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BioLineRx Provides Update on Phase 2 Open-Label Study for
BL-8040 as Novel Stem Cell Mobilization Treatment

On March 20, 2017 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported partial results data from its open-label Phase 2 trial for BL-8040 as a novel monotherapy approach for the mobilization and collection of blood forming stem and progenitor cells from the peripheral blood (Press release, BioLineRx, MAR 20, 2017, View Source [SID1234518185]).

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The study consists of donor and patient pairs for allogeneic hematopoietic cell transplantation. The first part of the study, which is nearing completion, is intended to enroll an initial cohort of 10 donor and recipient pairs, consisting of patients with advanced hematological malignancies and their HLA-matched sibling donors. Interim results show that a single injection of BL-8040 mobilized sufficient amounts of cells required for transplantation at a level of efficacy similar to that achieved by using 4-6 injections of G-CSF, the current standard of care. Furthermore, all recipients transplanted so far have experienced a successful neutrophil engraftment. The recipients will be followed for one year to assess acute and chronic GVHD events. As for the donors, BL-8040 treatment was safe and well tolerated.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, "We are very encouraged by these initial results of the Phase 2 clinical trial for assessing BL-8040, our lead oncology and hematology platform, as a single agent for hematopoietic stem cell mobilization for allogeneic transplantation. Hematopoietic stem cells are increasingly used as part of the treatment regimen for certain types of hematological cancers, as well as for severe anemia and immune deficiency disorders. These results, supporting BL-8040 as a one-day dosing and up-to-two-day collection regimen, for rapid mobilization of substantial amounts of stem cells, represent a significant improvement over the current standard of care, which requires four-to-six daily injections of G-CSF and one-to-four apheresis sessions. If there are no safety concerns regarding graft failure or rejection after the interim safety review of donor-recipient pairs participating in Part 1 of the study, we will continue with Part 2 of the study, which will permit enrollment of recipients with either matched sibling or haploidentical donors, up to a total enrollment in the study of 24 donor-recipient pairs. We are looking forward to the topline results expected by the end of 2017."

"We continue our efforts to maximize the potential of our unique BL-8040 oncology platform, with multiple clinical studies for additional indications up and running or expected to start in 2017, including several combination studies with immune checkpoint inhibitors and a registration study in stem-cell mobilization for autologous transplantation," added Mr. Serlin.

The Phase 2 open-label study is conducted in collaboration with the Washington University School of Medicine, Division of Oncology, and will enroll up to 24 donor/recipient pairs, aged 18-70. The trial is designed to evaluate the ability of BL-8040, as a single agent, to promote stem cell mobilization for allogeneic hematopoietic cell transplantation. On the donor side, the primary endpoint of the study is the ability of a single injection of BL-8040 to mobilize sufficient amounts of cells for transplantation following up to two apheresis procedures. On the recipient side, the study aims to evaluate the time to engraftment rate following transplantation of the BL-8040 collected graft.

The study will also evaluate the safety and tolerability of BL-8040 in healthy donors, as well as graft durability, the incidence of grade 2-4 acute and chronic GVHD, and other recipient related parameters in patients who have undergone transplantation of hematopoietic cells mobilized with BL-8040.

About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Stem Cell Mobilization
High-dose chemotherapy followed by hematopoietic cell transplantation has become an established treatment modality for a variety of hematologic malignancies, including multiple myeloma, as well as various forms of lymphoma and leukemia. Modern peripheral stem-cell harvesting often replaces the use of traditional surgical bone marrow stem-cell harvesting. In the modern method, stem cells are mobilized from the bone marrow using granulocyte colony-stimulating factor (G-CSF), often with the addition of a mobilizing agent such as Plerixafor (Mozobil), harvested from the donor’s peripheral blood by apheresis, and infused to the patient after chemotherapy ablation treatment.

An allogeneic hematopoietic cell transplant involves matching a patient’s tissue type, specifically their human leukocyte antigen (HLA) tissue type, with that of a related or unrelated donor. HLA proteins are found on all cells of our body and are the main way the immune system tells the difference between our own cells and foreign cells. The closer the HLA match between a donor and recipient, the greater the chance a transplant will be successful. If the HLA match is not close enough, the donor’s immune system, which accompanies the donated stem cells, recognizes the HLA mismatch, and will attack the recipient’s tissues. This process is known as graft versus host disease (GVHD).

Approximately 70% of people with a hematological malignancy or bone marrow failure syndrome who need an allogeneic transplant have an HLA-identical sibling or unrelated donor available. For patients who need a stem cell transplant but do not have an HLA-matched related or unrelated donor, recent medical advances have made possible the use of a partially matched or haploidentical related donor. A haploidentical related donor is usually a 50% match to the recipient and may be the recipient’s parent, sibling or child.

