# EDGAR Filing Document

**Accession Number:** 0000879407
**File Stem:** 0000879407-25-000019
**Filing Date:** 2025-11
**Character Count:** 55489
**Document Hash:** 9455607b956ca1f4b4f3ca7d087f4f19
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0000879407-25-000019.hdr.sgml**: 20251118

**ACCESSION NUMBER**: 0000879407-25-000019

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 58

**CONFORMED PERIOD OF REPORT**: 20251118

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251118

**DATE AS OF CHANGE**: 20251118

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** ARROWHEAD PHARMACEUTICALS, INC.
- **CENTRAL INDEX KEY:** 0000879407
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 460408024
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 0930

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-38042
- **FILM NUMBER:** 251494013

**BUSINESS ADDRESS:**
- **STREET 1:** 177 E COLORADO BLVD
- **STREET 2:** SUITE 700
- **CITY:** PASADENA
- **STATE:** CA
- **ZIP:** 91105
- **BUSINESS PHONE:** 626-696-4702

**MAIL ADDRESS:**
- **STREET 1:** 177 E COLORADO BLVD
- **STREET 2:** SUITE 700
- **CITY:** PASADENA
- **STATE:** CA
- **ZIP:** 91105

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** ARROWHEAD RESEARCH CORP
- **DATE OF NAME CHANGE:** 20040112

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** INTERACTIVE GROUP INC
- **DATE OF NAME CHANGE:** 20020509

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** INTERACTIVE INC
- **DATE OF NAME CHANGE:** 19940224

?xml version='1.0' encoding='ASCII'? arwr-20251118

**UNITED STATES** 

**SECURITIES AND EXCHANGE COMMISSION** 

**WASHINGTON, D.C. 20549** 

**FORM 8-K**

**CURRENT REPORT** 

**PURSUANT TO SECTION 13 OR 15(D) OF**

**THE SECURITIES EXCHANGE ACT OF 1934** 

November 18, 2025

**Date of Report** 

**(Date of earliest event reported)**

**Arrowhead Pharmaceuticals, Inc.**

(Exact name of registrant as specified in its charter)

Delaware 001-38042 46-0408024 <br> (State or other jurisdictionof incorporation) (CommissionFile Number) (IRS EmployerIdentification No.)

177 E. Colorado Blvd, Suite 700, Pasadena, CA 91105

**(Address of principal executive offices, including Zip Code)**

(626) 304-3400

**(Registrant's telephone number, including area code)** 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4 (c) under the Exchange Act (17 CFR 240.13e-4(c))

---

| | | |
|:---|:---|:---|
| **Securities registered pursuant to Section 12(b) of the Act:** | **Securities registered pursuant to Section 12(b) of the Act:** | **Securities registered pursuant to Section 12(b) of the Act:** |
| **Title of each class** | **Trading Symbol(s)** | **Name of each exchange on which registered** |
| **Common Stock, par value $0.001 per share** | **ARWR** | **The Nasdaq Global Select Market** |

---

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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**Item 8.01 Other Events**

On November 18, 2025, Arrowhead Pharmaceuticals, Inc. issued a press release announcing that the U.S. Food and Drug Administration has approved REDEMPLO<sup>®</sup> (plozasiran) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). Arrowhead subsequently held a conference call discussing the approval.

A copy of this press release is attached as Exhibit 99.1 to this Current Report and incorporated herein by reference. A copy of the slides presented at the conference call is attached as Exhibit 99.2 to this Current Report and incorporated herein by reference.

**Item 9.01. Financial Statements and Exhibits.** 

(d) Exhibits

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| | |
|:---|:---|
| **Exhibit No.** | **Description** |
| 99.1 | <u>[Press Release, dated November](arwr-202511188kex991.htm)[18](arwr-202511188kex991.htm)[, 2025.](arwr-202511188kex991.htm)</u> |
| 99.2 | <u>[R](redemploapprovalconfcall.htm)[E](redemploapprovalconfcall.htm)[D](redemploapprovalconfcall.htm)[E](redemploapprovalconfcall.htm)[M](redemploapprovalconfcall.htm)[PLO](redemploapprovalconfcall.htm)[Approval Conf](redemploapprovalconfcall.htm)[erence](redemploapprovalconfcall.htm)[Call Nov](redemploapprovalconfcall.htm)[ember 18,](redemploapprovalconfcall.htm)[2025](redemploapprovalconfcall.htm)</u> |
| 104 | Cover Page Interactive Data File (the cover page tags are embedded within the Inline XBRL document). |

---

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**SIGNATURES** 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

Date: November 18, 2025

---

| | |
|:---|:---|
| ARROWHEAD PHARMACEUTICALS, INC. | ARROWHEAD PHARMACEUTICALS, INC. |
| By: | /s/ Daniel Apel |
|  | Daniel Apel |
|  | Chief Financial Officer |

---

## Exhibit 99.1

**EXHIBIT 99.1**

![ghvnqo5ppwcq000001.jpg](ghvnqo5ppwcq000001.jpg)

**PRESS RELEASE**

**November 18, 2025**

**Arrowhead Pharmaceuticals Announces FDA Approval of REDEMPLO® (plozasiran) to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome (FCS)**

–REDEMPLO is the first and only FDA-approved medicine to be studied in patients with genetically confirmed and clinically diagnosed FCS

–People living with FCS have extremely high triglyceride levels and a substantially higher risk of acute pancreatitis and related long-term complications, often resulting in a reduced quality of life

–The FDA approval is based on positive results from the Phase 3 PALISADE study where REDEMPLO significantly reduced triglycerides from baseline and lowered the numerical incidence of acute pancreatitis compared to placebo

–Arrowhead will host a conference call and webcast today at 1:30 p.m. ET

**PASADENA, Calif., November 18, 2025** — Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that the U.S. Food and Drug Administration (FDA) has approved REDEMPLO (plozasiran), a small interfering RNA (siRNA) medicine, as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). FCS is a severe, rare disease, with an estimated 6,500 people in the U.S. living with genetic or clinical FCS, characterized by triglyceride levels that can be 10 to 100 times higher than normal leading to a substantially higher risk of developing acute, recurrent, and potentially fatal pancreatitis. REDEMPLO is the first and only FDA-approved siRNA medicine for people living with FCS and can be self-administered at home with a simple subcutaneous injection once every three months. REDEMPLO utilizes the proprietary and differentiated Targeted RNAi Molecule (TRiMTM) platform and is Arrowhead's first FDA-approved medicine, marking a major milestone for the company as it transitions into commercial-stage.

