On November 1, 2018 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported that it has received Fast Track designation from the United States Food and Drug Administration (FDA) for CPI-0610 in treatment of myelofibrosis (MF) based on preliminary results from the Company’s Phase 2 study, MANIFEST (Press release, Constellation Pharmaceuticals, NOV 1, 2018, View Source [SID1234530508]).

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Constellation is developing CPI-0610 with the goal of providing a new treatment option for patients with MF who have progressed after treatment with Jakafi (ruxolitinib), the only approved therapy for MF. Enrollment is ongoing in the Phase 2 portion of the open-label Phase 1/2 MANIFEST clinical trial, which is exploring CPI-0610’s potential both as a monotherapy and as a combination therapy with Jakafi. As previously reported, preliminary data demonstrated clinical activity, such as spleen volume reduction, symptom improvement, increase in hemoglobin levels, and conversion to transfusion independent status in a patient who was transfusion dependent. Constellation recently expanded the MANIFEST study to include a third cohort, designed to evaluate CPI-0610 as a first-line therapy in combination with ruxolitinib in JAK 1/2-inhibitor-naïve MF patients.

"We believe there is an opportunity to improve the standard of care for MF patients with agents that modify the underlying disease," said Adrian Senderowicz, Senior Vice President and Chief Medical Officer of Constellation Pharmaceuticals. "This Fast Track designation highlights CPI-0610’s potential to address a significant unmet need. Based on promising early data and our progress with site initiation and patient enrollment, we continue to expect to determine proof of concept in mid-2019."

The FDA grants Fast Track designation to facilitate the development and expedite the review of drugs to treat serious or life-threatening diseases and fill unmet medical needs. A drug that receives Fast Track designation is

eligible for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval, more frequent written communication about the design of the proposed clinical trials and use of biomarkers, eligibility for accelerated approval and priority review, and rolling review.

About Myelofibrosis

MF is part of a collection of progressive blood cancers known as myeloproliferative neoplasms and is associated with significantly reduced quality of life and shortened survival. As the disease progresses, the bone marrow produces fewer red blood cells. Within one year of diagnosis, the incidence of thrombocytopenia (a condition characterized by low platelet counts in the blood) and severe anemia (a condition characterized by low red blood cell counts) and the need for red blood cell transfusion increase significantly. Among other complications, most patients with MF have enlarged spleens, as well as many other physical symptoms, including abdominal discomfort, bone pain, and extreme fatigue.

About CPI-0610

CPI-0610 is a potent and selective small molecule designed to promote anti-tumor activity by selectively inhibiting the function of BET proteins to decrease the expression of abnormally expressed genes in cancer. Constellation’s epigenetics platform includes a deep understanding of the biological contexts in which BET proteins operate, including cancer pathways that are highly sensitive to CPI-0610. The results from preclinical studies, as well as translational insights from the successful first-in-human study of CPI-0610, led to prioritizing the clinical development of CPI-0610 in myelofibrosis (MF). Enrollment is ongoing in the Phase 2 portion of the open-label Phase 1/2 MANIFEST clinical trial of CPI-0610, either as a monotherapy or in combination with ruxolitinib, in patients with MF who are refractory or intolerant or have relapsed or lost response to the standard of care. MANIFEST also includes a third cohort designed to evaluate treatment with CPI-0610 in combination with ruxolitinib as a first-line therapy in JAK 1/2-inhibitor-naïve MF patients. The company expects to determine proof of concept for CPI-0610 in MF in mid-2019.

On November 1, 2018 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported third quarter 2018 financial results and provided a corporate update (Press release, OncoMed, NOV 1, 2018, View Source [SID1234530524]). As of September 30, 2018, cash, cash equivalents, and short-term investments totaled $70.9 million.

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"As anticipated, our development efforts have culminated in a stream of data this year and set the stage for additional data flow in 2019," said John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed. "The efficacy of navicixizumab, both as a single agent and in combination with chemotherapy, has been impressive in patients with heavily pretreated, late stage recurrent ovarian cancer. We continue to enroll additional patients in our ongoing Phase 1b clinical trial as we consider the possible next steps for this program. Concurrently, clinical investigation and proof of concept continues for our other clinical candidates: etigilimab (anti-TIGIT) and GITRL-Fc in metastatic solid tumor settings."

Pipeline Highlights

Navicixizumab (anti-DLL4/VEGF bispecific; OMP-305B83)

In the third quarter, OncoMed reported publication of results from its Phase 1a study of single-agent navicixizumab in patients with refractory solid tumors in Investigational New Drugs. The results showed that 19 of the 66 patients with various types of refractory solid tumors had tumor shrinkage following treatment with navicixizumab. Notably, 3 of the 12 (25%) heavily pretreated ovarian cancer patients treated in the trial achieved a partial response with single-agent navicixizumab therapy.

