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Halozyme Identifies Plasma Biomarkers As Potential Predictors Of Survival In Pancreatic Cancer

On June 1, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported it will present data evaluating certain biomarkers as potential predictors of survival in patients with previously untreated metastatic pancreatic ductal adenocarcinoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which takes place June 1-5 in Chicago (Press release, Halozyme, JUN 1, 2018, View Source [SID1234527045]). In addition, Halozyme partner Janssen will present five posters of clinical studies involving subcutaneous daratumumab using Halozyme ENHANZE technology.

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"Our goal at Halozyme is to develop new therapies for cancer patients, while minimizing the burden and impact of treatment on their lives," said Helen Torley, president and chief executive officer. "The exploratory plasma biomarker data may support efforts to identify patients who benefit from our investigational drug, PEGPH20, through a simple blood draw rather than a needle biopsy.

"Our ENHANZE technology allows certain drugs to be given subcutaneously in a shorter, simpler injection than when the drug is delivered intravenously, thereby reducing the treatment burden for patients. We are delighted that Janssen will be presenting five posters on their exploration of a subcutaneous version of daratumumab that can be given in 5 minutes or less using our ENHANZE technology."

The Halozyme research of peptide biomarkers measured maturation and degradation of type III collagen, a key component of the extracellular matrix, using baseline plasma samples from patients in Halozyme’s HALO-202 Phase 2 clinical study of PEGPH20 (pegvorhyaluronidase alfa) in combination with ABRAXANE (nab-paclitaxel) and gemcitabine (PAG arm) as compared to ABRAXANE and gemcitabine only (AG arm).

Highlights from the Halozyme biomarker analysis include:

In the Discovery cohort (Stage 1), median progression-free survival (PFS) was 8.0 months in the PAG arm versus 5.3 months in the AG arm for patients whose biomarker scores were equal or above a specific cut-off value. The proportion of this patient population to all subjects tested in Stage 1 is 50 percent.
In the Validation cohort (Stage 2), patients whose biomarker scores were equal to or above the cut-off value derived from the Discovery cohort experienced a median PFS of 8.8 months in the PAG arm versus 3.4 in the AG arm, as well as overall survival of 13.8 months in the PAG arm versus 8.5 months in the AG arm. The proportion of this patient population to all subjects tested in Stage 2 is 47 percent.
PEGPH20 is a proprietary enzyme that targets and degrades hyaluronan (HA), a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in higher concentrations around many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of other therapies.

Janssen’s daratumumab
Janssen (Janssen Research & Development, LLC) presentations will highlight development of subcutaneous daratumumab using Halozyme ENHANZE technology. Results from the Phase 1b PAVO study of patients with relapsed or refractory multiple myeloma showed daratumumab co-formulated with ENHANZE enabled dosing in 3 to 5 minutes and was well tolerated with low infusion-related reactions.

Additional Updates and Presentations at ASCO (Free ASCO Whitepaper)
In an update on the HALO-101 Lung/Gastric Phase 1b study, Halozyme said that in light of the evolution in the standard of care in first-line non-small-cell lung cancer, it is closing enrollment in the lung cohort in the study. Investigators are being given the option to continue treatment of ongoing patients, and data will be submitted to medical forum later this year.

Halozyme’s ASCO (Free ASCO Whitepaper) abstracts include:

Extracellular matrix (ECM) circulating peptide biomarkers as potential predictors of survival in patients (pts) with untreated pancreatic ductal adenocarcinoma (mPDA) receiving pegvorhyaluronidase alfa (PEPGH20), nab-paclitaxel (A), and gemcitabine (G). Abstract 12030. Monday, June 4, 1:15 to 4:45 p.m. CT.

Tumor hyaluronan (HA) as a novel biomarker to taxane therapy in non-small cell lung cancer (NSCLC). Publication only.

A Pilot study of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma: Interim Safety and Efficacy Analysis. Publication only.

Pegvorhyaluronidase alfa (PEPGH20) enhances FOLFIRINOX efficacy in a preclinical model of human pancreatic ductal adenocarcinoma. Publication only.

Affinity histochemical evaluation of hyaluronan accumulation in solid malignancies of the digestive system. Publication only.

