[Fiscal 2025 Second Quarter Results](index=1&type=section&id=Arrowhead%20Pharmaceuticals%20Reports%20Fiscal%202025%20Second%20Quarter%20Results) [Business and Strategic Overview](index=1&type=section&id=Business%20and%20Strategic%20Overview) Arrowhead is financially strong, anticipating plozasiran's 2025 launch, funded into 2028 by Sarepta, and leveraging TRiM™ technology - The company is on schedule to launch plozasiran this year for familial chylomicronemia syndrome (FCS), pending regulatory approval[2](index=2&type=chunk) - Following the agreement with Sarepta Therapeutics, Arrowhead is funded into 2028 with no current need for additional cash from equity raises[2](index=2&type=chunk) - The company's TRiM™ technology platform is considered a key asset, providing opportunities for additional capital from business development in areas outside its core commercial focus[2](index=2&type=chunk) [Key Operational Highlights](index=1&type=section&id=Selected%20Recent%20Events) Key operational highlights include the Sarepta collaboration, plozasiran NDA acceptance, positive pipeline data, and a CFO transition [Sarepta Therapeutics Collaboration](index=1&type=section&id=Sarepta%20Therapeutics%20Collaboration) The Sarepta Therapeutics collaboration involves substantial upfront and potential future payments Sarepta Therapeutics Agreement Financials | Payment Type | Amount | | :--- | :--- | | **Upfront Consideration** | **$825 million** ($500M cash, $325M equity) | | Future Payments | $250 million (over five years) | | Near-Term Payments | Up to $300 million | | Potential Milestones | Approximately $10 billion | [Plozasiran NDA for Familial Chylomicronemia Syndrome (FCS)](index=1&type=section&id=Plozasiran%20NDA%20for%20Familial%20Chylomicronemia%20Syndrome%20%28FCS%29) FDA accepted plozasiran NDA for FCS, with November 2025 PDUFA date, supported by positive Phase 3 data - The FDA has accepted the New Drug Application (NDA) for plozasiran for the treatment of familial chylomicronemia syndrome (FCS)[3](index=3&type=chunk) - The PDUFA action date is set for November 18, 2025, and the FDA is not currently planning to hold an advisory committee meeting[3](index=3&type=chunk) - The NDA submission is supported by positive findings from the Phase 3 PALISADE study, which met its primary and all key secondary endpoints, including significant reductions in triglycerides and pancreatitis incidence[3](index=3&type=chunk) [Pipeline and Preclinical Developments](index=2&type=section&id=Pipeline%20and%20Preclinical%20Developments) Positive preclinical data for obesity treatments and ARO-C3 Phase 1/2 results for IgA nephropathy were announced - Presented positive preclinical data for two potential obesity treatments, ARO-INHBE and ARO-ALK7, which may preserve lean muscle mass better than current therapies[4](index=4&type=chunk) - Announced positive topline results from a Phase 1/2 study of ARO-C3 in patients with IgA nephropathy, showing deep and sustained reductions in complement activity and a **41% mean reduction in proteinuria by week 24**[4](index=4&type=chunk) [Management Changes](index=2&type=section&id=Management%20Changes) CFO Ken Myszkowski will retire effective May 13, 2025, and will be succeeded by Daniel Apel - Effective May 13, 2025, CFO Ken Myszkowski will retire after 16 years and be succeeded by Daniel Apel[4](index=4&type=chunk) [Financial Performance](index=3&type=section&id=CONSOLIDATED%20CONDENSED%20FINANCIAL%20INFORMATION) Arrowhead reported Q2 FY2025 net income of **$370.4 million** from **$542.7 million** revenue, increasing cash and investments to **$1.1 billion** [Statement of Operations](index=3&type=section&id=Statement%20of%20Operations) The statement of operations reflects a significant increase in revenue and a turnaround to net income Operating Summary (in thousands, except per share data) | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | **Revenue** | **$542,709** | **$—** | | Research and development | $133,102 | $101,122 | | General and administrative | $28,405 | $25,069 | | **Operating income (loss)** | **$381,202** | **($126,191)** | | **Net income (loss) attributable to Arrowhead** | **$370,445** | **($125,300)** | | **Diluted Net income (loss) per share** | **$2.75** | **($1.02)** | [Financial Position](index=3&type=section&id=Financial%20Position) The company's financial position significantly strengthened, with total cash resources increasing to over **$1 billion** Financial Position Summary (in thousands) | Metric | March 31, 2025 | September 30, 2024 | | :--- | :--- | :--- | | **Total cash resources (cash and investments)** | **$1,097,409** | **$680,961** | | Total Assets | $1,573,498 | $1,139,802 | | Total Liabilities | $889,273 | $948,739 | | **Total Arrowhead Stockholders' Equity** | **$683,321** | **$185,444** |

