ATXN1

PASADENA, Calif.--( BUSINESS WIRE )--Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that the global licensing and collaboration agreement with Sarepta Therapeutics (NASDAQ: SRPT) announced on November 26, 2024, has now closed. Closing of the transaction was subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and other customary conditions. Summary Financial Terms Upon closing, Arrowhead receives a $500 million upfront payment and $325 million through the purchase by Sarepta of Arrowhead common stock priced at $27.25 per share. Arrowhead will also receive $250 million to be paid in annual installments of $50 million over 5 years. Arrowhead also has the potential to receive $300 million in near-term payments associated with the continued enrollment of certain cohorts of a Phase 1/2 study of ARO-DM1, which Arrowhead is on track to achieve during the next 12 months. Arrowhead is eligible to receive development milestone payments of between $110 million and $410 million per program and sales milestone payments of between $500 million and $700 million per program. Arrowhead is also eligible to receive tiered royalties on commercial sales up to the low double digits. Summary of Programs under License and Collaboration Agreement Clinical Stage ARO-DUX4, which is designed to target the gene that encodes the DUX4 protein as a potential treatment for patients with facioscapulohumeral muscular dystrophy type 1, currently dosing patients in a Phase 1/2 clinical study. ARO-DM1, which is designed to reduce expression of the dystrophia myotonica protein kinase (DMPK) gene in skeletal muscle as a potential treatment for patients with type 1 myotonic dystrophy, currently dosing patients in a Phase 1/2 clinical study. ARO-MMP7, which is designed to reduce expression of matrix metalloproteinase 7 (MMP7) in the lung as a potential treatment for idiopathic pulmonary fibrosis, currently dosing patients in a Phase 1/2 clinical study. ARO-ATXN2, which is designed to silence expression of the toxic ATXN2 protein in the CNS as a potential treatment for spinocerebellar ataxia 2 (SCA2), currently in a Phase 1/2 study that is open for enrollment. Preclinical Stage ARO-HTT for patients Huntington’s disease expected to be CTA-ready in 2025 ARO-ATXN1 for patients with spinocerebellar ataxia 1 (SCA1) expected to be CTA-ready in 2026 ARO-ATXN3 for patients with spinocerebellar ataxia 3 (SCA3) expected to be CTA-ready in 2026 Discovery During the five-year term, Sarepta can propose up to six new CNS or muscle targets for which Arrowhead will perform discovery and preclinical development. Sarepta would then receive an exclusive license to those programs and be responsible for clinical development and commercialization. Drug Manufacturing Under the agreement, Arrowhead will manufacture clinical drug supply for all programs arising out of the license and collaboration, and commercial drug product for the four programs currently in clinical trials. 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. 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These forward-looking statements include, but are not limited to, statements about 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. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, 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. Source: Arrowhead Pharmaceuticals, Inc.

