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News Article | April 11, 2016
Site: http://www.sciencedaily.com/news/

The mechanism of efficient lymphocyte motility within lymphoid tissues has remained unknown. A research group has found for the first time that a lipid called lysophosphatidic acid (LPA) plays a vital role in regulating lymphocyte motility within lymph nodes. Targeting LPA and its receptors may provide novel strategies to control immune responses.


Abstract: Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that three presentations are being made on ARC-520, its investigational medicine for the treatment of chronic hepatitis B infection, at The International Liver Congress™ 2016 (ILC 2016), in Barcelona, Spain, April 13-17, 2016. Collectively, these presentations demonstrate several important findings from Arrowhead's clinical and nonclinical studies of ARC-520, including the following: ARC-520 and entecavir produced rapid HBV DNA suppression with all hepatitis B e-antigen (HBeAg) positive, treatment naïve patients achieving serum HBV DNA reductions of up to 5.5 log (99.9997%), and all HBeAg negative, treatment naïve patients achieving reductions that put them below the limit of quantitation ARC-520 effectively inhibited HBV cccDNA-derived mRNA with observed viral protein reduction in HBV patients of up to 2.0 log (99%) after a single dose Based on HBsAg epitope profile analysis, poster authors and Arrowhead collaborators had previously identified a predictive hepatitis B surface-antigen (HBsAg) Clearance Profile associated with HBsAg clearance in antiviral therapy cohorts There was a significant association between the development of an HBsAg Clearance Profile and ARC-520 therapy in HBV patients Complexed HBsAg antibodies (anti-HBs) were developed and detected in HBV patients treated with ARC-520, which may represent a recovery of the immune system response After monthly administration of 6-11 doses of ARC-520 in chimpanzees chronically infected with HBV, the ARC-520 target site sequences remained virtually unchanged, indicating that no drug resistance developed during the treatment period Chris Anzalone, Ph.D., president and CEO of Arrowhead Pharmaceuticals, said: "These are exciting results that continue to show that ARC-520 can reduce the production of HBV viral proteins. We have ongoing multiple-dose and combination studies designed to assess if this will allow the body's natural immune defenses to control the virus and lead to a functional cure." Copies of the poster presentations are currently available as ePosters to ILC 2016 attendees, and we have also made them available on the Arrowhead website on the Events and Presentations page. About ARC-520 Arrowhead's RNAi-based candidate ARC-520 is being investigated in the treatment of chronic HBV infection. The small interfering RNAs (siRNAs) in ARC-520 intervene at the mRNA level, upstream of the reverse transcription process where current standard of care nucleotide and nucleoside analogues act. Arrowhead is investigating ARC-520 specifically to determine if it can be used to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without seroconversion. Approximately 350-400 million people worldwide are chronically infected with the hepatitis B virus, which can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally. Arrowhead is currently conducting Phase 2b multiple dose and combination studies in chronic HBV patients. In clinical studies to date, the most common reported adverse events in all subjects completing treatment were upper respiratory infection and headache. About Arrowhead Pharmaceuticals, Inc. 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. The company's pipeline includes ARC-520 and ARC-521 for chronic hepatitis B virus, ARC-AAT for liver disease associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary angioedema and thromboembolic disorders, ARC-LPA for cardiovascular disease, and ARC-HIF2 for renal cell carcinoma. For more information please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit ir.arrowheadpharma.com/alerts.cfm. Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. 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 various factors and uncertainties, including our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. DYNAMIC POLYCONJUGATES is a trademark of Arrowhead Pharmaceuticals, Inc. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