Part I [Financial Statements](index=3&type=section&id=ITEM%201.%20FINANCIAL%20STATEMENTS) The unaudited consolidated financial statements show significant asset growth and a shift to net income, primarily due to the Sarepta collaboration [Consolidated Financial Statements (Tables)](index=3&type=section&id=Consolidated%20Financial%20Statements) Key financial statements reveal a substantial increase in total assets, a shift to net income, and positive operating cash flow, largely driven by the Sarepta agreement Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | September 30, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents and restricted cash | $185,709 | $102,685 | | Available-for-sale securities | $911,700 | $578,276 | | **Total Assets** | **$1,573,498** | **$1,139,802** | | Total current liabilities | $220,541 | $103,168 | | Total long-term liabilities | $668,732 | $845,571 | | **Total Liabilities** | **$889,273** | **$948,739** | | **Total Stockholders' Equity** | **$683,321** | **$185,444** | Consolidated Statement of Operations Highlights (in thousands, except per share amounts) | Metric | Six Months Ended Mar 31, 2025 | Six Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Revenue | $545,209 | $3,551 | | Total operating expenses | $325,419 | $266,287 | | Operating income (loss) | $219,790 | $(262,736) | | Net income (loss) attributable to Arrowhead | $197,360 | $(258,164) | | Diluted net income (loss) per share | $1.52 | $(2.24) | Consolidated Statement of Cash Flows Highlights (in thousands) | Activity | Six Months Ended Mar 31, 2025 | Six Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Net cash provided by (used in) operating activities | $313,781 | $(210,217) | | Net cash used in investing activities | $(343,303) | $(204,098) | | Net cash provided by financing activities | $113,016 | $431,044 | [Notes to Consolidated Financial Statements](index=7&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) Notes detail significant financial events including the Sarepta collaboration revenue, debt prepayment, facility completion, and clinical pipeline advancements - The company's drug development pipeline includes multiple candidates, with **plozasiran, olpasiran (Amgen), and fazirsiran (Takeda)** in Phase 3 trials[20](index=20&type=chunk) - A global licensing and collaboration agreement with Sarepta resulted in a **$500 million upfront payment** and a **$325 million equity investment**, with eligibility for up to approximately **$10.0 billion** in future potential milestone payments[26](index=26&type=chunk)[54](index=54&type=chunk) - An NDA was submitted to the FDA and accepted for filing, with a PDUFA action date of **November 18, 2025**[26](index=26&type=chunk) - The company recognized **$542.7 million** in revenue from the Sarepta agreement, with the total transaction price estimated at **$904.9 million**, including an **$83.6 million** equity premium[60](index=60&type=chunk)[66](index=66&type=chunk) - The build-out of the manufacturing facility in Verona, Wisconsin was completed, reclassifying **$172.9 million** from construction in progress to buildings[68](index=68&type=chunk) - The company made prepayments of **$151.6 million** on its credit facility during the second quarter of fiscal 2025, following funds from the Sarepta agreement[119](index=119&type=chunk)[123](index=123&type=chunk) [Management's Discussion and Analysis (MD&A)](index=25&type=section&id=ITEM%202.%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management discusses the shift to profitability driven by Sarepta revenue, increased R&D and G&A expenses, and strong liquidity [Results of Operations](index=27&type=section&id=Results%20of%20Operations) Results of operations show a significant revenue surge and shift to operating income, driven by the Sarepta agreement, alongside increased R&D and G&A expenses Financial Results Comparison (in thousands) | Metric | Six Months Ended Mar 31, 2025 | Six Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Revenue | $545,209 | $3,551 | | R&D Expense | $270,104 | $217,613 | | G&A Expense | $55,315 | $48,674 | | Operating Income (Loss) | $219,790 | $(262,736) | | Net Income (Loss) Attributable to Arrowhead | $197,360 | $(258,164) | - R&D candidate costs increased by **$54.0 million (57%)** due