First clinical data of VO659 demonstrated 28% mean reduction in CSF mutant HTT at day 85 in HD patients in 40 mg dose cohort with an effect after the first dose No sustained increase in CSF neurofilament light chain (Nf-L) protein observed through day 85 VO659 is generally safe and well tolerated with an anticipated dosing regimen of 1-2 times per year in future studies Data highlighted in oral presentation at EHDN & Enroll-HD 2024 LEIDEN, Netherlands, Sept. 13, 2024 /PRNewswire/ -- Vico Therapeutics B.V., a clinical-stage genetic medicines company developing therapies for severe neurological diseases, today announced new positive interim data in Huntington's disease (HD) from the ongoing Phase 1/2a clinical trial of VO659, an investigational allele-preferential antisense oligonucleotide (ASO) therapy. Results will be highlighted in an oral presentation at the European Huntington's Disease Network's EHDN & Enroll-HD 2024 meeting on Friday, September 13, 2024 at 9:45 a.m. CET. This is the first clinical data reported of VO659, which is designed to target the CAG repeat expansion that causes all nine known polyglutamine diseases, including HD as well as spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3). VO659 has a unique allele-preferential mechanism of action that targets expanded CAG repeats in the mutant mRNA transcript and inhibits mRNA translation leading to a reduction of mutant protein, with the potential to halt or slow disease progression. VO659 is the only clinical-stage program that directly targets the underlying CAG repeat expansion that causes HD. The Phase 1/2a clinical trial is a multi-center, open-label, multiple ascending dose study designed to assess the safety and tolerability of four doses of VO659 administered intrathecally every four weeks in participants with early manifest HD, or mild to moderate SCA1 or SCA3. Exploratory endpoints include the assessment of pharmacodynamic (PD) biomarkers (mHTT, mATXN3, and Nf-L protein) in cerebrospinal fluid (CSF), pharmacokinetics in CSF and plasma, and clinical outcome measures. The interim analysis provides a look at available safety, tolerability and PD data for HD participants in the 40 mg cohort through at least day 85 of the study. The Phase 1/2a trial interim data presented at the EHDN meeting demonstrated: A mean reduction of 28% in CSF mutant huntingtin protein (mHTT) in treated HD participants at day 85 compared to baseline with an immediate effect observed after the first dose at day 29 No sustained increase or decrease in Nf-L protein in CSF across treated participants at day 85 compared to baseline VO659 appears generally safe and well tolerated at the 40 mg dose level in treated HD patients through the available clinical follow-up period VO659 has a long half-life, indicating the potential for infrequent dosing estimated at 1-2 times per year "We are very pleased to announce these first data from our Phase 1/2a clinical trial of VO659 in participants living with HD," said Micah Mackison, chief executive officer at Vico. "It is highly encouraging that we saw immediate reductions in CSF mHTT and no changes in Nf-L protein, two key biomarkers in HD, in treated patients over the available follow-up period. Given VO659's long anticipated half-life, there is clear potential for this therapy to have an infrequent dosing schedule, and we look forward to exploring this further in clinical trials. These data are a significant milestone for our team and for the HD community that so desperately needs treatment options, and we look forward to continuing assessments from the trial and advancing VO659 as quickly as possible for patients and their families." These interim data build on preclinical data of VO659 demonstrating potent target engagement across multiple disease models. Preclinical research showed significant and dose-dependent reductions of mHTT and improvement in motor function in vivo in disease mouse models of HD and allele-preferential reductions of mHTT in vitro in HD patient cell models. "VO659's allele-preferential action and direct targeting of the CAG repeat expansion that causes HD is a unique approach to treating this disease with a promising future for the HD community," said Scott Schobel, M.D., chief medical officer at Vico. "The Phase 1/2a interim clinical data reinforce the potent, targeted nature of VO659 and add to a growing body of evidence supporting VO659's advancement in the clinic for HD as well as its broad potential applications for all CAG repeat expansion diseases." The Phase 1/2a trial remains ongoing and Vico plans to meet with regulators later this year to discuss the optimal path forward for the VO659 program. The company plans to provide an update from the SCA1 and SCA3 patient cohorts at a future scientific meeting. About Huntington's Disease and VO659 Huntington's disease (HD) is a rare genetic, progressive neurodegenerative disorder characterized by movement disorders, cognitive impairment, and psychiatric manifestations including depression and psychosis. The disease varies in terms of age of onset, typically starting in mid-adulthood, and it is ultimately fatal. The disease is caused by a CAG