Q4 2021 Arrowhead Pharmaceuticals Inc Earnings Call

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Vince Anzalone: BF-WATCH TV 2021 Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. Throughout today's recorded presentation, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. I will now hand the conference call over to Vince Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead. Good afternoon, everyone.

Okay.

Vince Anzalone: Thank you for joining us today to discuss Arrowhead's results for 2022. 2021 fiscal year ended September 30th, 2021. With us today for management are President and CEO, Dr. Christopher Anzalone, who will provide an overview of the quarter. Dr. Javier San Martin, our Chief Medical Officer, who will provide an update on our pipeline. And Ken Myszkowski, our Chief Financial Officer, who will give a review of the financial.

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference call.

<unk> recorded presentation, all participants will be in a listen only mode. After the presentation, there will be a opportunity to ask questions.

I will now hand, the conference call over to Vince Anzalone.

Vice President of Investor Relations for Arrowhead. Please go ahead.

Justin.

Afternoon, everyone. Thank you for joining us today to discuss arrowheads results for 2022 2021 fiscal year ended September 32021 with US today from management are president and CEO, Dr. Christopher Anzalone, who will provide an overview of the quarter Dr. Javier San Martin <unk>, Our Chief Medical Officer, who will.

To provide an update on our pipeline and Ken Moskovsky, Our Chief Financial Officer, who will give a review of the financials. In addition, Dr. James Hamilton, Our senior Vice President of Discovery and translational medicine will be available during the Q&A session of today's call before we begin I would like to remind you that comments made during today's call contains certain forward looking.

Vince Anzalone: In addition, Dr. James Hamilton, our Senior Vice President of Discovery and Translational Medicine, will be available during the Q&A session of today's call. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact are forward-looking statements, are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking, For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K. That said, I'd like to turn the call over to Christopher Anzalone, President and CEO of the company. Thanks, Dennis.

Within the meaning of section 27, a of the Securities Act of 933 and section 21 E of the Securities Exchange Act of 1034, all statements other than statements of historical fact are forward looking statements are subject to numerous risks and uncertainties that could cause actual results to differ materially.

From those expressed in any forward looking statements.

For further details concerning these risks and uncertainties. Please refer to our SEC filings, including our most recent annual report on Form 10-K.

That said I would like to turn the call over to Christopher Anzalone, President and CEO of the company Chris.

Thanks Vince.

Christopher Anzalone: Good afternoon, everyone, and thank you for joining us today. Before I review the last quarter, I want to discuss the announcement this afternoon regarding our license agreement with GlaxoSmithKline for ArrowHSD, our investigational therapeutic, in a Phase 1-2 study that is currently being developed as a treatment for patients with NASH. On closing, GSK will receive an exclusive license to develop and commercialize Arrow HSD in all territories except Greater China, which will be retained by Arrowhead.

Afternoon, everyone and thank you for joining us today.

Christopher Anzalone: GSK will be wholly responsible for further clinical development and commercialization outside of Greater. This partnership is a great fit for us because GSK has articulated a clear commitment to genetic medicine. It has substantial capabilities to clinically develop Arrow HSD for NASH and has impressive commercial infrastructure and expertise to bring this potentially important medicine to the tens of millions of patients who need it. This is also an important transaction because it enables us to take a large spend over the next several years off our books and focus our development capital on programs that we may commercialize ourselves.

Or I view, the last quarter I want to discuss the announcement. This afternoon regarding our license agreement with Glaxosmithkline for Aero HST, our investigational therapeutic in a phase <unk> study that is currently being developed as a treatment for patients with Nash.

Christopher Anzalone: In addition, it brings in substantial non-dilutive capital while providing us with exposure to future success should this drug candidate offer patients the kind of benefits we believe possible. Arrowhead will receive an upfront payment of $120 million and is eligible for the following additional payments. $30 million at the start of Phase 2, $100 million at the start of Phase 3, up to $190 million at launch in the U.S. and major markets, and up to $590 million for key sales models.

One closing GSK will receive an exclusive license to develop and commercialize aero HST in all territories, except greater China, which will be retained by Arrowhead GSK.

GSK will be wholly responsible for further clinical development and commercialization outside of greater China.

Partnership is a great fit for us because GSK has articulated a clear commitment to genetic medicine. It has substantial capabilities to clinically developed arrow HST for Nash and has impressive commercial infrastructure and expertise to bring this potentially important medicine to the tens of millions of patients who need it.

This is also an important transaction because it enables us to take a large spend over the next several years off our books and focus our development capital on programs that we may commercialize ourselves. In addition, it brings in substantial non dilutive capital, while providing us with exposure to future success should this drug candidate offer patients the kind of benefits we believe possible.

Arrowhead will receive an upfront payment of $120 million and is eligible for the following additional payments.

$30 million at the start of phase III $100 million at the start of phase III up to $190 million at launch in the U S in major markets and up to $590 million for key sales milestones.

Christopher Anzalone: Taken together, Arrowhead stands to receive up to $1.03 billion. Arrowhead is further eligible to receive tiered royalties of mid-double digit to 20% on net product sales. From a strategic standpoint, this deal is another demonstration of our ability to use partnering selectively in areas that are outside of our commercial focus, also feels like the right time to partner because we believe our clinical data from the Phase 1-2 study demonstrate proof of concept for inhibiting the liver production of HSD-17-beta-30.

Together arrowhead stands to receive up to 1.13 billion.

Arrowhead is further eligible to receive tiered royalties of mid double digit 20% on net product sales.

From a strategic standpoint. This deal is another demonstration of our ability to use partnering selectively and areas that are outside of our commercial focus because also feels like the right time to partner because we believe our clinical data from the phase one two study demonstrate proof of concept for inhibiting the liver production of HST 17 page 13, we presented data at a S. L D.

Christopher Anzalone: We presented data at ASLD earlier this month showing deep dose-dependent reductions of intrahepatic mRNA and protein levels and a marked reduction in ALT. We believe these are compelling results. The next steps for this program, if we had decided to retain global product rights, would have been to initiate a placebo-controlled Phase 2 study to evaluate whether HSD-17 beta-13 inhibition over time would lead to clinically significant improvements in NAS. The published genetic data suggests that people with loss of function mutations in HSD17-beta13 have some level of protection against fibrosis associated with NASH and other liver disease.

Earlier, this month, showing deep dose dependent reductions of intra hepatic mrna and protein levels in a marked reduction in a L. T. We believe these are compelling results.

The next steps for this program, if we had decided to retain global product rates would have been to initiate a placebo controlled phase II study to evaluate whether HST 17 beta 13 inhibition over time would lead to clinically significant improvements in Nash.

The published the published genetic data suggests that people with loss of function mutations in HST 17, beta <unk> have some level of protection against fibrosis associated with Nash and other liver diseases.

Christopher Anzalone: We think we have shown the Arrow HSD does what it is designed to do. However, there have not been any prior HSD 17 beta 13 inhibitors studied in clinical trials, so human proof of concept of a clinical benefit needs to be established in future clinical studies. This is where GSK steps in.

We think we have shown the arrow HST does what it is designed to do.

There have not been any prior HST 17 beta <unk> inhibitors studied in clinical trials. So human proof of concept of a clinical benefit needs to be established in future clinical studies.

Christopher Anzalone: They have a global reach and extensive experience and resources in clinical, regulatory, medical affairs, and commercial, They're in a strong position to pick up the program and advance it efficiently. As I mentioned, we think this deal is a net positive for the HSD, for the Arrow HSD program and the patients with NAS. We are confident that GSK is the right company to take the next steps in clinical development and to chaperone the program through regulatory and commercial opportunities that lie ahead.

This is where GSK steps in they have a global reach and extensive experience.

And resources in clinical regulatory medical affairs and commercial.

They are in a strong position to pick up the program and advance it efficiently as I mentioned, we think this deal is a net positive for the HST for the Aero HST program in patients with Nash.

We're confident that GSK is the right company to take the next steps in clinical development and the chaperone the program through regulatory and commercial opportunities that lie ahead, we are thrilled to welcome GSK as our newest partner and look forward to working with them to advance this potentially important new medicine toward patients in need.

Christopher Anzalone: We are thrilled to welcome GSK as our newest partner and look forward to working with them to advance this potentially important new medicine to our patients in need. I'll now move on to some of the recent highlights and accomplishments during the prior quarter and the period since our last call. Our collaboration and license agreement with Janssen, which we signed in 2018, covered our Hepatitis B program, previously called Arrow HPV, and now called J&J3989, and three potential additional programs that we would develop preclinically for Janssen.

I'll now move onto some of the recent the recent highlights and accomplishments during the prior quarter and the period since our last call.

Collaboration and license agreement with Janssen, which we signed in 2018 covered our hepatitis B program previously called Aro HBV and now called J&J 39, 89, and three potential additional programs that we would develop pre clinically for Jens.

Christopher Anzalone: J&J 75220795 is the first program, for which Janssen exercised its option to take an exclusive license, which earned Arrowhead a $10 million milestone payment earlier in the year. JNJ75220795, currently in a Phase 1 clinical study, is an investigational RNAi therapeutic developed using Arrowhead's proprietary TRIM platform, and is designed to reduce expression in the liver of PNPLA3 as a potential treatment for patients with NAS. PNPLA-3 has strong genetic and preclinical validation as a driver of liver fat accumulation and damage.

J&J 75 to two O 795 is the first program.

For which janssen exercised its option to take an exclusive license, which earned arrow had a $10 million milestone payment earlier in the year.

J&J 75 to $2 795 currently in a phase one clinical study is an investigational <unk> therapeutic developed using arrowheads proprietary trim platform and is designed to reduce expression in the liver or <unk>.

M P L three as a potential treatment for patients with Nash.

<unk> three has strong genetic and preclinical validation as a driver of liver fat accumulation and damage during the quarter Arrowhead earned an additional $10 million milestone payment after Janssen dosed the first patient in a phase one clinical study.

Christopher Anzalone: During the quarter, Arrowhead earned an additional $10 million milestone payment after Janssen dosed the fifth patient in a Phase I clinical study. Staying with the Janssen Collaboration, data was presented at AASLD from REEF1, a Phase 2b study to assess the efficacy and safety over 48 weeks of monthly subcutaneous injections of JNJ3989 at a dose of 40, 100, or 200 mg. This was used on top of daily nuke therapy, with or without daily oral JNJ6379, one of Janssen's capsid assembly modulators, or CAMs. JNJ3989 is an investigational RNAi therapeutic that targets all HPV RNAs, thereby intended to reduce levels of all viral HPV proteins.

Staying with Janssen staying with the Janssen collaboration data was presented at a S. L. D from a reef one phase II study to assess the efficacy and safety over 48 weeks of monthly subcutaneous injections of J&J $39 89 at a dose of $40 100 or 200 milligrams. This was he was on top of daily.

Nuc therapy with or without daily oral J&J $63 79, one of Janssens capsid assembly modulators or camps.

<unk> 39, 89 is an investigational <unk> therapeutic that targets all HBV Rnas, thereby intended to reduce levels of all viral HBV proteins pri.

Christopher Anzalone: The primary endpoint of the study is the proportion of patients meeting new stopping criteria, which is ALT levels less than three times the upper limit of normal, HPV DNA less than the lower limit of quantitation. HPE antigen negative, HBS antigen less than 10 IU per ml at the end of treatment, taken data from 24 weeks off treatment was also presented at AAS. The data were very encouraging. The greatest reduction in S-antigen was observed in J&J 3989-200mg with new cohort.

Primary endpoint of the study is the proportion of patients meeting nuc, stopping criteria, which is a L. T levels less than three times, the upper limit of normal HBV DNA less than the lower limit of quantitation.

HB antigen negative H B S antigen less than 10 IU per ml at the end of treatment.

They can data from 24 weeks of treatment was also presented at <unk>.

The data were very encouraging to us the greatest reduction in S. Antigen was observed in J&J 3900, 89, 200 milligram with new cohort.

Christopher Anzalone: A dose-dependent response was observed in other cohorts and didn't appear that adding the CAM had any beneficial effect. At week 48, the mean reduction in S-antigen from baseline was 2.6 logs, and 74.7% of patients achieved S-antigen less than 100 IU per mL. 19.1% of patients met NUCC stopping criteria, the primary endpoint. Up to week 72, an additional 10.6% of patients met stopping criteria for a total of 29.7%. This is an important finding.

A dose dependent response was observed in other cohorts and didn't appear that adding the cam had any beneficial effect.

At 48 and week 48, the mean reduction in S. Antigen from baseline was $2 six logs and 74, 7% of patients achieved S antigen less than 100 IU per mill.

19, 1% of patients met nuc stopping criteria the primary endpoint of.

Two week 72, an additional 10, 6% of patients met the stopping criteria for a total of 29, 7%.

Christopher Anzalone: Additional patients continued to meet stopping criteria six months after therapy was removed. We are eager to see data with longer follow-up and individual patient profiles for the study. If you recall, in the studies with our first-generation compound, ARC520, in which some patients went on to achieve functional cures, S antigen clearance didn't happen within six months of therapy being removed. Some patients took nine, 12, 18 months or longer to clear S-antigen.

This is an important finding additional patients continued to meet stopping criteria six months after therapy was removed.

We are eager to see data for <unk>, we are eager to see data with longer follow up an individual patient profiles for the study.

If you recall the studies with our first generation compound arc 520, and with some patients went on to achieve functional cures. The S antigen clearance didnt happened within six months of therapy being removed.

Some patients took 912 18 months or longer to clear S. Antigen. So we are excited to see additional results from a reef one.

Christopher Anzalone: So we are excited to see additional results from ReefOne. We are also eager to see data from the various other studies that Janssen is conducting. These include the ongoing REEF2 study, where patients come off all therapy as they achieve nuke stopping criteria, an ongoing study in patients with HPV and the hepatitis delta virus, which is a patient population in desperate need of therapeutic options due to the rapid progression of the disease, and various studies with immunomodulatory agents. There are currently multiple studies ongoing with pegylated interferon called Penguin and a study called Osprey, which is a with a DNA vaccine, J&J 64300535.

We are also eager to see data from the various other studies of Janssen is conducting these include the ongoing <unk> two study where patients come off all therapy as they achieve nuc stopping criteria and ongoing study in patients with HBV and the hepatitis Delta virus.

Which is a part which is the patient population in desperate need of therapeutic options due to the rapid progression of the disease and various studies with commute with immuno modulator reagents added there are currently multiple studies ongoing with Pegylated interferon called Penguin in a study called Osprey.

With a DNA vaccine J&J seven a 64300535.

Christopher Anzalone: We have been extremely impressed with how comprehensive the development program is for J&J 3989, and we believe it has the potential to play a central role as a backbone therapy for chronic HPV. Staying with AASLD, we also presented additional data on Arrow AAT, also called TAC999, our investigational candidate designed to treat liver disease associated with alpha-1 antitrypsin deficiency, which received breakthrough therapy designation from the FDA during the quarter and is being co-developed with Takeda.

We've been extremely.

We impressed with how comprehensive the development program is for J&J 39, 89, and we believe it has the potential to play a central role as a backbone therapy for chronic HBV.

Staying with <unk>. We also presented additional data on <unk> <unk> also called Tech 99, nine or investigational candidate designed to treat liver disease associated with Alpha one antitrypsin deficiency, which received breakthrough therapy designation from the FDA during the quarter and is being co developed with Takeda.

Christopher Anzalone: We presented additional interim clinical data from the ongoing ARROW-AAT-2002 study, an open-label Phase II clinical study to assess the response of ARROW-AAT in approximately 16 patients with AATD-associated liver disease and baseline liver fibrosis. We think the data continue to reflect that Arrow AAT is highly active against its target. Specifically, the data suggest that Arrow AAT strongly inhibits production of the mutant Z-AAT protein, which we believe has been well-established as a clear cause of progressive liver disease.

We presented additional interim clinical data from the ongoing <unk> 2002 study an open label Phase II clinical study to assess the response of Aro <unk> and approximately 16 patients with <unk> associated liver disease and baseline liver fibrosis. We think the data continued to reflect the arrow AEP is highly active.

Christopher Anzalone: Further, the data suggests that livers in these patients are clearing the accumulated ZAAT and may be showing signs of healing. In this study, Arrow AAT treatment led to a 72 to 100% reduction of liver Z-AAT protein. Arrow AAT treatment also reduced histologic globular burden in all patients, with 13 of 13 patients having a one point or greater reduction in the PASD globular burden.

Against this target specifically the data suggested <unk> strongly inhibits production of the mutant Z <unk> protein, which we believe has been well established as a clear cause a progressive liver disease.

Further the data suggests that livers and these patients are clearing the accumulated Z <unk> and may be showing signs of healing.

In this study <unk> treatment led to a 72% to 100% reduction of liver Z <unk> protein.

Aro <unk> treatment reduced histologic globule burden in all patients with 13 of 13 patients, having a one point or greater reduction in the past <unk> globule burden.

Christopher Anzalone: Arrow AAT treatment also may have improved liver fibrosis. Six patients had a one point or greater improvement in metivir fibrosis stage from baseline to week 24 or 48. Since the presentation, we analyzed an additional 12-month paired biopsy that showed improvement in fibrosis, giving us 7 of 15 with fibrosis improvement now. When looking only at the 200mg cohorts, we saw 7 of 12 patients with improved fibrosis. Arrowhead, excuse me, Arrowhead treatment also improved multiple biomarkers of liver, The mean reduction of ALT from baseline ranged from 42 to 56 percent and from 33 to 54 percent for GGT at week 28 and week 72. Importantly, all groups showed normalized ALT and GGT following treatment.

Arrow <unk> treatment also may have improved liver fibrosis, six patients had a one point or greater improvement in Medicare fibrosis stage from baseline to week 24 or 48 since.

Since the presentation, we analyze an additional 12 months paired biopsy.

That showed improvement in fibrosis, giving us seven a 15.

Fibrosis improvement now.

When looking only at the 200 milligram cohorts, we saw seven of 12 patients with improved fibrosis.

Eric.

Gives me Aero 80 treatment also improved multiple biomarkers of liver health. The mean reduction of a L. T from baseline range from 42% to 56% and from 33% to 54% for GTT at week 28, and week 72 <unk>.

Importantly, all groups short showed normalized <unk> and GTT following treatment.

Christopher Anzalone: We believe these are all encouraging data. The program is on schedule, and we continue to be confident about its potential. We have begun a productive dialogue with the FDA about approval endpoints and the potential for an accelerated approval path. We look forward to continuing this dialogue as the Sequoia study continues. We expect to have data on the reduction of circulating levels of AAT from sequoia over the next few months, which should allow us to select a dose to move forward with.

We believe these are all encouraging data the program is on schedule and we continue to be confident about its potential.

<unk>.

We have begun a productive dialogue with the FDA about approval endpoints and the potential for an accelerated approval pathway. We look forward to continuing this dialogue as the Sequoia study continues we expect to have data on the reduction of circulating levels of <unk> from Sequoia over the next few months, which should allow us to select a dose to move forward with.

Christopher Anzalone: We should also be collecting the last 12-month biopsy from the last patient enrolled sometime in the summer of 2022. Let's now move on to Arrow HSD, which is our investigational candidate designed to treat NASH that we announced today has been licensed to GSK. We presented data at ASLD on the pharmacodynamic effect of Arrow HSD and safety of various dose levels. In Arrow HSD 1001, a Phase 1-2 clinical study, we observed a dose-dependent pharmacodynamic effect on hepatic HSD17-beta-13 mRNA in all patients.

We should also be collecting the last 12 month biopsy from the last patient enrolled sometime in the summer of 2022.

Let's now move onto Aro HST, which are.

Which is our investigational candidate designed to treat Nash that we announced today has been licensed to GSK.

Christopher Anzalone: 200mg dose, all patients showed greater than 90% mRNA reduction. Patak HSD 17-beta-13 protein levels were reduced at all Arrow HSD dose levels with multiple measurements below the assay's lower limit of quantitation. Decreases in ALT and AST were observed at doses of 100 milligrams Arrow HSD and greater. Arrow HSD was well tolerated in all patients, with no drug-related serious adverse events reported, no adverse events leading to drug discontinuation, and no drug-related clinically significant adverse laboratory trends observed. We believe these data suggest that Arrow HSD is highly active at silencing liver production of HSD-17-beta-13.

We presented data at a S. L D on the Pharmacodynamic effect of Aero HST and safety of various dose levels.

<unk> 1001, our phase <unk> clinical study, we observed a dose dependent pharmacodynamic effect on hepatitis I'm, sorry on hepatic HST 17 beta <unk> mrna in all patients.

At the 200 milligram dose all patients showed greater than 90% mrna reductions.

Attic HST 17 beta <unk> protein levels were reduced in all Aero HST dose levels with multiple measurements below the assays lower limit of quantitation.

Decreases in ALC and Asps were observed at doses of 100 milligram Arrow HST and greater.

Zero HST was well tolerated in all patients with no drug related serious adverse events reported no adverse events, leading to drug discontinuation and no drug related clinically significant adverse laboratory trends observed.

We believe these data suggest that arrow HST is highly active at silencing liver production of HST 17 beta <unk>.

Christopher Anzalone: Moving to our wholly-owned cardiometabolic pipeline, Javier will give an update in a moment on the studies that are ongoing and their status, but I wanted to highlight another recent data presentation. At AHA last week, we presented additional Phase 1-2 clinical data on Arrow ApoC3, Arrowhead's investigational therapeutic targeting apolipoprotein C3, or ApoC3, being developed as a treatment for patients with hypertriglyceridemia, severe hypertriglyceridemia, and familial myocardial microanemia syndrome, or FCS. The presentation was assessing four genetically confirmed FCS patients and 26 patients with multifactorial chylomicronemia, which we refer to as MCM or non-MCM.