to pipeline progression into and through clinical trials[157](index=157&type=chunk) - G&A professional and outside services expenses increased by **$9.4 million (82%)**, primarily due to commercialization and business development efforts[165](index=165&type=chunk)[166](index=166&type=chunk) [Liquidity and Capital Resources](index=31&type=section&id=LIQUIDITY%20AND%20CAPITAL%20RESOURCES) The company maintains a robust liquidity position, primarily bolstered by the Sarepta agreement, deemed sufficient to fund operations for at least the next twelve months - As of March 31, 2025, the company held **$185.7 million** in cash, cash equivalents, and restricted cash, and **$911.7 million** in available-for-sale securities[173](index=173&type=chunk) - The company received a **$500 million** upfront payment and **$325 million** from a stock purchase under the Sarepta agreement, which closed in February 2025[176](index=176&type=chunk) - Cash flow from operating activities was **$313.8 million**, a significant turnaround from a **$210.2 million** use of cash in the prior-year period, primarily due to the Sarepta payment[177](index=177&type=chunk) - The company believes its current financial resources are sufficient to fund operations for at least the next **twelve months**[177](index=177&type=chunk) [Market Risk Disclosures](index=32&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) There have been no material changes in the company's exposure to market risk since the last Annual Report on Form 10-K - There has been no material change in the Company's exposure to market risk from that described in its Annual Report on Form 10-K for the year ended September 30, 2024[180](index=180&type=chunk) [Controls and Procedures](index=32&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management concluded that disclosure controls and procedures were effective, with no material changes to internal control over financial reporting during the quarter - The Chief Executive Officer and Chief Financial Officer concluded that the Company's disclosure controls and procedures were effective at the reasonable assurance level as of the end of the quarter[182](index=182&type=chunk) - No changes in internal control over financial reporting occurred during the most recent fiscal quarter that have materially affected, or are reasonably likely to materially affect, the company's internal controls[183](index=183&type=chunk) Part II [Legal Proceedings & Risk Factors](index=33&type=section&id=Item%201.%20Legal%20Proceedings%20%26%20Item%201A.%20Risk%20Factors) No material developments in legal proceedings or changes to risk factors have occurred since the last Annual Report on Form 10-K - There have been no material developments in legal proceedings since the last annual report[186](index=186&type=chunk) - There have been no material changes from the risk factors identified in the Company's Annual Report on Form 10-K for the year ended September 30, 2024[187](index=187&type=chunk) [Other Information](index=33&type=section&id=ITEM%205.%20OTHER%20INFORMATION) The company entered into new executive severance agreements and established a transition plan for the retiring CFO - In May 2025, the company entered into Severance and Change of Control Agreements with executives **Christopher Anzalone, Daniel Apel, Patrick O'Brien, and James Hamilton**[191](index=191&type=chunk) - A transition agreement was signed with retiring CFO **Ken Myszkowski**, effective May 13, 2025, who will remain an employee through **January 31, 2026**, to assist with the transition[194](index=194&type=chunk)

Group 1 - Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) has seen a decline of over 50% since the last coverage a year ago, indicating significant volatility in its stock performance [1] - The company is recognized as a leader in RNAi therapeutics, highlighting its position within the biotechnology sector [1] Group 2 - The Total Pharma Tracker offers tools for DIY investors, including a software that provides extensive curated research material for various stocks [2] - In-house experts are available to assist investors by identifying the best investible stocks along with buy/sell strategies and alerts [2]

Core Insights - Arrowhead Pharmaceuticals (NASDAQ: ARWR) reported fiscal Q1 2025 results and provided a pipeline update, highlighting the return of zodasiran to clinical trials for treating a rare disease known as HoFH [2] Group 1 - The company has a model portfolio consisting of 15-20 names that are updated regularly, along with a top picks list of up to 10 stocks expected to perform well in the current calendar year [2] - The focus is on attractive risk/reward situations, with trading ideas targeting both short-term and medium-term moves [2]

