"Susan is an accomplished leader and we are excited to have her join the Arrowhead management team," said Christopher Anzalone, Ph.D., Arrowhead's President and Chief Executive Officer. "Her experience leading regulatory efforts through the development and commercialization process will be extremely valuable to Arrowhead as we move ARC-520 and ARC-AAT forward and, importantly, as we continue to expand our pipeline of RNAi therapeutics."
Susan Boynton is an accomplished regulatory affairs professional with 30 years of experience developing successful regulatory strategies, leading global filings, and ensuring regulatory compliance in the U.S., EU, and other major markets. Ms. Boynton comes to Arrowhead from Shire where she served as Vice President, Head of Regulatory Affairs, North America and Global Policy and Intelligence. In this capacity she was responsible for leadership and direction of North America regulatory staff supporting all Shire business units. As part of Shire Human Genetic Therapies, she also previously led all regional regulatory functions including operations, CMC, promotion, and labeling. Prior to her role at Shire, Ms. Boynton held leadership positions in regulatory affairs at Amgen, Abbott Laboratories, Sanofi, and Novartis in the U.S. and in Europe. Ms. Boynton earned a Bachelor of Science in Pharmacology with Honors from Sunderland University, U.K., a Graduate Diploma in Law from College of Law of England and Wales, and a Masters of Jurisprudence, Health Law from Beasley Institute of Health Law and Policy, School of Law, Loyola University, Chicago.
We?ve always believed that the DPC delivery platform and RNAi in general have some very attractive features that will allow us to rapidly expand our pipeline once we have proof of concepts for the underlying technologies.
In its most basic form, the technology platform enables the company to build multiple products in a cost effective way and should have a progressively lower risk profile. We believe the emerging ARC-520 Phase 2a data as well as upcoming Phase 2b data and ARC-AAT Phase 1 data can give us that proof of concept and technology validation.
We?re seeing scientifically important and potentially meaningful results. We hope to provide additional data throughout 2015, that supports this position.
So what are some of the key events that you should expect? As mentioned, we have filed to begin a Phase 1 study of ARC-AAT in up to 48 subjects including healthy volunteers and AATD patients. We plan to initiate this study shortly after receiving regulatory approval and believe we can achieve clinical proof of concept in 2015.
We plan to file with the regulatory authorities this quarter to begin a series of Phase 2b studies of ARC-520. Our goal is to develop a comprehensive data set on ARC-520s activity in various patient populations using various combinations and different dosing regiments. Expect to see additional details as we initiate these studies throughout 2015.
We?ll continue to dose finding Phase 2a study of ARC-520 and present a full data set once it is complete. We?re also working on additional drug candidates based on various formulations of the DPC delivery system.
We expect filings for our next clinical candidate in calendar 2015, and we hope to provide updates about progress on DPC that can be administered subcutaneously and DPC is targeting extra-hepatic tissues in calendar 2015.
We feel confident about where we are with ARC-520. We believe that it carries substantially lower risk now that we have established a base safety profile and have demonstrated that it is effectively hitting its target with the long duration of effect.
The next step is to establish that ARC-520 can lead to a clinical benefit in patients and enable functional cures. We also hope to demonstrate clinical activity with ARC-AAT as we enter clinical trials shortly. We expect 2015, to be an exciting year indeed. http://ir.arrowheadresearch.com/events.cfm
Estimated Enrollment: 60 Study Start Date: February 2015 Estimated Study Completion Date: March 2016 Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arrowhead Begins Phase 1 Trial of ARC-AAT for Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency
PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that it has initiated dosing in a Phase 1 clinical trial of ARC-AAT, the company's candidate for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disorder that severely damages the liver and lungs of affected individuals. Trial initiation followed successful completion of the Clinical Trial Notification (CTN) regulatory process in Australia. The study will be conducted in two parts, with Part A in healthy volunteers and Part B in patients with AATD. The primary objectives of the study are to determine the safety and tolerability of escalating doses of ARC-AAT, evaluate the pharmacokinetics, and determine the effect on circulating levels of alpha-1 antitrypsin. Initial data from this study is expected in late 2015.