In addition, the company announced interim results from its Phase 1b clinical trial of navicixizumab in combination with weekly paclitaxel in ovarian cancer patients who had received a median of four prior therapies. In addition, all patients had previously received paclitaxel and 69% had received bevacizumab. The results, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting, showed that 22 of the 26 patients (85%) treated with the novel regimen experienced clinical benefit. Notably 11 of the 26 patients (42%) achieved a partial response, the GCIG CA-125 response rate was 61% and the median progression-free survival was 5.4 months (95% CI: 3.5-8.0 months). Historical response rates for patients with heavily pretreated platinum-resistant ovarian cancer treated with chemotherapy are typically 15% or less.
Etigilimab (Anti-TIGIT monoclonal antibody; OMP-313M32)

Enrollment continues in the company’s Phase 1a/1b clinical trial of etigilimab. Specifically, the company is continuing to enroll patients with select tumor types in the single-agent expansion phase of the study and is also enrolling patients who have progressed on prior immunotherapy in the Phase 1b portion of the trial with these patients being treated with etigilimab plus anti-PD1 (nivolumab). Phase 1a data from the dose-escalation portion of the trial, designed to assess safety and tolerability of escalating doses of etigilimab monotherapy, will be reported at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting in a poster presentation on Friday and Saturday, November 9 and 10, 2018 and in a rapid oral presentation on Saturday, November 10, 2018 from 12:35-1:35 pm Eastern Time.
GITRL-Fc (OMP-336B11)

Enrollment continues in the Phase 1a single-agent study of its wholly-owned GITRL-Fc in patients with advanced or metastatic solid tumors. The company is pleased that enrollment in this trial has been robust to date. GITRL-Fc is a fusion protein with an Fc-linked fully human trimer ligand and is designed to activate the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) to enhance T-cell modulated immune responses. Data from the Phase 1a trial are expected to be presented in 2019.
Third Quarter 2018 Financial Results

Cash, cash equivalents and short-term investments totaled $70.9 million as of September 30, 2018, compared to $103.1 million as of December 31, 2017.

Revenues were $19.5 million for the third quarter of 2018, an increase of $14.4 million, compared to $5.1 million for the same period in 2017. The increase in revenue was due to the Company’s adoption of Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers effective January 1, 2018.

Research and development (R&D) expenses were $10.0 million for the third quarter of 2018, a decrease of $2.2 million, compared to $12.2 million for the same period in 2017. The decrease in R&D expenses was due to decreases in clinical development costs and a decrease in personnel cost, including stock-based compensation.

General and administrative (G&A) expenses were $3.7 million for the third quarter of 2018, a decrease of $0.2 million, compared to $3.9 million for the same period in 2017. The decrease in G&A expenses was primarily due to a decrease in personnel cost, including stock-based compensation.

Net income was $6.1 million ($0.16 net income per share, basic and diluted) for the third quarter of 2018, compared to a net loss of $10.7 million ($0.28 net loss per share, basic and diluted) for the same period of 2017. The net income in the third quarter of 2018 was primarily due to higher collaboration revenue as a result of the new revenue recognition accounting standard adopted on January 1, 2018 and lower operating expenses.

2018 Financial Guidance

With resource reprioritization and additional cash management measures, OncoMed’s current cash runway has been extended by one quarter and is now estimated to fund operations through at least the fourth quarter of 2019, without taking into account future potential milestone or opt-in payments from its partners. OncoMed estimates 2018 operating cash burn to be less than $55 million, before considering potential milestone or opt-in payments.

On November 1, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that three oral and four poster presentations detailing clinical and preclinical data will be featured at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The meeting will be held December 1-4, 2018 in San Diego, California (Press release, Fate Therapeutics, NOV 1, 2018, View Source [SID1234530540]).

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iPSC Product Platform

The Company’s iPSC product platform will be highlighted in two oral presentations and three poster presentations. An oral presentation will highlight new preclinical data of FT500, the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line. Using an in vitro three-dimensional tumor spheroid model, the Company demonstrated that FT500, in combination with activated T cells and an anti-PD1 antibody, led to near complete elimination of target cells (>99% reduction) as compared to FT500 or activated T cells alone. A second oral presentation will highlight in vitro proof-of-concept data demonstrating the anti-tumor activity of iPSC-derived, receptor-engineered NK cells in combination with tumor-specific engager molecules, such as a NKG2C/IL15/CD33 tri-specific killer engager. Additional off-the-shelf cell product candidates, including the Company’s first iPSC-derived chimeric antigen receptor (CAR) T-cell (FT819) and CAR NK cell (FT519) product candidates, will be featured in poster presentations.

