Arrowhead Pharmaceuticals(ARWR) - 2025 Q4 - Annual Report

Drug Development and Clinical Trials - The Company has 18 drug candidates in clinical trials, ranging from Phase 1 to Phase 3, with a robust discovery pipeline capable of generating multiple new clinical candidates each year[19] - REDEMPLO (plozasiran) was approved by the FDA in 2025 to reduce triglycerides in adults with Familial Chylomicronemia Syndrome (FCS), marking the Company's first commercial launch[20] - The Company plans to file a supplemental NDA for severe hypertriglyceridemia (sHTG) in 2026, pending successful completion of Phase 3 studies[20] - ARO-DIMER-PA is a dual functional RNAi molecule targeting PCSK9 and APOC3, representing a significant advancement in RNAi therapeutics[48] - The Company is investigating ARO-MAPT, designed to silence the MAPT gene, in a Phase 1/2a clinical trial for Alzheimer's and tauopathies[57] - ARO-CFB is being developed as a potential treatment for complement-mediated kidney diseases, currently in a Phase 1/2a clinical trial[61] - GSK is conducting Phase 2b clinical trials for GSK-4532990 targeting metabolic-dysfunction associated steatohepatitis (MASH) and alcohol-related liver disease (ALD)[65] - GSK received a worldwide exclusive license for daplusiran/tomligisiran (GSK5637608) to develop a potential therapy for chronic hepatitis B virus infection, with a Phase 2 study currently being initiated[66] - Takeda and the Company co-develop the fazirsiran program for liver disease associated with alpha-1 antitrypsin deficiency, with a 50/50 profit-sharing structure in the U.S.[67] - Fazirsiran aims to reduce the production of the mutant Z-AAT protein to prevent liver injury and fibrosis in patients with alpha-1 antitrypsin deficiency[70] - Amgen is responsible for the clinical development of olpasiran, designed to reduce elevated lipoprotein(a), a risk factor for atherosclerotic cardiovascular disease[73] Regulatory and Compliance - The FDA requires a user fee of approximately $4.682 million for NDA submissions requiring clinical data for fiscal year 2026[106] - The FDA's review process for NDAs typically aims for completion within ten months, with priority reviews targeted at six months[108] - The Company must comply with cGMP requirements to ensure consistent production of its products before the FDA approves an NDA[109] - The FDA may require a REMS plan to mitigate serious risks associated with a drug, which can affect market potential and profitability[110] - The FDA may impose conditions on approved products, including post-approval studies and distribution restrictions, which can materially affect market dynamics[113] - The FDA may not approve any other application to market the same drug for the same indication for seven years, except in very limited circumstances[116] - The FDA's interpretation of orphan drug exclusivity may change, potentially limiting the drugs that can receive such exclusivity[117] - Fast Track Designation allows for priority review and rolling review for drugs addressing serious conditions with unmet medical needs[118] - The FDA may approve a drug under the accelerated approval program if it provides a meaningful advantage over existing therapies and demonstrates an effect on a surrogate endpoint[119] - The Breakthrough Therapy designation provides more intensive guidance and expedited review for drugs showing substantial improvement over existing therapies[120] - Post-approval requirements include ongoing regulation by the FDA, including recordkeeping and reporting of adverse experiences[121] - Drug manufacturers must register with the FDA and are subject to periodic inspections to ensure compliance with cGMP requirements[122] - The FDA may withdraw approval if compliance with regulatory requirements is not maintained or if new problems are discovered post-market[123] Intellectual Property and Licensing - The Company controls approximately 643 issued patents and has around 833 pending patent applications worldwide, covering various RNAi technologies[85] - The Company may need to obtain additional patent licenses prior to commercialization of its candidates due to the complex patent landscape in RNAi and drug delivery[89] - The Company acquired RNAi assets and rights from Novartis, including patents related to RNAi therapeutics and delivery technologies[90] - The acquisition from Roche provided the Company with licenses to patents related to modifications of double-stranded oligonucleotides, enhancing its operational freedom in RNAi-trigger formats[91][92] - The Company