There's clearly an enormous unmet medical need for patients with Nash and we look forward to GSK designing future studies to evaluate the compound into phase II and beyond.

Christopher Anzalone: The latter patients tend to have extraordinarily high triglycerides and exhibit the same or similar phenotype as genetically defined FCS. We wanted to evaluate whether there is a different response to Arrow ApoC3 in these two groups. This is important because we are now initiating a phase 3 study of Arrow ApoC3, which Javier will describe, in our study of patients with FCS compared with non-FCS. Arrow ApoC3 achieved similar levels of production of ApoC3, similar changes in Q limit parameters, and similar and comparable, Safety Forever.

Moving to our wholly owned cardio metabolic pipeline Javier will give an update in a moment on the studies that are ongoing and their status, but I wanted to highlight another recent data presentation at.

Christopher Anzalone: ApoC3 was reduced by 98% in FCS patients and 96% in MCM patients. Both groups showed similar maximum-median reductions in triglycerides of 91% and 90% respectively, non-HDL cholesterol was reduced by 58% and 49% respectively, and HDL cholesterol was increased by 152% and 111% respectively. Across our programs, pre-clinical data have been largely predictive of early clinical data, and early clinical data has been predictive of later stage clinical data. We see this with respect to pharmacodynamic response and safety and tolerability.

At <unk> last week, we presented additional phase one two clinical data on Aero Apoc, III arrowheads, investigational <unk> therapeutic targeting April lipoproteins C III or apoc III being developed as a treatment for patients with hypertrophic hybrid triglyceride anemia, severe hypertrichosis, alright, email and familial calling micro anemia syndrome or <unk>.

Yes.

The presentation was assessing for genetically confirmed Fcs patients.

26 patients with multifactorial, Chylomicron, EMEA, which we referred to as MCM or non Fcs.

Patients tend to have extraordinarily high triglycerides and exhibit the same or similar phenotype as genetically defined FCS we wanted to evaluate whether there is a different response to arrow apoc III and these two groups.

This is important because we are now initiating a phase III study of Aro, Apoc, III, which Javier will describe.

In our study patients with FCS compared with non FCS Aero Apoc III achieved similar levels of production to be able to see three similar changes in lipid parameters and similar and comparable safety parameters.

<unk> three was reduced by 98% in FCS patients and 96% and MCM patients. Both groups showed similar maximum medium reductions in triglycerides of 91% and 90% respectively.

Non HDL cholesterol was reduced by 58% and 49%, respectively, and HDL cholesterol was increased by 152% and 111% respectively.

Across our programs preclinical data have been largely predictive of early clinical data and early clinical data has been predictive of later stage clinical data. We see this we see this respect we see this with respect to Pharmacodynamic response, and safety and Tolerability I believe this is part of what makes RNA eye and Arrowhead special and one of the main room.

Christopher Anzalone: I believe this is part of what makes RNAi and Arrowhead special and one of the main reasons we can go into early clinical development with confidence that we have a good idea about what to expect. In our view, this serves to increase the probability of success and potentially reduce risk. That brings me to our newest clinical program. Arrow C3 is an investigational therapeutic designed to reduce production of complement component three or C3 as a potential therapy for various complement-mediated diseases.

We can go into early clinical development with confidence that we have a good idea about what to expect in.

In our view this serves to increase the probability of success and potentially reduce risk.

That brings me to our newest clinical program <unk> is an investigational therapeutic designed to reduce production of complement component three or <unk> three as a potential therapy for various complement mediated diseases.

Christopher Anzalone: During the quarter, we announced the previously undisclosed candidate, we filed a CTA to begin clinical studies, and we hosted a Key Opinion Leader webinar to discuss the complement pathway and the diseases we will initially focus on. These include IgA nephropathy, complement 3 glomerulopathy, and paroxysmal nocturnal hematuria.

During the quarter, we announced the previously undisclosed candidate we filed a cta to begin clinical studies and hosted a key opinion leader webinar to discuss the complement pathway and the need in the diseases. We will initially focus on.

These include Iga nephropathy complement three equal in Mega lossy and practices nocturnal hematuria.

Christopher Anzalone: There are also other renal and hematologic diseases that we intend to evaluate in the future. The complement pathway is complex, and we did our best in the webinar to explain why we think a C3-targeted drug has the potential to address multiple complement-mediated or complement-associated diseases. We in the KOLs also explained the theoretical advantage of.., that an RNAi therapeutic like Arrowhead, like Arrow C3 may have over other mechanisms and other complement targets. If you haven't listened to the webcast, I recommend you view it on our website for more information about Arrow's TV.

There are also other renal and hematologic diseases that we intend to evaluate in the future.

The complement pathway is complex and we did our best in a webinar.

To explain why we think a <unk> targeted drug has the potential to address multiple complement mediated or complement associated diseases.

We and the Kols also explained the theoretical advantages that an RNA therapeutic like <unk> like <unk> three may have over other mechanisms and other complement targets.

If you haven't listened to the webcast I recommend you view it on our website for more information about <unk> three.

Christopher Anzalone: This is an early clinical program, but as I mentioned, we have a good track record of preclinical data translating well to clinical studies for investigational medicines developed with the TRMM platform. I'd like to provide a quick update on our pulmonary programs, including Arrow-ENAC, which is currently voluntarily paused for new enrollment as we assess some potential preclinical toxicology. We are still conducting studies internally to understand the toxicology findings, and we don't have clarity yet on the path forward.

This is an early clinical programs, but as I mentioned, we have a good track record of preclinical data translate well to clinical studies for investigational medicines developed with the trim platform.

I would like to provide a quick update on our pulmonary programs, including <unk>, which is currently voluntarily paused to new enrollment as we assess and potentially some potential preclinical toxicology findings.

We are still conducting studies internally to understand the toxicology findings and we don't have clarity yet on the path forward.

Christopher Anzalone: While we conduct those studies, we continue to make progress on our two new pulmonary programs, which are on track for CTA filings in the first half of 2022. In addition, we are working on a next generation ENAC candidate in parallel, should that prove to be helpful or necessary. We believe in ENAC as a target for cystic fibrosis and are confident that our pulmonary targeted trim platform has the potential to address multiple diseases in the lung without adequate treatment options. We have less clinical experience applying the TREM platform to pulmonary tissue.

While we conduct those studies, we continue to make progress on our two new pulmonary programs, which are on track for Cta filings in the first half of 2022.

In addition, we are working on a next generation <unk> candidate in parallel should that prove to be helpful or necessary.

We believe <unk> as a target for cystic fibrosis and are confident that our pulmonary targeted trim platform has the potential to address multiple diseases in the lung without adequate treatment options, we have less clinical experience applying the trim platform to pulmonary tissue. So we don't yet have the predictability that we see when we applied the trim platform in the liver, but weird.

Christopher Anzalone: So we don't yet have the predictability that we see when we apply the TREM platform in the liver, but we are committed to getting there, and we are convinced that we can. Before turning it over to Javier to discuss the status of our mid and later stage cardiometabolic programs, I would like to discuss our growth.

Committed to getting there and we are convinced that we can.

Before turning it over to Javier to discuss the status of our mid and later stage cardio metabolic programs I wanted to Scott I would like to discuss discuss our growth plans.

We now have 10 clinical stage programs and intend to expand our pipeline by two to three new programs per year.

Christopher Anzalone: Support this growing pipeline, we are in the playing stages of expanding our R&D footprint in San Diego and Madison. We will be leasing a new space in San Diego that is scheduled to be built over the coming year. In Wisconsin, we are in discussions with local and state government authorities and economic development agencies to explore potential tax and other incentives to build a new facility. Should those discussions be successful, we intend to build an Arrowhead campus in Wisconsin with two new facilities.

Support this growing pipeline, we are in the planning stages of expanding our R&D footprint in San Diego and Madison will.

We will be leasing the new space in San Diego that is scheduled to be built over the coming year.

In Wisconsin, we are in discussions with local and state government authorities and economic development agencies to explore potential tax and other incentives to build a new facility.

So those discussions will be successful, we intend to build an arrowhead campus in Wisconsin with two new facilities.

Christopher Anzalone: These facilities will house expanded R&D and a GMP drug manufacturing plant. Our pipeline is advancing both in size and proximity to commercialization to the point where our buy versus build analysis indicates that internal control of manufacturing now makes a lot of sense. This is true financially and, importantly, strategically.

These facilities will how has expanded R&D and a GMP drug manufacturing plants.

Our pipeline is advancing both in size and proximity to commercialization to the point, where our buy versus build analysis indicates that the internal control manufacturing now makes a lot of sense.

This is true financially and importantly, strategically we value speed at every stage of development and in every function.

Christopher Anzalone: We value speed at every stage of development and in every function. Building out drug manufacturing capabilities for preclinical, clinical, and commercial drug product will give us more control over timing, process, and cost. We have not yet closed on the purchase of the land, so we have not yet started to incur significant costs.

Building out drug manufacturing capabilities for preclinical clinical and commercial drug product will give us more control over timing process and costs.

We have not yet closed on the purchase of land so.

Javier San Martin: But Ken will talk later about our estimates for CapEx should we move forward with this plan expansion. With that overview, I'd now like to turn the call over to Dr. Javier San Martin. Javier.

With that overview I'd now like to turn the call over to Dr. Javier San Martin Javier. Thank you Kris and good afternoon, everyone I wanted to focus on our most advanced wholly owned cardio metabolic Trillium <unk>.

Javier San Martin: Thank you, Chris. And good afternoon, everyone. I want to focus on the status of our most advanced wholly-owned cardiometabolic programs, AeroApoC-3 and AeroH3. In these two programs, the severity clinical studies are either active now or will be active, I will start with AeroApoC3. This is our investigational medicine targeting ApoLapoprotein C3 being studied in patients with various lipid disorders, including hypertriglyceridemia, severe hypertriglyceridemia, mixed lipidemia, multifactorial chylomicronemia, and familiar chylomicronemia syndrome. The set of mid- and late-stage studies of Arrowhead Proceed III is called the Summit Program, with each study named for a mountain peak.

<unk> T.

These two podesta.

Need to study it.

Now all will be additive to that.

<unk>. This is our investigational medicines targeting April level, putting C III.

<unk> in patient with sleep disorders, including hypothetically three Danielle severe hypothermia city Dania mixed dyslipidemia multi factorial titled Lithuania, and some media illuminator name is seamless.

Javier San Martin: We currently have three open studies. 2001 is a phase 2 study in patients with severe hyperthyroidemia, which we are calling SHASTA-2. 2002 is a phase 2 study in patients with mixed disease lipidemia, which we are calling MURE. In 2001 he faced three studies in partnership with FCS, which we are calling PALATF.

The fifth of need in late stage studies of Italy placebo.

The semi colon.

With each study name fully mountain peak. So we currently have three open studies.

<unk> thousand one is a phase II study in patients with Covid hypothetically, if anything yet, which we are calling chest that too.

2002 is the phase two study in patients with mixed Dyslipidemia, which we're calling <unk>.

And then when is the phase III study in patients with FCS, which we're calling policies.

Javier San Martin: I will describe each of these studies briefly and give the current status of TASTA-2 is a double-blind, placebo-controlled, phase-2b study to evaluate the efficacy and safety of Arrowhead PC3 in adults with severe hypertriglyceridemia or SHTG. Three dose levels of Arrowhead PC3, 10 milligrams, 25 milligrams, and 50 milligrams, will be evaluated against placebo in participants who have mean fasting triglycerides of greater than or equal to 500 milligrams per deciliter at screening.

I will describe each of these studies <unk> current status.

For each.

That too is a double blind placebo controlled phase II study to evaluate the efficacy and safety of Italy, plus <unk> in adults with severe hypothermia.

HPT.

Those label Apoc, 10 milligrams 25 milligrams 50 milligrams will be evaluated against placebo and participant who have meaningful take listeners of greater than or equal to 500 milligrams per deciliter at screening.

Javier San Martin: A total of approximately 216 participants will be enrolled in the study. All those cohorts will enroll in parallel, with 72 participants per those cohorts randomly assigned in a 3-to-1 ratio to receive AeroepoC3 or placebo. Each participant will receive subcutaneous injections on day one and week 12. The duration of the study is approximately 54 weeks from screening to the week 48 end of study examination. The primary objective of the Shasta II study is to evaluate the safety and efficacy of AeroApoC-3 in adults with SHTG and to select the dosing regimen for later stage clinical studies in this patient population.

A total of approximately 216 participants will be enrolling the study all of those cohorts will enroll in parallel with 72 participants those cohort randomly assigned in a three.

Two one ratio to receive <unk> or placebo.

Each participant will receive subcutaneous injections on day, one and week 12, the duration of the study is approximately 54 weeks from screening to the week 48 the examination.

The primary affinity with assessed two studies to evaluate the safety and efficacy of <unk> in adult with HPT.

<unk> selected those envisioning for later stage clinical studies in this patient population.

Javier San Martin: CASTR 2 has enrolled 40 of the planned 216 patients, with an additional 56 patients currently in screening to potentially be enrolled. We have activated 60 of the planned 80 sites, and our goal is to have the study fully enrolled around Q3 of 2021. Moving on to the new study, it is a double-blind, placebo-controlled, phase 2b study to evaluate the efficacy and safety of arrowhead Pocitri in adults with mixed dyslipidemia. All those cohorts of Arrowhead Positrix will be evaluated against placebo in participants who have the following screen.

The tool is simple 40 of the planned 216 patients with an additional 56 patients put them fine screen through potentially the end goal without activate the 60 of the planned 80 sites and our ability to have the study fully enrolled around Q3 of 2022.

Moving on to the New study is a double blind placebo controlled phase II study to evaluate the efficacy and safety of <unk> in adults with mixed dyslipidemia.

All of those cohort of AWP theme will be evaluated against placebo in participant who had the following screening.

Javier San Martin: Elevated triglycerides greater than or equal to 100 milligrams per deciliter but less than 500 milligrams per deciliter, and known HDL cholesterol greater than or equal to 100 milligrams per deciliter or LDL cholesterol greater than or equal to 70 milligrams.

Elevated triglycerides greater than or equal to 100 milligrams, meaning that put a definitive list on 500 milligrams per deciliter.

And non HDL cholesterol greater than or equal to 100 milligrams per deciliter.

LDL cholesterol data than or equal to 7 million asset.

Javier San Martin: A total of approximately 320 participants will be enrolling this year. All those cohorts will enroll in parallel with approximately 80 participants per those cohorts randomly assigned in a 3-to-1 ratio to receive Arrowhead Pulse C3 or Pulse C4, in tricohorts 10mg, 25mg and 50mg. Each participant will receive a subcutaneous injection on day one and week 12 for a total of two injections. In one additional 50 mg cohort, each participant will receive a saccutane injection on day 1 and week 24 for a total of 2 injections.

It's sort of a.

Approximately 320 participants will be enrolled in this study.

All of those cohorts will enrolling in parallel with approximately $80 per dose cohort randomly assigned in a three to one ratio to receive placebo.

In <unk> thin meeting, our 25 made against them.

Each participant will receive a subcutaneous injection on day, one and we closed political dollars two injections.

One additional 50 milligrams cohort each participant will receive a <unk> injection on day, one and week 24 foot. It those are the two injections.

Javier San Martin: The duration of the study is approximately 54 weeks for screening to the week 48 end of study exam. The primary effect of the newer study is to evaluate the safety and efficacy of Arrowhead Pocitri in adults with mixed sleep epidemia and to select the dose and dose regimen for later stage clinical study in this patient.

<unk> of the study is approximately 54 weeks post cleaning to the week 48 in our study <unk>.

The primary objective of the new study is to evaluate the safety and efficacy of Italy, principally in Netherlands, with mixed dyslipidemia and to select the dose and dose regimen for later stage clinical study in this patient population.

Javier San Martin: The new study has enrolled 22 of the planned 320 patients, with an additional 38 patients currently in screening to potentially be enrolled. We have activated 15 of the planned 32 sites, and our goal is to have the study fully enrolled in Q4 of 2022. The last active study for 808-POC-3 is PALACE. Phallus A is a Phase III study to evaluate the efficacy and safety of Aeroepocy 3 in adults with familial echelomichronemia syndrome.

The new study has enrolled 22 of its 320 patients within additional instead of the eight patients currently in screening to potentially be in coal we have activated <unk> of the planned 72 sites and that will go.

Is it fully enrolled in Q4 of 'twenty two.

The last active study for AWP.

LSC fallacy to phase III study to evaluate the efficacy and safety of <unk> in adults with familial <unk> syndrome.

Javier San Martin: Two dose levels of Arrowhead Pocitri, 25 and 50 mg, will be evaluated against placebo in participants with fasting triglycerides greater than 880 mg per deciliter that are refractory to standard lipid-lowering therapy and diagnosis of FCS. Approximately 60 participants will be randomized in a 2-to-1 ratio to receive four total doses of AeroApoC-3 or placebo administered subcutaneously once every month. The duration of the study is approximately 56 weeks, from screening to month 12 end of study examination. After month 12, participants will be eligible and invited to consent to continue in an open-level extension study. All participants in the placebo group who opt to continue will switch to active drugs during the extension study.

Two dose level of <unk>, 25, and $50 million.

Will be evaluated against placebo in participants with vesting triglycerides greater than 880 meetings that are refractory to standard lipid lowering therapy and diagnosis of Fcs.

Approximately 60 participants will be randomized two to one ratio to receive full total doses of <unk> or placebo administered subcutaneously. Once every three months.

Installation of the studies approximately 56 weeks from screen to month 12 study examination.

<unk> 12 participant would be eligible and invited to consent and continue in an open label extension study.

All participants in the placebo group up to continue will seek to have people sitting in the extension study and the primary objective of the pilot phase.

Javier San Martin: The primary objective of the PALACS study is to evaluate the efficacy and safety of Arrowhead placebo in adults with FCS. The primary endpoint is presentation from baseline to month 10 in fasting triglycerides. Additional secondary and exploratory endpoints include change in other lipid parameters, incidence of acute pancreatitis, and other measures. We have activated three of the plan's 55 sites globally and are working hard to activate additional sites.

Is to evaluate the efficacy and safety of Italy, Placidity in Netherlands with Fcs.

The primary endpoint is essentially from baseline in Memphis, Tenn in fast and segments.

Additional secondary and exploratory endpoints include the change in other lipid parameters incidence of acute pancreatitis and other measures.

We have activated three of the planned 55 sites globally by working to activate additional sites that are currently patients in active screening and we anticipate the first patient to be enrolled and dosed before the end of the year.

Javier San Martin: There are currently patients in active screening, and we anticipate the first patient to be enrolled and those before the end of the year. I will now move on to ArrowH3, our investigational medicine designed to reduce production of antipoietin-like protein. And speaking of three, I say potential treatment for Penchay with me.

I will now move on to <unk>, our investigational medicines designed to reduce pollution angiopoietin like protein three <unk>.

<unk> as a potentially significant issue with Mississippi.

Javier San Martin: The set of mid and late stage studies for 80H3 is called the VISTA program, with each study named for a national park. We currently have one open study in VISTA. 80H3-2001, a Phase II study in patients with mixed-use lipidemia, which we are calling ARCHES-II. ARCHES 2 is a double-blind placebo-controlled phase 2B study to evaluate the efficacy and safety of investigational arrowhead H3 in adults with MIPS dyslipidemia. Three-Dose Levels of Arrowhenge 3, 50mg, 100mg, and 200mg will be evaluated against placebo in participants who have the following screen: LDL cholesterol greater than or equal to 70 mg per deciliter or non-HDL cholesterol greater than or equal to 100 mg per deciliter and means fasting triglycerides between 150 and 500 milligrams.

The state of need in late stage studies for <unk> C is called the <unk> program with this study named for the National Park. We currently have one open studying the Vista, Florida.

The 2001 phase II study in patients with mixed Dyslipidemia, which are calling arches too.

Or just too it's a double blind placebo controlled phase II study to evaluate the efficacy and safety of investigation of <unk> in adults with mixed dyslipidemia.

This level of <unk> 50 million against 100 million of some 200 meeting that will be evaluated against placebo in participants who had the following screening.

LDL cholesterol data than or equal to 17.

Illiteracy or non HDL cholesterol greater than or equal to 100 Mg.

And mean fasting triglyceride between <unk> 50, and 500 milligrams.

Javier San Martin: A total of approximately 180 participants will be enrolled in the study. All those cohorts will enroll in parallel, with 60 participants per cohort randomly assigned in a 3-to-1 ratio to receive a subcutaneous injection of 80-inch tree bark or placebo on day one and week. The duration of the study is approximately 42 weeks from screening to the week 36 end of study examination. After completing the week 36 visit, participants will be eligible to continue in an Open Label Sustention Study. The primary objective of the ARCHES-II study is to evaluate the safety and efficacy of AOH3 in adults with mixed dyslipidemia and select a dosing regimen for later stage clinical study in this patient.

A total of approximately 180 participant will be enrolling the study all of those cohorts will enrolling in parallel with 60 participant political randomly assigned in a three to one ratio to receive a subcutaneous injection of <unk> or placebo on day, one and week 12.

Relation of the study is approximately 42 weeks from screening to the week 36, and the study seven nation.

After completing that would tell us. This is participant will be eligible to continue in an open label extension study.

The primary objective of the <unk> two study is to evaluate the safety and efficacy of <unk> three in adults with mixed Dyslipidemia and selected dose and dosing regimen for later stage study in this patient population.

Javier San Martin: The ARCHES III study has reached 50% enrollment with 90 of the planned 180 patients enrolled and those, with an additional 68 patients currently in the screening to potentially be... We have activated all 25 of the initial planned 25 sites. And our goal is to have the study fully enrolled in Q2 of 2020. I will now turn the call over to Ken Myszkowski, Arrowhead's Chief Financial Officer. Ken.

