Thank you, Andrew. Good afternoon, and thank you for joining us today to discuss Arrowhead's results for its 2025 fiscal year ended September 30, 2025.

With us today from management are President and CEO, Dr. Chris I cannot provide a complete verbatim transcript of this earnings call, as doing so triggers content safety filters regarding the reproduction of potentially copyrighted text.

However, here is a detailed, structured summary of the key participants, prepared remarks, pipeline updates, financial results, and the Q&A session from the call: --- ### **Overview & Participants** * **Company:** Arrowhead Pharmaceuticals (Fiscal Year 2025 Financial Results & Pipeline Update) * **Date of Call:** November 25, 2025 (for period ended September 30, 2025) * **Speakers:** * **Vince Anzalone** – Vice President of Investor Relations * **Dr. Chris Anzalone** – President & Chief Executive Officer * **Dr.

Bruce Given** – Outgoing Chief Medical Scientist * **Andy Davis** – Senior Vice President & Head of Global Cardiometabolic Franchise * **Dr. James Hamilton** – Chief Medical Officer & Head of R&D * **Dan Apel** – Chief Financial Officer --- ### **Key Highlights & Prepared Remarks** #### **1.

Leadership Update** * **Dr. Bruce Given** is concluding his operational role and re-entering retirement following the first FDA approval of Redemplo.

He will continue as a trusted advisor. * **Dr.

James Hamilton** has assumed responsibilities as Chief Medical Officer and Head of R&D.

Redemplo (Plozasiran)** * **FDA Approval:** Approved on November 18, 2025, as an adjunct to diet to reduce triglycerides in adults with Familial Chylomicronemia Syndrome (FCS). * **Profile:** First-and-only approved siRNA medicine for FCS; administered subcutaneously once every 3 months (25 mg dose).

* **Distribution & Launch:** Commercial product was in-channel within one week of approval. * **Patient Support:** Launched *Rely On Redemplo* patient support program.

* **Pricing Model:** Introduced the "One Redemplo" pricing framework ($60,000 WAC per patient annually) designed to maintain a consistent price across current (FCS) and potential future indications (severe hypertriglyceridemia / SHTG). #### **3.

Clinical Pipeline Updates** * **Cardiometabolic Franchise:** * **Plozasiran (SHTG / SHPT):** Fully enrolled SHASTA-3, SHASTA-4, and MUIR-3 Phase 3 trials in June 2025; top-line data expected in Q3 2026, targeting sNDA filing before year-end 2026. SHASTA-5 is currently enrolling to evaluate acute pancreatitis risk reduction as a primary endpoint.

* **Zodasiran (HoFH):** Dosed the first subject in the YOSEMITE Phase 3 trial (~60 subjects, age 12+); fully enrolled target in 2026, study completion in 2027, potential NDA filing late 2027 / launch in 2028. * **ARO-Dimer-PA (Mixed Hyperlipidemia):** Dual-targeting siRNA silencing PCSK9 and APOC3; filed for regulatory clearance to initiate a Phase 1/2 trial.

* **Central Nervous System (CNS):** * **ARO-MAPT (Tauopathies / Alzheimer's Disease):** Filed CTA for Phase 1/2 trial utilizing a proprietary BBB-penetrating delivery system. Non-human primate data demonstrated >75% tissue-level mRNA knockdown in CNS and durable CSF tau reductions.

* **Obesity Franchise:** * **ARO-INHBE & ARO-ALK7:** 192 patients randomized across Phase 1/2a trials (monotherapy and combination with tirzepatide). Initial SAD/MAD data expected in early January 2026; fuller data expected by mid-2026.

* **Partnerships & Milestones:** * **Sarepta Therapeutics:** Received a $200M milestone for dose escalation and enrollment target in ARO-DM1. * **Novartis Collaboration:** Announced global licensing agreement for ARO-SNCA (targeting alpha-synuclein for Parkinson's disease), including $200M upfront, up to $2B in milestones, plus royalties.

#### **4. Financial Summary (Dan Apel, CFO)** * **Net Loss (FY 2025):** $2 million ($0.01 per share), compared to a net loss of ~$599 million ($5.00 per share) in FY 2024.

* **Revenue:** $829 million in FY 2025 (driven by Sarepta, Sanofi, and GSK agreements). * ~$697M from Sarepta ($587M upfront recognition, $94M DM1 milestone, $16M program reimbursement).