holds a worldwide, royalty-bearing, exclusive license under the Alnylam-Novartis License to research, develop, and commercialize 30 undisclosed gene targets[90] Market Exclusivity and Orphan Drug Designation - Orphan drug designation can provide the Company with incentives such as grant funding and tax advantages for drugs intended to treat rare diseases[114] - The company is subject to a 10-year market exclusivity for orphan medicinal products, which can be reduced to six years if criteria are not met[165] - Orphan drug designation provides up to ten years of market exclusivity in the EU, contingent on maintaining the designation at the time of marketing authorization review[163] Manufacturing and Workforce - The Company expanded its footprint with a new manufacturing and laboratory facility in Verona, Wisconsin during Q1 fiscal 2025[208] - The new state-of-the-art GMP manufacturing facility in Verona includes over 251,000 total square feet of laboratories and office space[211] - As of September 30, 2025, the Company employed 711 full-time employees across four facilities in the U.S.[212] - The Company continues to expand its workforce to increase in-house manufacturing capacity and enhance clinical and preclinical research expertise[213] - The Company offers a total compensation package targeting the 50 to 75 percentile of the market, including base salary, cash bonuses, and equity compensation[214] - The Company supports employee development through individualized plans, mentoring, and tuition reimbursement[214] - The Company is committed to fostering an inclusive environment with ongoing programs for awareness and engagement[215] Data Privacy and Security - The company must comply with various data privacy and security laws, including HIPAA and state privacy laws, which impose significant obligations regarding personal information[185] - Failure to comply with data privacy laws can result in substantial civil and criminal penalties, posing financial and reputational risks to the company[188] - The GDPR and UK GDPR impose fines of up to €20 million or 4% of annual global revenues for noncompliance, whichever is greater[191] - The complexity of data protection regulations in the EEA is heightened by varying enforcement and additional national regulations[191] - The transfer of personal data outside the EEA requires appropriate safeguards, such as standard contractual clauses[193] Pricing and Reimbursement - The pricing and reimbursement environment in the EU allows member states to control prices and reimbursement levels, which may affect market access for the company's products[177] - Health technology assessments (HTA) are increasingly influencing pricing and reimbursement decisions in EU member states, focusing on clinical efficacy, safety, and cost-effectiveness[179] - The company may be required to conduct cost-effectiveness studies to obtain favorable pricing and reimbursement conditions in certain EU member states[182] - Orphan pharmaceutical products may be exempted from providing certain clinical and economic data for pricing/reimbursement approval in some EU member states[183] Regulatory Changes in the EU - The UK government enacted the Medicines and Medical Devices Act 2021 to update regulatory frameworks for human medicines and clinical trials, ensuring public health is safeguarded[141] - The centralized procedure for Marketing Authorization (MA) in the EU has a standard evaluation timeframe of 210 days, which can be extended due to additional information requests[152] - New Chemical Entities (NCE) approved in the EU qualify for eight years of data exclusivity and ten years of marketing exclusivity, extendable to eleven years under certain conditions[157] - The European Medicines Agency (EMA) provides scientific advice for drug development, with fees significantly reduced for orphan medicines[149] - The Medical Devices (Amendment) (Great Britain) Regulations 2023 allow CE marked devices to be sold in the UK until 2028 or 2030, depending on the device type[144] - The Medicines and Healthcare products Regulatory Agency (MHRA) plans to implement new 'Pre-Market Regulations' in 2026, extending the sunset period for key EU-derived regulations[144] - The EU Clinical Trials Regulation (CTR) became applicable on January 31, 2022, streamlining the approval process for clinical trials across member states[145] - The current proposal for reforming European pharmaceutical legislation includes shortening data exclusivity from eight to six years, with incentives for developing new antibiotics[161]