Global Blood Therapeutics Announces Positive Phase 1/2 Data Supporting Development of GBT440 as a Potentially Disease-Modifying Therapy for Sickle Cell Disease

Results to be Presented During an Oral Session at the American Society of Hematology (ASH) Annual Meeting and Exposition Tomorrow, December 7 at 10:45 a.m. ET

Company to Host Webcast Tomorrow at 12:30 p.m. ET to Discuss Data

SOUTH SAN FRANCISCO, Calif., Dec. 06, 2015 (GLOBE NEWSWIRE) -- Global Blood Therapeutics, Inc. (GBT) (GBT), a biopharmaceutical company developing novel therapeutics for the treatment of grievous blood-based disorders with significant unmet needs, today announced positive clinical data from the Company's ongoing Phase 1/2 clinical trial (the GBT440-001 study) in sickle cell disease (SCD) supporting the potential of GBT440, an oral, once-daily therapy, as a mechanism-based and potentially disease-modifying treatment option. Specifically, the data demonstrate that GBT440 inhibits polymerization of sickle hemoglobin, increases hemoglobin concentration, reduces red blood cell damage, improves oxygen delivery, and reduces inflammation.  These results include data from 30 patients with SCD who have completed 28 days of treatment on GBT440 or placebo, and reinforce and expand on the safety and efficacy data previously reported in an initial cohort of eight patients.  The data will be featured today, Sunday, December 6 at 9 a.m. Eastern Time (ET) in an official American Society of Hematology (ASH) press briefing and will be presented in an oral session on Monday, December 7 at 10:45 a.m. ET (abstract #542). 

"Sickle cell is an extremely debilitating disease and typically results in a 25 to 30 year decrease in life expectancy due to limited, suboptimal treatment options," said Dr. Claire Hemmaway, MA (Hons) Cantab, MBBS, FRCP, FRCPATH, Queens Hospital, Essex, United Kingdom, a hematologist and investigator in the GBT440-001 study. "Our expanding experience with GBT440 shows that it is a promising and well-tolerated investigational treatment.  These results are exciting because patients with SCD desperately need a mechanism-based treatment option that can transform their disease."

GBT440-001 is a randomized, placebo-controlled, double-blind, single and multiple ascending dose study evaluating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GBT440 in both healthy subjects and patients with SCD. The study is being conducted in two parts: Part A (single dose administration) and Part B (multiple dose administration, daily for 15 days in healthy subjects and 28 days in SCD patients). As of November 20, 2015, eight SCD patients completed part A of the study, and 30 SCD patients have either completed or were ongoing in part B of the study.  Of the 30 SCD patients, 16 patients completed 700 mg per day dosing and follow-up (12 on GBT440: 4 on placebo) and 14 patients have completed or were ongoing at 500 mg per day dosing and follow-up (10 on GBT440: 4 on placebo).  A cohort of SCD patients on 1000 mg per day for 28 days is currently enrolling. The data showed that from baseline to day 28:

  • The median hemoglobin concentration increased rapidly with GBT440 treatment, with increases evident by day 4, and absolute increases of 0.5 and 0.7 g/dL (500 mg and 700 mg, respectively) compared with a 0.1 g/dL decrease with placebo.
  • The median reticulocyte count decreased by 31% and 37% (500 mg and 700 mg, respectively) with GBT440 compared with a 7% increase with placebo, indicating that the hemoglobin rise is due to decreased red blood cell destruction (hemolysis). Median erythropoietin levels decreased by 9 and 18 mU/mL (500 mg and 700 mg, respectively) with GBT440 treatment compared with an increase of 28 mU/mL with placebo.
  • Other markers of hemolysis also decreased with GBT440 treatment, including unconjugated bilirubin (median decrease of 31% and 43% with GBT440 at 500 mg and 700 mg, respectively, compared with an increase of 2% in placebo) and lactate dehydrogenase (LDH) (median decrease of 20% and 12% with GBT440 500 and 700 mg, respectively, compared with a decrease of 7% with placebo).
  • Median sickle cell counts decreased by 56% and 46% (500 mg and 700 mg, respectively) with GBT440 treatment as compared with a 14% increase with placebo. Consistent with previously reported experience, our emerging data showed high inter- and intra-patient variability in circulating sickle cell counts.
  • Inflammatory soluble adhesion molecules for the 700 mg dose cohort showed promising trends in improvement including P-Selectin (median decrease of 19% compared with increase of 20% in placebo) and ICAM-1 (median decrease of 6% compared with increase of 33% in placebo). Data for the 500 mg dose cohort has not yet been analyzed. A reduction in inflammation with GBT440 treatment is consistent with a reduction in red blood cell damage and downstream endothelial injury.
  • Pharmacokinetic data demonstrate linear and dose-proportional properties with a half-life amenable to once-daily dosing.
  • GBT440 was well tolerated over 28 days of dosing. No SCD patients discontinued GBT440. The most common adverse event was headache. There have been no serious adverse events that have been deemed to be drug-related. Decreases in erythropoietin and reticulocyte counts are consistent with improved oxygen delivery.