"The FDA approval of REDEMPLO is a transformational milestone for Arrowhead. This is a proud moment for all those involved in the discovery and development process and represents new hope for the estimated 6,500 people in the U.S. living with genetic or clinical FCS. This approval, and subsequent launch, marks the beginning of a new chapter in our journey—one rooted in our unwavering commitment to delivering life-changing therapies to patients with serious diseases," said Christopher Anzalone, Ph.D., President and CEO at Arrowhead Pharmaceuticals. "REDEMPLO also represents the first FDA-approval for a medicine that leverages Arrowhead's proprietary and differentiated Targeted RNAi Molecule (TRiMTM) platform. Arrowhead continues to lead the field in innovation, with the TRiMTM platform now potentially capable of delivering siRNA to seven different cell types in the body and the potential to simultaneously silence the expression of two genes in one molecule. The breadth of this

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technology with our growing commercial capabilities dramatically expands the diseases we can potentially address and the number of lives we can change."

The FDA approval was supported by clinical data from the Phase 3 PALISADE study, a randomized, double-blind, placebo-controlled trial in adults with clinically diagnosed or genetically confirmed FCS. The PALISADE study met its primary endpoint and all multiplicity-controlled key secondary endpoints, including demonstrating significant reductions in triglycerides and APOC3. In PALISADE, 25 mg REDEMPLO achieved deep and durable reductions in triglycerides, with a median change from baseline of -80% versus -17% in the pooled placebo group, and a lower numerical incidence of acute pancreatitis compared with placebo.

Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation added, "Today's approval marks a pivotal moment for people living with familial chylomicronemia syndrome and the physicians who support them. Because FCS symptoms are mostly invisible, this community historically has been often overlooked and misunderstood, making their journey to effective treatment especially difficult. We're grateful to Arrowhead for listening to patients and caregivers and incorporating their lived experiences into the development of this transformative therapy. Plozasiran offers real hope for a better future and shows what's possible when innovation is driven by empathy and collaboration addressing patients in need."

The most common adverse reactions in REDEMPLO treated patients (incidence ≥10% of patients treated with REDEMPLO and > 5% more frequently than with placebo) are hyperglycemia, headache, nausea, and injection site reaction. The US approved package insert contains no contraindications, warnings, or precautions associated with the use of REDEMPLO.

The efficacy and safety results from the PALISADE study were presented at the European Society of Cardiology (ESC) Congress 2024 and the American Heart Association Scientific Sessions 2024 (AHA24) and simultaneously published in The New England Journal of Medicine and Circulation, respectively. ESC, AHA24, and other plozasiran presentations may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.

Underscoring the company's commitment to improving patient outcomes, ensuring access for patients, and providing value to the health system, Arrowhead is developing best-in-class solutions for the FCS community. Arrowhead is launching Rely On REDEMPLO, a patient support program providing support services and resources for patients at each stage of the treatment journey with REDEMPLO, including financial assistance options for eligible patients.

REDEMPLO will be available in the U.S. before the end of the year.

REDEMPLO was granted Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation by the FDA for the treatment of patients with FCS and was granted Orphan Medicinal Product Designation by the European Medicines Agency for the treatment of patients with FCS.

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**Webcast and Conference Call and Details**

Arrowhead will host a conference call and webcast to discuss the REDEMPLO FDA approval today at 1:30 p.m. ET.

A live webcast may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. A replay of the webcast will be available approximately two hours after the conclusion of the call.

**About FCS**

Familial chylomicronemia syndrome (FCS) is a severe and rare disease leading to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, there are limited therapeutic options to adequately treat FCS.

**About the PALISADE Phase 3 Study**

The PALISADE study (NCT05089084) was a Phase 3 placebo-controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study was percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months. Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran.

**About REDEMPLO® (plozasiran)**

REDEMPLO (plozasiran) is approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome (FCS). REDEMPLO is an siRNA therapeutic designed to suppress the production of apoC-III, a protein produced in the liver that raises triglyceride levels by slowing their breakdown and clearance. By targeting apoC-III with sustained silencing, REDEMPLO delivers significant reductions in triglyceride levels. REDEMPLO is the first and only siRNA FDA-approved treatment studied in both genetically confirmed and clinically diagnosed patients living with FCS.

For more information about REDEMPLO, visit Our Medicines.

**IMPORTANT SAFETY INFORMATION** 

**CONTRAINDICATIONS**

None.

**ADVERSE REACTIONS**

Most common adverse reactions in REDEMPLO treated patients (incidence ≥10% of patients treated with REDEMPLO and >5% more frequently than with placebo) are hyperglycemia, headache, nausea, and injection site reaction.

**Please see full <u>Prescribing Information</u> for REDEMPLO®.**

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**About Plozasiran** 

Plozasiran is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of apolipoprotein C-III (apoC-III) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. ApoC-III increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver. The goal of treatment with plozasiran is to reduce the level of apoC-III, thereby reducing triglycerides and restoring lipids to more normal levels.

In addition to the FDA approval of REDEMPLO as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome, plozasiran has been submitted to additional global regulatory authorities for review and marketing authorization. Plozasiran is also being investigated in the SHASTA-3, SHASTA-4, and SHASTA-5 Phase 3 studies in patients with severe hypertriglyceridemia and the MUIR Phase 3 study in patients with mixed hyperlipidemia.

