Arrowhead Research Corp (NASDAQ:ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that it has nominated ARC-HIF2 as its first therapeutic candidate delivered using a new Dynamic Polyconjugate™ (DPC™) designed to target tissues outside of the liver. Arrowhead believes that ARC-HIF2, which uses RNA interference to silence transcription factor hypoxia-inducible factor 2α (HIF-2α), is a promising new candidate for the treatment of clear cell renal cell carcinoma (ccRCC). The company will present preclinical data at the European Cancer Congress 2015 (ECC2015) in Vienna on September 27in a session starting at 16:45 CEST. In a poster titled “HIF-2α targeting with a novel RNAi delivery platform as therapy for renal cell carcinoma,” (abstract #353), Arrowhead scientists will show data suggesting that HIF-2α inhibition through RNA interference may significantly impact late stage ccRCC progression. The company is in the process of manufacturing scale up to allow for initiation of IND-enabling studies. Timing for anticipated regulatory submission will be announced in the future.

“Preclinical data using our new extrahepatic DPC™ delivery system has been very promising. We think the ability to target tissues outside of the liver, including tumors, opens additional opportunities for Arrowhead to develop differentiated RNAi-therapeutics that address numerous diseases without adequate treatment options,” said Christopher Anzalone, Ph.D., Arrowhead’s president and chief executive officer. “This is an important milestone for Arrowhead and we look forward to continued development of the DPC™ delivery platform and product candidates based on it.”

ARC-HIF2 is designed to inhibit the production of HIF-2α, which has been linked to tumor progression and metastasis in ccRCC. ARC-HIF2 employs a novel extrahepatic-targeted DPC™ that comprises a membrane active polymer to promote RNAi trigger endosomal release, an active ligand that targets the DPC™ to tumor cells, reversible masking to prevent polymer activity prior to cellular uptake, and an RNAi trigger to HIF-2α conjugated directly to the DPC™.

Using ARC-HIF2 in a preclinical ccRCC tumor model, mice treated with weekly injections led to greater than 80% knockdown of HIF-2α mRNA in tumors. Furthermore, tumors from treated mice exhibited statistically significant reductions in size and weight, extensive tumor cell death, reduction in the tumor-expressed VEGF-A biomarker, and destruction of the blood vessels feeding the tumors.

Therapies for metastatic ccRCC including agents that target the VEGF/VEGFR or mTor signaling pathways, which are validated cancer targets, have become the standard-of-care and have improved patient outcomes. However, since emergence of resistance to these agents is common, novel therapies targeting alternative pathways are needed for patients with resistant tumors. Arrowhead believes that HIF2α is an attractive target for intervention because over 90% of ccRCC tumors express a mutant form of the Von Hippel-Landau protein that is unable to degrade HIF-2α, leading to its accumulation during tumor hypoxia and promoting tumor growth. (Original Source)

Shares of Arrowhead Researchclosed yesterday at $5.72. ARWR has a 1-year high of $16.99 and a 1-year low of $4.35. The stock’s 50-day moving average is $5.86 and its 200-day moving average is $6.71.

On the ratings front, RBC analyst Michael Yee maintained a Hold rating on ARWR, with a price target of $9, in a report issued on August 5. The current price target represents a potential upside of 57.3% from where the stock is currently trading. According to, Yee has a total average return of 6.7%, a 60.3% success rate, and is ranked #499 out of 3754 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.