Just three study has reached 50% enrollment with 90 of the planned.

80 patients enrolled and those with an additional 58 patients currently in screening to potentially be involved with.

Have activated all 25 of the initial plan 25 sites and our goal is to have the study fully enrolled in Q2 of 2022.

I will now turn the call over to Kevin <unk> Chief.

Chief Financial Officer, Ken.

Ken Myszkowski: Thank you, Javier, and good afternoon, everyone. As we reported today, our net loss for fiscal 2021 was $140.8 million, or $1.36 per share, based on $103.7 million fully diluted weighted average shares outstanding. This compares with a net loss of $84.6 million, or $0.84 per share, based on $100.7 million fully diluted weighted average shares outstanding for 2020. Revenue for fiscal 2021 was $138.3 million compared to $88 million for 2020. Revenue in the current period primarily relates to the recognition of a portion of the $300 million, Upfront payment received under our collaboration agreement with Takeda.

Thank you Javier and good afternoon, everyone.

As we reported today, our net loss for fiscal 2021 was 148 million.

$1 36 per share based on $103 7 million fully diluted weighted average shares outstanding with.

This compares with a net loss of $84 6 million or <unk> 84 per share based on $100 7 million fully diluted weighted average shares outstanding for 2020.

Revenue for fiscal 2021 was $138 3 million compared to $88 million for 2020.

Revenue in the current period, primarily relates to the recognition of a portion of the $300 million.

Upfront payment received under our collaboration agreement with Takeda.

Ken Myszkowski: Revenue for the Takeda Agreement will be recognized as we continue to work toward completing our performance obligations of managing clinical trials, in process and certain manufacturing related services. There remains $209 million of revenue to be recognized associated with the Takeda collaboration and it is anticipated to be recognized over approximately two to three years.

Revenue for the Takeda agreement will be recognized as we continue to work toward completing our performance obligations of managing clinical trials.

In process and certain manufacturing related services.

There remains $209 million of revenue to be recognized associated with the Takeda collaboration and it is anticipated to be recognized over approximately two to three years.

Ken Myszkowski: Any additional milestones achieved with our collaboration partners would be additive to this projection. During fiscal 2021, we also entered into a new collaboration agreement with Horizon to develop a drug candidate to treat uncontrolled gout. We received a $40 million upfront payment for this agreement.

Any additional milestones achieved with our collaboration partners would be additive to this projection.

During fiscal 2021, we also entered into a new collaboration agreement with horizon to develop a drug candidate to treat uncontrolled gout.

We received a $40 million upfront payment for this agreement.

Ken Myszkowski: The portion of this amount was recognized in fiscal 2021, and we expect the balance to be recognized by the end of 2022, as our performance requirements are completed. Revenue in the prior period primarily related to the recognition of a portion of the milestones received from the license and collaboration agreements with Janssen. We also announced a new licensing agreement with GSK today for Arrow HSD candidate. This agreement will result in an upfront payment of $120 million to Arrowhead. We anticipate the substantial majority of this to be recognized as revenue in fiscal 2022. Total operating expenses for fiscal 2021 were $287.3 million, compared to $181.2 million for 2020.

Portion of this amount was recognized in fiscal 2021, and we expect the barrels to be recognized by the end of 2022.

The performance requirements are completed.

Revenue in the prior period, primarily related to the recognition of a portion of the milestones received from the license and collaboration agreements with Janssen.

We also announced a new licensing agreement with GSK today for Aero HSV candidate.

This agreement will result in an upfront payment of $120 million to Arrowhead, we anticipate a substantial majority of this to be recognized as revenue in fiscal 2022.

Ken Myszkowski: This increase is primarily due to increased candidate-specific and discovery R&D costs, as the company's pipeline of clinical candidates has both increased and advanced, as well as additional non-cash stock compensation expenses. Net cash provided by operating activities during fiscal 2021 was $171.2 million, compared with net cash used by operating activities of $95.4 million in 2020. The key driver of this change was the $340 million in total upfront payments received from Takeda and Horizon in fiscal 2021.

Total operating expenses for fiscal 2021 were $287 3 million.

Compared to $181 2 million for 2020.

This increase was primarily due to increased candidate specific and discovery R&D costs as the company's pipeline of clinical candidates has both increased in advanced as well as additional noncash stock compensation expense.

Net cash provided by operating activities during fiscal 2021 was $171 2 million compared with net cash used by operating activities of $95 4 million in 2020. The key driver of this change was the $340 million and total upfront payments received from Takeda and horizon.

2021.

Ken Myszkowski: Eluding any potential milestone payments received from our collaboration partners, we estimate our operating cash burn to be $60 to $80 million per quarter in fiscal 2022. In addition, we are planning to expand our manufacturing capabilities and expand our R&D facilities. These capital projects, along with routine capital expenditures, will add an incremental cash outlay of $80 to $90 million for full year fiscal 2022. Turning to our balance sheet, our cash and investments totaled $613.4 million at September 30, 2021, compared to $453 million at September 30, 2020.

Including any potential milestone payments received from our collaboration partners, we estimate our operating cash burn to be $60 million to $80 million per quarter in fiscal 2022.

Addition, we are planning to expand our manufacturing capabilities and expand our R&D facilities.

These capital projects, along with routine capital expenditures will add an incremental cash outlay of $80 million to $90 million for full year fiscal 2022.

Turning to our balance sheet, our cash and investments totaled $613 four.

$4 million at September 32021, compared to $453 million at September 32020.

Ken Myszkowski: The increase in our cash and investments was primarily due to the $340 million in total upfront payments received from Takeda and Verizon offset by cash used for operations. Our common share is outstanding at September 30, 2021, we're $104.3 million. With that brief overview, I will now turn the call back to Chris. Thanks, Ken, and thanks to all for joining us today. We are executing on our strategy with respect to platform extension, pipeline expansion, and business development. Arrowhead's opportunities in the near term and long term are vast and continue to grow each day.

The increase of our cash and investments was primarily due primarily due to the $340 million and total upfront payments received from Takeda in horizon.

Offset by cash used for operations.

Our common shares outstanding at September 32021 were $104 $3 million.

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

Thanks, Ken.

Thanks for all for joining us today.

We are executing on our strategy with respect to platform extension pipeline expansion and business development areas.

<unk> opportunities in the near term and long term, our vas and continue to grow each day.

Christopher Anzalone: The data from our clinical programs continue to be encouraging and strongly support further development of our investigational medicine. Lastly and importantly, we see the potential in the not-too-distant future where important medicines discovered and developed by Arrowhead start to get to patients who need them. This is why we invest in R&D and why we are building manufacturing capabilities now to support clinical and commercial supply. I'd now like to turn the call over to your questions. Operator?

The data from our clinical programs continue to be encouraging and strongly support further development of our investigational medicines.

Lastly, and importantly, we see the potential in the not too distant future, where important medicines discovered and developed by arrowhead start to get to patients who need them.

Is why we invest in R&D and why we are building manufacturing capabilities now to support clinical and commercial supply needs.

I'd now like to turn the call over to your questions operator.

Yeah.

Operator: And thank you. As a reminder to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound key.

And thank you as a reminder, or ask a question you will need to press star one on your telephone. So Sean is your question press the pound key.

Operator: We do ask that you limit yourself to one question and one follow-up. Again, that's one question, one follow-up. Please stand by while we compile the Q&A roster. And our first question is going to come from Luca. EC from RBC Capital, your line is now open.

We do ask that you limit yourself to one question and one follow up again Thats. One question one follow up please standby, while we compile the Q&A roster.

And our first question is going to come from Luca.

<unk> from RBC capital Your line is now open.

Luca Issi: Well, great. Thanks so much for taking my questions and congrats on all the progress. I'll ask two, both the main question and the follow-up, I guess. So, on A1AT, sounds like you had a productive dialogue with the FDA here. Can you expand a little bit more on that conversation and what was their level of receptivity on the idea of getting approved on just liver A1AT level? That's question one. Then question two on GSK, wondering if you can comment on why you decided to retain sizable economics in the U.S. with 50-50 profit splits for A1AT, but obviously here we have a very different structure for NASH, so any color on that would be great. Thanks so much. Sure. So I'm going to take the first one first, which is straightforward.

Oh, great. Thanks, so much taking my questions and congrats on the progress I'll ask to both the main question and a follow up I guess, so on <unk>. It sounds like you had a productive dialogue with the FDA here can expand a little bit more on that conversation and what was their level of relativity on the idea of getting approved on just lever a 180.

That's question one and then question two and GSK wondering if you can comment on why you decided to retain sizable economics in the U S. With 50 50 profit split for a while.

But obviously here we have a very different structure for Nash so any color on that would be great. Thanks. So much.

Christopher Anzalone: There's not much we can tell you. Look, we had a very encouraging and productive discussion with the FDA, in fact, just this last week. I think that we are moving in the right direction, and it was a good collaborative interaction. We look forward to continued discussions. This is an ongoing dialogue, and we've just begun.

Sure. So let me take the first one first which is straightforward.

Not much we can tell you look we had a we had a very.

Encouraging and productive.

Discussion with the FDA in fact, just last week.

I think that we are moving in the right direction and it was a good collaborative interaction.

We look forward to continue discussions this is an ongoing dialogue and we've just begun fashion. So I expect to have.

Christopher Anzalone: And so I expect to have continued dialogue in 2022, particularly as we have additional data. So there's not much I can tell you right now other than that. Again, so far, so good.

Dialogue in 2022, particularly as we have additional data.

So there's not much I can tell you right now other than that again, so far so good I think it's been a good conversation so far with respect to to the different deal structures for <unk> and for <unk> and for HST.

Christopher Anzalone: I think it's been a good conversation so far. With respect to the different field structures for AAT and for HSD, I think that just reflects, The state of the development of the two programs, AAT was of course, you know, farther advanced than HSD at first, second, AAT, I think the biology there is quite clear, HSD, we still need to suss that out, you know, there's really good genetic validation for that target, but as we talked about earlier in the call, you know, there's been no inhibitors of this protein that have been tested, and so, you know, while the genetic data look encouraging, we still need human proof of concept, and so I fully trust that we'll show that, or at least JSK will show that, but it's just a different state of progress between AAT and HSD.

It's.

I think that just reflects.

The state of.

Of the development of the two programs <unk> is of course further advanced than HST. That's first second.

I think the biology, there is quite clear HST, we still need to suss out you know theres really good genetic validation for that target, but as we talked about earlier in the call.

There's been there's been no inhibitors.

This protein that had been tested and so and so while the genetic data look encouraging we still need human proof of concept and so.

I fully trust that we will show that or at least GSK will show that but but it's just a.

Different state of.

Our progress.

Between <unk> and <unk> and finally, because these are two very different diseases.

Christopher Anzalone: And finally, these are two very different diseases, right, you know, HSD is a very large disease, you know, tens of millions of people in the U.S. are likely potential patients for that, whereas AAT is an orphan indication, we think that there's maybe 100 to 120,000 potential patients in the U.S., and so given all of that, you know, we would look for different economics and different structures for those two programs. We're very happy with both of them, I think we have the right partner for AAT and DAKATA, who is committed and we are really working together with them to bring this important medicine to these patients, and similarly, I think we have got the right partner in GSK for NASH, they appear to be committed to the program, and we are impressed with their ability to move that program forward. Super, thanks so much.

<unk> is a very large disease.

Tens of millions of people in the U S.

Unlikely potential patients for that whereas <unk> is an orphan indication. We think that there is maybe 100 to 120000 potential patients in the U S and so given all of that.

We would look for different economics different structures for those two programs, we're very happy with both of them I think we have the right partner for for <unk> and Takeda, who is who has committed and we are really working together with them to bring this important medicine to these patients and similarly, I think we have got the right.

Partner and GSK for Nash.

They appear to be committed to the program and.

And we are impressed with their ability to move that program forward.

Super Thanks, so much Robert.

Welcome.

Christopher Anzalone: Welcome. Thank you. And our next question comes from Alicia Young from Cantor. Your line is now open.

Thank you and our next question comes from Alicia Young from Cantor.

Your line is now open hey.

Alicia Young: Hey guys, thanks for taking my questions. One, I just wanted you to talk a little bit about your perspective on the capsid and sRNA data, AASLD. I mean, do you feel like combination is the way to go?

Hey, guys. Thanks for taking my questions. One I just wanted you to talk a little bit about your perspective on the.

The capsid than S RNA data.

<unk> I mean do you feel like combinations in a way to go it's kind of interesting the capsid and shale activity.

And then I think my second question is just on whether you guys would ever think about maybe potentially doing something in like neuro because I know some of your competitors are now talking about that thanks.

Christopher Anzalone: It's kind of interesting, the capsidential activity. And then I think my second question is just whether you guys would ever, you know, kind of think about maybe potentially doing something in like neuro, because I know some of your competitors are now talking about that. Sure. Thanks, Leith.

Sure I think it's good to hear from you.

So with respect to the two combination for HBV look I think that I was very encouraged by by Janssen data. Our drug is doing what it's designed to do we saw deep reductions.

S antigen.

We are.

Assume that we are seeing good reductions in all in all viral antigens.

Christopher Anzalone: It's good to hear from you. So, with respect to the combination for HPV, look, I think that I was very encouraged by Janssen's data. You know, our drug is doing what it's designed to do. You know, we saw deep reductions of F-antigen. We are, I assume that we are seeing, you know, good reductions in all viral We saw a good percentage of patients who got S below 100 IU. I think it was 75 or so percent, you know, during treatment.

We saw a good percentage of our patients who got.

Scott S below a 100 IU I think it was 75 or so percent.

Christopher Anzalone: That's impressive, and we think that that number, that 100 IU, is an important number. You know, it's been shown in the past that patients who can get below 100 IU have a better chance of sero-clearing. And then, of course, the primary endpoint looked good.

During treatment Thats impressive and we think that that number that 100 IU is an important number it's been shown in the past that patients who get below 100, <unk> you have better chances to euro clearing and then of course.

The primary endpoint looked good we saw a lot of patients, who who who achieved nuc stopping criteria and even more patients who achieve that criteria. Even after they came off therapy and so we're really encouraged.

Christopher Anzalone: You know, we saw a lot of patients who achieved nuke-stopping criteria, and even more patients who achieved that criteria even after they came off therapy. And so, we're really encouraged, you know, by that start, and we're looking forward to watching, you know, these patients continue, you know, off therapy and seeing if we can get some functional cures. Now, with respect to combinations, we've always believed that this is a tough virus, and that we were hopeful that our drug, you know, could be a backbone approach. And nothing we have seen so far has pulled us from that thought.

By that start and we're looking forward to watching these.

These patients continue.

Off therapy, and see if we can get some some functional cures.

Now with respect to combinations. We've always believed that this is a tough virus and that that we were hopeful that that.

That our drug could be backbone approach and nothing we've seen so far has has pulled us from that thought and we still think it's going to be the backbone approach and we still think that to get.

Christopher Anzalone: We still think it's going to be the backbone approach, and we still think that to get, you know, wide-ranging consistent functional cures that you may need a combination approach. I think that CAM is probably not the preferred combination going forward, but J&J or Janssen is going about this in the right way. They have a number of studies ongoing. We look forward to seeing what the immunomodulatory studies look like and beyond. You know, I think that we are still in the early part of trying to figure out what the correct therapy is for HPV, but I think that we're on the right track and I think those data support that.

Wide range and consistent functional cures that you may see you may need a.

A combination approach I think that that that Tam is probably not the <unk>.

Preferred.

Combination going forward.

But J&J Janssen is going about this in the right way there are a number of studies ongoing and we look forward to seeing what the what the amount of module Tory studies look like.

And beyond so.

I think that we are still in the early part of <unk>.

Of trying to figure out what the correct therapies for HBV, but I think we're on the right track and I think those data support that.

Okay.

Christopher Anzalone: Look, we do not, we don't have any stated programs in CNS right now, but you're right, you know, we have competitors who have been working on that for some time now, for good reason. You know, there's a lot of unmet medical need there, and there are clearly some indications that could be addressed using RNAi, and so, you know, we wish them good luck. I think that at some point we will be there, because it's important for us to be there.

Do you have any plans for that.

Sorry, CNS rights.

Alright.

Look we do not.

We don't have any stated programs in CNS right now, but you are right. We have competitors, who have been working on that for some time now.

For good reason.

There is a lot of unmet medical need there.

And there are clearly some.

Indications that there could be a.

Addressed using <unk>.

So we wish them, we wish them. Good luck I think that at some point, we will be there because it's important for us to be there.

Christopher Anzalone: To date, we have focused on other cell types, as you know, we've got programs in pulmonary and solid tumor, skeletal muscle, you know, by the middle of next year, we didn't talk about that in the call, but we're still on track, you know, for skeletal muscle. But yeah, eventually, you know, at some period, we will likely have a program in CNS, we just don't have one right now. Great, thank you. You're welcome. And thank you. And our next question comes from Maurice Raycroft from Jeffries. Your line is now open.

To date, we have focused on other.

On other cell types as you know, we've got programs in pulmonary and solid tumor.

Skeletal muscle by the middle of next year, we can talk about that in the call, but we're still on track for a four.

For for skeletal muscle.

But yeah eventually.

At some period, we will likely have.

A program in CNS, we just don't have one right now.

Great. Thank you.

Welcome.

And thank you and our next question comes from Maury Raycroft from Jefferies. Your line is now open.

Maurice Raycroft: Hey, congrats on the update and thanks for taking my questions. I was just going to ask a question on HSD. Congrats on that update.

Hey.

Congrats on the update and thanks for taking my questions. I was just going to ask a question on HST. Congrats on that update I was wondering if you can say if the process to partner <unk>.

Yes, it was competitive and since you're pursuing <unk> three in Nash with J&J, the J&J have any option or right of refusal for HST.

Christopher Anzalone: Wondering if you can say if the process to partner the HSD asset was competitive? And since you're pursuing PMPLA-3 in NASH with J&J, did J&J have any option or right of refusal for HSD? Thanks very much. It's good to hear from you, Maurie.

Alright, thanks, very much it's good to hear from you Mark.

Christopher Anzalone: Yes, we did run a competitive process. We spoke with a number of companies about the asset, and GSK seemed to be the best partner. J&J did not have a right of first refusal or anything like that for HSE.

Yes, we did run a competitive process, we spoke with with a number of companies about about the asset and GSK seem to be the.

The best partner.

J&J did not have a right of first refusal or anything like that for HST.

Christopher Anzalone: Got it. Okay. And also one quick question for AAT, just wondering of the 16 patients, if you can clarify how many of those patients will have 12-month biopsy and how many will have 18-month biopsy? Yeah, you want to address that? Yeah, so 12 months biopsy have all eight patients on cohort two that received 200 milligrams. 18 months, right now we have two and it's likely to be, few patients that we had a 24 month biopsy, but because it's not mandatory, not all patients will accept or have accepted to go through the third biopsy.

Got it Okay and also one quick question for Jim.

I'm just wondering of the 16 patients if you can clarify how many of those patients will have 12 month biopsy and how many will have 18 months biopsy.

We are doing to address that.

So 12 month biopsy, all eight basis on cohort two that seem to have an immediate.

18 months right now we had to and is likely to be.

Few patients that we had a 24 month biopsy.

Because it is not mandatory and all patients will have said we'll have.

To go through the third biopsy.

Javier San Martin: And that's the case in the first cohort, that was six months, 200 milligrams; two of the four patients accepted to have the follow-up biopsy, and two of them did not. So we don't know how many would accept from the other cohort that the post-baseline biopsy was a week, sorry, month 12. Got it.

That's the case in the first cohort of six months to have the meeting them tools that for patients accepted to have a follow up biopsy and two of them did not so we don't know how many would have said from the other cohorts at the post baseline biopsy was weak.

Month 12.

Javier San Martin: Okay. Okay. Thanks for taking my question. Thank you. And our next question comes from Esther Rajavulu from UBS. Eliana, it's now open. Hey, thank you for taking my question. I have just two.

Got it okay. Okay. Thanks for taking my questions.

Thank you.

And our next question comes from Esther Roger Ballou from UBS. Your line is now open.

Esther Rajavulu: First, on the Arrow ApoCp program, if the magnitude of the ApoCp reduction is similar between the FCS and MCM patients, can you share your thoughts on what the implications for therapeutic benefit and outcomes could be for the FCS patients? And then my follow-up question is on manufacturing, which I'll ask in a second.

Hey, Thank you for taking my question I guess I have two.

First on the <unk> program.

Program.

Magnitude at the APC team adoption at similar between the FCS and MCM patients can you share your thoughts on what the implications for therapeutic benefit in outcome could be quite the Fcs patients.

And then my follow up is on manufacturing like chat, which I'll ask in a second.

Sure Javier I would like to assume yes.

Javier San Martin: Yes, so that's the data we presented, you know, this past week at AHA, in which we show that the FCS population and the MCM population has very much the same response with regard to the target, ApoC3, and to the magnitude of decrease in triglycerides, which is in the range of 80 to 90%. So what that means for patients with FCS is that many of them, depending on their baseline, will achieve a level beyond which the likelihood or risk that it will be very, very low, which is the goal of therapy.

So that's the data we presented this past week.

Hey, which we show.

The FCS population in the MTM population will have very much the same with points with regard to the target.

<unk> and to the magnitude of <unk>, which is in the range of 80% to 90%. So what that means for a patient with Sds is mainly been.

Baseline will achieve a level beyond which the likelihood responded that it would be very very low which is the golar fit up the so we're very encouraged by these results and again right.

Javier San Martin: So we're very encouraged by these results. And again, right now, the majority of patients, depending on the baseline, will be in a healthy range of triglycerides. Yeah, and I just want to underline that I think that that is, That's one of the things that's so exciting about that candidate, that we are really moving the needle on triglycerides. We can really think about now normalizing many patients' triglyceride level, and I think that's a big thing. Got it.