**About Arrowhead Pharmaceuticals**

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead's RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on X (formerly Twitter) at @ArrowheadPharma, LinkedIn, Facebook, and Instagram. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

**Safe Harbor Statement under the Private Securities Litigation Reform Act:**

*This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "expect," "believe," "anticipate," "hope," "intend," "plan," "project," "could," "estimate," "continue," "target," "forecast" or "continue" or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline, products or product candidate or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about our beliefs and expectations regarding the long-term impacts of REDEMPLO (plozasiran) on patient health and the health care system; our beliefs and expectations regarding the pricing, value, or expected timing for availability of our drugs and drug candidates; and our believes and expectations around the potential uses and value of the TRiM™ platform. These statements are based upon our current expectations and speak only as of the date hereof. Actual results or outcomes may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties the safety and efficacy of our products and product candidates, pricing and reimbursement decisions related to our products, demand for our products, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other* 

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*documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.*

**Contacts:**

Arrowhead Pharmaceuticals, Inc.

Vince Anzalone, CFA

626-304-3400

<u>ir@arrowheadpharma.com</u>

**Investors:**

LifeSci Advisors, LLC

Brian Ritchie

212-915-2578

<u>britchie@lifesciadvisors.com</u>

**Media:**

HAVAS PR

Erick Edwing 941-468-7534

<u>Erick.edwing@havasred.com</u>

**Source:** Arrowhead Pharmaceuticals, Inc.

\# \# \#

## Exhibit 99.2

![](redemploapprovalconfcall001.jpg)

REDEMPLO® (plozasiran) FDA Approval Conference Call November 18, 2025

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![](redemploapprovalconfcall002.jpg)

Welcome and Introductions Vince Anzalone, CFA Vice President, Finance and IR REDEMPLO® FDA Approval Conference Call November 2025

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![](redemploapprovalconfcall003.jpg)

3 Safe Harbor Statement This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "expect," "believe," "anticipate," "hope," "intend," "plan," "project," "could," "estimate," "continue," "target," "forecast" or "continue" or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline, products or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the cost-savings and other benefits of our pricing program for REDEMPLO (plozasiran); our beliefs and expectations regarding the impacts of REDEMPLO on patient health and the health care system; our beliefs and expectations regarding the anticipated launch of REDEMPLO and pricing, value, or expected timing for availability of REDEMPLO; our beliefs and expectations regarding the Rely On REDEMPLO patient support program; the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Actual results or outcomes may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties the safety and efficacy of our products and product candidates, pricing and reimbursement decisions related to our products, demand for our products, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. For investor communication only. Not for use in product promotion

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![](redemploapprovalconfcall004.jpg)

4 Agenda Topic Presenter Introductions and Agenda Vince Anzalone, CFA REDEMPLO® - Arrowhead's First FDA Approval Chris Anzalone, Ph.D. Disease Background and Label James Hamilton, M.D., MBA PALISADE Phase 3 Clinical Data Bruce Given, M.D. U.S. Commercial Launch Plan Andy Davis, MBA Key Takeaways and Arrowhead Looking Forward Chris Anzalone, Ph.D. Q&A Panel For investor communication only. Not for use in product promotion

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![](redemploapprovalconfcall005.jpg)

REDEMPLO® - Arrowhead's First FDA Approval Chris Anzalone, Ph.D. President and CEO REDEMPLO® FDA Approval Conference Call November 2025

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![](redemploapprovalconfcall006.jpg)

6 REDEMPLO® Now FDA-Approved • REDEMPLO is the first and only siRNA/RNAi-based medicine FDA- approved to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) • First FDA-approved medicine utilizing Arrowhead's proprietary Targeted RNAi Molecule (TRiMTM) platform For investor communication only. Not for use in product promotion

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![](redemploapprovalconfcall007.jpg)

7 REDEMPLO Positioned as Promising New Medicine for FCS Dramatic reductions in triglycerides in patients with genetically confirmed and clinically defined FCS Reduced numerical incidence of acute pancreatitis Convenient dosing once every three months with at home self-administration Strong label with no contraindications, warnings or precautions Commercial team ready to launch today For investor communication only. Not for use in product promotion

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![](redemploapprovalconfcall008.jpg)

8 ARO-APOC3 to Plozasiran to REDEMPLO - Path to First Approval ARO-APOC3 Nominated as Clinical Candidate July 2018 For investor communication only. Not for use in product promotion First Healthy Volunteer Dosed in Phase 1 March 2019 First SHTG Patient Dosed in SHASTA-2 Phase 2 May 2021 First Mixed Hyperlipidemia Patient Dosed in MUIR-2 Phase 2 September 2021 First FCS Patient Dosed in PALISADE Phase 3 January 2022 ARO-APOC3 Becomes Plozasiran June 2023 SHASTA-2 Results in NEJM April 2024 First HTG Patient Dosed in MUIR-3 Phase 3 May 2024 First SHTG Patients Dosed in SHASTA-3 and SHASTA-4 Phase 3 July 2024 PALISADE Results in NEJM September 2024 NDA submitted for Plozasiran in FCS November 2024 FDA-Approved to Reduce TGs in Patients with FCS November 2025

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![](redemploapprovalconfcall009.jpg)