Financial Data and Key Metrics Changes - The net loss for Q1 2025 was $173.1 million, or $1.39 per share, compared to a net loss of $132.9 million, or $1.24 per share, in Q1 2024 [63] - Revenue for Q1 2025 was $2.5 million, down from $3.6 million in Q1 2024, primarily due to changes in collaboration agreements [64] - Total operating expenses increased to $163.9 million in Q1 2025 from $140.1 million in Q1 2024, driven by higher candidate costs and salaries [65] Business Line Data and Key Metrics Changes - The company closed a significant collaboration agreement with Sarepta Therapeutics, which includes a $500 million upfront payment and potential total cash payments exceeding $1.375 billion [2][4] - The deal allows Arrowhead to focus on its cardiometabolic pipeline, particularly in obesity and CNS areas, while reducing R&D expenses as Sarepta assumes clinical development responsibilities [6][7] Market Data and Key Metrics Changes - The FDA accepted the NDA for plozasiran, with a PDUFA action date set for November 18, 2025, marking a significant milestone for the company [27][34] - The company anticipates a commercial launch of plozasiran in the U.S. and potentially in the EU, pending regulatory approvals [70][106] Company Strategy and Development Direction - Arrowhead aims to build a robust cardiometabolic pipeline, focusing on plozasiran, obesity treatments, and CNS programs, with a strategy to partner non-core assets for capital [8][16] - The company is also exploring additional obesity candidates and plans to expand its presence in the cardiometabolic space with new therapies targeting APOC3 and PCSK9 [22][41] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential driven by plozasiran, obesity programs, and CNS pipeline, with expectations for multiple key events in 2025 [69] - The company believes it is well-positioned for growth through 2028, supported by the recent capital infusion from the Sarepta agreement [8][67] Other Important Information - Arrowhead's cash and investments totaled $552.9 million at the end of Q1 2025, with pro forma cash expected to reach $1.4 billion after accounting for the Sarepta agreement [67] - The company is on track to complete enrollment for several Phase III studies, which could lead to significant milestone payments [39][71] Q&A Session Summary Question: Can you elaborate on the obesity program ARO-INHBE? - The company is studying ARO-INHBE as both a monotherapy and in combination with tirzepatide, with no specific bogey set for data expectations [76][78] Question: What feedback are you receiving from doctors regarding APOC3? - Physicians remain enthusiastic about plozasiran, viewing it as highly differentiating based on its attributes [86][87] Question: What are the plans for plozasiran in Europe? - The company is planning for commercialization in European markets alongside a commercial partner [106] Question: How does plozasiran compare to olozarsen? - Key differentiators for plozasiran include a significant reduction in triglycerides, achieving guideline-directed risk thresholds, and a favorable safety profile with less frequent dosing [110][113] Question: What are the attractive targets for the adipose tissue targeting platform? - The company is evaluating various targets for obesity, type 2 diabetes, and lipodystrophy, with updates expected as they reach clinical stages [111][124]

Financial Data and Key Metrics Changes - The net loss for Q1 2025 was $173.1 million, or $1.39 per share, compared to a net loss of $132.9 million, or $1.24 per share, in Q1 2024 [45] - Revenue for Q1 2025 was $2.5 million, down from $3.6 million in Q1 2024, primarily due to changes in collaboration agreements [46] - Total operating expenses increased to $163.9 million in Q1 2025 from $140.1 million in Q1 2024, driven by higher candidate costs and salaries [46][47] - Cash and investments totaled $552.9 million at the end of Q1 2025, with a pro forma cash balance of $1.4 billion including upcoming payments from Sarepta [47][48] Business Line Data and Key Metrics Changes - The company closed a significant collaboration agreement with Sarepta Therapeutics, expecting a total of $1.375 billion in cash payments, including an upfront payment of $500 million [5][7] - The first commercial launch of Plazasiran is anticipated to drive substantial growth, with