Christopher Anzalone, Ph.D., president and chief executive officer of Arrowhead said, "The ARC-AAT Phase 1 trial is the first human study of an RNAi therapeutic against liver disease associated with AATD, which has no current treatment options, short of liver transplant. ARC-AAT is our second clinical candidate using the DPC delivery system, after ARC-520 targeting the hepatitis B virus, and it is the first candidate that targets an endogenous gene to enter human trials. We expect the Phase 1 study to primarily generate safety and tolerability data, but it should also give a readout on the depth and duration of activity."
The Phase 1 trial is a multi-center, randomized, placebo-controlled, double-blind, single dose-escalation first-in-human study to evaluate the safety, tolerability, pharmacokinetics of ARC-AAT and the effect on circulating alpha-1 antitrypsin (AAT) levels. The study plans to enroll in dose cohorts of six participants each, with participants randomized at a ratio of 2:1 (active:placebo) to receive a single intravenous injection of either ARC-AAT or placebo (normal saline). The study will consist of two parts, with Part A planned to be conducted in healthy volunteers and Part B planned to be conducted in patients with PiZZ genotype AATD. In Part A, dose escalation will proceed until the achievement of certain target knockdown parameters. When these AAT knockdown parameters are achieved, dose escalation in healthy volunteers (Part A) is planned to stop and dosing in patients with AATD (Part B) is planned to begin at the highest dose level used in Part A and then dose escalation will proceed. We expect participants will be evaluated for 28 days following dosing with additional follow-up every 2 weeks until AAT levels return to baseline.
"The whole Alpha-1 community is excited to see this landmark clinical trial begin for Alpha-1 liver disease," said John Walsh, president and chief executive officer of the Alpha-1 Foundation. "We're proud that The Alpha-1 Project, the Foundation's venture philanthropy arm, is collaborating with Arrowhead on the development of this potentially lifesaving therapy for both adults and children with liver disease due to Alpha-1."
ARC-AAT is the second clinical candidate to use Arrowhead's proprietary Dynamic Polyconjugate (DPC) delivery platform and includes an optimized RNAi-trigger design that contains an unlocked nucleobase analog (UNA) and various chemical modifications that enhance activity and substantially extend the duration of effect in non-clinical studies. Arrowhead previously reported data from these studies at an analyst day the company held in June 2014 and in a plenary presentation at the AASLD Liver Meeting in November 2014. Injection of ARC-AAT in transgenic mice expressing the inflammatory human Z-AAT protein resulted in prevention and reduction of Z-AAT globules and, importantly, liver inflammation. In primate studies, a 90% reduction of AAT in serum was observed after a single injection, which persisted for over ten weeks with greater than 80 percent knockdown observed at the six-week time point. Multi-dose studies in primates showed a sustained reduction of AAT with once every six weeks dosing. The goal of treatment with ARC-AAT is to reduce the hepatic production of Z-ATT, thereby preventing further accumulation of Z-AAT in the liver and potentially reversing pre-existing liver injury and fibrosis. http://ir.arrowheadresearch.com/releasedetail.cfm?ReleaseID=897578
Und dass zu einem nicht unerheblichen Preis. Ob Novartis wohl das bessere Geschäft macht? Oder die haben heimlich in der Hinterhand schon Folge-Technologieen, die die alte Technik ad adsurdum führen?
Na ja, für Arrowhead ist es der Weg nach vorn, wenn die die Technik zwingend benötigen und sich diese mit ihrer eigenen Technik/Pipeline 100-%tig ergänzt / auf einander aufbaut. Chancen und Risiken von Arrowhead steigen deutlich - rechtfertigen aber wohl einen Kursaufschlag von bis zu ca. 1/3. Die nächsten Jahre werden es zeigen, ob der Deal das unternehmen wirklich vonan bringt ...
Das ist der Vertrauensbeweis in die DPC Technologie. Die 30 Targets müssen erreicht werden, und Novartis hat sich für Arrowhead entschieden. Von so einem Deal habe ich nur geträumt, Ihn aber anders herum erwartet(erträumt), so das Arrowhead Meilensteine und Umsatzerlöse erzielt.
Damit steigt ARWR für mich an Nummer 1 der RNAi Forschung.
Novartis and siRNA Novartis scientists are working on RNAi therapeutics to address a broad spectrum of human diseases: Age-related Macular Degeneration (AMD), cancer, cystic fibrosis, Alzheimer?s and Huntington?s Disease. ?The reason we?re really excited about siRNA is it gives us a generic platform for taking out a protein,? says John Hastewell, Global Head, NIBR Biologics Center. ?This is a mechanism in the body that we can use for therapeutic purposes which is applicable to all proteins. It is very powerful and very specific.?