9 Challenges around Diagnosis1 Human Cost Economic Cost of Acute Pancreatitis2,4 Each AP Event Associated With Significant Healthcare Burden \*Based on a 2013 study that used the Thomson MarketScan US Commercial Claims and Encounters and Medicare Supplemental Database to identify chylomicronemia (including FCS and non-FCS) cases between 2000 and 2009.5 †One-hundred and four episodes of acute pancreatitis were identified, with an average of 3 outpatient visits per episode. Average total medical costs were $31,820 per episode of acute pancreatitis, with inpatient stays accounting for $30,408.5 \*\* Company estimates of current costs References: 1. Stroes E et al. Atherosclerosis Supplements. 2017;23:1-7. 2. Davidson M et al. J Clin Lipidology. 2018;12(4):898-907. 3. Falko JM. Endocr Pract. 2018;24(8):756-763. 4. Gaudet D et al. Lipids Health Dis. 2020;19(1):120. doi: 10.1186/s12944-020-01302-x. 5. Gaudet D et al. J Med Econ. 2013;16(5):657–666. ▪ >$60,000 in estimated medical costs per episode of acute pancreatitis for patients with FCS5,\*,†,\*\* ▪ ~5 physicians typically seen before diagnosis2 ▪ 93% of episodes involved an inpatient stay, at an average of 10 days spent in an inpatient setting5 For investor communication only. Not for use in product promotion ▪ ~50% of patients are misdiagnosed2 ▪ Distributed treatment teams3 ▪ Endocrinologists ▪ Lipidologists ▪ Cardiologists ▪Pancreatologists ▪Primary care ▪Dietitians ▪ Acute pancreatitis events make subsequent events more likely and more severe ▪ Acute pancreatitis is always a serious medical condition and can be fatal ▪ FCS patients can experience severe brain fog and recurrent abdominal pain ▪ Compromised quality of life ▪ Lost productivity

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![](redemploapprovalconfcall010.jpg)

10 The FCS Lived Experience • Diagnosed after 23 years of symptoms and 25 persistent pancreatitis attacks. • Symptoms began in childhood. In his 20s, noticed eruptive xanthomas and stomach pains with no known cause. His TGs were tested, and numbers were "through the roof," although no action taken. • First acute pancreatitis episode at 30, launching a decade of medical crises. • Triglycerides hit 24,000 mg/dL during a hospitalization, still with no diagnosis. • In one year, he spent 2 weeks every 8 weeks in the ICU, missing life at home with family and work, unable to maintain existing career. • Doctors repeatedly accused him of alcoholism, placing blame on him, providing no answers to what was happening in his body. • Discovered FCS and subsequent diagnosis through relentless self-advocacy and online research, taking information to his doctor for discussion and confirmation. • For every Scott, there are countless others whose symptoms are overlooked and diagnoses delayed. Arrowhead's mission is to bring them answers and potential relief sooner. Meet Scott, Living with FCS For investor communication only. Not for use in product promotion

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![](redemploapprovalconfcall011.jpg)

11 One-REDEMPLO Pricing Model: Consistent Pricing Across Indications For investor communication only. Not for use in product promotion We are committed to sustainable innovation and rational pricing • Different patients should not pay different prices for this medicine based on their disease One-REDEMPLO is a pricing model that sets a single consistent product price for multiple potential indications One-REDEMPLO price is based on value for severe patients within the broader SHTG market: pending successful Phase 3 studies and subsequent regulatory review and approval One-REDEMPLO price is reflective of the long-term value to patients, providers, and the health system: we have time to work with payors to demonstrate this while SHASTA-3 and SHASTA-4 are ongoing REDEMPLO is launched with $60,000 WAC price and is intended to maintain price throughout the long lifecycle of the product

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![](redemploapprovalconfcall012.jpg)

12 Arrowhead Also Active Across TG/LDL and ASCVD/AP Spectrum Lipid Disorders, Including FCS, sHTG, Mixed Hyperlipidemia, and HoFH, Are Characterized by a Spectrum of Elevated Levels of TGs and/or Cholesterol1-12 ASCVD, atherosclerotic cardiovascular disease; FCS, familial chylomicronemia syndrome; HeFH, heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; sHTG, severe hypertriglyceridemia; TG, triglyceride; TRL, triglyceride-rich lipoprotein. \*REDEMPLO (plozasiran) is FDA-approved to reduce TGs in FCS in the U.S., investigational plozasiran has not been reviewed or approved to treat FCS outside the U.S. or sHTG in any countries 1. Malick WA, et al. J Am Coll Cardiol. 2023;81(16):1646-1658. 2. Larouche M, et al. Curr Atheroscler Rep. 2023;25(12):1101-1111. 3. Nordestgaard BG, et al. Lancet. 2014;384(9943):626-635. 4. Mach F, et al. Eur Heart J. 2020;41(1):111-188. 5. Lloyd-Jones DM, et al. J Am Coll Cardiol. 2022;80(14):1366-1418. 6. McGowan MP, et al. J Am Heart Assoc. 2019;8(24):e013225. 7. Yang Z, et al. Front Cardiovasc Med. 2022;9:913977. 8. Romandini A, et al. Pharmaceuticals (Basel). 2023;16(2):176. 9. Virani SS, et al. J Am Coll Cardiol. 2021;78(9):960-993. 10. Gaudet D, et al. N Engl J Med. 2014;371(23):2200-2206. 11. Berberich AJ, et al. Endocr Rev. 2022;43(4):611-653. ANGPTL3/ PCSK9 Residual risk of ASCVD is related to elevated TGs or cholesterol -Rare Disorder- HoFH LDL-C ≥400 mg/dL HeFH LDL-C ≥190 mg/dL Mixed Hyperlipidemia Elevated TRLs- remnant cholesterol sHTG TG ≥500 mg/dL -Rare Disorder- FCS TG ≥880 mg/dL Incremental risk of acute pancreatitis is associated with severely elevated TG levels Elevated TGElevated LDL Cholesterol APOC3 Investigational ARO-DIMER-PA Investigational Zodasiran Investigational Plozasiran\* For investor communication only. Not for use in product promotion

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![](redemploapprovalconfcall013.jpg)

Disease Background and Label James Hamilton, M.D., MBA Chief Medical Officer and Head of R&D REDEMPLO® FDA Approval Conference Call November 2025

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![](redemploapprovalconfcall014.jpg)

14 Genetic/Clinical FCS Caused by Inability to Break Down Chylomicrons References: 1. Gaudet D et al. N Engl J Med. 2014;371(23):2200-2206. 2. Shamsudeen I, Hegele RA. Expert Rev Clin Pharmacol. 2022;15(4):395-405. 3. Mszar R et al. J Clin Med. 2023;12(4):1382. Overview of TG Metabolism in Patients With FCS3 The buildup of chylomicrons causes significant risks2 - the most severe being acute pancreatitis and its life- threatening sequelae FCS Is Characterized by1,2: • Extremely high fasting plasma TGs, sustained above 880 mg/dL • Marked accumulation of chylomicron particles due to impaired lipolytic clearance For investor communication only. Not for use in product promotion