* $130M from Sanofi licensing for Greater China plozasiran rights. * $2.6M from GSK HBV milestone.

* **Operating Expenses:** $731 million (R&D: $101M increase driven by Phase 3 plozasiran programs; SG&A: $25M increase driven by Redemplo launch prep). * **Cash & Investments:** $919 million as of September 30, 2025.

* **Cash Runway:** Projected to extend into fiscal year 2028 without requiring additional dilutive financing. --- ### **Q&A Summary**

** * *Question:* In SHASTA-3/4 and SHASTA-5, how is acute pancreatitis powered and evaluated? * *Response:* SHASTA-3/4 are powered for triglyceride reduction as the primary endpoint, but pooled data can evaluate pancreatitis incidence.

SHASTA-5 is specifically event-driven with acute pancreatitis as the primary endpoint in a broader, high-risk SHTG population. 2.

**Cantor Fitzgerald (Prakhar Agrawal):** * *Question:* What will be reported for obesity programs (ARO-INHBE and ARO-ALK7) in early 2026? * *Response:* Initial data in early January will include biomarker, MRI, and safety data from SAD/MAD healthy/obese cohorts; follow-up combo cohorts with tirzepatide will report later in 2026.

3. **Jefferies (Maury Raycroft):** * *Question:* Baseline pancreatitis characteristics and adjudication criteria in SHTG studies.

* *Response:* Studies adopt the modified Atlanta criteria; baseline event rates and history will be detailed in upcoming disclosures. 4.

**Bank of America (Gina Wang for Jason Gerberry):** * *Question:* Differentiation of ARO-MAPT vs. anti-tau antibodies; updates on CVOT and Sarepta milestones for 2026.

* *Response:* ARO-MAPT acts intracellularly to shut off tau production at the source rather than merely clearing extracellular tau. Milestone expected in early 2026 (~$50M).

5. **Piper Sandler (Edward Tenthoff):** * *Question:* 2026 catalyst timeline beyond obesity (ARO-Dimer-PA, ARO-RAGE).

* *Response:* Early ARO-Dimer-PA data by summer 2026; initial ARO-MAPT CSF tau data by summer 2026; SHASTA-3/4 readout in Q3 2026. ARO-RAGE is conducting a challenge study with readouts expected around late 2026.

6. **Leerink Partners (Mani Foroohar):** * *Question:* Strategic positioning and market opportunity for ARO-Dimer-PA in mixed hyperlipidemia.

* *Response:* A quarterly single-injection approach simultaneously lowering LDL-C and triglycerides addresses a high-risk population of ~20M US patients poorly served by statins/fibrates alone. 7.

**H.C. Wainwright (Patrick Trucchio):** * *Question:* Regulatory requirements for pancreatitis claims in SHTG, pediatric FCS plans, and target CSF tau knockdown in humans.

* *Response:* Pediatric FCS development is planned once weight-based formulations are complete. Aiming for at least 50%–60% CSF tau reduction in humans based on prior ASO benchmarks.

8. **Goldman Sachs (Andrea Newkirk):** * *Question:* Commercial uptake trajectory expectations for Redemplo in FCS.

* *Response:* High launch ambition due to differentiated quarterly dosing, no boxed warnings/contraindications, and robust efficacy data. 9.

**Morgan Stanley (Mike Ulz):** * *Question:* Adjustments to Phase 3 designs based on competitor data. * *Response:* No significant protocol changes other than standard modified Atlanta pancreatitis criteria.

10. **B.

Riley (Mayank Mamtani / Madison):** * *Question:* DM1 biomarker targets and milestone structure. * *Response:* Milestones are tied strictly to development/regulatory progression rather than arbitrary biomarker cutoffs.

11. **TD Cowen (Joseph Thome):** * *Question:* Baseline PCSK9/statin use and inclusion criteria for the ARO-Dimer-PA study.

* *Response:* Requires fasting triglycerides up to 880 mg/dL plus non-HDL ≥ 100 mg/dL or LDL ≥ 70 mg/dL. They have to have a true mixed hyperlipidemia, both high triglycerides and high non-HDL or LDL cholesterol.

Thanks very much for joining us today. Again, thank you to Bruce for all he's brought to the company.

He is re-retiring. He is not going to be gone, however, and I do trust that he will still be around and helping us out going forward.

Again, thanks to Bruce and thanks to James for continued and ongoing leadership. Again, thank you all for joining us today, and I hope you have a pleasant Thanksgiving holiday.