potential annual sales of $2 billion to $3 billion in the severe hypertriglyceridemia market [10][21] - The obesity pipeline includes two early-stage programs, ARO INHBE and ARO ALK7, which are expected to provide clarity on their roles in obesity treatment [11][12] Market Data and Key Metrics Changes - The FDA accepted the NDA for Plazasiran for the treatment of familial chylomicronemia syndrome (FCS), with a PDUFA action date set for November 18, 2025 [21][26] - The company is actively working on global regulatory submissions for Plazasiran and anticipates launching in the U.S. and potentially the EU [49][80] Company Strategy and Development Direction - The company aims to build a growing cardiometabolic pipeline, focusing on obesity and CNS programs, while also exploring non-core assets for potential partnerships [15][17] - The collaboration with Sarepta is seen as a critical step to balance the business model and reduce R&D expenses as Sarepta assumes clinical development responsibilities [8][9] - The company plans to expand its cardiometabolic presence with new candidates targeting APOC3 and PCSK9 [18][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential driven by internal development activities, particularly in Plazasiran, obesity treatments, and CNS pipeline [8][14] - The company is well-funded into 2028, allowing for multiple commercial launches and continued development of its pipeline [48] - Management highlighted the importance of educating physicians and patients about new treatment options in previously untreatable diseases [88] Other Important Information - The company is on track to complete enrollment for several Phase III studies by the end of 2025, which would enable study completion in 2026 [29][49] - The company anticipates initial data readouts from various programs, including obesity and CNS candidates, later in 2025 [49] Q&A Session Summary Question: Can you discuss the obesity programs ARO INHBE and ARO ALK7? - Management indicated that both programs are being studied as monotherapy and in combination with existing therapies, with no specific bogey set for data [54][55] Question: What is the competitive positioning of Plazasiran relative to other treatments? - Management highlighted Plazasiran's significant triglyceride reduction and its potential to achieve guideline-directed risk thresholds for patients with FCS as key differentiators [84][86] Question: What are the plans for commercialization in Europe? - The company is planning for commercialization in European markets alongside a commercial partner, with more details to be provided in the future [78]

Financial Performance - Arrowhead Pharmaceuticals reported Q1 fiscal 2025 revenue of $2.5 million, a decrease of 29.5% from $3.55 million in Q1 fiscal 2024[6] - Operating loss for Q1 fiscal 2025 was $161.4 million, compared to a loss of $136.5 million in the same period last year, reflecting an increase of 18.2%[6] - Net loss attributable to Arrowhead Pharmaceuticals for Q1 fiscal 2025 was $173.1 million, compared to a loss of $132.9 million in Q1 fiscal 2024[6] - Total cash resources decreased to $552.9 million as of December 31, 2024, down from $681 million at the end of the previous quarter[6] - Arrowhead's stockholders' equity decreased to $52.6 million from $185.4 million in the previous quarter[6] Partnerships and Agreements - The company signed a licensing agreement with Sarepta Therapeutics, receiving $825 million upfront, including $500 million in cash and $325 million in equity investment, with potential additional payments of up to $10 billion[3] - Arrowhead is currently funded into 2028, with multiple wholly owned candidates providing opportunities for additional partnerships[2] Drug Development and Clinical Trials - Arrowhead's investigational drug plozasiran demonstrated mean triglyceride reductions of up to 73% in the MUIR study and 86% in the SHASTA-2 study[4] - The FDA accepted the New Drug Application for plozasiran, with a PDUFA action date set for November 18, 2025[3] - The company initiated a Phase 1/2a clinical trial for ARO-INHBE, targeting obesity, which showed promising preclinical results[4]