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15 Patients With FCS Have Multiple Clinical Manifestations, the Most Serious of Which Is Acute Pancreatitis References: 1. Gaudet D et al. Lipids Health Dis. 2020;19(1):120. doi: 10.1186/s12944-020-01302-x. 2. Machicado JD, Yadav D. Dig Dis Sci. 2017;62(7):1683-1691. 3. Davidson M et al. J Clin Lipidology. 2018;12(4):898-907. 4. Sue LY et al. Pancreas. 2017;46(7):874-879. 5. Brunzell JD, Bierman EL. Med Clin North Am. 1982;66(2):455-468. 6. Shamsudeen I, Hegele RA. Expert Rev Clin Pharmacol. 2022;15(4):395-405. 7. Wang P et al. J Clin Imaging Sci. 2020;10(64):1- 3. 8. Davidson D et al. J Patient Reported Outcomes. 2021;5(1):72. doi: 10.1186/s41687-021-00347-5. 9. Gaudet D et al. J Clin Lipidology. 2016;10(3):680-681. 10. Krauß LU et al. Dig Dis. 2023;41(4):647-655. Acute Pancreatitis Is Associated With Frequent Hospitalizations, Intensive Care, Plasmapheresis Therapy, and Surgeries That Significantly Impact Daily Living and Quality of Life1,8-10 Lipemia retinalis - ongoing Cognitive symptoms - daily to 2x/week (brain fog, lack of focus, memory loss) Fatigue - 2x/week Acute pancreatitis Hepatosplenomegaly - daily to every other week Severe abdominal pain - every other week, pancreatic pain - 1x/month, nausea & vomiting - daily Eruptive xanthomas - every other week (fatty deposits under the skin, usually on buttocks, trunk, knees, and elbows) ~5%–6% Overall mortality rate for TG-induced acute pancreatitis in patients with FCS3 30% The mortality rate in patients with FCS in cases of pancreatic necrosis following an infected pancreatic abscess or persistent multiple organ failure3 Acute Pancreatitis Is the Most Serious, Severe, and Potentially Fatal Complication of FCS, Which Affects ≥50% of Patients1 Clinical Signs and Symptoms of FCS3,5-7,\*The Pancreatitis Disease Continuum2 Acute Recurrent Acute Chronic 53% Prevalence 17% Prevalence 33% Risk of Progression ≥500 mg/dL Patients with high TG levels during the early phase of acute pancreatitis are at an increased risk of multisystem or persistent organ failure4 For investor communication only. Not for use in product promotion

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16 Professional Guidelines Recommend Reducing TG Levels to <500 mg/dL to Lower the Risk of Acute Pancreatitis \*The following organizations also contributed to these guidelines: American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), American Academy of Physician Associates (AAPA), Association of Black Cardiologists (ABC), American College of Preventive Medicine (ACPM), American Diabetes Association (ADA), American Geriatrics Society (AGS), American Pharmacists Association (APhA), American Society for Preventive Cardiology (ASPC), National Lipid Association (NLA), and Preventive Cardiovascular Nurses Association (PCNA). References: 1. Handelsman Y et al. Endocr Pract. 2020;26(10):1196-1224. 2. Grundy SM et al. Circulation. 2019;139(25):e1082-e1143. Recommendations To reduce the risk of acute pancreatitis, a fibrate, prescription-grade omega-3 fatty acid, and/or niacin should be given to all patients with severe hypertriglyceridemia (>500 mg/dL), with the goal of reducing TGs to well below 500 mg/dL1 American Association of Clinical Endocrinologists (AACE) American College of Endocrinology (ACE) Guideline(s) American College of Cardiology (ACC)\* American Heart Association (AHA)\* To prevent acute pancreatitis, it is reasonable to reduce TGs whenever levels exceed 500 mg/dL2 National Lipid Association (NLA) When the TG concentration is very high (≥500 mg/dL, and especially if ≥1000 mg/dL), reducing the concentration to <500 mg/dL to prevent pancreatitis becomes the primary goal of therapy3 For investor communication only. Not for use in product promotion

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17 REDEMPLO Mechanism of Action Targeting APOC3, a Key Regulator of TG and TRL Metabolism For investor communication only. Not for use in product promotion APOC3, apolipoprotein C3; HL, hepatic lipase; LPL, lipoprotein lipase; TG, triglycerides; TRL, triglyceride rich lipoproteins; VLDL, very low-density lipoprotein. 1. Van Zwol W et al. J Clin Med. 2019; 8:1085. 2. Ballantyne CM, et al. New Engl J Med. 2024; Published online: May 28, 2024. DOI: 10.1056/NEJMoa2404143. TRL Chylomicron VLDL LPL Independent LPL Dependent Hepatocyte TRL-Remnants APOC3 CHYLOMICRONEMIA1,2 REDEMPLO (plozasiran)2 APOC3 APOC3 Plozasiran TRL Chylomicron VLDL LPL Dependent LPL Independent Hepatocyte TRL-Remnants APOC3 APOC3 inhibits LPL and delays clearance of TRL-remnants by preventing uptake by liver receptors, increasing plasma TGs Silencing APOC3 enhances TG lipolysis and TRL-remnant clearance by hepatic receptors, reducing plasma TGs

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18 REDEMPLO Label – Indication Statement and Dosing For investor communication only. Not for use in product promotion -----------------------------INDICATIONS AND USAGE--------------------------- REDEMPLO is an apolipoprotein C-III (apoC-III)-directed small interfering ribonucleic acid (siRNA) indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). (1) ------------------------DOSAGE AND ADMINISTRATION----------------------- • The recommended dosage of REDEMPLO is 25 mg injected subcutaneously once every 3 months. (2.1) • Inject REDEMPLO subcutaneously into the front of the thigh or abdomen. The outer area of the upper arm can be used as an injection site if a healthcare provider or caregiver administers the injection. (2.2) ---------------------DOSAGE FORMS AND STRENGTHS---------------------- Injection: 25 mg/0.5 mL solution in a single-dose pre-filled syringe. (3)