trinucleotide repeat expansion in the coding region of exon 1 of the huntingtin (HTT) gene, which results in production of mutant HTT protein (mHTT) with an elongated polyglutamine (polyQ) stretch at its N-terminus. This expanded polyQ stretch confers a toxic gain-of-function to mutant protein forms, ultimately resulting in widespread neuronal death. Currently available therapies for HD focus on alleviating some of the movement and psychiatric symptoms, with a significant unmet need for disease-modifying therapies. VO659 is designed to suppress mHTT in an allele-preferential manner and slow or halt disease progression. VO659 was granted both FDA and EMA Orphan Drug designation for the treatment of HD. About Vico Therapeutics B.V. Vico Therapeutics is a clinical-stage genetic medicines company developing antisense oligonucleotide (ASO) RNA modulating therapies for patients with severe neurological diseases. Our lead product candidate, VO659, is currently in Phase 1/2a clinical development for the treatment of spinocerebellar ataxia types 1 and 3 and Huntington's disease and is the only ASO in the clinic that targets the underlying CAG repeat expansions that cause all nine known polyglutamine diseases. Vico's research platform designs fit-for-purpose ASOs by applying precision chemistry with mechanisms of action ideally suited to target genetic neurological diseases. For more information, visit . Media Contact Jenna Urban Berry & Company Public Relations [email protected] 212-253-8881 SOURCE Vico Therapeutics B.V. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

LEIDEN, Netherlands, April 3, 2023. Vico Therapeutics B.V., a clinical-stage genetic medicines company developing therapies for severe neurological diseases, today announced that the first patient has been dosed in a Phase 1/2a clinical study evaluating VO659 for the treatment of Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3). VO659 is an antisense oligonucleotide (ASO) investigational therapy designed to target the CAG repeat expansion that causes all nine known polyglutamine diseases including HD, SCA1 and SCA3. "We are encouraged by the continued progress of our development program and very pleased to announce the first patient dosed in this Phase 1/2a study of VO659 in HD, SCA1 and SCA3," said Scott Schobel, MD, chief medical officer at Vico. "VO659 is the first allele-preferential ASO in clinical development with broad application to all CAG repeat expansion diseases. The robust preclinical data package for VO659 demonstrates favorable brain uptake, potency and durability of effect, and we look forward to assessing the translation of these characteristics in this clinical trial." VO659's unique target and dual mechanism of action enable potent target engagement across multiple disease models. In preclinical studies, significant and dose-dependent reductions of mutant huntingtin protein (mHTT) and improvement in motor function were observed in vivo in disease mouse models of HD. Allele-preferential reductions of mHTT were observed in vitro in HD patient cell models. Preclinical data also showed VO659 induced a significant reduction of mutant ATXN1 (mATXN1) and mutant ATXN3 (mATXN3) protein levels in vivo and in vitro in disease mouse models and patient cell models of SCA1 and SCA3, respectively. The Phase 1/2a clinical trial is a multi-center, open-label basket study designed to assess the safety and tolerability of multiple ascending doses of VO659 administered intrathecally in participants with early manifest HD or mild to moderate SCA1 or SCA3. Exploratory endpoints include the assessment of pharmacodynamic biomarkers (mHTT, total HTT, mATXN3, total ATXN3 and neurofilament light chain) in cerebrospinal fluid, plasma pharmacokinetics, and clinical outcome measures. The study is expected to enroll approximately 71 participants. "It is our mission to bring safe, effective therapies to patients and families affected by devastating neurological diseases, and today marks an important milestone in our journey to realize this mission. We are grateful to the trial investigators and patients participating in our Phase 1/2a study as we assess the potential of VO659 in HD, SCA1 and SCA3. We also look forward to sharing more details about the study at CHDI's Annual Huntington's Disease Therapeutics Conference later this month," said Micah Mackison, chief executive officer at Vico. About Vico Therapeutics B.V. Vico Therapeutics is a clinical-stage genetic medicines company developing antisense oligonucleotide (ASO) RNA modulating therapies for patients with severe neurological diseases. Vico's platform designs ASOs to modulate RNA through multiple approaches including inhibition of translation, modulation of splicing, editing, degradation, and activation. We apply precision chemistry to identify an RNA modulator that achieves the desired target engagement and safety profile for different diseases. Our lead product candidate, VO659, is currently in Phase 1/2a clinical development for the treatment of Huntington's disease and spinocerebellar ataxia types 1 and 3. For more information, visit www.vicotx.com. SOURCE Vico Therapeutics B.V. Posted: April 2023