Galena Biopharma Presents GALE-401 (Anagrelide Controlled Release) Clinical Trial Data At The 56th American Society of

alena Biopharma, Inc. GALE, a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major medical needs across the full spectrum of cancer care, today announced that data from the Company's Phase 1 clinical trials of GALE-401, or Anagrelide Controlled Release (CR), were presented at the 56th American Society of Hematology (ASH) Annual Meeting & Exposition. The poster presentation also included preliminary data from the ongoing GALE-401 Phase 2 clinical trial in patients with elevated platelet counts due to myeloproliferative neoplasms (MPNs). "Final data from our GALE-401 Phase 1 trials showed the compound was well tolerated and demonstrated both a reduction in platelet counts and the desired pharmacokinetic profile with our controlled release version of anagrelide, providing the basis for our ongoing Phase 2 clinical trial," said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. "While early, the preliminary Phase 2 trial data, which was also presented at ASH, looks promising with rapid reductions in platelet counts. Our plan is to present top-line data from the Phase 2 trial at a scientific conference in mid-2015." GALE-401 Phase 1 Clinical Trials The poster entitled, "Phase 1 Study Results of a Novel Controlled-Release Formulation of Anagrelide (GALE-401) for the Treatment of Thrombocytosis," showed that GALE-401 (Anagrelide CR) is a promising, novel formulation of anagrelide. The Phase 1 trials demonstrated that GALE-401 possesses a pharmacokinetic (PK) profile of a significantly reduced C[max], or time to maximum plasma concentration, while maintaining adequate plasma exposure needed to induce platelet count reductions in the healthy subjects. Dose-related reductions in platelet counts were observed, and were similar to the marketed immediate release (IR) formulation of anagrelide in a cross-over, multiple dose study. The product was well tolerated with an adverse event (AE) profile that was not distinguishable from placebo. The Phase 1 trials included 5 studies that enrolled a total of 98 healthy adult subjects, including 12 placebo-control subjects and 86 subjects who received single or multiple doses of Anagrelide CR ranging from 0.2 to 0.6 mg twice daily (b.i.d.) for up to 41 days. The trials included an open-label, single dose developmental study to select a formulation; two placebo-controlled multiple dose ranging studies; a food effect study; and a comparative crossover PK study vs. IR reference product. Safety assessments included laboratory, electrocardiograms (ECGs), and clinical evaluations. Single doses of Anagrelide CR were well tolerated, and the only drug- related AE reported in two or more subjects was headache. In the b.i.d. dose-ranging studies, the frequency and severity of AEs were similar between Anagrelide CR and placebo groups, with the exception of decreased platelet counts in subjects receiving Anagrelide CR. All AEs were transient, mild or moderate in severity, and no severe or serious AEs were reported. GALE-401 demonstrated dose proportional PK characteristics, and plasma exposure was higher when CR was administered in the fed versus fasted state. In a placebo-controlled study of 0.2 to 0.6 mg b.i.d. dosing for up to 21 days (n=8 subjects/cohort randomized 2:1 to anagrelide or placebo), a dose-related decrease in platelet counts was observed, and the 0.6 mg cohort was halted early due to excessive platelet reductions. In a cross-over, multiple dose study of Anagrelide CR and IR (0.5mg b.i.d., N=20 subjects), similar reductions in platelet counts were observed despite differences in PK exposure. GALE-401 Phase 2 Preliminary Results The GALE-401 Phase 2 clinical proof-of-concept study is an open-label, single-arm, multicenter study in patients with an MPN-related thrombocytosis. The primary objective is to estimate the response rate in terms of platelet reduction, and the trial will also assess safety and tolerability, and measure plasma concentrations of anagrelide. The platelet lowering ability of GALE-401 will be measured by the proportion of patients that achieve a complete platelet response (CR = ≤400 x 10^9/L) or partial platelet response (PR = ≤600 x 10^9/L or a ≥50% reduction from baseline) maintained for at least four weeks during 24 weeks of treatment. With enrollment complete, patients are being followed for platelet response while they continue study treatment. Safety is assessed by frequency and severity of AEs. The poster also presented preliminary results for the Phase 2 trial, which enrolled 18 subjects with the following MPNs: 13 Essential Thrombocythemia, 4 Polycythemia Vera, 1 Primary Myelofibrosis. Patients were previously treated with hydroxyurea (n=8), Anagrelide IR (n=6), None (n=7), and were washed out of any prior therapies and their baseline platelet counts were returned to ≥600 x 10^9/L before treatment with Anagrelide CR. 
Patients were started on a dose of 0.5 mg b.i.d. (1.0 mg/day), and titrated at a dose of 0.5 mg/day/wk) to maintain platelet count of 150 - 400 x 10^9/L. Rapid reductions in platelet counts were observed with dose titration. Platelet responses to-date include confirmed and unconfirmed CRs and PRs among 9 subjects. AEs have all been Grade 1 or 2 and those reported in two or more subjects regardless of relationship to study drug included headache (5 subjects), abdominal pain (3), fatigue (3), nausea (3), AST elevation (2), diarrhea (2), edema (2), and tachycardia (2).