Alios BioPharma to Present Preclinical Data on Its Anti-HCV Nucleotides AL-335 and AL-516 at the 2014 American Association for the Study of Liver Diseases Annual Meeting

SOUTH SAN FRANCISCO, CA--(Marketwired - Nov 6, 2014) - Alios BioPharma, Inc., announced the upcoming presentation of preclinical data from two of its anti-hepatitis C virus (HCV) nucleotide analogs at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) beginning tomorrow in Boston. Data from two novel compounds -- AL-335, a potent uridine based nucleotide analog and AL-516, a potent guanosine based nucleotide analog -- will be presented in two poster sessions on Tuesday, November 11. 

AL-335 is a monophosphate prodrug of a uridine-based nucleotide analog and has been identified as a potent inhibitor of NS5B-directed HCV RNA replication. Results presented previously have shown that AL-335 demonstrates potent inhibition of HCV in the cell-based replicon assay across genotypes. In this most recent study, AL-335 was examined in pairwise combinations with multiple classes of compounds either approved for the treatment of chronic hepatitis C (CHC) or currently in clinical development. The classes of compounds tested included NS3/4A protease inhibitors, NS5A inhibitors, nucleoside/tide and non-nucleoside polymerase inhibitors, cyclophilin A inhibitors, type I and type III interferons (IFNs) and ribavirin (RBV). All of the combinations were either additive or synergistic in vitro, and no antagonistic effects were observed. The combination of AL-335 with the NS3/4A inhibitor simeprevir (Olysio) demonstrated a high level of synergy.

AL-516, the guanosine-based nucleotide analog, was evaluated using the HCV replicon system encoding NS5B sequences from multiple genotypes and resistant variants and was profiled for its effects on cell viability and mitochondrial toxicity. The nucleoside 5'-triphosphate (AL-516 NTP) was tested against the HCV polymerase NS5B and for selectivity against human DNA and RNA polymerases. In the stable genotype (GT) 1b replicon assay, AL-516 exhibited potent antiviral activity with an EC₅₀ of 7 nM. In transient chimeric GT-1b replicons with NS5B regions derived from GT 1-4, AL-516 demonstrated pan-genotypic activity with EC₅₀ values < 10 nM. AL-516 retained activity versus replicon mutants resistant to other nucleoside inhibitors. AL-516 exhibited an excellent selectivity profile with no inhibition of mitochondrial protein synthesis (IC₅₀ >100 μM).

"Preclinical characterization of AL-335 has demonstrated its potential to become the best-in-class HCV polymerase inhibitor," stated Leonid Beigelman, PhD, CSO of Alios. "Furthermore, the recent addition of AL-516, which has a complementary resistance profile, enhances our portfolio of pan-genotypic nucleotide inhibitors as a backbone of combination therapy."

Alios has completed preclinical studies with AL-335 and expects to enter Phase 1 clinical studies in December 2014. AL-516 is currently advancing through preclinical studies and is expected to enter Phase 1 clinical trials sometime in 2015.

Alios President and CEO Lawrence M. Blatt, PhD, commented, "The discovery and development of additional safe and effective nucleotide analogs remain an important need for the treatment of chronic hepatitis C. Of particular importance is the ability to use these compounds in combination with other therapies, and in particular with Johnson & Johnson's Olysio, to improve treatment outcomes and create alternatives for patients and healthcare providers. We are excited to be moving both potential products into the clinic, bringing improved treatments closer to reality."

About Alios BioPharma
Alios BioPharma, Inc. is a clinical stage biopharmaceutical company in South San Francisco, CA that is developing novel therapies for the treatment of viral diseases. The Alios virology discovery and development platform consists of a proprietary chemical library of nucleoside analogs as well as novel, proprietary virology-based screening systems. Alios is developing a portfolio of potential therapeutics for viral infections including respiratory syncytial virus (RSV), influenza, rhinovirus, coronavirus and hepatitis C. On September 30, 2014, Johnson & Johnson (NYSE: JNJ) announced a definitive agreement to acquire Alios for approximately $1.75 billion in cash. The transaction is expected to close in the fourth quarter of 2014. For more information please visit www.aliosbiopharma.com.

Olysio™ is a trademark of Johnson & Johnson.

Alios BioPharma Contact:
Bharath Kumandan (Investors & Media)
650-635-5561
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