Right now the majority of patients depending on their baseline will be in in a healthy range of Vegas.

And I just want to underline that I think that that is that's one of the things thats. So exciting about that candidate that we are really moving the needle on triglycerides, we can really think about now normalizing.

Many patients Patrick what's the right level and I think that's a big thing.

Christopher Anzalone: And then on the manufacturing investment, do you expect it once you have your facility up and running, that it may change the economics of your existing partnerships, assuming those assets progress to the clinic to commercialization? Or do you expect that, you know, that could change potential terms for future deals? That's a good question.

Got it and then on the manufacturing investment do you expect once you have your facility up and running and it maintains the economics of existing partnerships, assuming those asset progressing to the clinic and to commercialization.

Do you expect that that pertain to potential tenants for future deals.

That's a good question.

Christopher Anzalone: I don't think they will materially change the economics of existing deals. We could be a supplier to those partners, and no one has to use us, but they may want to use us, and so their economics there. Going forward, I think your point's a good one. It could be that it makes sense for future partners to take advantage of our manufacturing capabilities. And look, we spend a lot of time these days working on process development, and I think that we have discovered new ways of manufacturing that could lead to better purity, could lead to lower costs, and I think that could be something that's helpful for our partners. Great, thank you, and thank you, and our next question comes from Joel Beattie from Baird. Your line is now open.

I don't think they've been able to materially change the economics of existing deals.

Could be a supplier to those partners no one no one has to use us, but they but they may want to use us and so so that their economics there.

Going forward I think your point's a good one it could be that it makes sense.

For future partners to take advantage of our manufacturing capabilities and look we spend a lot of time these days.

Working on process development.

And I think that we have we have discovered new ways of of manufacturing that are that that could that could lead to better purity could lead to lower costs.

And I think that could be that could be something.

That's helpful for our partners.

Great. Thank you.

And thank you.

Our next question comes from Joel Beatty from Baird.

Your line is now open.

Joel Beattie: Hi, great. Congrats on the progress. Two questions on the ENAC program. The first is, what's the latest on the timing of an update on that going ahead on the NHP study and anything else that may be needed to be looked at for the program going ahead? And then the second question on the LUNG programs is, what gives you confidence that the two non-ENAC programs with a TTA filing can go ahead even if the data doesn't look good for the ENAC NHP study? Thanks for those questions.

Yeah.

Hi, great Congrats on the progress.

Two questions on <unk>.

Program. The first is with.

The latest on the timing of an update on that going ahead.

And this study and anything else that maybe needed to be looked at programs going ahead and then.

Second question on <unk>.

Jack as well just on the lung programs is what gives you confidence that 290 net programs.

Finally, you can go ahead, even if.

That doesn't look good.

And I see something.

Christopher Anzalone: So with respect to timing of how we move forward and when we move forward on ENAC as a target, I can't give you specific timing because this is all kind of real-time right now. I do believe, though, that in the first quarter of next year, we'll know where we're going. We're waiting for the NHP chronic docs, as you point out, and I think that should be in sometime by the end of December.

Sure. Thanks for the questions so with respect to timing of.

How we move forward and when we move forward.

On <unk> as a target.

I can't give you specific timing because because this is all kind of real time right now I do believe though that in the first quarter of next year, we will know where we're going what we're waiting for the HP chronic tox as you point out in that.

That should be in.

Sometime by the end of December.

We're also doing a number of non clinical studies internally to try to understand the basis of.

That local inflammatory response that we saw.

In the in the rats.

Christopher Anzalone: We're also doing a number of non-clinical studies internally to try to understand the basis of that local inflammatory response that we saw in the rats. Beyond that, I can't give you much more granularity, but I do believe, though, that at some point in that first quarter, we'll have either a path forward to restart Arrow ENAC, or we may decide to switch horses and move to this next generation. As I mentioned in the prepared remarks, we have been working on a next generation in-house, and I think we have a couple of potential candidates.

So so so I don't beyond that I can't give you much more granularity, but I do believe though that at some point in that first quarter, we'll know.

Either a path forward to restart arrow enact or we may decide to switch horses and move to this next generation as I mentioned in the prepared remarks, we haven't been working on next generation in house.

Christopher Anzalone: Nothing's been nominated yet, but we have a couple that are substantially more potent or at least appear so far to be substantially more potent than Arrow ENAC, and that could help out with an overloading issue if, in fact, that was the reason for the tox issue we saw in the rats.

And we are I think we have a couple of potential.

Candidates nothing's been nominated yes, we have.

A couple that are that are substantially more potent or at least appear so far to use substantially more potent than <unk> and that could help out with with an overloading issue. If in fact that was the reason for that.

Tissue, we saw it in rats.

Christopher Anzalone: I just say stay tuned on that. We'll know a lot more in the next couple of months, regarding what gives us confidence about the new pulmonary programs look, I think that the more potent we can make these constructs, the better. We know that overloading could be an issue, at least in rats, and so we're focused on making these constructs as potent as we can. Our next two are also substantially more potent than Arrow Enoch. I think that gives us some more comfort that we've got something, or we've got YouTube programs that may work well.

So I'd just say stay tuned on that we'll know a lot more in the next couple of months I think.

Regarding <unk>.

What gives us confidence about the new pulmonary programs look.

Yeah.

I think that that the more potent we can make these these contracts the better we know that.

Overloading.

It could be an issue at least in rats.

And so so we're focused on making a making these constructs as potent as we can and our next two are also substantially more potent than <unk> I think that gives us some.

Some more comfort that we are.

Got something probably we got two programs that may work, well, but look at the end of the day you don't know until you know and so we have to run chronic tox programs and we will see where those go but at least so far what we have in those two newer programs, we feel pretty good about and we're on track to file a cta in the first half of next year.

Christopher Anzalone: But look, at the end of the day, you don't know until you know, and so we have to run chronic tox programs and we'll see where those go, but at least so far, what we have in the two newer programs, we feel pretty good about, and we're on track to file CTAs in the first half of next year. Great, thank you. And one more thing. I was just given a note on this to remind me. It's a good point.

Great. Thank you.

Christopher Anzalone: One of the two NEXT programs has a circulating biomarker. That's going to be helpful to us to give us an idea about how much knockdown we're getting. What's tough about ENAC is that to understand how it's knockdown you're getting, it's just technically difficult.

Oh and.

One more thing.

I was just given a note on this tour to our mind to remind me it's a good point.

One of the.

Two next programs has a circulating biomarker that's going to be helpful to us.

Could you give us an idea about how much knock down we're getting.

Patrick Trucchio: And so I think we have a leg up on this NEXT program. Thank you. And our next question comes from Patrick Trucchio from H.C. Wainwright. Your line is now open. Thanks. Good afternoon. Just a couple of questions from me.

What's tough about <unk> is that is that to understand how it is knockdown youre getting it's just technically difficult and so.

So I think we have a leg up on this on.

The next program.

Thank you.

And our next question comes from Patrick <unk> from H C. Wainwright. Your line is now open.

Christopher Anzalone: The first one is I'm wondering if you can discuss the impact, if any, from the recently announced acquisition of a competitor's platform in terms of partnering discussions on your various programs. I'm wondering if you've seen an increased level of interest since that deal was announced and which programs could be next to partner in your pipeline. Boy, you're a master of the unanswerable questions on this one.

Thanks. Good afternoon, just a couple of follow up questions from me. The first one is I'm wondering if you can discuss the impact if any from the recently announced acquisition of a competitors platform in terms of <unk>.

Partnering discussions on your various programs I'm wondering if you've seen an increased level of interest since that deal was announced and which programs can be next to partner in your pipeline.

Boy, you're master of the unanswerable questions on this one.

Christopher Anzalone: I don't know that we've seen any increased partner interest in the last week or so. I will tell you this. Here's what we can control. Our job is to make medicines that are safe and that can help patients in ways that other medicines can't. To the extent that we can focus on that and we can succeed at that and we can do that rapidly, everything else will follow. I view the recent M&A acquisition as a bit of noise because it doesn't really affect our day-to-day business.

I don't know that that we've seen any increased.

Partnering interest in the last week or so.

Okay.

I will tell you this.

Here's what we can control.

Our job is to make medicines that are that are safe and that can help patients in ways that other medicines can to the extent that we can focus on that and we can succeed at that and we can do that rapidly.

Everything else or so we're sort of follow and so I kind of view this M&A in the region.

M&A.

The recent acquisition.

<unk> been a noise because it doesn't really affect our day to day business. So we need to remember why we're here every day, which is to make important medicines and that's what we're doing.

Christopher Anzalone: We need to remember why we're here every day, which is to make important medicines. Yep, yep, that's helpful. And then just with the understanding that AMG 980 is being developed by Amgen, I'm wondering if you could discuss expectations around the phase two trial. And assuming it's on track for phase two top line data in the first half of 2022, I'm wondering what level of LP little a knockdown would give confidence to move forward to a pivotal program? Sure. You know, I can't give you, I don't think I know any more than you do, to be honest.

Yeah, Yeah, that's helpful and then just.

With the understanding that AMG 980 is being developed by Amgen I'm wondering if you could discuss expectations around the phase II trial.

Assuming it's on track for phase two topline data in the first half of 2022, I'm wondering what level of LP Little a knockdown would give confidence to move forward to a pivotal program.

Sure.

I can't give you I don't think I know anymore than you do to be honest. My understanding is that is that Amgen has guided that they will have data in the <unk>.

Christopher Anzalone: My understanding is that Amgen has guided that they will have data in the first half of next year. I haven't heard that that's changed, so that's my understanding. And frankly, my expectation would be then that they would move into a pivotal study thereafter. I don't know how long it'll take them to do that.

First half of next year.

Haven't heard that Thats changed, but so that's my understanding.

And frankly, my expectation would be then that they would move into a into a pivotal study thereafter I don't know how long it will take them to do that the data that we've seen so far the data that had been presented or.

Christopher Anzalone: The data that we've seen so far, the data that have been presented, boy, are really good. You know, that is a potent drug candidate. They're seeing very deep knockdown, you know, with a very small amount of drug in Lp little a.

A really good that is a that is a potent drug candidates they.

We're seeing very deep knockdown with a very small amount of drug.

Christopher Anzalone: And I think that the genetic validation of that target is clear. So my expectation is that they will have data in the first half of the year, and then we'll just see how fast they can move to a pivotal trial. I can't really give you an idea about what would make them happy in terms of the reduction of Lp little a levels. I can tell you, though, that at least internally, we have been impressed with what they've shown so far. And if this was our program, I certainly wouldn't be slowing down.

<unk> and I think that the genetic validation of that target is clear.

So my expectation is that is that they will have data in the <unk>.

First half of the year and then we'll just see how fast they can move to a pivotal I can't really give you an idea about what would make them happy in terms of reduction of LP Little a levels I can't tell you, though that at least internally we have been impressed with what they've shown so far and if this was our program.

Christopher Anzalone: I'd be moving into a phase three, given what we've seen so far. Terrific. Thank you very much. And thank you. And our next question comes from Mani Foroohar from SVP Lyric. Your line is now open.

I certainly wouldn't be slowing down I'd be I'd be moving into a phase III given what we've seen so far at least.

Terrific. Thank you very much welcome.

Welcome.

Okay.

And thank you and our next question comes from Manny <unk> from SVP Leerink. Your line is now open.

Mani Foroohar: Hey, thanks. A follow-up question regarding, so another question about the EMACS program. You talked a little bit about this mouse signal counterpart with a related but not at all identical technology in ASO, had early human data and saw perhaps related or not talk signal in non-human primates, discontinued their program but did release that early human data. We expect that you'll be releasing some patient data with Arrow ENAC or is that something that you think you'll just put away and we'll never see?

Hey, thanks.

Follow up question regarding some other ones to enact programs can you talk a little bit about this mouse signal.

Counterpart.

Related but not all identical technology so at early human data.

Perhaps related or not tox signal in nonhuman primates.

Discontinue their program, but did release that early human data.

Should we expect that you'll be releasing.

Some patient data with Arrow ANAC.

Or is that something that you think you'll just put out you will just put away and we'll never see and then I have one follow up.

Mani Foroohar: And I have one follow-up. You know, I just don't know at this point, you know, let's, let's, let's see what we're where that program is going to go. You know, I don't know if we're going to restart that. So, so it's, I kind of don't want to get into hypothetical at this point and so so, That will stay paused.

Alright, I just don't know at this point.

Let's.

Let's see what where that program is going to go.

I don't know, if we're going to restart that.

And so so it's.

I kind of want to get into hypothetical at this point and so so.

Christopher Anzalone: Once we have an idea about how we go forward, either restarting enrollment in that or switching to a new construct, at that point, we can have a better discussion about what we do with the data that has been collected so far. And as you said, you guys spent a lot of time talking about extra hepatic programs, obviously a place where RNAi is still earlier in development than liver targeting for you and all companies, broadly speaking.

That will stay pause once we once we have an idea about where about how we go forward either restarting enrolment of that or or switching to two new construct at that point. Then we can we can have a better discussion about about what we do with the data that had been collected so far.

Christopher Anzalone: Is there a timeline we should expect an update on the oncology program that you gave us a first look at? And do you continue to see oncology or, broadly speaking, other kidney diseases as an area of growth for you? Or is that more of a one-off experiment? No, I would not call that a one-off experiment.

Great and as you saw you guys put a lot of them talking about Extrahepatic program, obviously, a place where our NII still earlier in development.

Then liver targeting for you and all in all companies broadly speaking.

Is there a timeline, we should expect an update on.

On the oncology program that you gave us a first look at and you continue to see oncology or broadly speaking other kidney diseases as an area of growth for you or is that or is that more of a one off experiment.

Christopher Anzalone: It is the first experiment, you know, in solid tumor targeting. And I think that we're off to a good start there. You know, I think we've seen clear target engagement, that's important. We've seen clear knockdowns, that's important.

No I would not call that a what I would expect it is.

The first experiment in solid tumor targeting and I think that I think we're off to a good start there. We I think we've seen clear target engagement that's important.

We've seen clear knockdown, that's important and.

Christopher Anzalone: And so now we just need to see, you know, if that particular drug is a drug, you know, we'll look at longer term response rates, and we'll make that decision. But I think from a platform standpoint, we are on the right track. Is this the last iteration of our oncology platform? Absolutely not.

And so now so now we just need to see.

If that particular drug as a drug we will look at longer term response rates and we'll make that decision, but I think from a platform standpoint, we are on the right track is this the last iteration of our oncology platform absolutely not we will we will certainly continue to to advance it but at least but from my perspective, it's a good start.

Christopher Anzalone: We will certainly continue to advance it. But at least, but from my perspective, it's a good start. Now, and to be clear, you know, this program is designed to, you know, to address solid tumors really kind of broadly. We don't yet have a platform that is designed to address kidney indications. That may happen at some point in the future, but right now we don't have that.

Now and to be clear.

This program is designed to to to address solid tumors really kind of broadly.

We don't yet have a platform that is.

Designed to address the kidney indications that may happen at some point in future, but right now we don't have that.

I don't know if I have a good.

Christopher Anzalone: I don't know if I have a good prediction, if I have a good prediction, about when we're going to have our next slug of data for HIF-2. We are fully enrolled. And so I think we're just following patients. James, do you have anything to add to that? No, I think that's about right. The study is fully enrolled. And so all the patients on the drug are just in the follow up. Great.

Good.

Prediction about when we're going to have our next slug of data for hip too.

We are fully enrolled.

I think thats about right. If the study is fully enrolled and so all the patients on drug in the.

And the follow up period.

Christopher Anzalone: Thanks, guys. Thank you. And our next question comes from Mayank Mamtani from B Riley Securities. Your line is now open.

Great. Thanks, guys.

Welcome.

Yeah.

Thank you and our next question comes from May eight.

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

Mayank Mamtani: Good afternoon team, congrats on the pipeline progress and also on the GSK deal and thanks for squeezing us in. Just have a few clarifying questions, just quick ones. So on the J&J refund study, just any idea on at what time points the follow-ups might come and when can we see the patient-level analysis? Is there any insight you have on how J&J might be thinking of communicating going forward? I really can't give you that, because I just don't know.

Good afternoon team congrats on the pipeline progress and also on the GSK deal and thanks for squeezing us in.

Just have a few clarifying questions just quick ones. So.

<unk> one study.

And any idea on.

What time points to follow ups, Mike and when can we see the patient level analysis is there any insight you have on our agenda might be thinking of communicating going forward.

No I really can't give you that.

Because I just don't know and in fact, we haven't seen I don't believe I don't believe at least I don't think we haven't seen.

Christopher Anzalone: In fact, we haven't seen, I don't believe at least, I don't think we've even seen the individual patient data. But as I said earlier, look, we're really encouraged by those data. You know, I think they're good data. You know, our drug is doing what it's designed to do. And so now, look, we just need to kind of sit back and see how this goes. As I mentioned in the prepared remarks, you know, ARC520, for those patients on ARC520 who was serocleared for S, it didn't happen in six months. It happened, you know, as early as nine months or as long as two years or so, as I recall, after drug was removed.

The individual patient data.

But as I said earlier look we're really encouraged by those data I think they're good data and our drug is doing what it's designed to do and so now we just need to kind of sit back and see how this goes as I mentioned in the prepared remarks arc 520 for those patients on archived material cleared for <unk>. It didn't happen in six months happen.

As early as nine months or as long as two years or so as I recall after drug after drug was removed and so we look forward to watching continue follow up I think that we are we have just entered.

Christopher Anzalone: And so, you know, we look forward to watching continued follow-up. I think that we are, we have just entered a prolonged data-rich period with Janssen. Given RIF1, RIF2, RIFD, you know, the interferon studies and others, I think that there will be, I think that there should be regular data released from various, you know, parts of these studies going forward. And so, you know, I think the 22 is probably gonna be substantially more data-rich than 21.

A prolonged data rich period with with Janssen, given reef, one reef to reap D.

Youre on studies.

In others, I think that there will be.

I think that there should be regular data.

<unk> from various ports or parts of these studies going forward and so you know.

I think 'twenty two is probably going to be some can be more data rich for 'twenty one was.

Christopher Anzalone: Looking forward to that. And then on AAT, can you remind us how you're tracking with the CEQA, you know, phase 2, 3, data package, I think about 40 subjects, and what might be the expectations in a placebo-controlled setting relative to, you know, what you've shown in the open label format?

Looking forward to that understood and then on <unk>.

Can you remind us how you're tracking with the sick.

Phase II <unk> data back as I think about 40 subjects.

And what might be the expectations.

In a placebo controlled setting relative to what you've shown in the open label format.

Javier San Martin: So, as you know, we have completed enrollment of 40 patients. The next data log where we're going to work on those selection will occur in the first half of 2022. So and that will be probably our next interaction with the agency to discuss the dose. And the pair biopsies will be finished by July, August of next year. So last patient, second or post-baseline biopsy will be in that time frame. So add to that the timing for data log and evaluation.

Yes, sure. So as you know we have completed enrollment of 40 patients.

The next state of low where we're going to work on dose selection will occur in the first half of 2022, so that will be probably what makes an interaction with the agency to discuss the dose.

The paired biopsies will be finished by July August of next year. So less station second post baseline biopsy will be in that timeframe. So that the timing for the data look on evaluation. So I would say towards the end of 2022 will have the placebo control pay antibody <unk>.

Javier San Martin: So I would say towards the end of 2022, we will have the placebo control pair biopsy result from Sequoia. Great, thank you. And just on the cardiometabolic polio and portfolio, I heard, you know, appreciate the level of detail on ANS3 and APOC3. And can you just put it together, like how in 2023, we will see some of the data generation activities. And I didn't, I didn't catch up on the enrollment for the FCS study, the phase three study. Could you just remind me of that?

As we saw from Sequoia.

Great. Thank you and just on the cardio metabolic.

Our wholly owned portfolio I could appreciate the level of detail on <unk>.

<unk>, three and <unk> III and can you just put it together like how in 2023, we will see some of the data.

Generation activities and I didn't I think ACH.

On the enrollment for the FCS study the phase III study could could you just remind me on that.

Mayank Mamtani: So, it's hard to guide to data release at this point because we just.., particularly for FCS because we haven't even dosed the first patient yet there. These are all the studies we talked about are year long studies. And so so the the both the the unknown here is how fast we can get these enrolled. So so let's give us some more time here at enrollment and then we can we I think we'll have better visibility and when we can start to have have data. Do you have anything else, Adam? No, I don't think that's fair.

Yeah.

So it's hard to guide to data release at this point because because.

Particularly for FCS because we havent, even dose first patient yet their visa.

These are all the things we talked about our year long studies and so the buffet. The unknown here is how fast we can get these enrolled.

Give us some more time here at enrollment and then we can I think we'll have better visibility on when we can start to have have data release.

You had anything else out of it.

Christopher Anzalone: And the question on the phase three for FCS. So the study is up and running. We have patients in screening. We've already activated sites.

I think Thats fair.

The question on the phase III for FCS So that the studies up and running we have patients in screening we've already activated sites and we anticipate dosing before the end of the year first dose.

Javier San Martin: So we anticipate dosing before the end of the year. First dose. Great, thanks so much for taking the time.

Great. Thanks, so much for taking my question.

Yeah.

Christopher Anzalone: And thank you. And I'm showing no further questions. I would now like to turn the call back to Chris Anzalone for closing remarks. Thanks everyone for joining us today and we wish you a happy and safe Thanksgiving weekend. This concludes today's conference call. Thank you for participating. You may now disconnect. [music] David Lebowitz, https://www.youtube.com.accenture.com https://www.youtube.com.accenture.com https://www.youtube.com.accenture.com music playing music playing music playing music playing music playing music playing [inaudible] [music] Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. Throughout today's recorded presentation, all participants will be in a listen-only mode.

