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ARC520 -Updates on the Phase2a study
Arrowhead Reports Fiscal 2014 Third Quarter Financial Results and Provides Update on ARC-520
- Conference Call Today at 4:30 p.m. EDT
PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced financial results for its fiscal 2014 third quarter ended June 30, 2014 and provided an update on the Phase 2a study of ARC-520, its RNAi-based candidate for the treatment of chronic hepatitis B infection. The company is hosting a conference call at 4:30 p.m. EDT to discuss results. Conference call and webcast details can be found below.
ARC-520 Phase 2a Study Update
Completed dosing of 1 mg/kg and 2 mg/kg dose cohorts
Initial blinded data suggest that the magnitude of HBsAg knockdown is similar to non-human primate studies, including the chronically infected chimpanzee reported on previously
Duration of knockdown appears to be substantially more sustained than in non-human primates, with patients in the 2 mg/kg group still demonstrating substantial knockdown after 8 weeks, which is the most recent time point available
HBsAg levels appear to continue to decline in a number of patients at the 8 week time point in the 2 mg/kg group
Based on initial review, dosing less frequent than once monthly will be explored in Phase 2b
ARC-520 continues to be well tolerated, with no dropouts or serious adverse events reported
The overall rate of AEs has been lower in the Phase 2a than in the Phase 1 normal volunteer study and safety labs continue to show no indication of end organ toxicity
Enrolled and dosed additional subjects at 3 mg/kg in the still open normal volunteer study and the dose performed well, without detected differences from safety and tolerability results at the other doses. Overall AEs do not appear to be increasing in frequency or severity with dose
Received IRB and DSMB approvals to proceed and began enrolling an additional dose cohort at 3 mg/kg in the Phase 2a patient study
Fiscal 2014 Third Quarter and Recent Company Highlights
Nominated a second clinical candidate using our DPC delivery system, ARC-AAT, for the treatment of a rare liver disease associated with alpha-1 antitrypsin deficiency and hosted an analyst day to present preclinical data
Signed an agreement with The Alpha-1 Project (TAP), the venture philanthropy subsidiary of the Alpha-1 Foundation. Under the terms of the agreement, TAP will partially fund the development of ARC-AAT. In addition, TAP will make its scientific advisors available to Arrowhead, assist with patient recruitment for clinical trials through the Alpha-1 Foundation Patient Research Registry, and engage in other collaborative efforts that support the development of ARC-AAT
Initiated the final steps required to file an IND or equivalent application for ARC-AAT, including necessary toxicology studies
Expanded intellectual property protection with U.S. Patent Application number 13/535,454 covering ARC-520's siRNA component, being recently allowed by the U.S. Patent and Trademark Office
Presented data on advancements made to the DPC delivery system at multiple scientific meetings
Arrowhead added to the broad-market Russell 3000 index and small-cap Russell 2000 index
Selected Fiscal 2014 Third Quarter Financial Results
Net loss attributable to Arrowhead for the quarter was $11.6 million, or $0.22 per share based on 51.9 million weighted average shares outstanding. This compares with a net loss attributable to Arrowhead of $6.1 million, or $0.23 per share based on 26.1 million weighted average shares outstanding, for the quarter ended June 30, 2013.
Total operating expenses for the quarter were $12.7 million, compared to $6.4 million for the quarter ended June 30, 2013. Research and development related expenses were $6.4 million and general and administrative expenses were $1.6 during the quarter.
Net cash used in operating activities for the first nine months of fiscal 2014 was $24.5 million, compared with $13.6 million in the prior year period.
The company's cash and investments of cash were $188.5 million at June 30, 2014, compared to $29.8 million at September 30, 2013. The increase in the cash balance reflects financings completed in October 2013 and February 2014, plus cash inflow from exercise of warrants and stock options of $12.4 million.
Common shares outstanding at June 30, 2014, were 52.9 million, and 58.5 million assuming conversion of preferred stock outstanding.
Conference Call and Webcast Details
To participate in the conference call, please dial 855-215-6159 (toll free from the US) or 315-625-6887 (for international callers) and enter Conference ID 82825377. Investors may also access a live audio webcast of this conference call on the Company's website at http://ir.arrowheadresearch.com/events.cfm.
A replay of the webcast will be available approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 7 days. The audio replay can be accessed by dialing 855-859-2056 (toll free from the US), or 404-537-3406 (for international callers) and entering Conference ID 82825377.
About ARC-520
Arrowhead's RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. The siRNAs in ARC-520 intervene at the mRNA level, upstream of where nucleotide and nucleoside analogues act. In transient and transgenic mouse models of HBV infection, a single co-injection of Arrowhead's Dynamic Polyconjugate (DPC) delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. The company is conducting a single dose Phase 2a study in chronic HBV patients, and expects to follow with a multi-dose, multi-national Phase 2b program. Approximately 350 million people worldwide are chronically infected with the hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally.
