With the big ASH meeting ongoing, we have more biotech stocks to watch for big news in the week ahead. I’m feeling better about risk-on biotech stocks with the Federal Reserve suggesting that it’s prepared to slow down rate hikes as we are just below the neutral policy rate and the U.S. and China has agreed to a 90 day ceasefire in the trade war. Still, we have to be cautious with the Russell 2000 sell-side volume outpacing buy-side volume going into next week.
Global Blood Therapeutics (GBT) GBT440 – HOPE for sickle cell disease in adults. Phase 3 Part A data released June 27, 2018. Primary endpoint met. Further data due at ASH December 3, 2018.
Global Blood Therapeutics (GBT) announced that four abstracts related to its sickle cell disease (SCD) development programs, including voxelotor, have been accepted for oral and poster presentation during the 60th American Society of Hematology (ASH) Annual Meeting & Exposition, taking place December 1-4, at the San Diego Convention Center.
“Our data presentations at ASH 2018, which include a meta-analysis of published literature showing that chronic anemia increases the risk for serious negative clinical outcomes like stroke, kidney failure and premature death in SCD patients, support that raising hemoglobin is meaningful, even at increases below 1 g/dL. These findings further strengthen the scientific rationale that a drug like voxelotor, that safely raises hemoglobin and improves tissue oxygenation, has the potential to be a disease-modifying treatment to reduce the morbidity and mortality of SCD,” said Ted W. Love, M.D., president and chief executive officer of GBT. “We look forward to presenting new longer-term exposure and safety data from Part A of our pivotal Phase 3 HOPE Study and data from the 1500 mg cohort of the HOPE-KIDS 1 Study as we continue to advance the clinical development of voxelotor with the goal of bringing it to children, adolescents and adults with this severe and debilitating disease.”
The voxelotor results that will be presented at the meeting will include longer-term exposure and safety data not available at the time the abstracts were submitted to the Congress, and, as such, remain under embargo until the time of presentation.
The systematic literature review and meta-analysis identified and evaluated data from approximately 140 SCD studies published in peer-reviewed journals over the past 20 years. This comprehensive evaluation showed a significant relationship between chronic anemia and negative clinical outcomes in SCD patients. Specifically, low hemoglobin levels increased the risk for:
Stroke, silent cerebral infarct and increased transcranial doppler-measured cerebral artery velocity (based on 10 studies of 3,397 patients);
Kidney disease as determined by the presence of microalbuminuria (based on eight studies of 1,579 pediatric patients);
Elevated estimated pulmonary artery systolic pressure (based on 12 studies of 1,465 patients); and
Premature death (based on six studies of 3,196 patients).
The meta-analysis found that hemoglobin was significantly lower by approximately 0.4 to 1 g/dL among patients experiencing negative outcomes. Further modeling of these data predicted that an increase in hemoglobin of 1 g/dL or greater might reduce the risk of stroke by 41 percent and of mortality by 64 percent.
Monday, December 3
Oral Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical
Abstract #118508: Results from Part A of the Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization (HOPE) Trial (GBT440-031), a Placebo-Controlled Randomized Study Evaluating Voxelotor (GBT440) in Adults and Adolescents with Sickle Cell Disease
Presenter: Elliott Vichinsky, M.D., Director of Hematology/Oncology, UCSF Benioff Children’s Hospital, Oakland, Calif.
Time: 7:00 a.m. PT
Location: Room 28D
Oral Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical
Abstract #117510: Efficacy and Safety of 1500mg Voxelotor in a Phase 2a Study (GBT440-007) in Adolescents with Sickle Cell Disease
Presenter: Clark Brown, M.D., Ph.D., Clinical Director, Children’s Healthcare of Atlanta
Time: 8:00 a.m. PT
Location: Room 28D
Poster Session: 901. Health Services Research—Non-Malignant Conditions
Abstract #119420: Societal Costs of Sickle Cell Disease in the United States
Presenter: Kartik Pappu, Ph.D., Associate Director, Commercial Planning, GBT, South San Francisco, Calif.