: Arrowhead stakes bigger claim to RNAi space in Nov
Arrowhead stakes bigger claim to RNAi space in Novartis deal Share
By Jennifer Boggs, Managing Editor
The latest foray in the oft-thorny RNAi patent landscape sees Arrowhead Research Corp. nabbing the entire RNAi portfolio of Novartis AG, picking up rights to a host of intellectual property (IP) and assets, including an existing license agreement with RNAi powerhouse Alnylam Pharmaceuticals Inc., a pipeline of three preclinical candidates and a patent estate the Pasadena, Calif.-based biotech said falls safely outside the scope of competitors? IP. ?This is a big leap forward for us,? acknowledged Chris Anzalone, president and CEO of Arrowhead, which had operated largely as a holding company until a few years ago when management decided to sink funds into building an internal pipeline, leading with promising hepatitis B virus (HBV) candidate ARC-520. (See BioWorld Today, May 7, 2013.)
Having waded into RNAi via a 2012 licensing deal with Alnylam for IP related to HBV that would eventually become ARC-520, Arrowhead is no stranger to the perils of working in that space.
The Novartis deal ?speaks to two of the three great challenges? in RNAi, Anzalone said, specifically efficiency of process and freedom to operate. The third challenge is the delivery of RNAi therapeutics, the main bugaboo that sent big pharma fleeing the field a few years ago but one Arrowhead already has a handle on.
?I think we?ve solved delivery,? he told BioWorld Today. The company picked up rights to the Dynamic Polyconjugate (DPC) delivery technology in 2011 when Roche AG decided to divest the RNAi technology it had acquired only a few years before. DPCs are nanoparticles ? 5 nm to 20 nm in size ? targeted to deliver the siRNA into the endosome, where it releases the siRNA into the cytoplasm to knock down target gene expression. In animal models, it has shown an impressive degree of knockdown. ?We think it?s the best in the field,? he added.
Establishing a clear freedom to operate in RNAi is much trickier, particularly for a small biotech with limited resources, as is building on ways to improve the efficiency of RNAi therapeutics.
Novartis, like many of its big pharma brethren, had jumped into RNAi a decade ago. It inked the Alnylam agreement in 2005 for access to RNAi IP against 30 targets of its choice. The Basel, Switzerland-based firm later declined to extend that collaboration, but it had accumulated a significant amount of R&D during the last 10 years, Anzalone said. (See BioWorld Today, Sept. 8, 2005, and Sept. 27, 2010.)
?We knew they were exiting the space,? opting against building an internal pipeline of RNAi drugs at Novartis, he said. ?We assumed they?d developed some pretty valuable assets.?
So Arrowhead took a look. ?When we approached it, we viewed as nice to have, not need to have,? he added. ?So we were only interested in the assets if they were special, and it turns out they were. These will be powerful tools in our toolbox.?
Under the agreement terms, Arrowhead made a previous $7 million cash payment to Novartis and will provide an additional $3 million in cash and $25 million in Arrowhead common stock within 30 days. Shares of Arrowhead (NASDAQ:ARWR) closed Wednesday at $7.51 and was up to $8.15 in premarket trading this morning.
On top of that, Novartis is eligible for undisclosed milestones and single-digit royalties. Further details were not disclosed.
In exchange, Arrowhead gets patent families relating to RNAi trigger design rules and modifications. Not only do those fall outside of patents owned by competitors. Novartis spent ?a tremendous amount of resources [on how] to create RNAi trigger structures,? Anzalone said. ?We looked through an awful lot of data. [Novartis was] able to find new structures and new chemistries.?
That innovation in RNAi triggers is ?not just to enable us not to be sued,? he added. ?It now gives us freedom to operate in any indication.?
Novartis? intracellular targeting ligands also are part of the package. Those ligands are designed boost the activity of RNA triggers by targeting the RNA-induced silencing complex, or RISC, to improve stability once RISC is loaded. ?The intracellular targeting ligand approach is novel and it really turbocharges RNAi triggers,? Anzalone explained. ?They take the RNAi trigger and make it more effective.?