About PEGPH20
PEGPH20 (pegvorhyaluronidase alfa) is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan. PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies. In January, Halozyme announced the positive topline results as of December 2016 of its randomized phase 2 HALO-202 study of PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine chemotherapy in metastatic pancreatic cancer. In the study, PEGPH20 met key endpoints, including in the targeted HA-High patient population.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreas cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreas cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreas cancer.

GlycoMimetics to Present at Jefferies 2018 Global Healthcare Conference

On June 1, 2018 GlycoMimetics, Inc. (NASDAQ: GLYC) reported that Chief Executive Officer Rachel King will provide a company overview at the Jefferies Annual Health Care Conference in New York, on Thursday, June 7, 2018, at 11:30 a.m. ET (Press release, GlycoMimetics, JUN 1, 2018, View Source [SID1234527044]).

To access the live webcast and subsequent archived recordings for the presentation, please visit the GlycoMimetics website at www.glycomimetics.com.

Updated Results of Ongoing Multicenter Phase I Study of bb2121 anti-BCMA CAR T Cell Therapy Continue to Demonstrate Deep and Durable Responses in Patients with Late-Stage Relapsed/Refractory Multiple Myeloma at ASCO Annual Meeting

On June 1, 2018 Celgene Corporation (NASDAQ:CELG) and bluebird bio, Inc. (NASDAQ:BLUE) reported updated results from the ongoing CRB-401 phase I clinical study of bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 43 patients with late-stage relapsed/refractory multiple myeloma (Press release, bluebird bio, JUN 1, 2018, View Source [SID1234527043]). These data were the subject of an oral presentation by Noopur Raje, M.D. at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

"We are encouraged by the continuing deep and durable responses seen in this study and look forward to the results of our pivotal study, KarMMa, which is currently enrolling," said Jay Backstrom, Chief Medical Officer for Celgene. "We continue to see BCMA as an excellent target in multiple myeloma and we believe bb2121 has the potential to have a significant impact on the treatment approach and outcomes for these patients. We and our partners at bluebird bio are fully committed to the continued rapid clinical development of bb2121 and the evaluation of its potential in the treatment of patients with relapsed and refractory multiple myeloma."

"To see a median PFS of 11.8 months in this heavily pretreated patient population is very encouraging," said David Davidson, M.D., Chief Medical Officer, bluebird bio. "As the data from this program continue to mature, bb2121 has set a high bar as the leading investigational anti-BCMA CAR T cell candidate for relapsed and refractory multiple myeloma. In addition, the deep MRD-negative responses, the activity seen across myeloma with high and low levels of BCMA expression, as well as adverse events observed support the evaluation of bb2121 in earlier lines of multiple myeloma, where patients may experience more durable outcomes."

The open-label phase I CRB-401 study (NCT02658929) is evaluating the preliminary safety and efficacy of bb2121 anti-BCMA CAR T cell therapy in patients with relapsed/refractory multiple myeloma.

Patients in the study were heavily pre-treated, with a median of seven prior myeloma treatment regimens (min, max: 3,14) in the dose escalation cohort (n=21) and eight prior regimens (min, max: 3, 23) in the dose expansion cohort (n=22). More than 90% of patients had received prior treatment with two IMiD therapies, two proteasome inhibitors, daratumumab and an autologous stem cell transplant.

As of the March 29, 2018 data cut-off, 43 patients had been enrolled and dosed in either the dose-escalation cohort of the study, at four dose levels (50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells), or in the dose expansion cohort in a dose range between 150-450 x 106 CAR+ T cells.

Patients received a lymphodepleting conditioning regimen of fludarabine and cyclophosphamide, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using a proprietary lentiviral vector encoding the anti-BCMA CAR.

Responses were dose-related and observed for both low and high BCMA expression levels. In patients treated with 450 x 106 CAR+ T cells whose myeloma cells expressed low levels of BCMA (0 to 50% of cells BCMA positive), 8 of 8 had a response. In those expressing high BCMA (≥50% BCMA positive), 10 of 11 had a response.