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19 REDEMPLO Label – No Contraindications, Warnings or Precautions, and Acceptable Adverse Event Profile For investor communication only. Not for use in product promotion -------------------------------CONTRAINDICATIONS------------------------------- None. (4) -------------------------------ADVERSE REACTIONS------------------------------ Most common adverse reactions in REDEMPLO treated patients (incidence ≥10% of patients treated with REDEMPLO and >5% more frequently than with placebo) are hyperglycemia, headache, nausea, and injection site reaction. (6.1)

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20 14 CLINICAL STUDIES REDEMPLO Label – Clinical Efficacy Table 2: Baseline (BL) and Percent Changes from Baseline in Lipid/Lipoprotein Parameters in Patients with FCS at Month 10 in Trial 1 Parameter (mg/dL) REDEMPLO 25 mg N=26 Placebo (pooled) N=25 REDEMPLO 25 mg vs. Placebo BL % change at Month 10 BL % change at Month 10 Treatment Difference % change (95% CI) at Month 10 Triglyceridesb 2008 -80 2053 -17 -59a (-90, -28) Non-HDL-Cc 279 -39 268 4 -42 (-67, -18) LDL-Cc 24 112 28 20 92 (4, 180) Total ApoBc 72 27 79 12 15 (-16, 46) ApoB-48c 10 -61 11 45 -106 (-180, -33) Abbreviations: ApoB = apolipoprotein B; CI= confidence interval; BL = baseline; FCS=familial chylomicronemia syndrome; non-HDL-C = non high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol. a Reached statistical significance (p value < 0.0001). b Median; Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% confidence interval for percent changes. Missing data were imputed using washout imputation. c Mean; Analysis of covariance (ANCOVA) model was used to estimate the mean difference and its corresponding 95% confidence interval for percent changes. Missing data were imputed using washout imputation. Median percent change in TG from baseline (Figure 1) and median absolute TG values (Figure 2) over time demonstrated a consistent lowering effect during the 12-month treatment period. Figure 1: Median Percent Change from Baseline in Fasting Triglycerides Over Time in Trial 1 Figure 1: Median Absolute Fasting Triglyceride Levels (mg/dL) in Trial 1 For investor communication only. Not for use in product promotion

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PALISADE Phase 3 Clinical Data Bruce Given, M.D. Chief Medical Scientist REDEMPLO® FDA Approval Conference Call November 2025

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22 PALISADE Phase 3 Study Enrolled Patients with FCS Defined Clinically or Genetically Confirmed For investor communication only. Not for use in product promotion \*Supportive genetic testing includes but is not limited to homozygous, compound heterozygous, or double heterozygote for loss-of-function or otherwise inactivating mutations in genes affecting lipoprotein lipase activity including LPL, APOC2, APOA5, GPIHBP1, GPD1, or LMF1; or evidence of low LPL activity (<20% of normal) based on source-verifiable documentation; § not caused by alcohol or cholelithiasis. FCS, familial chylomicronemia syndrome; HTG, hypertriglyceridemia; TG, triglycerides. Criteria included history of multiple TG measurements above 1000 mg/dL (at least 880 mg/dL at screening), despite standard of care; plus at least one of the following: 1. Prior genetic testing diagnostic of FCS\* OR 2. Recurrent episodes of acute pancreatitis§ OR 3. Recurrent hospitalizations for severe abdominal pain without other explainable cause OR 4. History of childhood pancreatitis OR 5. Family history of HTG-induced acute pancreatitis Genetic testing was done on all patients not previously tested for FCS variants

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23 PALISADE: Randomized Placebo-Controlled Phase 3 Study of Plozasiran in Patients with FCS For investor communication only. Not for use in product promotion APOC3, apolipoprotein C3; FCS, familial chylomicronemia syndrome; EOS, end of study. Primary Endpoint: • Placebo-adjusted median percent change in triglycerides at Month 10 Multiplicity-controlled key secondary endpoints: 1. Percent change from baseline at Months 10 and 12 (averaged) in fasting triglycerides 2. Percent change from baseline at Month 10 in fasting APOC3 3. Percent change from baseline at Month 12 in fasting APOC3 4. Incidence of positively adjudicated events of acute pancreatitis during the randomized period Primary Endpoint EOS R an do m iz at io n SCREENING (Diet, medications, and laboratory values) ≤8 weeks before randomization 0 1263Month 9 Doses Plozasiran 50 mg (N=24) Plozasiran 25 mg (N=26) Placebo (N=25)

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24 PALISADE Baseline Characteristics For investor communication only. Not for use in product promotion Data are reported as mean (±SD) unless otherwise noted. Note: Diabetic patients are defined as having HbA1c ≥6.5% or fasting glucose ≥126 mg/dL or with medical history of 'diabetes' or receiving diabetic medications at baseline. \*% = 100 x n/N', N' is the number of diabetic or prediabetic patients at baseline. Characteristic Pooled Placebo (N=25) Plozasiran 25 mg (N=26) 50 mg (N=24) Mean (SD) age, years 47 (14) 48 (14) 43 (11) Female, n (%) 11 (44) 14 (54) 13 (54) Male, n (%) 14 (56) 12 (46) 11 (46) White, n (%) 19 (76) 19 (73) 17 (71) Mean (SD) BMI, kg/m2 25 (4) 26 (4) 25 (5) Median (Q1, Q3) APOC3, mg/dL 39 (29, 50) 39 (27, 44) 30 (18, 37) Mean (SD) APOC3, mg/dL 40 (18) 39 (17) 33 (20) Median (Q1, Q3) triglyceride, mg/dL 2053 (1435, 2755) 2008 (1204, 3361) 1902 (1434, 2948) Mean (SD) triglyceride, mg/dL 2272 (1141) 2350 (1375) 2492 (1523) Receiving statins n (%) 11 (44) 11 (42) 12 (50) Fibrates, n (%) 16 (64) 19 (73) 15 (63) Omega-3 fatty acids, n (%) 6 (24) 9 (35) 7 (29) Diabetes or pre-diabetes, n (%) 11 (44) 10 (39) 7 (29) Genetic confirmation of FCS, n (%) 14 (56) 14 (54) 16 (67) Previous episode of pancreatitis, n (%) 22 (88) 23 (89) 22 (92) APOC3, apolipoprotein C3; BMI, body mass index; FCS, familial chylomicronemia syndrome; N, number; Q, quartile; SD, standard deviation; W, week.

