Agios Pharmaceuticals Inc (NASDAQ:AGIO) announced the initial data from the Phase 1 integrated single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial of AG-519 in healthy volunteers at the 21st Congress of the European Hematology Association (EHA) taking place June 9-12, 2016 in Copenhagen. These data provide early proof-of-mechanism for AG-519, a potent, oral, selective second pyruvate kinase-R (PKR) activator that is wholly owned by Agios. Agios is also developing AG-348, a first-in-class, oral PKR activator that is being evaluated in an ongoing Phase 2 study, DRIVE-PK.

In this Phase 1 study, dosing of AG-519 over 14-days in healthy volunteers resulted in a dose-dependent increase in PKR activity as evidenced by a substantial increase in ATP (adenosine triphosphate) and decrease in 2,3-DPG  (2,3-diphosphoglycerate) levels, which are important biomarkers of PKR activation in healthy volunteers. These data support the hypothesis that AG-519 enhances PKR activity and has the potential to correct the underlying defect of pyruvate kinase (PK) deficiency, a rare, potentially debilitating, congenital anemia.

“Achieving proof-of-mechanism for AG-519, our second PKR activator, further advances Agios’ novel approach to the treatment of rare metabolic disorders,” said Chris Bowden, M.D., chief medical officer of Agios. “These Phase 1 data from AG-519 bring us closer to our goal of delivering the first disease-modifying treatment for patients with PK deficiency.”

Results from the Completed SAD Portion of the Phase 1 Study

  • Four cohorts with doses of AG-519 ranging from 50 mg to 1250 mg were tested against placebo in 32 healthy volunteers.
  • AG-519 demonstrated a favorable safety profile in all doses tested. There were no serious adverse events (SAEs) reported, with all adverse events (AEs) being mild to moderate, and the most common being headache. In addition, there were no early discontinuations due to AG-519 and the maximum tolerated dose was not reached.
  • Mean decreases in blood 2,3-DPG levels up to 43 percent from baseline were observed in the SAD cohorts, reaching minimum levels after 24 hours. As expected, ATP levels did not change after a single dose of AG-519, consistent with SAD findings from AG-348.  Healthy volunteers receiving placebo showed no changes in 2,3-DPG or ATP levels.

Preliminary Results from the Ongoing MAD Portion of the Phase 1 Study

  • The first two cohorts reported data from 16 healthy volunteers dosed twice daily with 125 mg or 375 mg of AG-519 or placebo for 14 days.
  • There were no SAEs reported, with all AEs being mild to moderate, and the most common being headache. One subject receiving AG-519 at the 375 mg dose experienced a low blood platelet count (Grade 2 thrombocytopenia) on Day 14. Platelet levels started to recover within five days of the last dose and returned to normal levels seven days after the last dose.
  • Pharmacodynamic data from these cohorts showed a mean decrease of up to 47 percent in blood 2,3-DPG levels and a mean increase of up to 62 percent in blood ATP levels from baseline. In contrast, healthy volunteers receiving placebo showed no changes in 2,3-DPG or ATP levels.
  • Subjects treated with AG-519 exhibited no significant changes in sex steroids levels, consistent with a lack of aromatase enzyme inhibition.
  • Enrollment into additional MAD cohorts is ongoing. (Original Source)

Shares of Agios Pharmaceuticals are down nearly 8% to $60.86 in early trading Tuesday. AGIO has a 1-year high of $124.12 and a 1-year low of $33.50. The stock’s 50-day moving average is $51.15 and its 200-day moving average is $48.77.

On the ratings front, Agios has been the subject of a number of recent research reports. In a report released today, J.P. Morgan analyst Anupam Rama maintained a Hold rating on AGIO, with a price target of $50, which reflects a potential downside of -24.3% from last closing price. Separately, on May 24, Cowen’s Eric Schmidt reiterated a Buy rating on the stock .

According to, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Anupam Rama and Eric Schmidt have a total average return of 4.8% and 20.6% respectively. Rama has a success rate of 48.3% and is ranked #1243 out of 3903 analysts, while Schmidt has a success rate of 63.6% and is ranked #42.

Overall, 3 research analysts have assigned a Hold rating and 3 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $63.00 which is -4.7% under where the stock closed yesterday.

Agios Pharmaceuticals, Inc. is a biopharmaceutical company which engages in applying scientific leadership in the field of cellular metabolism to transform the lives of patients with cancer and rare genetic disorders of metabolism. Its products include IDH1 AND IDH2, PKR, II D-2 hydroxyglutaric aciduria, AG-221 and AG-120.