Arrowhead Research Corp (NASDAQ:ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, presented data at HEP DART 2015 showing that in chronically HBV-infected chimpanzees treated with ARC-520 in combination with nucleoside analogs, 7 of 9 (78%) exhibited signs of immune reactivation, which is likely a necessary step for achieving a functional cure of chronic HBV. One chimpanzee also exhibited an on-treatment therapeutic ALT flare and sustained virologic improvements 31 weeks off all treatment. ARC-520 is currently being studied in multiple Phase 2b global clinical trials.

“The hepatitis B virus causes infected cells to produce several proteins that suppress the host immune system, and, therefore, enable chronic viral infection by removing immune control. Our goal with ARC-520 is to reduce expression of those proteins and thereby enable reconstitution of the immune system. We now have shown that ARC-520 can do that, and not just in 1 or 2 infected chimps, but in 7 of the 9 chimps we treated, and this is a big deal,” said Christopher Anzalone, Ph.D., Arrowhead president and CEO. “ARC-520 deeply reduces HBV proteins and we believe the elevations in T-cell responsive serum cytokines observed in this study represent a strong proof of principle that ARC-520 can begin the process of immune reconstitution that many believe can lead to functional cure. These data are particularly encouraging when combined with our recent human data. Our Phase 2a clinical trial, which we reported at AASLD last month, showed that ARC-520 can dramatically reduce s-antigen, e-antigen, and core-related antigen in humans after a single dose. During the ongoing Phase 2b clinical trials, we are studying ARC-520 as monotherapy as well as in combination with other agents with the goal of identifying a regimen that leads to consistent functional cures.”

Christine Wooddell, Ph.D., director of liver targeting for Arrowhead, presented poster number 152 titled, “Sustained reduction of HBV DNA, RNA and proteins, and HBeAg seroconversion in a chronically HBV-infected chimpanzee treated with nucleoside analog/ARC-520 combination therapy.

In this presentation, Dr. Wooddell and co-authors show that 7 of 9 chimps, HBeAg positive and negative, exhibited indications of an immune response during ARC-520 treatment, as evidenced by elevations in T-cell responsive serum cytokines. Chimp Manetta exhibited deep decreases in HBV DNA, RNA and viral proteins during ARC-520/NUC treatment. The sustained induction of CXCL9 in Manetta was associated with a therapeutic ALT flare (218 U/L) followed by HBeAg seroconversion. Sustained virologic improvements were still observed 31 weeks after all treatment was removed. At this final time point, serum HBV DNA was 5 log10 lower, HBsAg was 1.7 log10 lower, and liver HBV RNA was 99% lower than pre-study.

HBV suppresses the immune system to allow chronic HBV infection. Interferon gamma (IFN-γ) is a key antiviral cytokine critical to innate and adaptive immune responses. IFN-γ produced by natural killer cells and natural killer T cells induces the chemokines CXCL9 and CXCL10 to mediate a T-cell response. An elevation of CXCL9 in the chimps studied is a promising sign of immune system reactivation.

8 out of 9 chimps exhibited episodes of serum cytokine CXCL9 elevation. For 7 chimps these occurred during ARC-520 treatment and in one chimp (Tattoo) these coincided with seroclearance of HBeAg that began prior to study.

To reduce viral replication prior to treatment with ARC-520, chimps were treated for 8-24 weeks with entecavir or in one case (chimp Michele) with entecavir and tenofovir. Following the NUC lead-in period, animals were administered ARC-520 intravenously at 4-week intervals (q4w). Dose levels were 2, 3, or 4 mg/kg ARC-520, along with maintenance doses of entecavir or entecavir and tenofovir. All 9 chimpanzees responded to ARC-520 with HBsAg reductions of 0.5 – 2.7 log10 at nadir, the greater reductions being in HBeAg positive chimps. HBsAg levels in all chimps continued to decrease with repeat dosing. Chimps were monitored for up to 31 weeks off all treatment.(Original Source)

Shares of Arrowhead Research are up 2.71% to $5.69 in early morning trading. ARWR has a 1-year high of $9.36 and a 1-year low of $4.35. The stock’s 50-day moving average is $5.50 and its 200-day moving average is $6.12.

On the ratings front, Piper Jaffray analyst Edward Tenthoff reiterated a Buy rating on ARWR, with a price target of $20, in a report issued on September 25. The current price target represents a potential upside of 261.0% from where the stock is currently trading. According to, Tenthoff has a total average return of 10.3%, a 46.9% success rate, and is ranked #445 out of 3645 analysts.

Arrowhead Research Corp is engaged in developing novel drugs to treat intractable diseases by silencing the genes. The Company’s drug candidate ARC-520 is designed to treat chronic hepatitis B infection.