Lastly, Arrowhead inherits Novartis? deal with Alnylam, covering RNAi IP for 30 targets ? and those are good targets, targets chosen by a big pharma,? Anzalone noted ? as well as three programs that have progressed to the preclinical stage. Whether Arrowhead takes any or all of them into the clinical will be have to be determined.
Anzalone declined to offer specifics on those programs but said all ?were quite interesting. Any time you can benefit from the big pharma funnel it?s a good thing. Big pharma has a way of deciding good targets to go after.?
May 6, 2015 Arrowhead Presents Data on Potential RNAi Candidate Targeting Factor 12 Mediated Angioedemic and Thromboembolic Diseases
PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today presented data at IBC's 17th Annual TIDES Conference in San Diego on the preclinical development of an RNAi therapeutic as a potential treatment for factor 12 (F12) mediated angioedemic and thromboembolic diseases. The presentation included data from in vitro screenings, in vivo evaluations, a disease model, and a multiple dose study in nonhuman primates. These data support advancement of ARC-F12 as a potential new candidate in Arrowhead's growing pipeline of RNAi-based therapeutics enabled by the company's Dynamic Polyconjugate (DPC) delivery platform. A copy of the presentation may be viewed on the Events and Presentations section of the company's website at http://ir.arrowheadresearch.com/events.cfm.
"We see factor 12 as an extremely attractive target to add to our pipeline. There is clear unmet need in thrombosis and angioedema and the biology of factor 12 as part of the coagulation cascade and the kinin-kallikrein system suggest that its reduction through RNAi may present opportunities in both disease areas," said Christopher Anzalone, Ph.D., president and chief executive officer. "We will be conducting additional studies in relevant disease models shortly to provide us with further data to decide on the advancement of ARC-F12 as a clinical candidate and initiation of IND enabling studies."
David Lewis, Ph.D., chief scientific officer, presented initial data from wild type mice, showing that various RNAi triggers selected from in vitro screening sets and co-administered with DPCs achieved significant and sustained knockdown of F12 levels of greater than 99% at nadir for most triggers. Strategic incorporation of various modifications to the most potent RNAi trigger increased the depth and duration of F12 knockdown activity as shown in dose response studies. In a study in mice, these modified triggers exhibited a dose-dependent increase in F12 knockdown. A single intravenous dose of 0.5 mg/kg reduced F12 by greater than 80%. When the dose was increased to 2 mg/kg, the reduction increased to greater than 95% at nadir, with greater than 70% knockdown observed at the one month time point. The lead RNAi trigger was also highly active in multiple dose nonhuman primate studies. With four intravenous doses of 2 mg/kg given once every four weeks, approximately 90% F12 knockdown was achieved after the first dose with even greater knockdown following subsequent doses. Knockdown was also highly durable with greater than 80% reduction maintained between monthly doses. The combination of RNAi trigger and DPC appeared to be generally well-tolerated and no drug-related changes in toxicity markers were observed as measured by clinical chemistry and hematologic parameters.
Dr. Lewis also presented data from a relevant disease model on the lead RNAi trigger and DPC combination. In this mouse model, thromboembolism is induced by exposure of carotid artery to ferric chloride. The time to blood flow occlusion is then measured as a clinically relevant indicator of physiological response to F12 knockdown. Animals were treated with saline or the lead RNAi trigger and DPC combination 15 days prior to ferric chloride challenge. Treated animals showed approximately 99% knockdown in serum F12 levels at Day 15 relative to baseline, while animals receiving saline showed no reduction. A dramatic increase in occlusion times as a measure of the inhibition of thrombus formation was observed in treated mice.
Arrowhead believes that ARC-F12 may present opportunities to target multiple diseases, including in thrombosis. The company is currently planning to investigate ARC-F12 in hereditary angioedema (HAE) as the first target indication. HAE is a rare genetic disorder with a prevalence of approximately 1/5,000-1/10,000 that is most commonly caused by mutations in the complement factor 1 esterase inhibitor gene (C1INH). Patients with HAE can experience recurrent and dangerous acute inflammatory attacks in multiple tissues, with attacks of laryngeal edema being particularly serious and potentially fatal. Current treatments seek to reduce the severity, duration, and frequency of acute HAE attacks, but frequent intravenous dosing of 1-3 times weekly is required and many patients do not respond adequately. Arrowhead believes the novel mechanism of ARC-F12 may fill an unmet need for patients and physicians who desire long term prophylaxis and may view intravenous dosing every 4-6 weeks as a significant advance.