FATE-NK100

An oral presentation will describe a next-generation, GMP-compliant protocol established by Dr. Karl-Johan Malmberg for production of adaptive memory NK cells having homogeneous expression of a single inhibitory killer cell immunoglobulin-like receptor (KIR). Notably, the NK cells also lack expression of the HLA-E binding inhibitory receptor NKG2A, which is a dominant NK cell immune checkpoint receptor. The approach, which was developed under the Company’s research collaboration with Oslo University Hospital, enables highly-specific, adaptive memory NK cells to be robustly expanded ex vivo for administration to KIR-mismatched patients to maximize anti-tumor potency.

ProTmune

The Company will present new clinical data from the Phase 1 PROTECT study of ProTmune, the Company’s next-generation hematopoietic cell graft for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT). Key clinical outcomes, including disease-free survival and freedom from chronic graft-versus-host disease (GvHD), cancer relapse, and death at one-year following HCT, from the seven subjects receiving ProTmune in the Phase 1 clinical trial will be featured in a poster presentation.

2018 ASH (Free ASH Whitepaper) Oral Presentations

FT500 iPSC-Derived NK Cell Cancer Immunotherapy
Title: iPSC-Derived NK Cells and Anti-PD1 Antibody Synergize to Enhance T-Cell Cytokine and Cytolytic Responses Against Multiple Tumors
Last Author: Jeffrey S. Miller, MD, Deputy Director of the Masonic Cancer Center, University of Minnesota
Publication Number: 730
Session: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Pre-clinical T and NK Cell Immunotherapies
Date and Time: Monday, December 3, 2018, 3:30 PM
Location: San Diego Convention Center, Room 8
iPSC Product Platform
Title: iPSC-Derived NK Cells Genetically Modified to Express NKG2C/DAP12 Mediate Potent Function When Targeted through an NKG2C/IL15/CD33 Tri-Specific Killer Engager (TriKE)
Last Author: Jeffrey S. Miller, MD, Deputy Director of the Masonic Cancer Center, University of Minnesota
Publication Number: 729
Session: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Pre-clinical T and NK Cell Immunotherapies
Date and Time: Monday, December 3, 2018, 3:15 PM
Location: San Diego Convention Center, Room 8
Adaptive Memory NK Cells
Title: Efficient Scale-up and Preclinical Evaluation of NKG2C+ Adaptive NK Cell Expansion for Therapy Against High-risk AML/MDS
Last Author: Karl-Johan Malmberg, MD, PhD, Group Leader, Department of Cancer Immunology, Oslo University Hospital
Publication Number: 195
Session: 711. Cell Collection and Processing II
Date and Time: Saturday, December 1, 2018, 2:30 PM
Location: Manchester Grand Hyatt San Diego, Grand Hall A
2018 ASH (Free ASH Whitepaper) Poster Presentations

FT819 iPSC-derived CAR T-Cell Cancer Immunotherapy
Title: Pluripotent Cell-Derived Off-the-Shelf TCR-Less CAR-Targeted Cytotoxic T Cell Therapeutic for the Allogeneic Treatment of B Cell Malignancies
Last Author: Bob Valamehr, PhD, Chief Development Officer, Fate Therapeutics
Publication Number: 4546
Session: 703. Adoptive Immunotherapy: Poster III
Date and Time: Monday, December 3, 2018, 6:00 PM – 8:00 PM
Location: San Diego Convention Center, Hall GH
FT519 iPSC-derived CAR NK Cell Cancer Immunotherapy
Title: Off-the-Shelf Natural Killer Cells with Multi-Functional Engineering Using a Novel Anti-CD19 Chimeric Antigen Receptor Combined with Stabilized CD16 and IL15 Expression to Enhance Directed Anti-Tumor Activity
Last Author: Dan S. Kaufman, MD, PhD, Director of Cell Therapy, UCSD
Publication Number: 4541
Session: 703. Adoptive Immunotherapy: Poster III
Date and Time: Monday, December 3, 2018, 6:00 PM – 8:00 PM
Location: San Diego Convention Center, Hall GH
FT538 iPSC-derived hnCD16, CD38-null NK Cell Cancer Immunotherapy
Title: CD38 Deficient, CD16 Engineered NK Cells Exhibit Enhanced Antibody Dependent Cellular Cytotoxicity without NK Cell Fratricide to Augment Anti-Myeloma Immunity in Combination with Daratumumab
Last Author: Jeffrey S. Miller, MD, Deputy Director of the Masonic Cancer Center, University of Minnesota
Publication Number: 3224
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster II
Date and Time: Sunday, December 2, 2018, 6:00 PM – 8:00 PM
Location: San Diego Convention Center, Hall GH
ProTmune
Title: ProTmune, a Next-Generation Graft for GvHD Prophylaxis in Allogeneic Hematopoietic Cell Transplantation: 1-Year Safety and Efficacy Phase 1 Data
First Author: Richard Maziarz, MD, Principal Investigator, Oregon Health Sciences University
Session: 732. Clinical Allogeneic Transplantation: Results
Publication Number: 2167
Date and Time: Saturday, December 1, 2018, 6:15 PM – 8:15 PM
Location: San Diego Convention Center, Hall GH
About ProTmune
ProTmune is an investigational next-generation hematopoietic cell graft for the prevention of acute graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT). ProTmune is manufactured by pharmacologically modulating a donor-sourced, mobilized peripheral blood graft ex vivo with two small molecules (FT1050 and FT4145) to decrease the incidence and severity of acute GvHD while maintaining the anti-leukemia activity of the graft. ProTmune has been granted Orphan Drug and Fast Track Designations by the U.S. Food and Drug Administration, and Orphan Medicinal Product Designation by the European Commission. ProTmune is currently being investigated in a randomized, controlled and double-blinded Phase 2 clinical trial in adult subjects with hematologic malignancies undergoing matched unrelated donor HCT.