The advantage of having a haploidentical transplant is that it increases the chance of finding a donor as almost everyone has at least one haploidentical relative. Relatives can usually be asked to donate stem cells much more quickly than unrelated volunteer donors, particularly when the volunteer donors live in other countries, thereby allowing transplants to be done in a more timely manner.

With improvements in medical treatment, complications of a haploidentical transplant, such as GVHD, rejection of the graft and slow recovery of the immune system appear not to be increased compared to transplants using HLA-matched related or unrelated donors. Since this is a relatively new approach to stem cell transplantation, a haploidentical transplant is a treatment option that is not offered at all treatment centers, but is becoming more common.

Cerulean Pharma and Daré Bioscience Enter into Stock Purchase Agreement

On March 20, 2017 Cerulean Pharma Inc. (NASDAQ:CERU) and Daré Bioscience, Inc., a privately-held, clinical-stage pharmaceutical company advancing products for women’s reproductive health, reported that the two companies, together with the equityholders of Daré Bioscience, have entered into a definitive stock purchase agreement under which the equityholders of Daré Bioscience will become the majority owners of Cerulean (Press release, Cerulean Pharma, MAR 20, 2017, View Source [SID1234525204]).

The transaction and the Cerulean asset sales mentioned below would result in a NASDAQ-listed company with a focus on the development and commercialization of products for women’s reproductive health. Daré Bioscience’s product candidate, Ovaprene, is a clinical stage, non-hormonal contraceptive ring for monthly use that potentially addresses a significant unmet need. Contraception is a $16 billion global market. However, since the approval of the birth control pill by the FDA in 1960, most innovation has focused on hormones. Daré Bioscience’s product candidate, Ovaprene, is a non-hormonal option that is intended to be easy to use and provide protection over multiple weeks. To the knowledge of Daré’s management, no comparable product currently is being marketed. The combined company will operate under the name Daré Bioscience, and its Chief Executive Officer will be Sabrina Martucci Johnson, current Chief Executive Officer of Daré Bioscience. The transaction is subject to approval by stockholders of Cerulean.

"We are thrilled to have the opportunity to grow our business as a public company," said Ms. Johnson. "Women’s reproductive health encompasses a broad spectrum of categories, many of which have unmet needs. Daré is committed to developing a portfolio that expands options, improves outcomes, and enhances safety for women."

Cerulean also announced today that it has entered into two agreements for the sale of assets, the proceeds of which will be used to help fund the combined company’s operations. Cerulean sold its clinical product candidates, CRLX101 and CRLX301, for $1.5 million to BlueLink Pharmaceuticals, a subsidiary of NewLink Genetics Corporation, a biopharmaceutical company engaged in the discovery, development and commercialization of novel immuno-oncology product candidates to improve the lives of patients with cancer. Cerulean also entered into an agreement with Novartis, an existing collaborator with the Company, pursuant to which Novartis will acquire all rights to Cerulean’s Dynamic Tumor Targeting Platform for $6 million. The closing of the sale to Novartis is subject to approval of the sale by holders of at least a majority of the outstanding shares of Cerulean’s common stock and satisfaction of other closing conditions.

Cerulean also announced that, in connection with these transactions, it is paying off its debt facility with Hercules Capital, Inc.

"Cerulean conducted an extensive review of strategic alternatives with the goal of maximizing value for our stockholders," said Christopher D. T. Guiffre, President & Chief Executive Officer of Cerulean. "We believe the Daré transaction, in conjunction with the asset sales, achieves this goal and provides Cerulean stockholders with an exciting opportunity in women’s health under an experienced leadership team. Based on Daré’s current projections, with proceeds from the sale of Cerulean’s assets, we believe the combined company will be well funded to advance Ovaprene through the completion of a postcoital proof of concept study that is expected to be a value inflection point and is expected to commence following closing of this transaction."

Cerulean also announced that it is reducing its workforce by 11 people, or approximately 58%, to a total of eight full-time equivalent employees, under a plan expected to be completed during the second quarter of 2017. Affected employees are being offered transition benefits.

Stock Purchase Agreement Details

Under the terms of the stock purchase agreement, the stockholders of Daré Bioscience will receive shares of newly issued Cerulean common stock, while outstanding Daré Bioscience options and convertible securities will be assumed by Cerulean. Following the issuance of the shares, depending on the relative net cash positions of Cerulean and Daré Bioscience at the time of closing, it is expected that existing Cerulean stockholders will own between 30% and 49% of the combined company, and existing Daré Bioscience stockholders will own between 51% and 70% of the combined company. The transaction has been unanimously approved by the boards of directors of both companies. The transaction is expected to close during the second quarter of 2017, subject to customary closing conditions, including approval by stockholders of Cerulean.

Aquilo Partners, L.P. advised Cerulean. Wilmer Cutler Pickering Hale and Dorr LLP served as legal counsel to Cerulean, and Mintz, Levin, Cohn, Ferris, Glovsky and Popeo PC served as legal counsel to Daré Bioscience.