- Conference Call Today at 4:30 p.m. EDT
PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced financial results for its fiscal 2014 third quarter ended June 30, 2014 and provided an update on the Phase 2a study of ARC-520, its RNAi-based candidate for the treatment of chronic hepatitis B infection. The company is hosting a conference call at 4:30 p.m. EDT to discuss results. Conference call and webcast details can be found below.
ARC-520 Phase 2a Study Update
Completed dosing of 1 mg/kg and 2 mg/kg dose cohorts
Initial blinded data suggest that the magnitude of HBsAg knockdown is similar to non-human primate studies, including the chronically infected chimpanzee reported on previously
Duration of knockdown appears to be substantially more sustained than in non-human primates, with patients in the 2 mg/kg group still demonstrating substantial knockdown after 8 weeks, which is the most recent time point available
HBsAg levels appear to continue to decline in a number of patients at the 8 week time point in the 2 mg/kg group
Based on initial review, dosing less frequent than once monthly will be explored in Phase 2b
ARC-520 continues to be well tolerated, with no dropouts or serious adverse events reported
The overall rate of AEs has been lower in the Phase 2a than in the Phase 1 normal volunteer study and safety labs continue to show no indication of end organ toxicity
Enrolled and dosed additional subjects at 3 mg/kg in the still open normal volunteer study and the dose performed well, without detected differences from safety and tolerability results at the other doses. Overall AEs do not appear to be increasing in frequency or severity with dose
Received IRB and DSMB approvals to proceed and began enrolling an additional dose cohort at 3 mg/kg in the Phase 2a patient study
Fiscal 2014 Third Quarter and Recent Company Highlights
Nominated a second clinical candidate using our DPC delivery system, ARC-AAT, for the treatment of a rare liver disease associated with alpha-1 antitrypsin deficiency and hosted an analyst day to present preclinical data
Signed an agreement with The Alpha-1 Project (TAP), the venture philanthropy subsidiary of the Alpha-1 Foundation. Under the terms of the agreement, TAP will partially fund the development of ARC-AAT. In addition, TAP will make its scientific advisors available to Arrowhead, assist with patient recruitment for clinical trials through the Alpha-1 Foundation Patient Research Registry, and engage in other collaborative efforts that support the development of ARC-AAT
Initiated the final steps required to file an IND or equivalent application for ARC-AAT, including necessary toxicology studies
Expanded intellectual property protection with U.S. Patent Application number 13/535,454 covering ARC-520's siRNA component, being recently allowed by the U.S. Patent and Trademark Office
Presented data on advancements made to the DPC delivery system at multiple scientific meetings
Arrowhead added to the broad-market Russell 3000 index and small-cap Russell 2000 index
Selected Fiscal 2014 Third Quarter Financial Results
Net loss attributable to Arrowhead for the quarter was $11.6 million, or $0.22 per share based on 51.9 million weighted average shares outstanding. This compares with a net loss attributable to Arrowhead of $6.1 million, or $0.23 per share based on 26.1 million weighted average shares outstanding, for the quarter ended June 30, 2013.
Total operating expenses for the quarter were $12.7 million, compared to $6.4 million for the quarter ended June 30, 2013. Research and development related expenses were $6.4 million and general and administrative expenses were $1.6 during the quarter.
Net cash used in operating activities for the first nine months of fiscal 2014 was $24.5 million, compared with $13.6 million in the prior year period.
The company's cash and investments of cash were $188.5 million at June 30, 2014, compared to $29.8 million at September 30, 2013. The increase in the cash balance reflects financings completed in October 2013 and February 2014, plus cash inflow from exercise of warrants and stock options of $12.4 million.
Common shares outstanding at June 30, 2014, were 52.9 million, and 58.5 million assuming conversion of preferred stock outstanding.
Conference Call and Webcast Details
To participate in the conference call, please dial 855-215-6159 (toll free from the US) or 315-625-6887 (for international callers) and enter Conference ID 82825377. Investors may also access a live audio webcast of this conference call on the Company's website at http://ir.arrowheadresearch.com/events.cfm.
A replay of the webcast will be available approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 7 days. The audio replay can be accessed by dialing 855-859-2056 (toll free from the US), or 404-537-3406 (for international callers) and entering Conference ID 82825377.
About ARC-520
Arrowhead's RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. The siRNAs in ARC-520 intervene at the mRNA level, upstream of where nucleotide and nucleoside analogues act. In transient and transgenic mouse models of HBV infection, a single co-injection of Arrowhead's Dynamic Polyconjugate (DPC) delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. The company is conducting a single dose Phase 2a study in chronic HBV patients, and expects to follow with a multi-dose, multi-national Phase 2b program. Approximately 350 million people worldwide are chronically infected with the hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally.