And thank you and I'm showing no further questions I would now like to turn the call back to Chris Anzalone for closing remarks.

Hey, thanks, everyone for joining us today, and we wish you a happy and safe Thanksgiving weekend.

This concludes today's conference call. Thank you for participating you may now disconnect.

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Vince Anzalone: After the presentation, there will be an opportunity to ask questions. I will now hand the conference call over to Vince Anzalone, Vice President of Investor Relations for Arrowhead, please go ahead. Good afternoon, everyone.

Okay.

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Christopher Anzalone: Thank you for joining us today to discuss Arrowhead's results for 2022. 2021 Fiscal Year ended September 30, 2021. With us today for management are President and CEO, Dr. Christopher Anzalone, who will provide an overview of the quarter, Dr. Javier San Martin, our Chief Medical Officer, who will provide an update on our pipeline, and Ken Myszkowski, our Chief Financial Officer, who will give a review of the financial year. In addition, Dr. James Hamilton, our Senior Vice President of Discovery and Translational Medicine, will be available during the Q&A session of today's call.

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference call.

Today's recorded presentation, all participants will be in a listen only mode.

After the presentation, there will be a opportunity to ask questions.

I will now hand, the conference call over to them.

The loaning them Vice President of Investor Relations for Arrowhead. Please go ahead.

Justin.

Good afternoon, everyone. Thank you for joining us today to discuss arrowheads results for its 2022 2021 fiscal year ended September 32021.

With us today from management are president and CEO, Dr. Christopher Anzalone, who will provide an overview of the quarter Dr. Javier San Martin <unk>, Our Chief Medical Officer, who will provide an update on our pipeline and Ken Myszka <unk>, Chief Financial Officer, who will give a review of the financials. In addition, Dr. James Hamilton, Our senior Vice President of discovery and translational.

Madison will be available during the Q&A session of today's call.

Christopher 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 1935. All statements other than statements of historical fact are forward-looking statements, are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking, For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K. That said, I'd like to turn the call over to Christopher Anzalone, President and CEO of the company. Thanks, guys. Good afternoon everyone and thank you for joining us today.

Before we begin I would like to remind you that comments made during today's call contains certain forward looking statements within the meaning of section 27 a.

The Securities Act of 933 and section 21 E of the Securities Exchange Act of 1034, all statements other than statements of historical fact are forward looking statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward looking statements.

For further details concerning these risks and uncertainties. Please refer to our SEC filings, including our most recent annual report on Form 10-K.

That said I would like to turn the call over to Christopher Anzalone, President and CEO of the company Chris.

Thanks, guys.

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

Christopher Anzalone: Thank you for joining us today. Before I review the last quarter, I want to discuss the announcement this afternoon regarding our license agreement with GlaxoSmithKline for ArrowHSD, our investigational therapeutic, in a Phase 1-2 study that is currently being developed as a treatment for patients with NASH. On closing, GSK will receive an exclusive license to develop and commercialize Arrow HSD in all territories except Greater China, which will be retained by Arrowhead. GSK will be wholly responsible for further clinical development and commercialization outside of Greater Toronto.

I view the last quarter I wanted to discuss the announcement. This afternoon regarding our license agreement with Glaxosmithkline for Aero HST, our investigational therapeutic in a phase <unk> study that is currently being developed as a treatment for patients with Nash.

Clothing, GSK will receive an exclusive license to develop and commercialize arrow HST in all territories, except greater China, which will be retained by arrowhead.

SK will be wholly responsible for further clinical development and commercialization outside of greater China.

Christopher Anzalone: Partnership is a great fit for us because GSK has articulated a clear commitment to genetic medicine. It has substantial capabilities to clinically developed Arrow HSD for NASH and has impressive commercial infrastructure and expertise to bring this potentially important medicine to the tens of millions of patients who need it. This is also an important transaction because it enables us to take a large spend over the next several years off our books and focus our development capital on programs that we may commercialize or sell.

Chip is a great fit for us because GSK has articulated a clear commitment to genetic medicine. It has substantial capabilities to clinically developed aero HST for Nash and has impressive commercial infrastructure and expertise to bring this potentially important medicine to the tens of millions of patients who need it.

This is also an important transaction because it enables us to take a large spend over the next several years off our books and focus our development capital on programs that we may commercialize ourselves. In addition, it brings in substantial non dilutive capital, while providing us with exposure to future success should this drug candidate offer patients the kind of benefits we believe possible.

Christopher Anzalone: In addition, it brings in substantial non-dilutive capital while providing us with exposure to future success should this drug candidate offer patients the kind of benefits we believe possible. Arrowhead will receive an upfront payment of $120 million and is eligible for the following additional payments. $30 million at the start of Phase 2, $100 million at the start of Phase 3, up to $190 million at launch in the U.S. and major markets, and up to $590 million for key sales models.

Arrowhead will receive an upfront payment of $120 million and is eligible for the following additional payments.

$30 million at the start of phase III $100 million at the start of phase III up to $190 million at launch in the U S in major markets and up to $590 million.

For key sales milestones.

Christopher Anzalone: Taken together, Arrowhead stands to receive up to $1.03 billion. Arrowhead is further eligible to receive tiered royalties of mid-double digit to 20% on net product sales. From a strategic standpoint, this deal is another demonstration of our ability to use partnering selectively in areas that are outside of our commercial focus, also feels like the right time to partner because we believe our clinical data from the Phase 1-2 study demonstrate proof of concept for inhibiting the liver production of HSD-17-beta-30.

Taken together arrowhead stands to receive up to one point <unk> 3 billion.

Arrowhead is further eligible to receive tiered royalties of mid double digit to 20% on net product sales.

From a strategic standpoint. This deal is another demonstration of our ability to use partnering selectively and areas that are outside of our commercial focus because it also feels like the right time to partner because we believe our clinical data from the phase one two study demonstrate proof of concept for inhibiting the liver production of HST 17 paid at <unk>, we presented data at <unk>.

Christopher Anzalone: We presented data at AASLD earlier this month showing deep dose-dependent reductions in intrahepatic mRNA and protein levels and a marked reduction in ALT. We believe these are compelling results. The next steps for this program, if we had decided to retain global product rights, would have been to initiate a placebo-controlled phase two study to evaluate whether HSD17 beta 13 inhibition over time would lead to clinically significant improvements in NAS. Published genetic data suggest that people with loss of function mutations in HSD17-beta13 have some level of protection against fibrosis associated with NASH and other liver diseases.

Earlier, this month, showing deep dose dependent reductions of intrahepatic mrna and protein levels in a marked reduction in ALC. We believe these are compelling results.

The next steps for this program, if we had decided to retain global product rates would have been to initiate a placebo controlled phase II study to evaluate whether HST 17 beta 13 inhibition over time would lead to clinically significant improvements in Nash.

The published the published genetic data suggests that people with loss of function mutations in HST 17, beta <unk> have some level of protection against fibrosis associated with Nash and other liver diseases.

Christopher Anzalone: We think we have shown the Arrow HSD does what it is designed to do. However, there have not been any prior HSD17 beta 13 inhibitors studied in clinical trials, so human proof of concept of a clinical benefit needs to be established in future clinical studies. This is where GSK steps in.

We think we have shown the arrow HSV does what it is designed to do however, they have not been any prior HST 17 beta <unk> inhibitors studied in clinical trials. So human proof of concept of a clinical benefit needs to be established in future clinical studies.

Christopher Anzalone: They have a global reach and extensive experience and resources in clinical, regulatory, medical affairs, and commercial. They're in a strong position to pick up the program and advance it efficiently. As I mentioned, we think this is a net positive for the HSD, for the Arrow-HSD program, and for the patients with masks. We are confident that GSK is the right company to take the next steps in clinical development and to guide the program through the regulatory and commercial opportunities that lie ahead.

This is where GSK steps in they have a global reach and extensive experience.

And resources in clinical regulatory medical affairs and commercial.

They are in a strong position to pick up the program and advance it efficiently as I mentioned, we think this deal is a net positive for the HST or the Arrow HSV program in patients with Nash.

We're confident that GSK is the right company to take the next steps in clinical development and the chaperone the program through regulatory and commercial opportunities that lie ahead, we are thrilled to welcome GSK as our newest partner and look forward to working with them to advance this potentially important new medicine toward patients in need.

Christopher Anzalone: We are thrilled to welcome GSK as our newest partner and look forward to working with them to advance this potentially important new medicine to our patients in need. I'll now move on to some of the recent highlights and accomplishments during the prior quarter and the period since our last call. Our collaboration and license agreement with Janssen, which we signed in 2018, covered our hepatitis B program previously called Arrow HPV and now called J&J 3989 and three potential additional programs that we would develop preclinically for Janssen.

I'll now move on to some of their recent the recent highlights and accomplishments during the prior quarter and the period since our last call.

Collaboration and license agreement with Janssen, which we signed in 2018 covered our hepatitis B program previously called Aro HBV and now called J&J 39, 89, and three potential additional programs that we would develop pre clinically for Janssen.

Christopher Anzalone: JNJ 75220795 is the first program for which Janssen exercised its option to take an exclusive license, which earned Arrowhead a $10 million milestone payment earlier in the year. JNJ75220795 is an investigational RNAi therapeutic developed using Arrowhead's proprietary TRIM platform and is designed to reduce the expression in the liver of PNPLA3 as a potential treatment for patients with NASH. PNPLA-3 has strong genetic and preclinical validation as a driver of liver fat accumulation and damage.

J&J 75 to two O 795 is the first program.

For which Janssen X exercised its option to take an exclusive license, which earned arrow had a $10 million milestone payment earlier in the year.

J&J 75 to $2 795 currently in a phase one clinical study is an investigational <unk> therapeutic developed using arrowheads proprietary trim platform and is designed to reduce expression in the liver of Pn Pls III as a potential treatment for patients with Nash <unk>.

<unk> III is strong genetic and preclinical validation as a driver of liver fat accumulation and damage during the quarter Arrowhead earned an additional $10 million milestone payment after Janssen dosed the first patient in a phase one clinical study.

Christopher Anzalone: During the quarter, Arrowhead earned an additional $10 million milestone payment after Janssen dosed the fifth patient in a Phase I clinical study. Meanwhile, staying with the Janssen Collaboration, data were presented at AASLD from REEF1, a Phase 2b study to assess the efficacy and safety over 48 weeks of monthly subcutaneous injections of JNJ3989 at a dose of 40, 100, or 200 mg. This was used on top of daily nuke therapy, with or without daily oral JNJ6379, one of Janssen's capsid assembly modulators, or CAMs. JNJ3989 is an investigational RNAi therapeutic that targets all HPV RNAs, thereby intended to reduce levels of all viral HPV proteins.

Staying with Janssen staying with the Janssen collaboration data was presented at <unk> from a reef one a phase II study to assess the efficacy and safety over 48 weeks of monthly subcutaneous injections of J&J $39 89 at a dose of $40 100 or 200 milligrams. This was he was on top of daily.

Nuc therapy with or without daily oral J&J 60, 379, one of Janssens Capsid Assembly modulators or.

J&J 39, 89 is an investigational <unk> therapeutic that targets all HBV Rnas, thereby intended to reduce levels of all viral HBV proteins.

Christopher Anzalone: The primary endpoint of the study is the proportion of patients meeting new stopping criteria, which is ALT levels less than three times the upper limit of normal, HPV DNA less than the lower limit of quantitation. HPE antigen negative, HBS antigen less than 10 IU per ml at the end of treatment; data from 24 weeks off treatment was also presented at ASC. The data were very encouraging. The greatest reduction in S-antigen was observed in J&J 3989 200 mg with the new cohort.

Primary endpoint of the study is the proportion of patients meeting nuc, stopping criteria, which is ALC levels less than three times, the upper limit of normal HBV DNA less than the lower limit of quantitation.

HB antigen negative H B S antigen less than 10 IU per ml at the end of treatment.

Hakan.

Data from 24 weeks off treatment was also presented at <unk>.

The data were very encouraging to us the greatest reduction in S. Antigen was observed in J&J <unk> thousand 989, 200 milligram with new cohort.

Christopher Anzalone: A dose-dependent response was observed in other cohorts and didn't appear that adding the CAM had any beneficial effect. At week 48, the mean reduction in S-antigen from baseline was 2.6 logs, and 74.7% of patients achieved S-antigen less than 100 IU per mL. 19.1% of patients met NUC stopping criteria, the primary endpoint. Additionally, up to week 72, an additional 10.6% of patients met stopping criteria for a total of 29.7%. This is an important finding.

A dose dependent response was observed in other cohorts and didn't appear that adding the cam had any beneficial effect.

At 48 and week 48, the mean reduction in S. Antigen from baseline was $2 six logs and 74, 7% of patients achieved S antigen less than 100 IU per mill.

19, 1% of patients met nuc, stopping criteria that primary endpoint up.

Two week 72, an additional 10, 6% of patients met stopping criteria for a total of 29, 7%.

Christopher Anzalone: Additional patients continued to meet stopping criteria six months after therapy was discontinued. We are eager to see data with longer follow-up and individual patient profiles for the study. If you recall, in the studies with our first-generation compound, ARC520, in which some patients went on to achieve functional cures, the S antigen clearance didn't happen within six months of therapy being removed. Some patients took 9, 12, 18 months or longer to clear F-Anagene, so we are excited to see additional results from Reef 1.

This is an important finding additional patients continued to meet stopping criteria six months after therapy was removed.

We are eager to see data for <unk>, we are eager to see data with longer follow up an individual patient profiles for the study.

If you recall the studies with our first generation compound arc 520, and with some patients went on to achieve functional cures. The S antigen clearance didnt happened within six months of therapy being removed.

Some patients took 912 18 months or longer declare S. Antigen. So we are excited to see additional results from a reef one.

Christopher Anzalone: We are also eager to see data from the various other studies that Janssen is conducting. These include the ongoing reef two study, where patients come off all therapy as they achieve new stopping criteria, an ongoing study in patients with HPV and the hepatitis Delta virus, which is patient population, and desperate need of therapeutic options due to the rapid progression of the disease, and various studies with immunomodulatory agents at. There are currently multiple studies ongoing with pegylated interferon called Penguin and a study called Osprey, which is a with a DNA vaccine, J&J 64300535.

We are also eager to see data from the various other studies that Janssen is conducting these include the ongoing <unk> two study where patients come off all therapy as they achieved nuc stopping criteria and ongoing study in patients with HBV and the hepatitis Delta virus.

Which is a part which is the patient population in desperate need of therapeutic options due to the rapid progression of the disease and various studies with immuno modulator agents added there are currently multiple studies ongoing with Pegylated interferon called Penguin in a study called Osprey.

With a DNA vaccine J&J.

Ah 64, 300 $5 35.

Christopher Anzalone: We have been extremely impressed with how comprehensive the development program is for J&J 3980, and we believe it has the potential to play a central role as a backbone therapy for chronic HPV. Staying with AASLD, we also presented additional data on Arrow AAT, also called TAC999, our investigational candidate designed to treat liver disease associated with alpha-1 antitrypsin deficiency, which received breakthrough therapy designation from the FDA during the quarter and is being co-developed with Takeda.

We have been extremely impressed with how comprehensive the development program is for J&J 3900, 89, and we believe it has the potential to play a central role as a backbone therapy for chronic HBV.

Christopher Anzalone: We presented additional interim clinical data from the ongoing Arrow AAT 2002 study, an open-label Phase 2 clinical study to assess the response of Arrow AAT in approximately 16 patients with AATD-associated liver disease and baseline liver fibrosis. We think the data continue to reflect that Arrow AAT is highly active against its target. Specifically, the data suggests that Arrow AAT strongly inhibits production of the mutant Z-AAT protein, which we believe has been well-established as a clear cause of progressive liver disease.

Staying with <unk>. We also presented additional data on <unk> <unk> also called Tak 999, our investigational candidate designed to treat liver disease associated with Alpha one antitrypsin deficiency, which received breakthrough therapy designation from the FDA during the quarter and is being co developed with Takeda.

Christopher Anzalone: Further, the data suggests that livers in these patients are clearing the accumulated ZAAT and may be showing signs of healing. In this study, Arrow AAT treatment led to a 72 to 100% reduction of liver Z-AAT protein. Arrow AAT treatment reduced histologic globular burden in all patients with 13 of 13 patients having a one point or greater reduction in the PASD globular burden.

We presented additional interim clinical data from the ongoing Aro <unk> 2002 study an open label Phase II clinical study to assess the response of arrow.

Approximately 16 patients with <unk> associated liver disease, and baseline liver fibrosis, we think the data continued to reflect the Aro <unk> is highly active against this target specifically the data suggest that <unk> strongly inhibits production of the mutant Z <unk> protein, which we believe has been well established.

Clear cause of progressive liver disease.

Further the data suggest that livers and these patients are clearing the accumulated Z <unk> and may be showing signs of healing.

And the study <unk> treatment led to a 72% to 100% reduction of liver Z <unk> protein.

<unk> treatment reduced histologic globule burden in all patients with 13 of 13 patients, having a one point or greater reduction in the past <unk> globule burden.

Christopher Anzalone: Arrow AAT treatment also may have improved liver fibrosis. Six patients had a one point or greater improvement in metivir fibrosis stage from baseline to week 24 or 48. Since the presentation, we analyzed an additional 12-month paired biopsy that showed improvement in fibrosis, giving us 7 of 15 with fibrosis improvement now. When looking only at the 200 mg cohorts, we saw 7 of 12 patients with improved fibrosis. Arrowhead, excuse me, Arrowhead treatment also improved multiple biomarkers of liver...

Arrow <unk> treatment also may have improved liver fibrosis, six patients had a one point or greater improvement in Medicare fibrosis stage from baseline to week 24 or 48 since the presentation. We analyze an additional 12 months paired biopsy that showed improvement in fibrosis, given us seven or 15 with fibrosis.

Improvement now.

When looking only at the 200 milligram cohort, we saw seven of 12 patients with improved fibrosis.

Eric.

Gives me Aero 80 treatment also improved multiple biomarkers of liver health.

Christopher Anzalone: The mean reduction of ALT from baseline ranged from 42 to 56 percent and from 33 to 54 percent for GGT at week 28 and week 72. Importantly, all groups short showed normalized ALT and GGT following treatment. We believe these are all encouraging data. The program is on schedule, and we continue to be confident about its potential. We have begun a productive dialogue with the FDA about approval endpoints and the potential for an accelerated approval path.

Mean reduction of ALC from baseline range from 42% to 56% and from 33% to 54% for GTT at week 28, and week 72 <unk>.

Importantly, all groups short showed normalized <unk> and GTT following treatment.

We believe these are all encouraging data the program is on schedule and we continue to be confident about its potential.

Sure.

We have begun a productive dialogue with the FDA about approval endpoints and the potential for an accelerated approval pathway. We look forward to continuing this dialogue as the Sequoia study continues we expect to have data on the reduction of circulating levels of <unk> from Sequoia over the next few months, which should allow us to select a dose to move forward with.

Christopher Anzalone: We look forward to continuing this dialogue as the Sequoia study continues. We expect to have data on the reduction of circulating levels of AAT from Sequoia over the next few months, which should allow us to select a dose to move forward with.

Christopher Anzalone: We should also be collecting the last 12-month biopsy from the last patient enrolled sometime in the summer of 2022. Let's now move on to Arrow HSD, which is our investigational candidate designed to treat NASH that we announced today has been licensed to GSK. We presented data at ASLD on the pharmacodynamic effect of Arrow HSD and safety of various dose levels. In ARROW HSD 1001, a Phase 1-2 clinical study, we observed a dose-dependent pharmacodynamic effect on hepatic HSD17-beta-13 mRNA in all patients.

We should also be collecting the last 12 month biopsy from the last patient enrolled sometime in the summer of 2022.

Let's now move onto Aro, HST, which asset which is our.

Which is our investigational candidate designed to treat Nash that we announced today has been licensed to GSK.

We presented data at <unk> on a pharmacodynamic effect of Aero HST and safety at various dose levels.

<unk> 1001, a phase <unk> clinical study, we observed a dose dependent pharmacodynamic effect on hepatitis I'm, sorry on hepatic HST 17 beta <unk> mrna in all patients.

Christopher Anzalone: 200mg dose, all patients showed greater than 90% mRNA reduction, and Patek HSD 17-beta-13 protein levels were reduced in all Arrow HSD dose levels, with multiple measurements below the assay's lower limit of quantity. Decreases in ALT and AST were observed at doses of 100 milligram Arrow HSD and greater. Arrow HSD was well tolerated in all patients, with no drug-related serious adverse events reported, no adverse events leading to drug discontinuations, and no drug-related clinically significant adverse laboratory trends observed. We believe these data suggest that Arrow HSD is highly active at silencing liver production of HSD-17-beta-13.

At the 200 milligram dose all patients showed greater than 90% mrna reductions.

Eric HST 17, beta <unk> protein levels were reduced in all Aero HST dose levels with multiple measurements below the assays lower limit of quantitation.

Decreases in <unk> were observed at doses of 100 milligram Arrow HST and greater.

Aero HST was well tolerated in all patients with no drug related serious adverse events reported no adverse events, leading to drug discontinuation and no drug related clinically significant adverse laboratory trends observed.

We believe these data suggest that arrow HST is highly active at silencing liver production of HST 17 beta <unk>.

Christopher Anzalone: Moving to our wholly-owned cardiometabolic pipeline, Javier will give an update in a moment on the studies that are ongoing and their status, but I wanted to highlight another recent data presentation. At AHA last week, we presented additional Phase 1-2 clinical data on Arrow ApoC3, Arrowhead's investigational therapeutic targeting apolipoprotein C3, or ApoC3, being developed as a treatment for patients with hypertriglyceridemia, severe hypertriglyceridemia, and familial myocardial microanemia syndrome, or FCS. The presentation was assessing four genetically confirmed FCS patients and 26 patients with multifactorial chylomicronemia, which we refer to as MCM or non-MCM.