"While these data are still early, we are encouraged by the expanding clinical evidence demonstrating that GBT440 improves hemolytic anemia, reduces red blood cell damage, reduces inflammation, and improves oxygen delivery. These data further support our belief that GBT440 may be capable of modifying the progression of SCD," said Ted W. Love, M.D., chief executive officer of GBT. "We are committed to serving the sickle cell disease community and believe that GBT440 has the potential to become the first mechanism-based and disease-modifying therapeutic for this grievous disease." 

"In addition to completing Part A and B of this ongoing Phase 1/2 trial, we have extended the study with a Part C to explore the effect of GBT440 treatment over a 90 day dosing period," continued Dr. Love. "In 2016, we plan to share full results from this Phase 1/2 trial, begin a PK study in pediatric patients, and subject to agreement with regulatory authorities, initiate a pivotal trial in adult patients with SCD."

In addition to the oral presentation, a poster presentation of pharmacokinetic data titled, "GBT440 Demonstrates High Specificity for Red Blood Cells in Nonclinical Species" will be presented at ASH. These data demonstrate the potency and selectivity of GBT440 including a half-life suitable for once-daily dosing (abstract #2172).

Investor Event Webcast Details
On Monday, December 7 at 12:30 p.m. ET, members of GBT's management team and Dr. Claire Hemmaway, will review the GBT440 data. The presentation will be webcast live and will be available for replay from the Investors section of GBT's website at for 30 days.

About GBT440
GBT440 is being developed as an oral, once-daily therapy for patients with sickle cell disease. GBT440 works by increasing hemoglobin's affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, we believe 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.

About Sickle Cell Disease (SCD) 
Sickle cell disease (SCD) is an inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, leading to formation of abnormal hemoglobin known as sickle hemoglobin, or HbS. In its deoxygenated state, HbS has a propensity to polymerize, or bind together forming long, rigid rods within a red blood cell (RBC). The polymer rods deform RBCs to assume a sickled shape and to become inflexible, which can cause blockage in small blood vessels. Beginning in childhood, SCD patients suffer unpredictable and recurrent episodes or crises of severe pain due to blocked blood flow to organs, which often lead to psychosocial and physical disabilities. This blocked blood flow, combined with hemolytic anemia (the destruction of RBCs), can eventually lead to multi-organ damage and early death.

About Global Blood Therapeutics 
Global Blood Therapeutics, Inc. (GBT) 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 initial product candidate, GBT440, as an oral, once-daily therapy for sickle cell disease (SCD) and is currently evaluating GBT440 in both healthy subjects and SCD patients in a randomized, placebo-controlled, double-blind Phase 1/2 clinical trial. In addition to GBT440 for the treatment of SCD, GBT is engaged in research and development activities targeted toward hypoxemic pulmonary disorders, including idiopathic pulmonary fibrosis (IPF) and acute respiratory distress syndrome (ARDS), as well as hereditary angioedema (HAE). To learn more, please visit:

Forward-Looking Statements
Statements we make in this press release may include statements which are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act. We intend these forward-looking statements, including statements regarding the therapeutic potential of GBT440 and its ability to serve as a mechanism-based and disease-modifying treatment for SCD, 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 the data observed in our Phase 1/2 clinical trial to date may not be consistent with data generated in subsequent cohorts of patients at longer durations of exposure and that drug-related adverse events may be observed in later stages of the trial, along with those risks set forth in the prospectus for our initial public offering of common stock that was filed with the U.S. Securities and Exchange Commission (the "SEC") on August 12, 2015, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the SEC. 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: 
Joey Fleury (investors) 
[email protected]

Ryan Flinn (media) 
[email protected]