Abstract: Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today presented a poster on ARC-HIF2, its preclinical development program targeting HIF2-α for the treatment of renal cell carcinoma (RCC), at the American Association for Cancer Research Annual Meeting 2016 (AACR16), in New Orleans. ARC-HIF2 is Arrowhead's first RNAi therapeutic program to target tissues outside the liver. The poster titled, "Novel HIF-2α targeted RNAi therapeutic for renal cell carcinoma" (abstract 2064), describes data from various stages of development of ARC-HIF2, including RNAi trigger selection, HIF2-α target validation, delivery and targeting ligand validation, and multiple RCC tumor models. These data show that important advancements are being made in this program and for Arrowhead's Dynamic PolyconjugateTM (DPCTM) delivery platform generally, including the following key findings: Proof-of-concept ligand dependent, functional delivery was demonstrated using the DPC targeted delivery platform Silencing HIF2-α expression by RNA interference resulted in reduction of HIF-2α regulated genes In two different RCC tumor bearing mouse models, ARC-HIF2 inhibited tumor growth and promoted tumor cell death and structural degeneration A copy of the poster presentation is available on the Events and Presentations page under the Investors section of the Arrowhead website. About Arrowhead Pharmaceuticals, Inc. 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. The company's pipeline includes ARC-520 and ARC-521 for chronic hepatitis B virus, ARC-AAT for liver disease associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary angioedema and thromboembolic disorders, ARC-LPA for cardiovascular disease, and ARC-HIF2 for renal cell carcinoma. For more information please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/alerts.cfm. Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. 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 various factors and uncertainties, including our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. DYNAMIC POLYCONJUGATES is a trademark of Arrowhead Pharmaceuticals, Inc. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article
Site: http://www.nanotech-now.com/

Home > Press > Arrowhead Presents Promising New Preclinical Data on ARC-F12 at AAAAI 2016 Abstract: Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today presented additional preclinical data suggesting that ARC-F12, an RNAi therapeutic that inhibits the production of Factor XII (F12), has the potential to treat hereditary angioedema and to prevent thrombosis. Data presented in a poster at the 2016 American Academy of Allergy, Asthma & Immunology Annual Meeting (AAAAI), show that ARC-F12 had the desired effects of significantly reduced swelling in a rat model of edema and inhibition of blood clot formation in a mouse model of thrombosis, without the undesired effect of increased bleeding risk. In a carrageenan-induced paw edema model in rats, treatment with ARC-F12 seven days prior to carrageenan challenge led to a significant reduction in edema (p < 0.001). The reduction in swelling in ARC-F12 treated rats is similar to that seen in rats treated with a kallikrein-targeted antibody. This supports Arrowhead's position that F12 inhibition could be an attractive target for the rare genetic disorder, hereditary angioedema (HAE). In a mouse model of thrombosis, a dramatic increase in occlusion times was observed in mice receiving ARC-F12. The time to blood flow occlusion is measured as a clinically relevant indicator of physiological response to F12 knockdown and is a measure of the inhibition of thrombus formation. Further, in multiple relevant models of bleeding risk, ARC-F12 did not cause an increase in bleeding times or bleeding risk. Anticoagulants can be used to reduce thrombus formation and thromboembolism occurrence, but also can cause an increase in serious bleeding risk. ARC-F12 may be able to reduce the risk of blood clot formation, without the undesirable bleeding risk caused by anticoagulants. In vivo studies in wild type mice showed that a single 2 mg/kg dose of ARC-F12 achieved greater than 95% knockdown of F12 levels. In multi-dose primate studies, a 4 mg/kg dose resulted in greater than 90% knockdown with even greater knockdown following subsequent doses. Knockdown was also highly durable with greater than 80% reduction maintained between monthly doses. ARC-F12 appeared to be generally well-tolerated and no drug-related changes in toxicity markers were observed as measured by clinical chemistry and hematologic parameters. F12 is a key component of the contact activation pathway involved in thrombosis and the kinin-kallekrein system involved in angioedema. It is predominantly produced in the liver and circulates in plasma, so Arrowhead believes that it is a uniquely suited target for an RNAi-therapeutic delivered with the proprietary Dynamic PolyconjugateTM (DPCTM) delivery system. Consistent with its process for all of its RNAi-therapeutic candidates, Arrowhead's discovery of ARC-F12 followed a screening funnel process that includes: bioinformatic selection of RNAi trigger sequences; trigger synthesis and in vitro screening; synthesis of cholesterol-RNAi triggers and in vivo screening; multiple iterations of structure-activity relationship (SAR) studies and in vivo screening to assess various chemical modifications to improve RNAi trigger activity; in vivo screening in non-human primates; efficacy testing in disease relevant models; non-GLP toxicology studies; and lastly, the selection of a lead candidate. About ARC-F12 Arrowhead's RNAi-based candidate ARC-F12 is in preclinical development as a potential treatment for factor XII (F12) mediated diseases. Arrowhead sees clear unmet need in hereditary angioedema (HAE) and thromboembolic diseases. 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. The company is currently conducting studies in order to advance ARC-F12 into clinical trials. About Arrowhead Research Corporation Arrowhead Research Corporation is a biopharmaceutical company developing targeted RNAi therapeutics. The company is leveraging its proprietary Dynamic Polyconjugate™ delivery platform to develop targeted drugs based on the RNA interference mechanism that efficiently silences disease-causing genes. Arrowhead's pipeline includes ARC-520 and ARC-521 for chronic hepatitis B virus, ARC-AAT for liver disease associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary angioedema and thromboembolic diseases, ARC-LPA for cardiovascular disease, and ARC-HIF2 for renal cell carcinoma. For more information please visit www.arrowheadresearch.com, or follow us on Twitter @ArrowRes. To be added to the Company's email list and receive news directly, please visit ir.arrowheadresearch.com/alerts.cfm. Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. 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 various factors and uncertainties, including our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Arrowhead Research Corporation's most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. DYNAMIC POLYCONJUGATES is a trademark of Arrowhead Research Corporation. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article
Site: http://www.nanotech-now.com/