Time: 6:00-8:00 p.m. PT
Location: Hall GH
Investor Webcast Details
GBT will host an investor event webcast on Monday, December 3, 2018, at 12:00 p.m. PT/3:00 p.m. ET to review the data being presented at the 2018 ASH Annual Meeting. The event will be webcast live and available for replay from GBT’s website at www.gbt.com in the Investors section.
Sickle Cell Disease (SCD) is a lifelong inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin, which leads to the formation of abnormal hemoglobin known as sickle hemoglobin (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 causes hemolytic anemia (the destruction of RBCs) that can lead to multi-organ damage and early death. This sickling process also causes blockage in capillaries and small blood vessels. Beginning in childhood, SCD patients typically 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.
Institutional transactions reveal institutional ownership is up 19.69% over the previous 3 month period.
The long lower shadow candlestick that formed on Friday, November 30, 2018, could signal that a low in the stock is near; however, the CMF looks horrible as sell-side volume continues to outpace buy-side volume. I would stay out of GBT stock at this time.
MacroGenics (MGNX) Flotetuzumab for AML/MDS. Phase 1 interim data to be released at ASH December 3, 2018.
MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today provided an update on its corporate progress and reported financial results for the quarter ended September 30, 2018.
“During the third quarter, MacroGenics made tremendous progress in advancing its portfolio of immuno-oncology product candidates towards multiple near-term data read-outs,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “Given the Company’s substantial pipeline progress over the past several months, we believe that the next twelve months are poised to be transformative for MacroGenics, during which we expect to continue to advance our core mission of developing breakthrough biologics that may become life-changing medicines for patients.”
Key Pipeline Updates
Margetuximab. Recent highlights related to the Company’s Fc-optimized monoclonal antibody (mAb) that targets the human epidermal growth factor receptor 2, or HER2, include:
Fully Enrolled Phase 3 Metastatic Breast Cancer Study. The Company has completed enrollment of 530 relapsed/refractory HER2-positive metastatic breast cancer patients in its pivotal SOPHIA study. MacroGenics anticipates disclosure of topline PFS data in the first quarter of 2019. In anticipation of a potential future product launch, MacroGenics is progressing its U.S. commercial planning and actively exploring ex-U.S. development and commercialization partnership opportunities.
Phase 2 Gastric Cancer Study Demonstrated Antitumor Activity. At the 2018 European Society of Medical Oncology (ESMO) Congress in October, MacroGenics presented updated interim clinical data from a Phase 2 study of margetuximab plus an anti-PD-1 agent in patients with HER2-positive gastroesophageal adenocarcinoma. This chemotherapy-free combination, designed to coordinately engage innate and adaptive immunity, demonstrated antitumor activity in patients with advanced gastric cancer. The Company recently completed enrollment of 25 additional gastric cancer patients and expects to present data from this ongoing portion of the study in the first quarter of 2019.
PD-1 Franchise. MacroGenics is advancing multiple PD-1-directed programs to provide further differentiation from existing PD-1-based treatment options and enable a broad set of combination opportunities across the Company’s portfolio. Recent program highlights include:
MGA012 Achieves Development Milestones. This anti-PD-1 mAb, also known as INCMGA0012, was licensed to Incyte Corporation in 2017 under a global collaboration and license agreement. MacroGenics retains the rights to develop MGA012 in combination with its pipeline assets.
MGA012 met certain clinical proof-of-concept criteria, triggering a total of $15 million in milestones from Incyte, $10 million of which has been recognized in the third quarter and $5 million of which is expected to be recognized in the fourth quarter. Incyte plans to present updated data from the cohort expansion portion of the Phase 1 study of MGA012 in a poster session at the upcoming Society for Immunotherapy for Cancer (SITC) Annual Meeting. Incyte has announced its intention to pursue monotherapy development of MGA012 in MSI-high endometrial cancer, Merkel cell carcinoma and anal cancer through registration-directed studies with initial data anticipated in 2020. In addition, across both Incyte and MacroGenics, multiple studies have been initiated which will feature various combination regimens with MGA012.