Stef, you're really big on the peginterferon combo and I can understand why. The numbers themselves prove it works. But I think this drug's goal is to actually get away from this kind of treatment and work QUICKER. I've known a few Hep C patients that did interfereon who have said the side effects were terrible to deal with. Some people may respond better to it than others, but most had bad sides and that is something I believe they want to do away with with this drug.
I do agree with you that without seroconversion, this is not useful. As you suggested, I guess it can known out hbsag and a vaccination can be provided. That could always be a course of action and a great suggestion. Wonder if they tried that yet?
I, of course, do have questions regarding this:
-They did a study with Entecavir. Will this work with Tenofovir?!
-If you are already undetectable, can you stop the anti-viral and just have this knock out the rest of hbsag?
-Once hbsag is knocked out, will you have to continue taking this drug or any other drug for maintenance to make sure it does not come back?
-What kind of side affects, if any, will this have?
-Is there anything that interfes with the drug (any vitamins, foods, drinks, etc.)?
So many questions left unanswered. I'm sure there are more. I'll be curious to see what happens in Phase IIb
I do agree with you that without seroconversion, this is not useful. As you suggested, I guess it can known out hbsag and a vaccination can be provided. That could always be a course of action and a great suggestion. Wonder if they tried that yet?
I, of course, do have questions regarding this:
-They did a study with Entecavir. Will this work with Tenofovir?!
-If you are already undetectable, can you stop the anti-viral and just have this knock out the rest of hbsag?
-Once hbsag is knocked out, will you have to continue taking this drug or any other drug for maintenance to make sure it does not come back?
-What kind of side affects, if any, will this have?
-Is there anything that interfes with the drug (any vitamins, foods, drinks, etc.)?
So many questions left unanswered. I'm sure there are more. I'll be curious to see what happens in Phase IIb
Pre results were communicated yesterday and were very strong at lower doses, they are moving up to 3 and 4 mg/kg to achieve greater knockdown.
Full Data on 1 and 2 mg/kg and also 3 should be available at AASLD in Nov
One of the most encouraging results from yesterday is the continued decrease at 8 weeks of Hbsag with only one dose.
Full Data on 1 and 2 mg/kg and also 3 should be available at AASLD in Nov
One of the most encouraging results from yesterday is the continued decrease at 8 weeks of Hbsag with only one dose.
we will see they showed too little data for now and poor quality trials (i mean too small and too little tests)
i also think combo with nucs alone is of little help, the real benefit will be from pegintf which will remove the infection by activating immune system.anyway we ll see from this study what it can do
hcv is not comparable to hbv as regards peginterferon treatment.they have a huge response to clear hcv by peg from 50 to 80% clearance according to genotypes but they also have a very potent immune activation by peg.
you ll never see such extreme sides on an hbv patient, most just experience fatigue or even no sides
i also think combo with nucs alone is of little help, the real benefit will be from pegintf which will remove the infection by activating immune system.anyway we ll see from this study what it can do
hcv is not comparable to hbv as regards peginterferon treatment.they have a huge response to clear hcv by peg from 50 to 80% clearance according to genotypes but they also have a very potent immune activation by peg.
you ll never see such extreme sides on an hbv patient, most just experience fatigue or even no sides
"Poor quality trials" that is the nature if phase 2a, they are looking for the right dose at this point. 2b which starts in the next 6 months will be larger
IMO this has the potential as a single agent providing seroconversion
IMO this has the potential as a single agent providing seroconversion
To understand how ARC520 will work, you must understand how REP9AC work, how TDF for few years then add-on PEGIFN is supposed to work. It is all about reducing all the suppression of the immune system caused by serum virions(HBVdna) , HBeAg, and HBsAg. The theory is that with the removal of these suppressions, our cd8 T cells immunity will recover and works to clear the infection. Not all experts believe this is sufficient for a majority of patients, something else to boost the immune system will also be needed. If you listen to the webcast by Arrowhead, all these will be explored in the phase2b trials to be conducted in the USA, Europe, and Asia, starting Q4 this year. At the same time, there will be separate studies to consider combinations with immune modulating agents.
My understanding.
My understanding.
That was my understanding as well, but the fact that Hbsag is still declining in the 2mg/kg group 8 weeks after a single dose may change that. If 3mg/kg can provide greater initial knockdown at longer duration (coupled with a repeat dose if needed) it may stimulate the immune system enough to clear without Peg.
The fact that no sides developed in the 3mg/kg is very encouraging and going to 4 is interesting as well. They will find the sweet spot
The fact that no sides developed in the 3mg/kg is very encouraging and going to 4 is interesting as well. They will find the sweet spot
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