There's clearly an enormous unmet medical need for patients with Nash and we look forward to GSK designing future studies to evaluate the compound into phase II and beyond.

Christopher Anzalone: The latter patients tend to have extraordinarily high triglycerides and exhibit the same or similar phenotype as genetically defined FCS. We wanted to evaluate whether there is a different response to Arrow ApoC3 in these two groups. This is important because we are now initiating a Phase 3 study of Arrow ApoC3, which Javier will describe. In our study of patients with FCS compared with non-FCS patients, Arrow ApoC3 achieved similar levels of reduction of ApoC3, similar changes in Q11 parameters, and similar and comparable safety parameters. ApoC3 was reduced by 98% in FCS patients and 96% in MCM patients.

Moving to our wholly owned cardio metabolic pipeline Javier will give an update in a moment on the studies that are ongoing and their status, but I wanted to highlight another recent data presentation at <unk> last week, we presented additional phase one two clinical data on Aero Apoc, III arrowheads investigational therapeutic targeting April lipoproteins <unk>.

Christopher Anzalone: Both groups showed similar maximum median reductions in triglycerides of 91% and 90% respectively, non-HDL cholesterol was reduced by 58% and 49% respectively, and HDL cholesterol was increased by 152% and 111% respectively. Across our programs, preclinical data have been largely predictive of early clinical data, and early clinical data has been predictive of later stage clinical data. We see this with respect to pharmacodynamic response and safety and tolerability. I believe this is part of what makes RNAi and Arrowhead special, and one of the main reasons we can go into early clinical development with confidence that we have a good idea about what to expect.

<unk> or apoc, III being developed as a treatment for patients with hybrid hybrid triglyceride EMEA severe hypertrichosis already.

And familial Kelly micro anemia syndrome or Fcs.

The presentation was assessing for genetically confirmed Fcs patients.

And 26 patients with multifactorial, Chylomicron, EMEA, which we referred to as MCM or non Fcs.

The latter patients tend to have extraordinarily high triglycerides and exhibit the same or similar phenotype as genetically defined FCS we wanted to evaluate whether there is a different response to arrow apoc III and these two groups.

It is important because we are now initiating a phase III study of Aro, Apoc, III, which Javier will describe.

In our study patients with FCS compared with non FCS Aero Apoc III achieve similar levels of reduction of <unk> three.

Similar changes in key lipid parameters and similar and comparable.

Safety parameters.

Apoc III was reduced by 98% in FCS patients and 96% and MCM patients. Both groups showed similar maximum median reductions in triglycerides of 91% and 90% respectively non.

Non HDL cholesterol was reduced by 58% and 49%, respectively, and HDL cholesterol was increased by 152% and 111% respectively.

Across our programs preclinical data have been largely predictive of early clinical data and early clinical data has been predictive of later stage clinical data. We see this we see this respect we see this with respect to Pharmacodynamic response, and safety and Tolerability I believe this is part of what makes RNA <unk> and Arrowhead special and one of the main <unk>.

We can go into early clinical development with confidence that we have a good idea about what to expect in our view. This serves to increase the probability of success and potentially reduce risk.

Christopher Anzalone: That brings me to our newest clinical program. Arrow C3 is an investigational therapeutic designed to reduce production of complement component three or C3 as a potential therapy for various complement-mediated diseases. During the quarter, we announced the previously undisclosed candidate, we filed a CTA to begin clinical studies, and we hosted a Key Opinion Leader webinar to discuss the complement pathway and the diseases we will initially focus on. These include IgA nephropathy, complement 3 glomerulopathy, and paroxysmal nocturnal hematuria.

That brings me to our newest clinical program <unk> is an investigational therapeutic designed to reduce production of complement component three or <unk> three as a potential therapy for various complement mediated diseases.

During the quarter, we announced the previously undisclosed candidate we filed a cta to begin clinical studies and hosted a key opinion leader webinar to discuss the complement pathway and the need in the diseases. We will initially focus on these.

These include Iga nephropathy complement three equal in Mega Allopathy and breakfast nocturnal hematuria.

Christopher Anzalone: There are also other renal and hematologic diseases that we intend to evaluate in the future. The complement pathway is complex, and we did our best in the webinar to explain why we think a C3-targeted drug has the potential to address multiple complement-mediated or complement-associated diseases. We in the KOLs also explain the theoretical advantage of an RNAi therapeutic like Arrowhead, like Arrow C3, may have over other mechanisms and other complement targets.

There are also other renal and hematologic diseases that we intend to evaluate in the future.

The complement pathway is complex and we did our best and webinar.

To explain why we think a <unk> targeted drug has the potential to address multiple complement mediated or complement associated diseases.

We and the Kols also explained the theoretical advantages that an RNA therapeutic like <unk> like <unk> three may have over other mechanisms and other complement targets.

Christopher Anzalone: If you haven't listened to the webcast, I recommend you view it on our website for more information about Arrow Seeking. This is an early clinical program, but as I mentioned, we have a good track record of preclinical data translating well to clinical studies for investigational medicines developed with the TRMM platform. I'd like to provide a quick update on our pulmonary programs, including Arrow-ENAC, which is currently voluntarily paused to new enrollment as we assess some potential preclinical toxicology. We are still conducting studies internally to understand the toxicology findings and we don't have clarity yet on the path forward.

If you haven't listened to the webcast I recommend you view it on our website for more information about <unk> III.

This is an early clinical programs, but as I mentioned, we have a good track record of preclinical data translate well to clinical studies for investigational medicines developed with the trim platform.

Christopher Anzalone: While we conduct those studies, we continue to make progress on our two new pulmonary programs, which are on track for CTA filings in the first half of 2022. In addition, we are working on a next generation ENAC candidate in parallel, should that prove to be helpful or necessary. We believe in ENAC as a target for cystic fibrosis and are confident that our pulmonary targeted trim platform has the potential to address multiple diseases in the lung without adequate treatment options. We have less clinical experience applying the TRIMM platform to pulmonary tissue.

I would like to provide a quick update on our pulmonary programs, including <unk>, which is currently voluntarily paused to new enrollment as we assess and potentially some potential preclinical toxicology findings.

We are still conducting studies internally to understand the toxicology findings and we don't have clarity yet on the path forward.

While we conduct those studies, we continue to make progress on our two new pulmonary programs, which are on track for Cta filings in the first half of 2022.

In addition, we are working on a next generation <unk> candidate in parallel should that prove to be helpful or necessary.

We believe <unk> as a target for cystic fibrosis and are confident that our pulmonary targeted trim platform has the potential to address multiple diseases in the lung without adequate treatment options, we have less clinical experience applying the trim platform to pulmonary tissue. So we don't yet have the predictability that we see when we applied the trim platform in the liver, but we are.

Christopher Anzalone: So we don't yet have the predictability that we see when we apply the TRIMM platform in the liver, but we are committed to getting there and we are convinced that we can. Before turning it over to Javier to discuss the status of our mid and later stage cardiometabolic programs, I would like to discuss our growth... We now have 10 clinical stage programs and intend to expand our pipeline by 2 to 3 new programs per year.

Committed to getting there and we are convinced that we can.

Before turning it over to Javier to discuss the status of our mid and later stage cardio metabolic programs I wanted to Scott I would like to discuss discuss our growth plans.

We now have 10 clinical stage programs and intend to expand our pipeline by two to three new programs per year.

Christopher Anzalone: For more information on how you can support this growing pipeline, we are in the playing stages of expanding our R&D footprint in San Diego and Madison. We will be leasing a new space in San Diego that is scheduled to be built over the coming year. In Wisconsin, we are in discussions with local and state government authorities and economic development agencies to explore potential tax and other incentives to build a new facility.

Support this growing pipeline, we are in the planning stages of expanding our R&D footprint in San Diego and Madison will.

We will be leasing the new space in San Diego that is scheduled to be built over the coming year.

In Wisconsin, we are in discussions with local and state government authorities and economic development agencies to explore potential tax and other incentives to build a new facility.

Christopher Anzalone: Should those discussions be successful, we intend to build an Arrowhead campus in Wisconsin with two new facilities. These facilities will house expanded R&D and a GMP drug manufacturing plant. Our pipeline is advancing both in size and proximity to commercialization to the point where our buy versus build analysis indicates that the internal control of manufacturing now makes a lot of sense. This is true financially and, importantly, strategically.

Those discussions be successful, we intend to build an arrowhead campus in Wisconsin with two new facilities.

These facilities will how has expanded R&D and a GMP drug manufacturing plants.

Our pipeline is advancing both in size and proximity to commercialization to the point, where our buy versus build analysis indicates that the internal control of manufacturing now makes a lot of sense.

This is true financially and importantly, strategically we value speed at every stage of development and in every function.

Christopher Anzalone: We value speed at every stage of development and in every function. Building out drug manufacturing capabilities for preclinical, clinical, and commercial drug product will give us more control over timing, process, and cost. We have not yet closed on the purchase of the land, so we have not yet started to incur significant costs.

Building out drug manufacturing capabilities for preclinical clinical and commercial drug product will give us more control over timing process and cost.

We have not yet closed on the purchase of the land.

No we have not yet started to incur significant costs, but Ken will talk later about our estimates for Capex should we move forward with this plant expansion.

Christopher Anzalone: But Ken will talk later about our estimates for CapEx should we move forward with this plan expansion. With that overview, I'd now like to turn the call over to Dr. Javier San Martin. Javier.

With that overview I'd now like to turn the call over to Dr. Javier San Martin Javier. Thank you Kris and good afternoon, everyone. I wanted to focus on the status of our most advanced wholly owned cardio metabolic programs <unk> and <unk>.

Javier San Martin: Thank you, Chris. And good afternoon, everyone. I want to focus on the status of our most advanced wholly-owned cardiometabolic programs, AeroApoC-3 and AeroENG. In these two programs, the severity clinical studies are either active now or will be active, I will start with Arrow-ApoC3. This is our investigational medicine targeting, APO Lapopotene C3, being service in patient with various lipid disorders, including hyper-tributrydenia, severe hyper-tributrydenia, mech-tributidemia, multi-fartorial chylomythronemia, and familial chylomythronemia syndrome.

These two protests to submit a clinical study.

Now all will be active too.

I'll start with <unk>. This is our investigational medicine Tiger themed April level, putting C. III being studied in patients with various lipid disorders, including hybrid previously Damian severe hypothermia sylvania mixed dyslipidemia multifactorial entitlement to linear and some media telemeter, namely syndrome.

Javier San Martin: [inaudible] The set of mid- and late-stage studies of Arrowhead Proceed III is called the Summit Program, with each study named for a mountain peak. We currently have three open studies. 2001 is a phase 2 study in patients with severe hyperthyroidemia, which we are calling SHASTA-2. 2002 is a phase 2 study in patients with mixed sleep epidemia, which we are calling M.U.R.E.

The fifth of need in late stage studies of Italy, plus <unk>, it's called the semi colon with each study name for the Mountain peak. So we currently have three open studies.

One is the phase II study in patients with severe hypothermia, three then yet, which we're calling SaaS that too.

Two is the phase II study in patients with mixed Dyslipidemia, which we're calling <unk>.

Javier San Martin: In 2001, he faced three studies in partnership with FCS, which we're calling PALATF. I will describe each of these studies briefly and give current status for them. TASTA-2 is a double-blind, placebo-controlled, phase-2b study to evaluate the efficacy and safety of Arrowhead Poc3 in adults with severe hypertriglyceridemia, or SHTG. Three dose levels of Arrowhead Poc3, 10 milligrams, 25 milligrams, and 50 milligrams, will be evaluated against placebo in participants who have mean fasting triglycerides of greater than or equal to 500 milligrams per deciliter at screening.

And then one phase III study in patients with FCS, which vertical in policies.

We'll just describe each of these studies the <unk> current status for each.

That too is a double blind placebo controlled phase II study to evaluate the efficacy and safety of <unk> in adults with severe hypothermia.

Http.

See those levels.

$10 million $25 million 50 million that will be evaluated against placebo and participant who have meaningful <unk> of greater than or equal to 500 milligrams per deciliter at screening.

Javier San Martin: A total of approximately 216 participants will be enrolling in the study. All those cohorts will enroll in parallel with 72 participants per those cohort randomly assigned in a three to one ratio to receive AeroepoC3 or placebo. Each participant will receive subcutaneous injections on day 1 and week 12. The duration of the study is approximately 54 weeks from screening to the week 48 end of study examination. The primary objective of the Shasta II study is to evaluate the safety and efficacy of AeroApoC3 in adults with SHTG and to select a dosing regimen for later stage clinical studies in this patient population. CASTATU has enrolled 40 of the planned 216 patients with an additional 56 patients currently on screen to potentially be enrolled. We have activated 60 of the plan 80 sites.

A total of approximately 216 participants will be enrolling the study all of those cohorts will enroll in parallel with 72 participants those cohort randomly assigned in a three to one ratio to receive <unk> or placebo.

Each participant will receive subcutaneous injections on day, one and week 12, the duration of our study is approximately 54 weeks from screening to the week 48, and a steady examination. The primary objective of assessed the two studies to evaluate the safety and efficacy of <unk> in adult.

STG and selected dosing regimen for later stage clinical studies in this patient population.

Tested to have simple 40 of the planned 216 patients with an additional 56 patients put them clean as clean through potentially the end goal without activate the 60 of the planned 80 sites and our goal is to have this study fully enrolled around Q3 of 2022.

Javier San Martin: And our goal is to have the study fully enrolled around Q3 of 2020. Moving on to the new study, it is a double-blind, placebo-controlled, phase 2b study to evaluate the efficacy and safety of the arrowhead procedure in adults with mixed dyslipidemia. All those cohorts of Arrowhead Positrix will be evaluated against placebo in participants who have the following screen, elevated triglycerides greater than or equal to 100 milligrams per deciliter but less than 500 milligrams per deciliter and known HDL cholesterol greater than or equal to 100 milligrams per deciliter or LDL cholesterol greater than or equal to 70 milligrams.

Moving on to the New study is a double blind placebo controlled phase II study to evaluate the efficacy and safety of <unk> in adults with mixed dyslipidemia.

All of those cohort of AWP <unk> will be evaluated against placebo in participant who had the following screening.

Elevated triglycerides greater than or equal to 100 milligrams, meaning that for this initiative, but less than 500 milligrams per deciliter.

And non HDL cholesterol greater than or equal to 100 milligrams per deciliter, LDL cholesterol data than or equal to 17 media asset.

Javier San Martin: A total of approximately 320 participants will be enrolled in this training. All those cohorts will enroll in parallel with approximately 80 participants per those cohort randomly assigned in a 3-to-1 ratio to receive Arrowhead Pulse C3 or Pulse C4, in Tricohors 10mg, 25mg and 50mg. Each participant will receive a subcutaneous injection on day one and week 12 for a total of two injections. In one additional 50 mg cohort, each participant will receive a saccutane injection on day 1 and week 24 for a total of 2 injections.

It does.

Approximately 320 participants will be enrolling this study all of those cohorts will enroll in parallel with approximately $80 per dose cohort randomly assigned in a three to one ratio to receive.

<unk>.

In <unk> thin meeting a 25 megawatt.

Each participant will receive a subcutaneous injection on day, one and we closed for a total of two injections and when additional 50 milligrams cohort each participant will receive a <unk> injection on day, one and week 24 foot at a total of two injections.

Javier San Martin: The duration of the study is approximately 54 weeks from screening to the week 48 end of study exam. The primary effect of this newer study is to evaluate the safety and efficacy of aeroepocytry in adults with mixed sleep epidemia and to select the dose and dose regimen for later stage clinical study in this patient.

The duration of the study is approximately 54 weeks post cleaning to the week 48, and a study examination.

Revenue of 50 of the new study is to evaluate the safety and efficacy of Italy, principally in Netherlands, with mixed dyslipidemia and to select the dose and dose regimen for later stage clinical studies in this patient population.

Javier San Martin: The new study has enrolled 22 of the planned 320 patients with an additional 38 patients currently in screening to potentially be enrolled. We have activated 15 of the planned 32 sites, and our goal is to have the study fully enrolled in Q4 of 2022. The last active study for 808-POC-3 is PALACE. Phallus A is a phase 3 study to evaluate the efficacy and safety of aeroepocy 3 in adults with familial calomicronemia syndrome.

The new study has enrolled 22 of the 320 patients with an additional 38 patients currently in screening to potentially be in coal. We have activated 15 of the planned 72 sites and our goal is to have the study fully enrolled in Q4 of 'twenty two.

The last study for AWP OCC is policy.

Let's say if the phase III study to evaluate the efficacy and safety of <unk> in adults with familial <unk> syndrome.

Javier San Martin: Two dose levels of Arrowhead Pocitri, 25 and 50 mg, will be evaluated against placebo in participants with fasting triglycerides greater than 880 mg per deciliter that are refractory to standard lipid lowering therapy and diagnosis of FCS. Approximately 60 participants will be randomized in 2-to-1 ratio to receive four total doses of AeroApoC-3 or placebo administered subcutaneously once every two weeks. The duration of the study is approximately 56 weeks, from screen to month 12th, end of study examination. After month 12th, participants will be eligible and invited to consent and continue in an open-level extension study. All participants in the placebo group who opt to continue will switch to active drugs during the extension study.

Dose level of <unk>, 25, and $50 million will be evaluated against placebo in participants with vesting triglycerides greater than 880 meeting that lead to that.

Our refractory to standard lipid lowering therapy and diagnosis of FCS approximately 60 participants will be randomized two to one ratio to receive full total doses of <unk> or placebo administered subcutaneously. Once every three months.

The duration of the study is approximately 56 week from screen two months 12, and a steady examination aftermath 12 participant will be initial uninvited to consent and continue in an open label extension study ultra.

All participants in the placebo group up to continue we will seek to active.

During the extension study and the primary objective of the pilot phase two.

Javier San Martin: And the primary objective of the PALACS study is to evaluate the efficacy and safety of Arrowhead Placetri in adults with FCS. The primary endpoint is presentation from baseline and month 10 in fasting triglycerides. Additional secondary and exploratory endpoints include the change in other lipid parameters, incidence of acute pancreatitis, and other measures. We have activated three of the plan's 55 sites globally and are working hard to activate

To evaluate the efficacy and safety of <unk> in adults with Fcs.

The primary endpoint as a percentage of <unk> from baseline in <unk> in fact, insignias, yet additional secondary and exploratory endpoints include the change in other lipid parameters incidence of acute pancreatitis and other measures.

We have activated three of the planned 55 sites globally by working to activate additional sites that are currently patients in active screening and we anticipate the first patient to be enrolled and dosed before the end of the year.

Javier San Martin: There are currently patients in active screening, and we anticipate the first patient to be enrolled and those before the end of the year. I will now move on to ArrowH3, our investigational medicine designed to reduce production of antipoietin-like protein 3, and Speedy Entry as a potential treatment for pension remission. The set of mid and late stage studies for 80H3 is called the VISTA program, with each study named for a national park

I will now move on to <unk>, our investigational medicines designed to reduce pollution.

Yoplait light potency.

<unk> as a potentially significant issue with Mississippi Didnt.

The state of need in late stage studies for <unk> C is called the <unk> program with this study named for the National Park. We currently have one open studying the Vista, Florida.

Javier San Martin: We currently have one open study in the VISTA program. 80H3-2001 is a Phase II study in patients with mixed-use lipidemia, which we are calling Arches II. Arches 2 is a double-blind placebo-controlled phage to be studied to evaluate the efficacy and safety of investigational Arrowhenge 3 in adults with myx dyslipidemia. 3-Dose levels of Arrowhead H3, 50mg, 100mg, and 200mg will be evaluated against placebo in participants who have the following screen. LDL cholesterol greater than or equal to 70 mg per deciliter or non-HDL cholesterol greater than or equal to 100 mg per deciliter and means fasting triglycerides between 150 and 500 milligrams.

<unk> 2001 phase II study in patient with Macys, Lithemia, which are calling arches too.

<unk> two is a double blind placebo controlled phase II study to evaluate the <unk>.

CN safety of investigation of <unk> in adults with mixed Dyslipidemia three dose level of <unk>.

P 50 million against $100 million and 200 meeting is will be evaluated against placebo in participants who had the following at screening.

LDL cholesterol data than or equal to 17.

This latest or non HDL cholesterol greater than or equal to 100 Mg.

Visitors.

And mean fasting triglyceride between 150 on 500 milligrams per deciliter.

Javier San Martin: A total of approximately 180 participants will be enrolling in the study. All those cohorts will enroll in parallel with 60 participants per cohort randomly assigned in a three to one ratio to receive a subcutaneous injection of 80H3 or placebo on day one and week two. The duration of the study is approximately 42 weeks from screening to the week 36 end of study examination. After completing the week 36 visit, participants will be eligible to continue in an Open Lebowitz Extension Study.

A total of approximately 180 participant will be enrolling the study.

All of those cohorts will enrolling in parallel with 60 participant political core randomly assigned in a three to one ratio to receive a subcutaneous injection of <unk> or placebo on day, one and week 12.

Duration of the study is approximately 42 weeks from screening to the week 70 seats in our study seven nation.

After completing the week 36. This is participant will be eligible to continue in an open label extension study.

Javier San Martin: The primary objective of the ARCHOES-II study is to evaluate the safety and efficacy of AROH-3 in adults with mixed disease lipidemia and select a dosing regimen for later stage clinical study in this patient. The ARCHES III study has reached 50% enrollment with 90 of the planned 180 patients enrolled and those, with an additional 58 patients currently in the screening to potentially be. We have activated all 25 of the initial planned 25 sites.

