start dosing patients this quarter and then we'll see how this goes

<unk>.

Just.

Escalation, but it was as you are looking at that if that is disclosed yeah.

Nine and 13 need for T. weekly I.V.

<unk>.

Oh well.

This is <unk>, it's too late yeah, yeah, Yeah, B. nine and 13 me repeat what else we P.I.D.

Right.

Thank you I appreciate your taking my questions with.

Sure.

Your next question as far as a line not <unk> Kumar your line of some okay.

unknown: Can you remind us of the dose escalation, the doses you are looking at, if that is disclosed? Three, nine, and 13 meet per key weekly single-dose.

Then drinking or questions. So curious about the Inco's T. three program. They focus on multiple multi factorial column I couldn't you need a syndrome, how does like targeting that population that affect the kind of <unk> you might look at so obviously, there's evidence that multifactorial <unk> syndrome has a lower pancreatitis incidence.

unknown: .. .. .. Week.

unknown: Yeah, yeah, it's three, nine, and...

unknown: and 13 Meat per Kilograms Weekly Ideas. Thank you. I appreciate you taking the time to answer my questions.

I can't take besides incident, but have C.S.

Has a higher incidence of cardiovascular complication. So you plan to look at both ends then coins or or how do you think about that.

unknown: Your next question is from the line of Madhu Kumar. Your line is now open. Thanks for taking our questions. So curious about the APOC3 program, the focus on multifactorial chylomicronemia syndrome. How does targeting that population affect the kind of endpoints you might look at? So obviously, there's evidence that multifactorial chylomicronemia syndrome has lower pancreatitis.

Well so that's a great question now we've been thinking about that quite a bit well that would say if the number one study it would be looking at cause accidents level, we want to have that some decision with the agency <unk>. This is not gonna be there are still that food to three.

<unk>, we've about 500 meet again, so basically the without specifically teeny got outcome us and and.

unknown: Incidents, acute pancreatitis incidents, and FCS.

Yes. They go look that up you will be two reviews, Oh, good that'd be waist and at least <unk> you have people, we've very highly some very high.

unknown: That has a higher incidence of cardiovascular complications. So do you plan to look at both as endpoints, or how do you think about that?

unknown: Well, so that's a great question, and we've been thinking about that quite a bit. What I would say is the number one study, it would be looking at triglycerides levels. And we want to have that conversation with the agency that is precedent for that. This is not going to be the first drug approved to treat patients with about 500 milligrams per deciliter without a specifically clinical outcome as an endpoint. Yes, the goal of therapy will be to reduce pancreatitis risk, and the risk of pancreatitis in this population varies. You have people with very high risk and very high triglycerides levels, and you have people with lower risk. So we're working on the study design because we do want to select a population that wouldn't be an excessive risk compared with the average high proliferative sterility patients to be part of the study.

Today Siverling cut people know what race. So why working on this study decided to go and do what's the latest population that wouldn't be an excess ways compared with the avatars hype. It up into said he didn't he patients to be buzzer system. So this is any input then discussion that we've had that that would be F.D.A.. What what happens easily then the next couple of month.

And so we'll see how it goes of course in the future I think April C. has a huge for Finnish helpful. Because you're black lab and something that I think we need to think about it I don't know cause she wanted to.

No I think if <unk> if it's on 2021, you would think of it as as and likely voters in the on the M.C.M. violation and then going for it we can be considered brought in that at some point, we'll see.

unknown: So this is an important discussion that we have to have with the FDA, and we're going to do this within the next couple of months. And so we'll see how it goes. But of course, in the future, I think ApoC has huge potential for cardiovascular outcomes and something that I think we need to think about it, and I don't know, Chris, you want to... call. Yeah.

Okay, and then pouring M.C.M. trial would you <unk> <unk> medications or would you allow them to going to stay on can copy medications in parallel.

Oh with allows us pay income coming on medication that they thought we happen to faceless studying those pages why would come comes on medication. It just seems ridiculous you kind of the of the defense. So I see we we we probably enough where I live medication those deep level that'd be and any other theme for the D.C.P., then yet and they will they will remain on it.

unknown: Yep, I think that's good. For 2021, you know, think of this as life, and then going forward. Okay, and then for an MCM trial, would you restrict other concomitant triglyceride-lowering medications? Or would you allow them to kind of stay on them in parallel?

Okay, then that'd be back he Lincoln several times and they prepared remarks, P.D. finds inappropriate venue. So totally push comes to Szubin kinda, there's a prolonged darts medical conferences for presenting just kind of assemblage of clinical data you guys are building over this year What'd you plan to kind of do something internally or.

unknown: Oh, we will allow them to stay on concomitant medication. The data we have from the phase 1 study in those phases while we're in concomitant medication is extremely good. You can't tell the difference, so I think we will probably allow for other medications that people are studying, so any other thing for this epidemic, they will remain on.

<unk>.

