Global Blood Therapeutics Presents GBT440 Data that Continue to Support Durability, Safety and Mechanism of Action in Sickle Cell Disease

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Global Blood Therapeutics Presents GBT440 Data that Continue to Support Durability, Safety and Mechanism of Action in Sickle Cell Disease
Data Presented at 10th Anniversary Conference of Academy for Sickle Cell and Thalassemia (ASCAT)

SOUTH SAN FRANCISCO, Calif., Oct. 07, 2016 (GLOBE NEWSWIRE) -- Global Blood Therapeutics, Inc. (GBT) (NASDAQ:GBT), a biopharmaceutical company developing novel therapeutics for the treatment of grievous blood-based disorders with significant unmet needs, today announced that an encore presentation of the GBT440-001 study data supporting the durability, safety and mechanism of action of GBT440 in sickle cell disease were presented today in an oral session at the Academy for Sickle Cell and Thalassemia (ASCAT) 10thAnniversary Conference in London.

“Hemoglobin oxygen affinity modulation is a very promising approach for modifying disease in SCD because it intervenes on the fundamental pathologic process- HbS polymerization. GBT440 is an exciting hemoglobin modifier in development because of excellent specificity and pharmaceutical properties resulting in both increased potency and an improved safety profile. Over three months of dosing, GBT440 has shown profound and durable reductions in hemolysis and sickling, which provides further support that this novel hemoglobin modifier has the potential to be a once-daily treatment for patients with sickle cell disease,” said Dr. Jo Howard, consultant hematologist and head of the red cell/sickle cell service at Guy's and St Thomas' NHS Foundation Trust in London. “Further, given that all 34 SCD patients dosed with GBT440 for 28 to 90 days have shown a positive hematologic response, I believe that GBT440 could potentially transform the treatment of this devastating disease.”

“The data showing a rapid and durable reduction in hemolytic anemia and sickling over 90 days support both the mechanism of action and the efficacy profile of GBT440 as a potentially disease-modifying therapy for SCD,” said Ted W. Love, M.D., president and chief executive officer of GBT. “We are currently in discussions with the FDA regarding details of our regulatory path forward for GBT440 in SCD. Based on these promising results, we believe that GBT440 has the potential to improve the clinical course of sickle cell disease and look forward to exploring this further in a pivotal trial that remains on track to initiate by year-end. In addition, we look forward to presenting our full 90 day data for our 900 mg per day cohort at the upcoming American Society of Hematology meeting.”

Design of Ongoing Phase 1/2 GBT440-001 Trial
GBT440-001 is a randomized, placebo-controlled, double-blind, single and multiple ascending dose study evaluating the safety, tolerability, PK and PD of GBT440 in both healthy subjects and patients with SCD. The study is being conducted in three parts: Part A (single dose administration), Part B (multiple dose administration, daily for 15 days in healthy subjects and 28 days in SCD patients) and Part C (multiple dose administration, daily for 90 days in SCD patients).

Data Presentation Highlights
The data presented at ASCAT were previously presented at the European Hematology Association's 21st Congress in June.

In the six patients treated with GBT440 700 mg/day for 90 days, results showed:

  • A durable reduction in hemolysis (red blood cell destruction) from baseline to day 90, as evidenced by a rapid and sustained reduction in bilirubin starting as early as day 4 and continuing through day 90 (median decrease of greater than 35% compared with an increase of approximately 20% with placebo).
  • A median 1.1 g/dL increase in hemoglobin concentration with GBT440 treatment compared with a 0.2 g/dL decrease with placebo.
  • A median decrease of approximately 20% in reticulocyte count compared with an approximately 20% increase with placebo, suggesting that the observed increase in hemoglobin is due to a decrease in hemolysis.
  • Steady improvement in hemoglobin and reticulocyte counts through day 60 to 90 after initial variability of hemoglobin and reticulocytes during the first 3-6 weeks (likely due to bone marrow adjusting to dramatic reduction in hemolysis).
  • A sustained reduction in irreversibly sickled cells, with a median decrease of approximately 70% within 90 days compared to an increase of approximately 15% with placebo.
  • GBT440 was well tolerated over 90 days of dosing. The most common adverse event was headache, seen in both the placebo and GBT440 arms. There have been no drug-related serious adverse events.

Complete 28-day results from three dosing cohorts of GBT440 (500 mg [n=10]), 700 mg [n=12] and 1,000 mg administered as 500 mg BID [n=5]) showed:

  • A consistent beneficial effect was seen in at least one key parameter: hemolysis, reticulocytosis or sickle cell counts.
  • The therapeutic target between 10-30% Hb modification was achieved at GBT440 doses ≥500 mg.

GBT440-001 Overall Safety Summary
Across the GBT440 clinical development program, GBT440 has now been dosed in 252 adults, including 128 subjects in multiple dosing cohorts up to 90 days. It has been shown to be well tolerated with no drug-related serious adverse events. There has been no evidence of tissue hypoxia in healthy subjects up to approximately 40% Hb modification or in SCD subjects up to approximately 30% Hb modification.

About GBT440
GBT is developing GBT440 as an oral, once-daily therapy for patients with sickle cell disease. GBT440, a hemoglobin modifier, works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, GBT believes GBT440 blocks polymerization and the resultant sickling of red blood cells (RBCs). With the potential to restore normal hemoglobin function and improve oxygen delivery, GBT440 may be capable of modifying the progression of SCD. The U.S. Food and Drug Administration (FDA) has granted GBT440 both Fast Track and Orphan Drug designation for the treatment of patients with SCD in recognition of the critical need for new treatments.

About Global Blood Therapeutics
Global Blood Therapeutics, Inc. is a clinical-stage biopharmaceutical company dedicated to discovering, developing and commercializing novel therapeutics to treat grievous blood-based disorders with significant unmet need. GBT is developing its lead product candidate, GBT440, as an oral, once-daily therapy for sickle cell disease (SCD) and is currently evaluating GBT440 in a Phase 1/2 study in both healthy subjects and adults with SCD and a Phase 2a study in adolescents with SCD. GBT is also investigating GBT440 for the treatment of hypoxemic pulmonary disorders in an ongoing Phase 2a study in patients with idiopathic pulmonary fibrosis. Additionally, GBT is also engaged in research and development activities with an oral kallikrein inhibitor for the prevention of hereditary angioedema attacks. To learn more, please visit:

Forward-Looking Statements 
Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. We intend these forward-looking statements, including statements regarding the therapeutic potential and safety profile of GBT440, our ability to initiate a pivotal trial of GBT440 in SCD, our ability to generate 90 day data from the 900 mg per day cohort in our Phase 1/2 GBT440-001 trial, and the timing of these events, to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. We can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved, and furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, the risks that our clinical and preclinical development activities may be delayed or terminated for a variety of reasons, that regulatory authorities may disagree with our clinical development plans or require additional studies or data to support further clinical investigation of our product candidate, and that GBT440 may not provide the clinical benefits that we anticipate, along with those set forth in our Annual Report on Form 10-K for the fiscal year ended December 31, 2015, and in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2016, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the U.S. Securities and Exchange Commission. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Contact Information:
Myesha Edwards (investors)
Global Blood Therapeutics

Julie Normart (media)

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