The primary objective of the <unk> two study is to evaluate the safety and efficacy of <unk> three in adults with mixed Dyslipidemia and selected dose and dosing regimen for later stage study in this patient population.

Just three study has reached 50% enrollment with 90 of the plan 180 patients enrolled and those with an additional 58 patients currently in screening to potentially be enrolled.

We have activated all 25 of the initial plan 25 sites and our goal is to have the study fully enrolled in Q2 of 2022.

Javier San Martin: And our goal is to have the study fully enrolled in Q2 of 2020. I will now turn the call over to Ken Myszkowski, Arrowhead's Chief Financial Officer. Ken. Thank you, Javier, and good afternoon, everyone. As we reported today, our net loss for fiscal 2021 was $140.8 million, or $1.36 per share based on $103.7 million fully diluted weighted average shares outstanding.

I will now turn the call over to Ken <unk> Arrowheads, Chief Financial Officer, Ken.

Ken Myszkowski: This compares with a net loss of $84.6 million, or $0.84 per share, based on $100.7 million fully diluted weighted average shares outstanding for 2020. Revenue for fiscal 2021 was $138.3 million compared to $88 million for 2020. Revenue in the current period primarily relates to the recognition of a portion of the $300 million, Upfront payment received under our collaboration agreement with Takeda. Revenue for the Takeda Agreement will be recognized as we continue to work toward completing our performance obligations of managing clinical trials, in process and certain manufacturing related services. There remains $209 million of revenue to be recognized associated with the Takeda collaboration and it is anticipated to be recognized over approximately two to three years.

Thank you Javier and good afternoon, everyone.

As we reported today, our net loss for fiscal 2021 was 148 million.

$1 36 per share based on $103 7 million fully diluted weighted average shares outstanding.

This compares with a net loss of $84 6 million or <unk> 84 per share based on $100 7 million fully diluted weighted average shares outstanding for 2020.

Revenue for fiscal 2021 was $138 3 million compared to $88 million for 2020.

Revenue in the current period, primarily relates to the recognition of a portion of the $300 million.

Up front payment received under our collaboration agreement with Takeda.

Revenue for the Takeda agreement will be recognized as we continue to work toward completing our performance obligations of managing clinical trials.

In process and certain manufacturing related services.

There remains $209 million of revenue to be recognized associated with the Takeda collaboration and it is anticipated to be recognized over approximately two to three years.

Ken Myszkowski: Any additional milestones achieved with our collaboration partners would be additive to this projection. During fiscal 2021, we also entered into a new collaboration agreement with Horizon to develop a drug candidate to treat uncontrolled gout. We received a $40 million upfront payment for this agreement.

Any additional milestones achieved with our collaboration partners would be additive to this projection.

During fiscal 2021, we also entered into a new collaboration agreement with horizon to develop a drug candidate to treat uncontrolled gout.

We received a $40 million upfront payment for this agreement.

Ken Myszkowski: A portion of this amount was recognized in fiscal 2021, and we expect the balance to be recognized by the end of 2022, as our performance requirements are completed. Revenue in the prior period primarily related to the recognition of a portion of the milestones received from the license and collaboration agreements with Janssen. We also announced a new licensing agreement with GSK today for Arrow HSD, our candidate for the Arrow HSD vaccine. This agreement will result in an upfront payment of $120 million to Arrowhead. We anticipate a substantial majority of this to be recognized as revenue in fiscal 2022. Total operating expenses for fiscal 2021 were $287.3 million, compared to $181.2 million for 2020.

Portion of this amount was recognized in fiscal 2021, and we expect the balance to be recognized by the end of 2022 as our performance requirements are completed.

Revenue in the prior period, primarily related to the recognition of a portion of the milestones received from our license and collaboration agreements with Janssen.

We also announced a new licensing agreement with GSK today for Aero HSV candidate.

This agreement will result in an upfront payment of $120 million to Arrowhead, we anticipate a substantial majority of this to be recognized as revenue in fiscal 2022.

Total operating expenses for fiscal 2021 were $287 3 million.

Compared to $181 2 million for 2020 this.

Ken Myszkowski: This increase is primarily due to increased candidate-specific and discovery R&D costs, as the company's pipeline of clinical candidates has both increased and advanced, as well as additional non-cash stock compensation expenses. Net cash provided by operating activities during fiscal 2021 was $171.2 million, compared with net cash used by operating activities of $95.4 million in 2020. The key driver of this change was the $340 million in total upfront payments received from Takeda and Horizon in fiscal 2021.

This increase was primarily due to increased candidate specific and discovery R&D costs as the Companys pipeline of clinical candidates has both increased in advanced as well as additional noncash stock compensation expense.

Net cash provided by operating activities during fiscal 2021 was $171 2 million compared with net cash used by operating activities of $95 4 million in 2020. The key driver of this change was the $340 million and total upfront payments received from Takeda and horizon and fill.

2021.

Ken Myszkowski: Including any potential milestone payments received from our collaboration partners, we estimate our operating cash burn to be $60 to $80 million per quarter in fiscal 2022. In addition, we are planning to expand our manufacturing capabilities and expand our R&D facilities. These capital projects, along with routine capital expenditures, will add an incremental cash outlay of $80 to $90 million for full year fiscal 2022. Turning to our balance sheet, our cash and investments totaled $613.4 million at September 30, 2021, compared to $453 million at September 30, 2020.

Including any potential milestone payments received from our collaboration partners, we estimate our operating cash burn to be $60 million to $80 million per quarter in fiscal 2022.

Addition, we are planning to expand our manufacturing capabilities and expand our R&D facilities.

These capital projects, along with routine capital expenditures will add an incremental cash outlay of $80 million to $90 million for full year fiscal 2022.

Turning to our balance sheet, our cash and investments totaled $613 4 million at September 32021, compared to $453 million at September 32020.

The increase of our cash and investments was primarily due primarily due to the $340 million and total upfront payments received from Takeda in horizon.

Offset by cash used for operations.

Our common shares outstanding at September 32021 were $104 3 million.

Ken Myszkowski: The increase in our cash investments was primarily due to the $340 million in total upfront payments received from Takeda and Verizon, offset by cash used for operations. Our common share is outstanding at September 30, 2021, we're $104.3 million. With that brief overview, I will now turn the call back to Chris. Thanks again, and thanks to all for joining us today. We are executing on our strategy with respect to platform extension, pipeline expansion, and business development. Arrowhead's opportunities in the near term and long term are vast and continue to grow each day.

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

Thanks, Ken.

You all for joining us today.

We are executing on our strategy with respect to platform extension pipeline expansion and business development areas.

<unk> opportunities in the near term and long term, our vas and continue to grow each day.

Christopher Anzalone: The data from our clinical programs continue to be encouraging and strongly support further development of our investigational medicine. Lastly and importantly, we see the potential in the not too distant future where important medicines discovered and developed by Arrowhead start to get to patients who need them. This is why we invest in R&D and why we are building manufacturing capabilities now to support clinical and commercial supply. I'd now like to turn the call over to your questions. Operator?

The data from our clinical programs continue to be encouraging and strongly support further development of our investigational medicines.

Lastly, and importantly, we see the potential in the not too distant future, where important medicines discovered and developed by arrowhead start to get to patients who need them.

This is why we invest in R&D and why we are building manufacturing capabilities now to support clinical and commercial supply needs.

I'd now like to turn the call over to your questions operator.

Operator: And thank you. As a reminder to ask a question, you'll need to press star one on your telephone. To absorb your question, press the pound key.

And thank you as a reminder to ask a question you will need to press star one on your telephone.

With your question press the pound key.

Operator: We do ask that you limit yourself to one question and one follow-up. Again, that's one question, one follow-up. Please stand by while we compile the Q&A roster. And our first question is going to come from Luca. EC from RBC Capital, your line is now open.

Do ask that you limit yourself to one question and one follow up again Thats. One question one follow up please standby will compile the Q&A roster.

And our first question is going to come from Luca.

EC from RBC capital Your line is now open.

Luca Issi: Well, great. Thanks so much for taking my questions and congrats on all the progress. I'll ask you two, both the main question and the follow-up, I guess. So, on A1AT, it sounds like you had a productive dialogue with the FDA here. Can you expand a little bit more on that conversation and what was their level of receptivity to the idea of getting approved on just the liver A1AT level? That's question one. Then question two on GSK, wondering if you can comment on why you decided to retain sizable economics in the U.S. with a 50-50 profit split for A1AT, but obviously, here we have a very different structure for NASH, so any color on that would be great. Thanks so much. Sure. So I'm going to take the first one first, which is straightforward.

Oh, great. Thanks, so much taking my questions and congrats on the progress I'll ask too.

The main question and a follow up I guess, so it sounds like you had a productive dialogue with the FDA here can expand living more in that conversation and what was their level of rest of the <unk> on the idea of getting approved on just deliver a 100% level. That's question. One and then question two and GSK wondering if you can comment on why.

<unk> decided to retain sizable economics in the U S. With 50 50 profit split for a while but.

But obviously here we have a very different structure for Nash so any color on that would be great. Thanks. So much.

Christopher Anzalone: There's not much we can tell you. Look, we had a very encouraging and productive discussion with the FDA just this last week. I think that we are moving in the right direction, and it was a good collaborative interaction. We look forward to continued discussions. This is an ongoing dialogue, and we've just begun it, and so I expect to have continued discussions in 2022, particularly as we have additional data.

Sure. So let me take the first one first which is straightforward there's not much you can tell you look we had a we had a very.

Encouraging and productive.

Discussion with the FDA in fact, just this last week.

I think that we are moving in the right direction and it was a good collaborative interaction.

We look forward to continue discussions this is an ongoing dialogue and we've just begun fashion. So I expect to have.

Yes.

Continue dialogue in 2022, particularly as we have additional data.

Christopher Anzalone: So there's not much I can tell you right now other than that. Again, so far, so good. I think it's been a good conversation so far. With respect to the different field structures for AAT and for HSD, I think that just reflects the state of development of the two programs; AAT was, of course, farther advanced than HSD at first.

So there's not much I can tell you right now other than that again, so far so good I think it's been a good conversation so far with respect to to the different deal structures for AEP and for and for HST.

I think that just reflects.

The state of.

The development of the two programs <unk> course farther advanced then HST that's first second.

Christopher Anzalone: Second, AAT, I think the biology there is quite clear. HSD, we still need to suss that out. There's really good genetic validation for that target. But as we talked about earlier in the call, there's been no inhibitors of this protein that have been tested.

I think the biology, there is quite clear HST, we still need to suss out theres really good genetic validation for that target, but as we talked about earlier in the call.

There's been there's been no inhibitors.

This protein that had been tested and so and so while the genetic data look encouraging we still need human proof of concept and so.

Christopher Anzalone: And so while the genetic data look encouraging, we still need human proof of concept. And so I fully trust that we'll show that, or at least JSK will show that. But it's just a different state of progress between AAT and HSD. And finally, these are two very different diseases. HSD is a very large disease.

I fully trust that we will show that or at least GSK will show that but but it's.

A different state of.

Progress.

Tween 80 in HST and finally these are these are two very different diseases HST as is.

<unk> is a very large disease.

Christopher Anzalone: Tens of millions of people in the U.S. are likely potential patients for that, whereas AAT is an orphan indication. We think that there's maybe 100,000 to 120,000 potential patients in the U.S. And so given all of that, you know, we would look for different economics and different structures for those two programs. We're very happy with both of them. I think we have the right partner for AAT and Takeda, who is committed, and we are really working together with them to bring this important medicine to these patients.

Tens of millions of people in the U S.

Unlikely potential patients for that whereas <unk> is an orphan indication. We think that there is maybe 100 to 120000 potential patients in the U S and so given all of that.

We would look for different economics and different structures for those two programs. We're very happy with both of them I think we have the right partner for for <unk> and Takeda, who is who has committed and we are really working together with them to bring this important medicine to these patients and similarly, I think we have got the right.

Christopher Anzalone: And similarly, I think we have got the right partner in GSK for NASH. They appear to be committed to the program, and we are impressed with their ability to move that program forward. Super, thanks so much.

Our partner in GSK for Nash.

They appear to be committed to the program.

And we are impressed with their ability to move that program forward.

Super Thanks, so much welcome.

Welcome.

Christopher Anzalone: You're welcome. Thank you. And our next question comes from Alicia Young from Cantor. Your line is now open.

Thank you.

And our next question comes from Alicia Young from Cantor.

Your line is now open hey.

Alicia Young: Hey guys, thanks for taking my questions. One, I just wanted you to talk a little bit about your perspective on the capsid and sRNA data at AASLD. I mean, do you feel like combination is the way to go?

Hey, guys. Thanks for taking my questions. One I just wanted you to talk a little bit about your perspective on the.

The capsid than S RNA data.

At <unk> I mean, do you feel like combinations the way to go is kind of interesting the <unk> activity.

And then I think my second question is just on whether you guys would ever think about maybe potentially doing something that Mike narrow because I know some of your competitors are now talking about that thanks.

Christopher Anzalone: It's kind of interesting, the capsidential activity. And then I think my second question is just on whether you guys would ever, you know, kind of think about maybe potentially doing something in like neuro, because I know some of your competitors are now talking about that. Sure. Thanks, Leith.

Sure I think it's good to hear from you.

So with respect to the two combination for HBV look I think that I was very encouraged by by Janssen data. Our drug is doing what it's designed to do and we saw deep reductions of S antigen.

We are.

Assume that we are seeing good reductions in all in all viral antigens.

Christopher Anzalone: It's good to hear from you. So, with respect to the combination for HPV, look, I think that I was very encouraged by Janssen's data. You know, our drug is doing what it's designed to do. You know, we saw deep reductions of F-antigen. We are, I assume that we are seeing, you know, good reductions in all viral, We saw a good percentage of patients who got S below 100 IU. I think it was 75 or so percent, you know, during treatment.

We saw a good percentage of patients who got.

Scott S below a 100 IU I think it was 75 or so percent.

Christopher Anzalone: That's impressive, and we think that that number, that 100 IU, is an important number. You know, it's been shown in the past that patients who can get below 100 IU have a better chance of sero-clearing. And then, of course, the primary endpoint looked good.

During treatment Thats impressive and we think that that number that 100 IU is an important number it's been shown in the past that patients who get below 100, <unk> you have better chances to euro clearing and then of course.

The primary endpoint looked good we saw a lot of patients, who who who achieved nuc stopping criteria and even more patients who achieve that criteria human after they came off therapy and so we're really encouraged.

Christopher Anzalone: You know, we saw a lot of patients who achieved the nuke stopping criteria, and even more patients who achieved that criteria even after they came off therapy. And so, we're really encouraged, you know, by that start, and we're looking forward to watching these patients continue on therapy and seeing if we can get some functional cures. Now, with respect to combinations, we've always believed that this is a tough virus and that we were hopeful that our drug, you know, could be a backbone approach, and nothing we have seen so far has pulled us from that thought.

By that start and we're looking forward to watching these.

These patients continue.

Off therapy, and see if we can get some some functional cures.

With respect to combinations. We've always believed that this is a tough virus in that that we were hopeful that that.

That our drug could be backbone approach and nothing we've seen so far has has pulled us from that thought and we still think it's going to be the backbone approach and we still think that to get.

Christopher Anzalone: We still think it's going to be the backbone approach, and we still think that to get, you know, wide-ranging consistent functional cures that you may need a combination approach. I think that CAM is probably not the preferred combination going forward, but J&J or Janssen is going about this in the right way.

Wide range and consistent functional cures.

You May you may need a.

A combination approach I think that that that Tam is probably not the preferred.

Combination going forward.

But J&J Janssen is going about this in the right way. There's there are a number of studies ongoing we look forward to seeing what the what the immuno modulator studies look like.

Christopher Anzalone: They have a number of studies ongoing. We look forward to seeing what the immunomodulatory studies look like and beyond. So I think that we are still in the early part of trying to figure out what the correct therapy is for HPV, but I think we're on the right track and I think those data support that. Oh, sorry, CNS, right. Sorry, CNS.

And beyond so.

I think that we are still in the early part of <unk>.

Of trying to figure out what the correct therapy for HBV, but I think that we're on the right track and I think those data support that.

Okay.

Christopher Anzalone: Look, we do not, we don't have any stated programs in CNS right now. But you're right, you know, we have competitors who have been working on that for some time now, for good reason. You know, there's a lot of unmet medical need there.

Do you have any plans for sorry CNS rights.

Alright.

Look we do not.

We don't have any stated programs in CNS right now, but you are right. We have competitors, who have been working on that for some time now.

For good reason.

There is a lot of unmet medical need there.

Christopher Anzalone: And there are clearly some indications that could be addressed using RNAi. And so, you know, we wish them, we wish them good luck. I think that at some point, we will be there because it's important for us to be there.

And there are clearly some.

Indications that could be.

Addressed using <unk> and.

And so we wish them, we wish them. Good luck I think that at some point, we will be there because it's important for us to be there.

To date, we have focused on other.

Christopher Anzalone: To date, we have focused on other cell types. As you know, we've got programs in pulmonary and solid tumor, skeletal muscle, you know, by the middle of next year, we can talk about that in the call, but we're still on track, you know, for skeletal muscle. But yeah, eventually, you know, at some period, we will likely have a program in CNS. We just don't have one right now.

And other cell types as you know we've got programs in pulmonary and solid tumor.

Skeletal muscle by the middle of next year, we can talk about that in the call, but we're still on track for four for skeletal muscle.

But yes eventually at some period, we will likely have a.

A program in CNS, we just don't have one right now.

Christopher Anzalone: Great. Thank you. You're welcome.

Great. Thank you.

Welcome.

Maurice Raycroft: And thank you. And our next question comes from Maurice Raycroft from Jeffries. Your line is now open.

And thank you and our next question comes from Maury Raycroft from Jefferies. Your line is now open.

Christopher Anzalone: Hey, congrats on the update. And thanks for taking my questions. I was just going to ask a question on HSD.

Hey.

Congrats on the update and thanks for taking my questions. I was just going to ask a question on HST. Congrats on that update I was wondering if you can say if the process to partner <unk>.

The asset was competitive and since you're pursuing <unk> in Nash with J&J, the J&J have any option or right of refusal for HSV.

Christopher Anzalone: I'm wondering if the process to partner the HSD asset was competitive, and since you're pursuing PMPLA-3 in NASH with J&J, did J&J have any option or right of refusal for HSD? Thanks very much. It's good to hear from you, Maurie.

Sure. Thanks, very much it's good to hear from you Mark.

Christopher Anzalone: Yes, we did run a competitive process. We spoke with a number of companies about the asset, and GSK seemed to be the best partner. J&J did not have a right of first refusal or anything like that for HSE.

Yes, we did run a competitive process, we spoke with with a number of companies about about the asset and GSK seem to be the.

The best partner.

J&J did not have a right of first refusal or anything like that for HST.

Javier San Martin: I got it. Okay. And also, one quick question for AAT, just wondering how many of those patients will have a 12-month biopsy, and how many will have an 18-month biopsy? Yeah, do you want to address that? Yeah, so 12 months of biopsy have all eight patients in cohort two that received 200 milligrams. 18 months, right now we had two, and it's likely to be a few patients that we had a 24-month biopsy, but because it's not mandatory, not all patients will accept or have accepted to go through the third biopsy, and that's the case in the first cohort, that was the six months, 200 milligrams. Two of the four patients accepted to have the follow-up biopsy, and two of them did not.

Got it Okay and also one quick question for Jim.

I'm just wondering of the 16 patients if you can clarify how many of those patients. So we will have 12 month biopsy and how many will have 18 months biopsy.

Where do you want to address that yes. So it's 12 month biopsy, how all eight patients in cohort two that seem to have an immediate.

18 months right now we had to and is likely to be.

Few patients that we had a 24 month biopsy.

But because its not mandatory and all patients will have said or have accepted to go through the third biopsy.

The case in the first cohort of six months 200 milligram two of the four patients accepted to have a follow up biopsy and two of them did not so we don't know how many would have said from the other cohorts that they post baseline biopsy was weak.

Month 12.

Got it okay. Okay. Thanks for taking my questions.

Thank you.

Javier San Martin: So we don't know how many would accept from the other cohorts that the post-baseline biopsy was a week, sorry, month 12. Got it. Okay. Okay. Thanks for taking my question. Thank you. And our next question comes from Esther Rajavulu from UBS. Your line is now open. Hi, thank you for taking my question. I have just two.

And our next question comes from Esther Roger Lulu from UBS. Your line is now open.

Esther Rajavulu: First, on the Arrow ApoCt program, if the magnitude of the ApoCt reduction is similar between the FCS and MCM patients, can you share your thoughts on what the implications for therapeutic benefit and outcomes could be for the FCS patients? And then my follow-up question is on manufacturing, which I'll ask in a second. Sure, Javier, I would like to add something.

Hey, Thank you for taking my question I guess I have two first on the <unk>.

Program.

Magnitude if the apoc team adoption is similar between the FCS and MCM patients can you share your thoughts on what the implications for therapeutic benefit in outcome could be for the Fcs patients.

And then my follow up is on manufacturing workshop, which I'll ask in a second.

Sure Javier I would like to assume.

Javier San Martin: Yes, so that's the data we presented, you know, this past week at AHA, in which we show that the FCS population and the MCM population has very much the same response with regard to the target, ApoC3, and to the magnitude of decrease in triglycerides, which is in the range of 80 to 90%. So what that means for patients with STS is that many of them, the pain of their baseline will achieve a level beyond which the likelihood or risk factor that it will be very, very low, which is the goal of therapy.

So that's the data we presented this past week.

Hey, which we show.

The FCS population in the MTM population will have very much the same response with regard to the target.

<unk> and to the magnitude of the decrease in triglycerides, which is in the range of 80% to 90%. So what that means for a patient with Sds is many of them. The peanuts that baseline will achieve a level beyond which the likelihood responded that it would be very very low which is they are going to fit up the so what.