The median progression-free survival (PFS) estimate for patients in the dose-escalation phase treated at active doses (≥150 x 106 CAR+ T cells) was 11.8 months (95% CI 8.8, NE), while patients receiving 50 x 106 CAR+ T cells had a median PFS of 2.7 months (95% CI 1.0, 2.9).

In the dose-escalation and expansion phase of the study, all patients who responded and were evaluable for minimal residual disease (MRD as measured by adaptive next-generation sequencing assay) (n=16) were MRD negative at one or more time points. Additionally, two patients who did not have a response and were evaluated for MRD were MRD positive at month one. The median PFS estimate in MRD negative responders was 17.7 months (95% CI: 5.8, NE).

Among all infused patients (n=43), 63% had cytokine release syndrome (CRS), mostly Grade 1 & 2, with 2 patients experiencing Grade 3 CRS (5%). Nine patients (21%) received tocilizumab, including 4 patients (9%) who also received steroids and the median duration of CRS was 6 days (1,32). For patients receiving 150 x 106 CAR+ T cells (n=18), the rate of CRS was 39% with no grade 3 cases. For patients receiving ≥150 x 106 CAR+ T cells (n=22), the rate of CRS was 82% with 9.1% of patients experiencing grade 3 events. Also among all infused patients, there were 14 patients (33%) who experienced neurotoxicity, with one patient experiencing a grade 3 or higher event. Other frequent Grade 3/4 AEs included cytopenias commonly associated with lymphodepleting chemotherapy such as neutropenia (79%), thrombocytopenia (51%) and anemia (44%), as well as infection (any grade) with a frequency of 61% overall and 23% in the first month. Grade 3 or higher infection occurred with a frequency of 21% overall and 5% in the first month.

"The continuing high, durable response rates and MRD-negative results in this heavily pre-treated population of multiple myeloma patients further illustrates BCMA as a promising target in this incurable disease and bb2121 as an investigational therapy of great potential in patients with relapsed and refractory multiple myeloma with both high and low BCMA expression," said Dr. Raje., Professor of Medicine at Harvard Medical School and Director of the Multiple Myeloma Center at Massachusetts General Hospital. "We will continue to evaluate the long-term effect of bb2121 as we learn more about the potential for this investigational therapy."

bb2121 is an investigational compound that is not approved for any use in any country. bb2121 received Breakthrough Therapy Designation from the U.S. FDA and PRIME eligibility from the EMA. Celgene has also sponsored an open-label, single-arm, pivotal, phase 2 study (KarMMa), which is recruiting in North America and Europe, to evaluate bb2121 further in patients with relapsed and refractory multiple myeloma (NCT03361748).

Clinical Data for Zymeworks’ Novel Bispecific Antibody, ZW25, Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting

On June 1, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the presentation of ZW25 clinical data by Funda Meric-Bernstam, MD, Principal Investigator for the ZW25 study at the University of Texas MD Anderson Cancer Center (Press release, Zymeworks, JUN 1, 2018, View Source [SID1234527042]). Data from the ongoing multi-center Phase 1 study showed single agent ZW25 induced anti-tumor activity and was well tolerated in heavily pretreated patients across a range of HER2-expressing cancers.

"Since the first patient treated, ZW25’s compelling single agent activity has consistently exceeded our expectations," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "The expanded body of data presented today supports our confidence that ZW25 is an active agent with the potential to become an approved cancer treatment."

ZW25 Clinical Results Presented Today

To date, a total of 50 patients have been enrolled in the study; data from 42 patients were available as of the data cut-off date of April 18, 2018 for ASCO (Free ASCO Whitepaper) and presented today. Durable cytotoxin-free single agent activity was observed in patients with heavily pretreated HER2-expressing cancers across a range of tumor types.

The best overall response observed with ZW25 as a single agent therapy in 33 response-evaluable patients (defined as having measurable disease and at least one tumor restaging or clinical progression) was 12 partial responses (36%), six stable disease (18%) and 15 progressive disease (45%). Overall, 68% (21/31) of all patients with measurable disease (at least one restaging scan) had a decrease in target lesions.