: Erstverhandlungsrechte Novartis wie bei Roche
NOTE 2. ACQUISITIONS
On March 3, 2015, the Company entered into an Asset Purchase and Exclusive License Agreement (the ?RNAi Purchase Agreement?) with Novartis Institutes for BioMedical Research, Inc., a Delaware corporation (?Novartis?), pursuant to which the Company acquired Novartis? RNAi assets and rights thereunder. Pursuant to the RNAi Purchase Agreement, the Company acquired or licensed certain patents and patent applications owned or controlled by Novartis related to RNAi therapeutics, assignment of a third-party license, rights to three pre-clinical RNAi candidates, and other related assets (collectively, the ?Purchased Assets?). The acquisition of the Purchased Assets closed on March 3, 2015, concurrent with execution of the RNAi Purchase Agreement (the ?Closing?).
In consideration for the Purchased Assets, the Company made certain payments to Novartis, including: (a) an initial payment of $10,000,000 in cash of which $7,000,000 was paid during the Company?s first fiscal quarter of 2015 to secure an exclusivity period whereby the Company was able to exclusively examine the Novartis RNAi assets prior to finalizing the purchase, and the remaining $3,000,000 was paid in April, and 3,321,383 shares of the Company?s common stock (the ?Shares?) were issued during the Company?s second fiscal quarter; (b) escalating royalties in the single digits based upon annual net sales thresholds for certain RNAi products sold by the Company; and (c) milestone payments tied to the achievement of certain development and sales milestones for each target being developed by the Company.
Pursuant to the RNAi Purchase Agreement, prior to initiation of a phase 2 Clinical Trial for a given RNAi Product or Arrowhead RNAi Product directed to an Initial Target , Novartis has an exclusive right to negotiate a license under any Intellectual Property Rights owned or exclusively licensed to the Company to make, sell or otherwise commercially exploit such RNAi Product or Arrowhead RNAi Product (as such italicized terms are defined in the RNAi Purchase Agreement). After initiation of a phase 2 Clinical Trial for a given Arrowhead RNAi Product (?ROFN Candidiate?), Novartis shall have a right of first negotiation on the ROFN Candidate developed by the Company and its affiliates relating to the purchased assets. If the Company proposes to out-license, or enters into substantive negotiations to out-license, any ROFN Candidate, the Company must give notice of the ROFN Candidate it proposes to out-license and negotiate exclusively and in good faith with Novartis for a period of time regarding the applicable out-license.
In addition to the consideration paid by the Company at the closing of the Transaction, the Company is obligated to make certain royalty and milestone payments to Novartis upon the occurrence of certain events. For sales of any RNAi Products for which Novartis and the Company do not enter into a licensing arrangement, the Company will be obligated to pay royalty rates ranging in the low to mid-single digits on Net Sales depending upon the type of RNAi Product provided that the royalty rate may be reduced or offset in certain circumstances. The obligation to pay royalties on such candidates will last until the later of (i) the expiration of the last to Valid Claim Covering such RNAi Product in such country and (ii) 11 years after the first commercial sale of such RNAi Product (as such italicized terms are defined in the RNAi Purchase Agreement).
The Company will also be obligated to make cash payments to Novartis upon the achievement of various milestones for any RNAi Products for which Novartis and the Company do not enter into a licensing arrangement. These milestones include the initiation of a phase 2 and 3 clinical trials, US and other regulatory approvals, and annual sales milestones. These milestone payments could amount to the mid to upper double digit millions of dollars.
Du tust grad so,als ob Arrowhead hier am expldieren wäre wie alnylam,die von 6 dollar auf 130 Dollar hoch sind und schlappe 11 MRD wert sind ? Was ich ich noch steigen sehe ist bestenfalls Galena biopharma (GALE),aber bei ARWR rührt sich nix,wie kommts ?
Empfohlen von CAPITAL, Welt am Sonntag und extraETF: OSKAR ist die neue Art der Geldanlage: ETF-basiert, weltweit gestreut, kosteng?nstig und intelligent, aber dabei ganz einfach: Du bestimmst, wieviel Risiko Du m?chtest, wir machen den Rest!