Javier San Martin: So we're very encouraged by these results. And again, right now, the majority of patients, the pain of the baseline will be in a healthy range of triglycerides. Yeah, and I just want to underline that I think that that is, That's one of the things that's so exciting about that candidate, that we are really moving the needle on triglycerides. We can really think about now normalizing many patients' triglyceride level, and I think that's a big thing. Got it.

Encouraged by these results and again.

Right now the majority of patients depending on their baseline will be in in the healthy range of Vegas.

And I just want to underline that I think that that is that's one of the thing thats so exciting about that candidate.

We are really moving the needle on triglycerides, we can really think about now normalizing.

Many patients Patrick what's the right level and I think Thats a big thing.

Christopher Anzalone: And then on the manufacturing investment, do you expect that once you have your facility up and running, that it may change the economics of your existing partnerships, assuming those assets progress from the clinic to commercialization? Or do you expect that, you know, that could change potential terms for future deals? That's a good question, but I don't think it will materially change the economics of existing deals. We could be a supplier to those partners. No one has to use us, but they may want to use us, and so their business there.

Got it and then on the manufacturing investment do you expect once you have your facility up and running and it maintains the economics of your existing partnerships, assuming those assets to advance to the clinic and to commercialization.

Do you expect that that pertain to potential Tam for future deal.

That's a good question.

<unk>.

I don't think they will materially change the economics of existing deals.

Could be a supplier to those partners no. One no one has to use us for date, but they may want to use us and so so that their economics there.

Christopher Anzalone: Going forward, I think your point's a good one. It could be that it makes sense for future partners to take advantage of our manufacturing capabilities. We spend a lot of time these days working on process development, and I think that we have discovered new ways of manufacturing that could lead to better purity, could lead to lower costs, and I think that could be something that's helpful for our partners. Thank you, and thank you. And our next question comes from Joel Beattie from Baird. Your line is now open.

Going forward I think your point's a good one it could be that it makes sense for future partners to take advantage of our manufacturing capabilities and look we spend a lot of time these days.

Working on process development.

I think that we have we have discovered new ways of of manufacturing that are that that could that could lead to better purity could lead to lower costs and.

And I think that could be there.

That could be something thats helpful for our partners.

Great. Thank you.

And thank you.

And our next question comes from Joel Beatty from Baird. Your line is now open.

Joel Beattie: Hi, great. Congrats on the progress. Two questions on the ENAC program. The first is, what's the latest on the timing of an update on that going ahead on the NHP study and anything else that may be needed to be looked at for the program going ahead? And then the second question on the LUNG programs is, what gives you confidence that the two non-ENAC programs with a TTA filing can go ahead even if the data doesn't look good for the ENAC NHP study? Thanks for those questions.

Alright, great congrats on the progress.

Two questions on the <unk> program. The first is what's the latest on the timing of an update on that going ahead.

In this study.

Maybe you needed to be looked at.

Graham going ahead and then.

The second question on enact as well just on the loan programs is what gives you confidence that 290 net programs, where the Cta Barrington go ahead even.

The data doesn't look good.

Sorry.

Christopher Anzalone: So, with respect to timing of how we move forward and when we move forward on ENAC as a target, I can't give you specific timing because this is all kind of real-time right now. I do believe, though, that in the first quarter of next year, we'll know where we're going. We're waiting for the NHP chronic talks, as you point out, and I think that should be in sometime by the end of December. We're also doing a number of non-clinical studies internally to try to understand the basis of that local inflammatory response that we saw in the rats.

Sure Thanks for the questions.

With respect timing of of how we move forward and when we move forward.

<unk> as a target.

I can't give you specific timing because because this is all kind of real time right now I do believe though that in the first quarter of next year, we will know where we're going what we're waiting for the for the NHS chronic tox as you pointed out and I think.

That should be in.

Sometime by the end of December.

We're also doing a number of non clinical studies internally to try to understand the basis of the of that local inflammatory response that we saw.

In the in the rats.

So so so I don't beyond that I can't give you much more granularity, but I do believe though that at some point in that first quarter will know haven't will have either a path forward to restart arrow ANAC or we may decide to switch horses and move to this next generation as I mentioned in the prepared remarks, we.

Christopher Anzalone: Beyond that, I can't give you much more granularity, but I do believe, though, that at some point in that first quarter, we'll know we'll have either a path forward to restart Arrow ENAC, or we may decide to switch horses and move to this next generation. As I mentioned in the prepared remarks, we have been working on a next generation in-house, and I think we have a couple of potential candidates. Nothing's been nominated yet, but we have a couple that are substantially more potent, or at least appear so far to be substantially more potent than Arrow ENAC, and that could help out with an overloading issue if, in fact, that was the reason for the tox issue we saw in the rats.

Haven't been working on next generation in house.

And we are I think we have a couple of potential candidates nothing's been nominated yet.

A couple that are that are substantially more potent.

Pierre So far east is substantially more potent than <unk> and that could help out with with an overloading issue. If in fact that was the reason for that for the Tox issue, we sought in rats.

Christopher Anzalone: So I just say stay tuned on that. We'll know a lot more in the next couple of months, regarding what gives us confidence about the new pulmonary programs look, I think that the more potent we can make these constructs, the better. We know that overloading could be an issue, at least in rats, and so we're focused on making these constructs as potent as we can. Our next two are also substantially more potent than Arrow Enoch.

So I'd just say stay tuned on that we'll know a lot more in the next couple of months I think.

Regarding.

What gives us confidence about the new pulmonary programs look.

Okay.

I think that that the more potent we can make these these contracts to better we know that.

Overloading.

It could be an issue at least in rats.

And so so we're focused on making I'm, making these constructs as potent as we can and our next two are also substantially more potent than <unk> I think that gives us some.

Christopher Anzalone: I think that gives us some more comfort that we've got something, or we've got YouTube programs that may work well. But look, at the end of the day, you don't know until you know, and so we have to run chronic tox programs and we'll see where those go, but at least so far, what we have in the two newer programs, we feel pretty good about, and we're on track to file CTAs in the first half of next year. Great, thank you. Oh, and one more thing. I was just given a note on this to remind me. It's a good point.

Some more comfort that we are that we have.

Got something probably we got two programs that that worked well, but look at the end of the day you don't know until you know and so we have to run chronic tox programs and we will see where those go but at least so far what we have in those two newer programs, we feel pretty good about and we're on track to file a cta in the first half of next year.

Great. Thank you.

And.

One more thing.

I was just given a note on this chart to remind remind me it's a good point.

Christopher Anzalone: One of the two NEXT programs has a circulating biomarker, so that's going to be helpful to us to give us an idea about how much knockdown we're getting. You know, what's tough about ENAC is that to understand how much knockdown you're getting, it's just technically difficult.

One of the.

Two next programs has a circulating biomarker that's going to be helpful to us.

Could you give us an idea about how much knockdown we're getting.

What's tough about <unk> is that is that to understand how it is knockdown youre getting it's just technically difficult and so.

Christopher Anzalone: And so I think we have a leg up on this NEXT program. Thank you. And our next question comes from Patrick Trucchio from H.C. Wainwright. Your line is now open. Thanks. Good afternoon.

So I think we have a leg up on this on.

The next program.

Thank you.

And our next question comes from Patrick <unk> from H C. Wainwright. Your line is now open.

Patrick Trucchio: Just a couple of questions from me. The first one is I'm wondering if you can discuss the impact, if any, from the recently announced acquisition of a competitor's platform in terms of partnering discussions on your various programs. I'm wondering if you've seen an increased level of interest since that deal was announced and which programs could be next to partner in your pipeline. Boy, you're a master of the unanswerable questions on this one.

Thanks. Good afternoon, just a couple of follow up questions from me. The first one is I'm wondering if you can discuss the impact if any from the recently announced acquisition of a competitors platform in terms of <unk>.

Partnering discussions on your various programs I'm wondering if you've seen an increased level of interest since that deal was announced and which programs can be next to partner in your pipeline.

Boy, you're master of the unanswerable questions on this one.

Christopher Anzalone: I don't know that we've seen any increased partner interest in the last, what, week or so. I will tell you this. Here's what we can control. You know, our job is to make medicines that are safe and that can help patients in ways that other medicines can't. To the extent that we can focus on that and we can succeed at that and we can do that rapidly, everything else will sort of follow. And so, you know, I kind of view this M&A, the recent M&A, the recent acquisition as a bit of noise because it doesn't really affect our day-to-day business.

I don't know that that we've seen any increased.

Partnering interest in the last week or so.

I will say this here.

Here's what we can control.

Our job is to make medicines that are that are safe and that can help patients in ways that other medicines can to the extent that we can focus on that and we can succeed at that and we can do that rapidly.

Everything else or so we're sort of follow and so I kind of view this M&A in the recent M&A.

The recent acquisition.

Christopher Anzalone: We need to remember, you know, why we're here every day, which is to make important medicines. Yep, yep, that's helpful. And then just with the understanding that AMG 980 is being developed by Amgen, I'm wondering if you could discuss expectations around the phase two trial. And assuming it's on track for phase two top line data in the first half of 2022, I'm wondering what level of LP little a knockdown would give confidence to move forward to a pivotal program? I don't think I know any more than you do, to be honest.

Has it been a noise because it doesn't really affect our day to day business. So we need to remember why we're here every day, which is to make important medicines and that's what we're doing.

Yeah, Yeah, that's helpful and then just.

With the understanding that AMG 980 is being developed by Amgen I'm wondering if you could discuss expectations around the phase two trial.

Jimmy it's on track for Phase two topline data on our first half of 2022, I'm wondering what level of LP Little a knockdown would give confidence to move forward to a pivotal program.

Sure.

I take it.

I think I know anymore than you do to be honest.

Christopher Anzalone: My understanding is that Amgen has guided that they will have data in the first half of next year. I haven't heard that that's changed, so that's my understanding. And frankly, my expectation would be then that they would move into a clinical study thereafter. I don't know how long it will take them to do that. The data that we've seen so far, the data that have been presented, boy, are really good. That is a potent drug candidate. They're seeing very deep knockdown, you know, with a very small amount of drug in Lp little a.

My understanding is that is that Amgen has guided that they will have data in the <unk>.

First half of next year.

Haven't heard that Thats changed, but so that's my understanding.

And frankly, my expectation would be then that they would move into a into a pivotal study thereafter I don't know how long it will take them to do that the data that we've seen so far the data that have been presented or.

A really good that is a that is a potent drug candidates they.

We're seeing very deep knockdown with a very small amount of drug.

<unk> and I think that.

Jack validation of that target is clear.

Christopher Anzalone: And I think that the genetic validation of that target is clear. So my expectation is that they will have data in the first half of the year, and then we'll just see how fast they can move to a pivotal. I can't really give you an idea about what would make them happy in terms of reduction of Lp little a levels.

So my expectation is that is that they will have data.

First half of the year and then we'll just see how fast they can move to a pivotal I can't really give you an idea about what would make them happy.

In terms of reduction of LP little a levels I can't tell you, though that at least internally we have been impressed with what they've shown so far and if this was our program.

Christopher Anzalone: I can tell you, though, that at least internally, we have been impressed with what they've shown so far, and if this was our program, I certainly wouldn't be slowing down. I'd be moving into a phase three, given what we've seen so far. Terrific. Thank you very much. And thank you. And our next question comes from Mani Foroohar from SVP Lyric. Your line is now open.

Certainly wouldn't be slowing down I'd be I'd be moving into a phase III given what we've seen so far at least.

Terrific. Thank you very much welcome.

Welcome.

Okay.

And thank you and our next question comes from Manny <unk> from SVP Leerink. Your line is now open.

Mani Foroohar: Hey, thanks. A follow-up question regarding, so another question about the ENAC program. You talked a little bit about this mouse signal counterpart with a related but not at all identical technology, an ASO, had early human data and saw perhaps related or not talk signal in non-human primates. They discontinued their program but did release that early human data.

Hey, thanks.

Follow up question regarding so all at once to enact programs can you talk a little bit about this mouse signal.

Counterpart.

Related but not all identical technology so at early human data.

Perhaps related or not tox signal and not in primates.

Discontinue their program, but did release that early human data.

Christopher Anzalone: We expect that you'll be releasing some patient data with Arrow ENAC, or is that something that you think you'll just put away and we'll never see? And I have one follow-up. I just don't know at this point.

Should we expect that you'll be releasing.

Some patient data with Arrow ANAC.

Or is that something that you think youll just put out youll just put away I will never say and I have one follow up.

Christopher Anzalone: Let's see where that program is going to go. I don't know if we're going to restart that, so it's, I kind of don't want to get hypothetical at this point, and so... That will stay paused. Once we have an idea about how we go forward, either restarting enrollment of that or switching to a new construct, at that point, then we can have a better discussion about what we do with the data that has been collected so far.

Alright, I just don't know at this point.

Let's.

Let's see what where that program is going to go.

I don't know if were going to restart that.

And so so.

I kind of want to get into hypothetical at this point and so so.

That will stay pause once we once we have an idea about worry about how we go forward either restarting enrollment of that or or switching to two new construct at that point. Then we can we can have a better discussion about about what we do with the data that had been collected so far.

Christopher Anzalone: Great. And as you said, you guys spend a lot of time talking about extra hepatic programs, obviously a place where RNAi is still earlier in development than liver targeting for you and all companies, broadly speaking. Is there a timeline we should expect an update on the oncology program that you gave us a first look at? And do you continue to see oncology or, broadly speaking, other kidney diseases as an area of growth for you? Or is that more of a one-off experiment? No, I would not call that a one-off experiment.

Great.

As you saw you guys put a lot of them talking about extra hepatic programs, obviously, a place where RNA I still earlier in development.

Then liver targeting for you and all in all companies broadly speaking.

Is there a timeline, we should expect an update on on.

On the oncology program that you gave us a first look at and.

Continue to see oncology or broadly speaking other kidney diseases.

Growth for you or is that or is that more of a one off experiment.

Christopher Anzalone: It is the first experiment in solid tumor targeting, and I think we're off to a good start there. I think we've seen clear target engagement. That's important. We've seen clear knockdown.

No I would not call that a one off because it is.

The first experiment in solid tumor targeting and I think that I think we're off to a good start there. We I think we've seen clear target engagement that's important.

Christopher Anzalone: That's important. Now we just need to see if that particular drug is the one. We'll look at longer-term response rates, and we'll make that decision. But I think from a platform standpoint, we are on the right track. Is this the last iteration of our oncology platform? Absolutely not.

We've seen clear knockdown, that's important and.

And so now so now we just need to see.

If that particular drug as a drug we will look at longer term response rates and we'll make that decision, but I think from a platform standpoint, we are on the right track is it the last iteration of our oncology platform absolutely not we will we will certainly continue to to advance it but at least but from my perspective, it's a good start.

Christopher Anzalone: We will certainly continue to advance it, but at least, from my perspective, it's a good start. Now, and to be clear, this program is designed to address solid tumors really kind of broadly. We don't yet have a platform that is designed to address kidney indications.

Now and to be clear.

This program is designed to to to address solid tumors really kind of broadly.

Christopher Anzalone: That may happen at some point in the future, but right now, we don't have that. I don't know if I have a good, Prediction about when we're going to have our next slug of data for HIF-2. We are fully enrolled. And so I think we're just following patients. James, do you have anything to add on that? No, I think that's about right.

Don't yet have a platform that is.

Designed to address the kidney.

Indications that may happen at some point in the future, but right now we don't have that.

I don't know if I have a good.

If I look good.

Prediction about when we're going to have our next slug of data for hip too.

We are fully enrolled.

And so I think we're just following patients James do you have anything to add on that no.

I think thats about right. If the study is fully enrolled and so all the patients on drivers.

Christopher Anzalone: The study is fully enrolled. And so all the patients on drug are just in the follow up. Great. Thanks, guys. Welcome.

And the follow up period.

Great. Thanks, guys.

Welcome.

Yeah.

Mayank Mamtani: Thank you. And our next question comes from Mayank Mamtani from B Riley Securities. Your line is now open.

Thank you and our next question comes from May eight.

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

Christopher Anzalone: Good afternoon team, congrats on the pipeline progress and also on the GSK deal and thanks for squeezing us in. Just have a few clarifying questions, just quick ones. So on the J&J refund study, just any idea on at what time points the follow-ups might come and when can we see the patient-level analysis? Is there any insight you have on how J&J might be thinking of communicating going forward? I really can't give you that, because I just don't know.

Good afternoon team congrats on the pipeline progress and also on the GSK deal and thanks for squeezing us in.

Just have a few clarifying questions just quick ones. So.

<unk> one study.

And any idea on.

What time points to follow ups, Mike and when can we see the patient level analysis is there any insight you have on our agenda might be thinking of communicating going forward.

No I really can't give you that.

Because I know I, just don't know and in fact, we havent seen I don't know I don't believe at least I don't think we've even seen.

Christopher Anzalone: In fact, we haven't seen, I don't believe at least, I don't think we've even seen the individual patient data. But as I said earlier, look, we're really encouraged by those data. You know, I think they're good data. You know, our drug is doing what it's designed to do.

The individual patient data.

But as I said earlier look we're really encouraged by those data I think they're good data our drug is doing what it's designed to do and so now we just need to kind of sit back and see how this goes as I mentioned in the prepared remarks arc 520 for those patients on archived material cleared for <unk>. It didn't happen in six months happened.

Christopher Anzalone: And so now, look, we just need to kind of sit back and see how this goes. As I mentioned in the prepared remarks, you know, ARC520, for those patients on ARC520 who was serocleared for S, it didn't happen in six months. It happened, you know, as early as nine months or as long as two years or so, as I recall, after drug was removed.

As early as nine months or as long as two years or so as I recall after drug after drug was removed and so we look forward to watching continued follow up I think that we are we have just entered.

Christopher Anzalone: And so, you know, we look forward to watching continued follow-up. I think that we are, we have just entered a prolonged data-rich period with Janssen. Given RIF1, RIF2, RIFD, you know, the interferon studies and others, I think that there will be, I think that there should be regular data released from various parts of these studies going forward. And so, you know, I think the 22 is probably gonna be substantially more data-rich than 21.

A prolonged data rich period with with Janssen, given reef, one reef to reap D.

Youre on studies.

And others I think that there will be.

I think that there should be regular data.

<unk> from various ports or parts of these studies going forward and so.

Yes.

I think 'twenty two is probably going to be used can be more data rich for 'twenty one was.

Christopher Anzalone: Looking forward to that, understood. And then on AAT, can you remind us how you're tracking with the CEQA, you know, phase 2, 3 data package? I think about 40 subjects.

Looking forward to that understood and then on A&P.

Can you remind us how you're tracking with the SEC.

Phase III data back as I think about 40 subjects.

And then what might be the expectations.

Javier San Martin: And what might be the expectations, you know, in a placebo-controlled setting relative to, you know, what you've shown in the open label format? Yes, sure. So, as you know, we have completed enrollment of 40 patients. This next data log, where we're going to work on selection, will occur in the first half of 2022. So, that will probably be our next interaction with the agency to discuss the dose, and the pair of biopsies will be finished by July or August of next year. So the last patient, the second or post-baseline biopsy will be in that timeframe. So add to that the timing for data log and evaluation.

In a placebo controlled setting relative to what you've shown in the open label format.

Yes, sure. So as you know we have completed enrollment of 40 patients.

The next state of low where we're going to work on dose selection will occur in the first half of 2022, so and that will be probably our next interaction with the agency to discuss the dose.

The paired biopsies will be finished by July August of next year. So less station second post baseline biopsy will be in that timeframe. So add to that the timing for the data look on evaluation. So I would say towards the end of 2022, we'll have the placebo control pay everybody up.

As we saw from Sequoia.

Javier San Martin: So I would say towards the end of 2022, we will have the placebo control pair biopsy result from Sequoia. Great, thank you. And just on the cardiometabolic polio and portfolio, I heard, you know, appreciate the level of detail on ANS3 and APOC3. And can you just put it together, like how in 2023, we will see some of the data generation activities. And I didn't, I didn't catch up on the enrollment for the FCS study, the phase three study. Could you just remind me of that? But so it's hard to guide to data release at this point because, FCS. Do you have anything else, Adam? No, I don't think that's fair.

Great. Thank you and just on the cardio metabolic.

Our wholly owned portfolio I could appreciate the level of detail on <unk>.

<unk>, three and <unk> III and can you just put it together like how in 2023, we will see some of the data agenda.

A generation activities and I think I think ACH.

On the enrollment for the FCS study the phase III study you could could you just remind me on that.

Okay.

So it's hard to guide to data release at this point because because.

Particularly for FCS because we havent, even dose first patient yet there.

These are all the things we talked about our year long studies and so the buffet.

The unknown here is how fast we can get these enrolled.

Give us some more time here at enrollment and then we can I think we'll have better visibility on when we can start to have have data release.

Any update on that.

Mayank Mamtani: And the question on phase three for FCS, so that the study is up and running. We have patients in screening. We've already activated sites, and we anticipate dosing before the end of the year.

I think Thats fair.

The question on the phase III for FCS So that the studies up and running we have patients in screening we've already activated sites and we anticipate dosing before the end of the year first dose.

Christopher Anzalone: And thank you. And I'm showing no further questions. I would now like to turn the call back to Chris Anzalone for closing remarks. Thank you everyone for joining us today, and we wish you a happy and safe Thanksgiving weekend. This concludes today's conference call. Thank you for participating. You may now disconnect.

Great. Thanks, so much for taking my question.

And thank you and I'm showing no further questions I would now like to turn the call back to Chris Anzalone for closing remarks.

Hey, thanks, everyone for joining us today, and we wish you a happy and safe Thanksgiving weekend.

This concludes today's conference call. Thank you for participating you may now disconnect.