Abstract: Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that the company will make presentations at the following upcoming events. The International Liver Congress™ 2016 (ILC 2016) - The Annual Meeting of the European Association for the Study of the Liver - Barcelona, Spain, April 13-17, 2016 April 14, 8:00 a.m. CEST - Zhao Xu, Ph.D., Arrowhead senior scientist, and coauthors, will deliver a poster presentation titled, "Treatment of chronically HBV-infected chimpanzees with RNA interference therapeutic ARC-520 led to potent reduction of viral mRNA, DNA and proteins without observed drug resistance" (abstract THU-213) April 14, 8:00 a.m. CEST - Man-Fung Yuen, M.D., Ph.D., chair of gastroenterology and hepatology, The University of Hong Kong, and deputy chief of service, Queen Mary Hospital department of medicine, Hong Kong, and coauthors, will deliver a poster presentation titled, "Differential reductions in viral antigens expressed from cccDNA vs integrated DNA in treatment naïve HBeAg positive and negative patients with chronic HBV after RNA interference therapy with ARC-520" (abstract THU-193) April 15, 8:00 a.m. CEST - Renae Walsh, Ph.D., senior scientist, Victorian Infectious Diseases Reference Laboratory, and coauthors, will deliver a poster presentation titled, "Predicting HBsAg clearance responses during ARC-520 RNA interference (RNAi) therapy based on HBsAg epitope profile analysis" (abstract FRI-144) American Association for Cancer Research Annual Meeting 2016 (AACR16) - New Orleans, April 16-20, 2016 April 18, 1:00 p.m. CDT - So Wong, Ph.D., Arrowhead director of oncology, and coauthors, will deliver a poster presentation titled, "Novel HIF-2α targeted RNAi therapeutic for renal cell carcinoma" (abstract 2064) Copies of presentation materials can be accessed by visiting the Events section of the company's website after each presentation is delivered. About ARC-520 Arrowhead's RNAi-based candidate ARC-520 is being investigated in the treatment of chronic HBV infection. The small interfering RNAs (siRNAs) in ARC-520 intervene at the mRNA level, upstream of the reverse transcription process where current standard of care nucleotide and nucleoside analogues act. Arrowhead is investigating ARC-520 specifically to determine if it can be used to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without seroconversion. Approximately 350-400 million people worldwide are chronically infected with the hepatitis B virus, which can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally. Arrowhead is currently conducting Phase 2b multiple dose and combination studies in chronic HBV patients. In clinical studies to date, the most common reported adverse events in all subjects completing treatment were upper respiratory infection and headache. About Arrowhead Research Corporation Arrowhead Research Corporation is a biopharmaceutical company developing targeted RNAi therapeutics. The company is leveraging its proprietary Dynamic Polyconjugate™ delivery platform to develop targeted drugs based on the RNA interference mechanism that efficiently silences disease-causing genes. Arrowhead's pipeline includes ARC-520 and ARC-521 for chronic hepatitis B virus, ARC-AAT for liver disease associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary angioedema and thromboembolic diseases, ARC-LPA for cardiovascular disease, and ARC-HIF2 for renal cell carcinoma. For more information please visit www.arrowheadresearch.com, or follow us on Twitter @ArrowRes. To be added to the Company's email list and receive news directly, please visit ir.arrowheadresearch.com/alerts.cfm. Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. 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 various factors and uncertainties, including our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Arrowhead Research Corporation's most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. DYNAMIC POLYCONJUGATES is a trademark of Arrowhead Research Corporation. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

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