Yeah. Thanks for asking the question. So so yes, we are low we're we're committed to pushing based out when we can you know as as you know <unk>. We've been really good I think at at at not press release in data generally, but but but presented at appropriate conferences. We used the got the right way to go and so that's obviously our preference.

unknown: Okay, then stepping back, you've mentioned several times in the prepared remarks the idea of finding an appropriate venue. So, kind of like if push comes to shove, and there's a prolonged drought of medical conferences for presenting this kind of assemblage of clinical data you guys are building over this year, would you plan to kind of do something internally? Or how are you envisioning it?

You know shouldn't this should these companies continue to be disruptive and we will find other ways to do it in that can be via Pressrelease via the web in R. You know what have you I'll give me a young an example, though you were were still submitting abstract course in fact, we have we have approval. We can ask that's improved from both and you must be three and H.P.T.L. three at.

unknown: Yeah, thanks for asking that question. So yes, we are, look, we're committed to pushing data out when we can. As you know, Madhu, we've been really good, I think, at not press-releasing data generally but presenting it at appropriate conferences. We think that's the right way to go. And so that's obviously our preference. Should these conferences continue to be disrupted, then we will find other ways, the webinar, what have you. I'll give you an example, though.

Yeah, and and it had an apple than the National Women's Association a conference forget forget both those as well as a European.

Decided cardiology.

Okay, Great thing pretty much.

Thank you.

Once again to ask questions. He really depressed fire one on your thumb.

Mm.

[noise] Yeah next question as from the line <unk>, let's see see in day care line itself and.

unknown: We're still submitting abstracts, of course. In fact, we have abstracts approved for both APOC3 and HPTL3 for the National Lipid Association conference for both those as well as the European Society of Cardiology. Okay, great, thank you very much. Thank you. Once again, to ask a question, you will need to press star 1 on your telephone.

A good afternoon guys in thank you so much for taking my question.

To grad southern exciting quarter I was curious about your new facility in San Diego.

When do you expect it to be fully staffed and running a will focus on a specific areas developments such as pulmonary in what benefit or advantage are you looking at 16 with it for example will help increase the number of drugs to click on a yearly basis.

unknown: Your next question is from the line of Robert Tuksisi, and your line is now open. Good afternoon, guys. Thank you so much for taking my question. Congratulations on an exciting quarter.

Of course, you run 100 times, so certainly the I mean, it's not.

Of course, if we had chosen our timing it's unfortunate in terms of the current environment, but we are staffing in today.

unknown: I was curious about your new facility in San Diego. When do you expect it to be fully staffed and running? Will it focus on a specific area of development such as pulmonary? And what benefit or advantage are you looking to gain with it? For example, will it help increase the number of drugs to clinic on a yearly basis? Certainly not.

We're we're in the early stages of filling the facility up and really the intention theirs is yes to increase our capacity and or drug pipeline ultimately and it also to tap into scientific expertise in in California about from California, biotech. So there's a lot of.

Skills, such that we're looking for to increase both our throughput and our sophistication in terms of the.

Some of the newer programs that we have under way.

unknown: Of course, if we had chosen our timing, it's unfortunate in terms of the current environment, but we are staffed, and we're in the early stages of filling the facility out. Really, the intention there is, yes, to increase our capacity and the Drug Pipeline, Ultimate and also to tap into the scientific talent of California from California Biotech. So there's a lot of skill sets that we're looking for to increase both our throughput and our sophistication in terms of some of the newer programs that we have underway. Yeah, look, you know, as you know, we've got this platform, but it's, and now that we've gotten out..., you know we've got there are so many indications and so many that phenomenal team there. We've had no problem. You know, I don't think there's any one single area anywhere where you can attract all the talent that you want with a platform.

Yeah.

You know we've got this platform that is so flexible and now we we've gotten out on the liver you know we can go out for so many indications. So many gene targets that this isn't coming on asset to maximize that now like and while mass and has been great and we'll continue to be great. A phenomenal team there I mean, we've had no.

And and doing that Alan you know I don't think there's any one single area anywhere where where you can attract all the talent that you want a with a with a platform just flexible as broad. So it just makes sense for us to you know to open up a second a second orange facilities.

We'll see how it must be all goes I I don't know that we that we know rang out how that's going to interact with Madison and and and you know when each facilities going to do you know we're going to see what our needs are and see see where we can bring people you know, whether it's madison or or for San Diego, but but it's going to be big elsewhere.

I think it's gonna, it's going to allow us to continue to to to push a lot of a drug Canada's in the clinic.

unknown: So it just made sense for us to open up a second R&D session. We'll see how it goes. I don't know that we know right now how that's going to interact with Madison and what each facility is going to do. But it's going to be a big help to us, I think. It's going to allow us Excellent. Thank you so much. And congratulations to Bruce out there on his retirement. At this time, I would like to turn it back to Chris Anzalone for any further comments. Well, thanks everyone for joining the call today, and I hope everyone stays safe.

Excellent. Thank you so much N.P. gretz the Bruce out there on his retirement.

Thanks very much.

[noise] at this time I would like to turn it back to increase Chris until only for any cricket comments.

Well thanks, everyone for join the call that Ain't hope at once they save copy soon.

[noise] need some gentlemen's does concede studies conference call. Thank you for for thinking you may not disconnect.

Goodbye.

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unknown: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Goodbye.

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