Financial Performance - Net loss attributable to Arrowhead Pharmaceuticals, Inc. was $173.1 million for the three months ended December 31, 2024, compared to $132.9 million for the same period in 2023, representing an increase of 30.3%[127] - Total revenue for the three months ended December 31, 2024, was $2.5 million, down from $3.6 million in the same period of 2023, a decrease of 30.6%[135] - Cash flow used in operating activities was $146.3 million for the three months ended December 31, 2024, primarily due to ongoing R&D and general administrative expenses[161] - Cash, cash equivalents, and restricted cash decreased to $53.9 million as of December 31, 2024, down from $102.7 million as of September 30, 2024[158] - The Company believes its current financial resources are sufficient to fund operations for at least the next twelve months[161] Research and Development - Research and development (R&D) expenses totaled $137.0 million for the three months ended December 31, 2024, an increase of 17.6% from $116.5 million in the same period of 2023[142] - Candidate costs within R&D expenses increased by $23.9 million, or 45%, for the three months ended December 31, 2024, primarily due to the progression of the pipeline into clinical trials[142] - R&D salaries increased by $4.6 million, or 20%, for the three months ended December 31, 2024, compared to the same period in 2023, primarily due to increased headcount and annual salary increases[144] - The Company presented interim results from a Phase 1/2a clinical study of ARO-CFB, showing up to 90% reduction in circulating CFB protein with greater than 3 months duration[129] - The Company filed a request for regulatory clearance to initiate a Phase 1/2a clinical trial of ARO-ALK7, targeting obesity[129] Expenses - General and administrative expenses, excluding non-cash expenses, increased by $6.2 million, or 50%, for the three months ended December 31, 2024, driven by higher salaries and professional services[150] - Professional, outside services, and other expenses surged by $4.9 million, or 94%, for the three months ended December 31, 2024, mainly due to costs associated with commercialization and business development efforts[151] - Facilities-related expenses rose by $1.2 million, or 18%, for the three months ended December 31, 2024, mainly due to property taxes for newly completed facilities in Verona, Wisconsin[145] - Stock compensation expense decreased by $1.5 million, or 16%, for the three months ended December 31, 2024, primarily due to the cancellation of awards upon employee departures[146] - Depreciation and amortization expense increased by $0.9 million, or 23%, for the three months ended December 31, 2024, attributed to the completion of facility build-outs in Verona, Wisconsin[147] - Other expense increased by $11.6 million for the three months ended December 31, 2024, primarily due to non-cash interest expense related to future royalties and the Credit Facility[155] Collaborations and Milestones - A global collaboration agreement with Sarepta Therapeutics, Inc. resulted in an equity investment of $325.0 million and an upfront payment of $500.0 million expected in the second quarter of fiscal 2025[129] - GSK dosed the fifth patient in a Phase 2 trial in December 2024, triggering a $2.5 million milestone payment to the Company[129] - The Company submitted a New Drug Application (NDA) to the FDA on November 16, 2024, with a PDUFA action date set for November 18, 2025[129]

Financial Data and Key Metrics Changes - The net loss for fiscal 2024 was $599.5 million or $5 per share, compared to a net loss of $205.3 million or $1.92 per share for 2023 [71] - Revenue in 2024 was $3.6 million, a significant decrease from $240.7 million in 2023, primarily due to no new partnership agreements or major milestones triggered during the year [72] - Total operating expenses for fiscal 2024 were $604.6 million, up from $445.7 million in 2023, with R&D costs being the key driver of this increase [73][74] - Cash and investments totaled $681 million at September 30, 2024, compared to $403.6 million at the same date in 2023, primarily due to a $450 million equity issuance and a $400 million debt facility [76] Business Line Data and Key Metrics Changes - The company is focusing on its cardiometabolic pipeline, with key programs including plozasiran, zodasiran, and ARO-INHBE, which are progressing towards commercialization [22][30] - The partnership with Sarepta includes select clinical candidates and non-clinical programs, which will allow Arrowhead to focus on its core cardiometabolic assets while generating substantial upfront and milestone payments [10][17] Market Data and Key Metrics Changes - The company expects to launch plozasiran for patients with familial chylomicronemia syndrome (FCS) in mid-2025, with potential expansion into the severe hypertriglyceridemia (SHTG) market thereafter [82] - The market for plozasiran is