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25 In PALISADE Median TGs Reduced 80% from Baseline at 1 month to Below Guideline Directed AP Risk Thresholds For investor communication only. Not for use in product promotion AP, acute pancreatitis; Q1, 1st quartile; Q3, 3rd quartile; SEM, standard error of mean; TG, triglycerides. Between group differences are not statistically significant through all time points. M ed ia n (Q 1, Q 3) L ev el s, m g/ dL Plozasiran 25 mg Plozasiran 50 mgPooled Placebo 0 1 2 3 4 5 6 7 8 9 10 11 12 0 500 1000 1500 2000 2500 3000 3500 4000 Study Month 75% of patients reached TGs < 880 mg/dL & 50% reached < 500 mg/dL at 10 months The effects were similar between genetic and non-genetic FCS1 M ed ia n (Q 1, Q 3) L ev el s, m g/ dL 0 1 2 3 4 5 6 7 8 9 10 11 12 0 1000 2000 3000 4000 Study Month With FCS Genetic Confirmation Plozasiran 25 mg Without FCS Genetic Confirmation Plozasiran 25 mg 1. Circulation 2025 Mar 11;151(10):733-736. doi:10.1161/CIRCULATIONAHA.124.072860. Epub 2024 Nov 16., and Presented at AHA Scientific Sessions 2024

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26 Plozasiran Significantly1 Reduced the Incidence of AP† in the Phase 3 PALISADE Study\* For investor communication only. Not for use in product promotion 1. In prespecified pooled analysis of 25 mg plozasiran group and 50 mg plozasiran group (50 mg plozasiran has not been reviewed or approved to treat any disease.\*Odds ratio, 95% CI, and P-value were based on CMH test stratified by baseline TG category. 7 incident cases occurred in 5 of 25 (20%) participants receiving placebo and 2 incident cases occurred in 2 of 50 (4%) participants in the plozasiran-treated group. † 4 patients with AP events were FCS genotype negative CI=confidence interval; CMH=Cochran-Mantel-Haenszel; TG=triglyceride. Time to First Pancreatitis Event No at Risk Placebo 25 23 23 23 22 22 21 21 21 20 20 20 20 20 Plozasiran 50 50 49 49 49 49 48 48 48 48 48 48 48 48 50% 60% 70% 80% 90% 100% 0 4 8 12 16 20 24 28 32 36 40 44 48 52 CensoredPe rc en t o f P at ie nt s W it ho ut a n Ev en t of A cu te P an cr ea ti ti s Study Weeks Odds Ratio (95% CI) vs Placebo:\* 0.17 (0.03, 0.94); P=0.029 n (%) Placebo (pooled) (N=25) Plozasiran (pooled) (N=50) Patients with Positively Adjudicated Acute Pancreatitis Event 5 (20.0) 2 (4.0) Plozasiran Placebo \*Presented at AHA Scientific Sessions 2024 This is based on a prespecified analysis of the PALISADE study in which 25 mg plozasiran and 50 mg plozasiran were pooled. 50 mg plozasiran has not been reviewed or approved to treat any disease.

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27 Summary of Safety and Tolerability from PALISADE Phase 3 For investor communication only. Not for use in product promotion 1 Adverse Reactions noted in the US Package Insert 2 Premature discontinuation from blinded therapy HbA1c, glycosylated hemoglobin; SD, standard deviation; SAE, serious adverse event; TEAE, treatment emergent adverse event. Hyperglycemia and injection site reactions are a composite of associated adverse event terms • A greater proportion of placebo-treated patients experienced SAEs • Fewer premature discontinuations from blinded therapy with plozasiran • No effect on platelet counts • No deaths Pooled Placebo (N=25) Plozasiran 25 mg (N=26) 50 mg (N=24) Adverse Reactions1 Hyperglycemia 2 (8) 5 (19) 5 (21) Headache 2 (8) 3 (12) 5 (21) Nausea 2 (8) 4 (15) 3 (13) Injection site reactions 2 (4) 4 (15) 1 (4) Severe TEAEs 5 (20) 3 (12) 3 (13) Serious TEAEs 7 (28) 5 (19) 2 (8) Deaths 0 (0) 0 (0) 0 (0) Premature discontinuations2 Any Reason 6 (24) 3 (12) 2 (8) Adverse Event 0 (0) 2 (8) 1 (4) HbA1c, mean % (SD) Baseline 6.1 (1.33) 5.7 (0.90) 5.59 (1.15) Month 12 6.2 (1.17) 5.98 (1.00) 5.83 (1.56) Platelet count, 109/liter, mean (SD) Baseline 217.9 (80.5) 204.4 (70.4) 192.9 (50.7) Mean change from baseline at Month 10 25.9 (38.2) 28.7 (61.2) -4.4 (48.2) Mean change from baseline at Month 12 8.6 (47.5) -4.3 (40.8) -8.7 (50.8)

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U.S. Commercial Launch Plan Andy Davis, MBA Senior Vice President, Global Cardiometabolic Franchise REDEMPLO® FDA Approval Conference Call November 2025