In 18 breast cancer patients, with a median of six prior systemic regimens, including trastuzumab, pertuzumab, T-DM1, and lapatinib in the majority of patients, the disease control rate (DCR, percentage of patients with either a partial response or stable disease) was 50%. In nine gastroesophageal cancer patients, with a median of four prior systemic regimens, including trastuzumab in all cases, the DCR was 56%, and in six other HER2-expressing cancer patients, including colorectal cancer, the DCR was 67%. Anti-tumor activity was assessed per RECIST every eight weeks.

"Our hope is to bring these promising new therapies to patients who have run out of treatment options," said Dr. Meric-Bernstam, Professor and Chair of the Department of Investigational Cancer Therapeutics, Medical Director of the Institute for Personalized Cancer Therapy at University of Texas MD Anderson Cancer Center. "To see this level of single agent activity without any concomitant chemotherapy in these advanced heavily pretreated patients is encouraging."

In the study, ZW25 was well tolerated at all dose levels and schedules and there were no dose-limiting toxicities observed at any dose (n=42). Treatment-related adverse events were primarily Grade 1 or 2, and no treatment-related serious adverse events or discontinuations were seen.

"Given ZW25’s anti-tumor activity and safety profile, we are excited to expand the number of clinical trials we have underway for this program," said Diana Hausman, MD, Zymeworks’ Chief Medical Officer. "We believe ZW25 could be used as monotherapy or readily combined with a number of approved anti-cancer treatments to further leverage its activity."

Clinical Development Plans

Based on the clinical data generated to date, Zymeworks plans to focus development of ZW25 in three areas:

First, as a single agent treatment for advanced HER2 high gastroesophageal cancer in patients who have received prior trastuzumab therapy, as well as in other HER2 high cancers, such as colorectal, where a HER2-targeted agent has not yet been approved;
Second, in combination with chemotherapeutics in earlier lines of therapy for HER2 high gastroesophageal and breast cancers; and
Third, in combination with other anti-cancer agents in patients with lower HER2-expressing cancers.
Zymeworks’ top priority is to focus on advanced gastroesophageal cancer. A potential Phase 2/3 study could begin as early as the second half of 2019 pending discussion with the US Food and Drug Administration (FDA). In addition, new studies to evaluate combinations beyond those ongoing in the current Phase 1 study are planned to start later this year.

About the Trial

Zymeworks’ adaptive Phase 1 study has three parts. Enrollment in the first portion of the study (the dose-escalation phase) has been completed. The recommended single agent dose was determined to be 20 mg/kg once every two weeks. In the second part of the study (the cohort expansion phase) now underway, additional patients are being enrolled to further assess ZW25’s single agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase), which is also underway, is evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

June 4, 2018 Webcast and Conference Call

Zymeworks will host a webcast and conference call on June 4th, at 8:30 a.m. ET (5:30 a.m. PT) to review the ZW25 clinical data presented at ASCO (Free ASCO Whitepaper) and discuss next steps.

Interested parties can access a live webcast of the presentation via a link from Zymeworks’ website at View Source A recorded replay will also be available on the website shortly after the call concludes.

The live call and Q&A may be accessed by dialing 1-800-319-4610 for North American callers, or 1-604-638-5340 for international callers. Callers should dial in five to 10 minutes prior to the scheduled start time and ask to join the "Zymeworks call".

About ZW25

ZW25 is being evaluated in a Phase 1 clinical trial in the United States and Canada. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function and has led to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Orphan Drug Designation to ZW25 for the treatment of both gastric and ovarian cancers.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving them the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering and degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug-resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life, and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity with the potential to significantly reduce drug development costs and timelines.

Fate Therapeutics to Present at the Jefferies 2018 Global Healthcare Conference

On June 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 Scott Wolchko, President and Chief Executive Officer, will present at the Jefferies 2018 Global Healthcare Conference in New York on Thursday, June 7, 2018 at 9:30 a.m. ET (Press release, Fate Therapeutics, JUN 1, 2018, View Source [SID1234527040]).

A live webcast of the presentation will be available through the investor relations section of the Company’s website at www.fatetherapeutics.com. Following the live webcast, an archived replay will be available on the Company’s website.