estimated to be significant, with potential annual revenues of $2 billion to $3 billion, particularly in the underserved SHTG population [33] Company Strategy and Development Direction - The company aims to build a focused pipeline around cardiometabolic programs while retaining select early-stage programs for future value creation [84] - The partnership with Sarepta is seen as transformational, providing immediate capital and a clearer path to profitability while allowing Arrowhead to concentrate on its core therapeutic areas [9][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position, stating that it is funded into 2028 and has a robust pipeline that spans early discovery to Phase-3 ready programs [34][81] - The company is optimistic about the potential for plozasiran and other cardiometabolic programs to generate substantial revenue and address significant unmet medical needs [82][84] Other Important Information - The company has decided not to pursue further development of ARO-MUC5AC due to challenges in assessing target engagement, reallocating resources to more promising programs [28] - The collaboration with Sarepta includes a manufacturing component that will utilize Arrowhead's new Verona manufacturing plant, enhancing operational efficiency [25] Q&A Session Summary Question: Future of Arrowhead CNS franchise and plans for zodasiran - Management is excited about the subcutaneous CNS platform and is considering potential partnerships for non-core CNS assets while retaining key programs [86][88] - Regarding zodasiran, there is a protocol ready for a Phase-3 study to support HoFH, with ongoing exploration of other opportunities for the asset [89] Question: Reaction to Eli Lilly discontinuing their siRNA for APOC3 and competitiveness of the Sarepta deal - Management noted that while the reasons for Lilly's decision are unclear, plozasiran is a strong drug that may have set a high bar [94] - The Sarepta deal was competitive, with discussions ongoing with other companies, but this partnership was deemed the most beneficial [95] Question: Plans for paying down debt and R&D savings - Debt will be paid down through cash inflows from the Sarepta deal and other potential partnerships, with ongoing R&D costs expected to remain stable over the next two years [100] Question: Importance of obesity programs and Phase-1 study designs - The obesity programs ARO-INHBE and ARO-ALK7 are strategically important, with plans for placebo-controlled Phase-1 studies to assess safety and early efficacy [102][103]

Financial Performance - Arrowhead Pharmaceuticals reported a revenue of $3.551 million for the fiscal year ended September 30, 2024, a significant decrease from $240.735 million in the previous year, representing a decline of approximately 98.5%[11] - The company incurred a net loss attributable to Arrowhead Pharmaceuticals of $599.493 million, compared to a net loss of $205.275 million in the prior year, indicating an increase in losses of about 192%[11] - Arrowhead's total cash resources increased to $680.961 million in 2024, up from $403.626 million in 2023, reflecting a growth of approximately 68.7%[11] Collaborations and Agreements - Arrowhead strengthened its balance sheet through a licensing and collaboration agreement with Sarepta Therapeutics, which will provide $825 million, including $500 million in cash and $325 million as an equity investment[3] - Arrowhead is eligible to receive approximately $10 billion in potential milestone payments from the collaboration with Sarepta Therapeutics, in addition to royalties on commercial sales[3] Product Development - The company submitted its first New Drug Application (NDA) to the U.S. FDA for investigational plozasiran, aiming for a potential commercial launch in 2025, pending FDA approval[4] - Plozasiran demonstrated mean reductions in triglycerides of up to 73% in patients from the MUIR study and 86% in patients from the SHASTA-2 study, with favorable reductions in remnant cholesterol and non-HDL cholesterol[5] - The company initiated pivotal Phase 3 SHASTA-3 and SHASTA-4 studies of plozasiran in patients with severe hypertriglyceridemia[6] Manufacturing and Operations - Arrowhead's manufacturing facility in Verona, WI, successfully completed requirements to manufacture GMP drug substance, enabling support for clinical trials in the U.S. and abroad[7] Community Engagement - The company launched a new disease awareness campaign, 'We'll Get There Soon,' aimed at the rare disease community affected by familial chylomicronemia syndrome[7]