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29 The Genetically Confirmed and Clinically Diagnosed FCS Population Is Estimated to be 6,500 People In The U.S. High-Risk SHTG Severe Hypertriglyceridemia (SHTG) SHTG ▪ TGs ≥ 500 mg/dL ▪ > 3 million people ▪ Elevated Risk of AP High-Risk SHTG ▪ TGs ≥ 880 mg/dL or ≥ 500 mg/dL With Prior AP History ▪ ~ 1 million people ▪ High Risk of AP FCS (Genetic or Clinical) ▪ Persistently Elevated TGs ≥ 880 mg/dL ▪ Prevalent Prior History of AP ▪ ~ 6500 people ▪ Extremely High Risk of APSource: Nemeth, Journal of Clinical Medicine 2022; Rabacchi, Atherosclerosis 2015; Company Estimates FCS (Genetic or Clinical) Figure Not to Scale For investor communication only. Not for use in product promotion

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30 FCS Prescriber Base by Specialty FCS patients in the U.S. HCPs Identified Across 4 Specialties Who Primarily Treat FCS Patients ENDOCRINOLOGISTS LIPIDOLOGISTS PREVENTIVE CARDIOLOGISTS INTERNAL MEDICINE/OTHER ~6,500 For investor communication only. Not for use in product promotion

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31 The REDEMPLO GO LO Campaign Features Key Messages That Support Quality Use of Medicine For investor communication only. Not for use in product promotion

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32 In PALISADE, REDEMPLO Delivered Sustained TG Reductions Median Level Below 500 mg/dL at Multiple Timepoints For investor communication only. Not for use in product promotion

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33 The Patient And HCP Support Ecosystem Is Now Ready To Deliver High Quality Service Field Reimbursement Navigator Care Coordinator Patient Support Program Patient Rare Disease Specialist Pharmacist For investor communication only. Not for use in product promotion

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34For investor communication only. Not for use in product promotion Rely On REDEMPLO Patient Support Program

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35 Feedback From Physicians, Payers, Patients, And Caregivers Has Been Very Encouraging There is high unmet need for FCS patients, so a product with such impressive efficacy cannot come soon enough. – Endocrinologist Plozasiran has been on our radar and we are looking forward to its approval for the unmet need in FCS. – Payer I'm impressed by the results showing similar TG reductions from baseline in study participants with genetically and clinically confirmed FCS – Cardiologist I'd be motivated to get on this treatment to get my triglycerides down and regain a lot of moments with my kids I missed because I wasn't feeling well. – FCS Patient It's remarkable how many patients reach triglyceride levels below 500 mg/dL. – Lipidologist This new therapy is going to propel us into a new life that we've never had access to before. We're not standing still; we're not looking back. We're returning our lifestyle to some normalcy. – Caregiver Source: Market Research, Discussion Notes For investor communication only. Not for use in product promotion

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Key Takeaways and Arrowhead Looking Forward Chris Anzalone, Ph.D. President and CEO REDEMPLO® FDA Approval Conference Call November 2025

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37 REDEMPLO Positioned as Promising New Medicine for FCS Dramatic reductions in triglycerides in patients with genetically confirmed and clinically defined FCS Reduced numerical incidence of acute pancreatitis Convenient dosing once every three months with at home self-administration Strong label with no contraindications, warnings or precautions Innovative, consistent, One-REDEMPLO price model across indications Commercial team ready to launch today For investor communication only. Not for use in product promotion

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38 Bringing RNA Interference to Patients Financial Resources • Additional non-dilutive capital expected from Sarepta, Amgen, Takeda, GSK, Novartis, and Royalty Pharma as milestones are achieved • Strong balance sheet with funding into fiscal 2028 to push candidates to commercialization Proprietary Platform • Targeted RNAi Molecules platform (TRiM) designed for deep and durable gene silencing • Fulfilling the promise of bringing RNAi therapeutics to diseases outside of the liver • Potential to be best-in-class across several tissue types Arrowhead Pharmaceuticals is a RNAi therapeutics platform company with a broad pipeline of wholly owned and partnered candidates and achieved its first commercial launch in 2025 Broad Pipeline • 19 clinical stage programs (10 wholly-owned; 9 partnered) • Mix of early, mid, and late-stage candidates targeting rare and high prevalence diseases • Growing pipeline with 2-3 new clinical programs planned per year First Commercial Launch in 2025 • REDEMPLO® (plozasiran) approved by US FDA as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) • Additional regulatory review/approvals anticipated in 2026 • Potential Multi-billion-dollar opportunity across future indications For investor communication only. Not for use in product promotion

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39 TRiMTM Platform Enables Delivery to Seven Cell Types Liver Lung Skeletal Muscle CNS Adipose Ocular Cardio- myocyte Arrowhead is Fulfilling the Promise of Bringing RNAi Throughout the Body Strong clinical validation Deep lung clinical validation (RAGE) Early clinical stage Early clinical stage Early clinical stage Preclinical Stage Preclinical Stage For investor communication only. Not for use in product promotion

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40 Robust Pipeline with Multiple Mid- and Late-Stage Opportunities For investor communication only. Not for use in product promotion \*Sanofi holds product rights to plozasiran and ARO-DIMER-PA in Greater China only

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41 Arrowhead's Growth Drivers in 2026 and Beyond Arrowhead's first commercial sales of REDEMPLO in familial chylomicronemia ARO-DIMER-PA targeting PCSK9 and APOC3 first clinical readout in 2H 2026 Phase 3 studies of plozasiran in severe hypertriglyceridemia (potential multi-billion-dollar opportunity) on pace to readout in Q3 2026 Funded into 2028, potentially through multiple independent and partner launches Robust pipeline and productive discovery engine provide opportunities for additional capital inflows from business development Emerging potential high value obesity and CNS pipelines including systemic delivery across blood brain barrier For investor communication only. Not for use in product promotion

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42 FCS SHTG HOFH And We Anticipate Additional Cardiometabolic Launches ASCVD For investor communication only. Not for use in product promotion

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43 Questions? Answers. For investor communication only. Not for use in product promotion

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