MGD013 Dose Expansion Initiated. This first-in-class DART® molecule provides co-blockade of two immune checkpoint molecules expressed on T cells, PD-1 and LAG-3, for the potential treatment of a range of solid tumors and hematological malignancies. MacroGenics recently established the dose and schedule for MGD013 administration and has initiated dose expansion in up to nine tumor types in a Phase 1 study.
MGD019 IND Cleared. This DART molecule is designed to provide co-blockade of both PD-1 and CTLA-4, two immune checkpoint inhibitors, on T cells. MacroGenics’ Investigational New Drug (IND) application for MGD019 was cleared by the FDA and the Company is currently engaged in Phase 1 study startup.
B7-H3 Franchise. MacroGenics is developing a portfolio of therapeutics that target B7-H3, a member of the B7 family of molecules involved in immune regulation. The Company is advancing multiple programs that target B7-H3 through complementary mechanisms of action that take advantage of this antigen’s broad expression across multiple solid tumor types. Recent program highlights include:
Enoblituzumab Oral Presentation at SITC: Clinical data from MacroGenics’ study of this Fc-optimized mAb that targets B7-H3 combined with an anti-PD-1 mAb was selected for oral presentation at the upcoming SITC Annual Meeting. Like the combination of margetuximab and anti-PD-1, enoblituzumab and anti-PD-1 is designed to leverage Fc-optimization and checkpoint blockade to coordinately engage innate and adaptive immunity, the two major components of the immune response. As an update of the recently released abstract, the combination of enoblituzumab and anti-PD-1 demonstrated antitumor activity in checkpoint inhibitor-naïve patients who had squamous cell carcinoma of the head and neck (SCCHN) and in checkpoint inhibitor-naïve patients with non-small cell lung cancer (NSCLC) with tumor PD-L1 expression of <1%. In these two cohorts, objective responses occurred in 6/18 (33%) response-evaluable SCCHN patients and in 5/14 (36%) response-evaluable NSCLC patients. Additional details will be provided at SITC.
Orlotamab Studies Ongoing: This DART molecule targeting B7-H3 and CD3 is being evaluated in a Phase 1 monotherapy study in multiple tumor types. In addition, a combination study of orlotamab and MGA012 is ongoing.
MGC018 Phase 1 Startup Initiated: MacroGenics’ IND submission for this anti-B7-H3 antibody-drug conjugate (ADC) was cleared by the FDA and the Company is initiating a Phase 1 study. This first-in-man study is designed to study MGC018 both as monotherapy and in combination with MGA012 in patients with solid tumors.
Flotetuzumab. Recent highlights of the Company’s bispecific, humanized DART molecule that recognizes both CD123 and CD3, include:
Oral Presentations at ASH. MacroGenics plans to present both updated clinical data as well as gene signature data from its completed acute myeloid leukemia (AML) dose expansion cohort in two oral presentations at the American Society of Hematology (ASH) Annual Meeting next month. The Company’s collaborator, Servier, has development and commercialization rights outside North America, Japan, Korea and India for flotetuzumab, also known as S80880.
Combination Study with MGA012 Planned. MacroGenics has previously presented data supporting the rationale for using checkpoint blockade as an approach to potentially enhance the anti-leukemic activity of flotetuzumab and plans to commence a combination study with MGA012.
There’s a big rectangle consolidation pattern but volume looks bad. Sell-side volume continues to outpace buy-side volume. The negative CMF suggests this biotech stock could continue to chop out sideways next week. I do not recommend taking a long position in MGNX stock at this time.
Below are more upcoming biotech stock events over the next week. I do not hold any position in the biotech stocks mentioned above.
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