About FATE-NK100
FATE-NK100 is an investigational, first-in-class, allogeneic donor-derived natural killer (NK) cell cancer immunotherapy comprised of adaptive memory NK cells, a highly specialized and functionally distinct subset of activated NK cells expressing the maturation marker CD57. Higher frequencies of CD57+ NK cells in the peripheral blood or tumor microenvironment in cancer patients have been linked to better clinical outcomes. In August 2017, non-clinical data describing the unique properties and anti-tumor activity of FATE-NK100 were published by Cancer Research (doi:10.1158/0008-5472.CAN-17-0799), a peer-reviewed journal of the American Association of Cancer Research. Three clinical trials of FATE-NK100 are currently being conducted: VOYAGE for the treatment of refractory or relapsed acute myelogenous leukemia; APOLLO for the treatment of recurrent ovarian cancer; and DIMENSION for the treatment of advanced solid tumors, including in combination with monoclonal antibody therapy.

On November 1, 2018 Alliance for Cancer Gene Therapy (ACGT), the nation’s only public charity exclusively funding cancer cell and gene therapy research, reported that Kevin Honeycutt will be joining ACGT as its new CEO and President, effective December 3, 2018 (Press release, Alliance Pharma, NOV 1, 2018, View Source [SID1234530649]). Mr. Honeycutt was most recently the President and CEO of the Avon Breast Cancer Crusade (ABCC) since 2015. At ACGT, his principal role will be to enhance the vision of ACGT, begun in 2001 by its co-founders, Barbara Netter and her late husband Edward, to spearhead ACGT’s current focus on funding the next generation of challenges brought by metastatic cancers and solid tumors, and to continue to build our alliances and joint ventures.

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Mrs. Netter stated that, "We are delighted to have Kevin as ACGT’s new CEO and President at this momentous time in the field of cancer cell and gene therapy. His experience at ABCC, in which he led several highly successful fundraising campaigns, positions him to hit the ground running to oversee ACGT‘s fundraising and grants program. Kevin brings a depth of knowledge and experience in the oncology space and strategic thinking which perfectly fits within the ACGT model."

Mr. Honeycutt said that, "ACGT’s outstanding Board of Directors and pre-eminent Scientific Advisory Council, together with the leadership of Barbara Netter, the ACGT staff, and ACGT’s current and past grant recipients, were key to my enthusiasm in joining ACGT. Given the remarkable advances being made in the field of cancer cell and gene therapy, it is an opportune time to be working in cancer research with significant opportunities to advance the understanding of how to treat the disease and give patients the best chances for successful long-term favorable outcomes."

Prior to his years at ABCC, Mr. Honeycutt served as Executive Director of the Avon Foundation for Women for five years, and in cause marketing. He previously led projects for, among others, the American Diabetes Association, DaVita, Inc. / The Kidney Trust, the Entertainment Industry Foundation and the Jane Goodall Institute

On November 1, 2018 West Pharmaceutical Services, Inc. (NYSE: WST), a global leader in innovative solutions for injectable drug administration, reported that its Management Team will present an overview of the Company’s business at two investor conferences in November (Press release, West Pharmaceutical Services, NOV 1, 2018, View Source [SID1234530467]). Management will present at the Stephens Investment Conference in New York, New York on Wednesday, November 7, 2018, and the Jefferies 2018 London Healthcare Conference in London, United Kingdom on Thursday, November 15, 2018.

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