Management and Organization

Upon the close of the proposed transaction, the board of directors of the combined company will consist of five members, three to be designated by Daré and two to be designated by Cerulean. Officers of the combined company will include Sabrina Martucci Johnson, Chief Executive Officer, and Lisa Walters-Hoffert, Chief Financial Officer.

ERYTECH PRESENTS NEW PRECLINICAL ANTI-TUMOR DATA ON ERYMETHIONASE AT AACR 2017

On March 20, 2017 ERYTECH Pharma (Paris:ERYP) (ADR:EYRYY), a French clinical-stage biopharmaceutical company developing innovative therapies for rare forms of cancer and orphan diseases based on its proprietary ERYCAPS platform, encapsulating therapeutic drug substances inside red blood cells, reported the presentation of new anti-tumor data supporting the Company’s preclinical product erymethionase (ERY-MET) at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 1 – 5, 2017 in Washington, D.C (Press release, ERYtech Pharma, MAR 20, 2017, View Source [SID1234518224]).

Results from the preclinical study demonstrate that erymethionase, methionine gamma-lyase (MGL)-encapsulated in red blood cells using ERYTECH’s proprietary encapsulation platform technology, represents a promising new treatment approach against a broad range of cancers that rely on methionine metabolism. The research will be presented by Dr. Vanessa Bourgeaux, Program Leader at ERYTECH, during a poster session at the conference.

Dr. Bourgeaux stated, "Methionine dependence has emerged as a unique target for anti-cancer activity during the last two decades. While methionine gamma-lyase is a promising strategy for these cancers, its very short half-life in the body prohibited all attempts to develop MGL as cancer therapy. However, our work here shows that when encapsulated in red blood cells using our ERYCAPS technology, MGL is protected from degradation and overcomes the pharmacokinetic limitations resulting in increased half-life in vivo for effective potential use in a broad-range of methionine-dependent cancers."

Gil Beyen, Chairman and CEO of ERYTECH, added, "Erymethionase represents a novel product candidate in our tumor starvation arsenal. ERYTECH is progressively building its cancer metabolism platform with this second product candidate to complement eryaspase (GRASPA), ERYTECH’s lead product candidate. The posters presented at two immunotherapy medical meetings earlier this month and now promising data with erymethionase at AACR (Free AACR Whitepaper) underscore ERYTECH’s intention to develop the scope of products and applications for its technology platform."

Methionine is an essential amino acid, which is necessary for all cells to grow and multiply. More specifically, fast-growing tumor cells exhibit very high requirements of methionine to proliferate. The enzyme methionine gamma-lyase (MGL) mediates tumor starvation via systemic lowering of methionine levels. MGL is an enzyme with a short half-life and is dependent on a co-factor, a Vitamin B6 derivative which is naturally present in red blood cells, to demonstrate enzymatic activity. The preclinical studies in mouse models of erymethionase aimed to investigate the protection of MGL against degradation and immune reactions through encapsulation in erythrocytes (red blood cells).

ERYTECH researchers demonstrated that encapsulation of MGL in red blood cells both strongly improved the half-life of the enzyme and provided active co-factor to increase MGL activity and therefore, tumor starvation. The half-life of MGL increased from less than 24 hours when free to more than 10 days when encapsulated in red blood cells, with no toxicity reported. The preclinical study showed that combining a single weekly intravenous injection of erymethionase with daily pyridoxine (PN) supplementation led to a sustained methionine depletion in the plasma, and an inhibition of tumor growth for 45 days following the fifth erymethionase dose of 85% in the glioblastoma mouse model, and of 72% in the gastric cancer mouse model. Repeated injections of ERY-MET were also effective against established tumors in the gastric cancer model leading to a complete tumor regression.

Full details of the AACR (Free AACR Whitepaper) presentation follow:

Abstract # 2134 / Poster # 3: Use of methionine gamma-lyase-loaded erythrocytes to induce effective methionine depletion of cancer therapy
Presenter: Dr. Vanessa Bourgeaux
Poster Session/Section: PO.ET01.09 – New Targets 2/Section 6
Date: Monday, April 3
Time: 1:00 – 5:00 p.m. EDT
Location: Convention Center, Halls A-C

Blueprint Medicines Announces Enrollment of First Patient in Phase 1 Clinical Trial for BLU-667

On March 20, 2017 Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported that it has dosed the first patient in a Phase 1 clinical trial of BLU-667, an investigational RET inhibitor for patients with non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other advanced solid tumors that harbor a RET alteration (Press release, Blueprint Medicines, MAR 20, 2017, View Source [SID1234518223]).

"By rapidly initiating a clinical trial for our potent and selective RET inhibitor BLU-667, we have successfully achieved a key 2017 milestone," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "This continued progress underscores our commitment to build Blueprint Medicines into a sustainable company. BLU-667 has a unique product profile differentiated from our other clinical-stage programs by its potential to address predicted resistance mutations that may arise. With BLU-667 enrollment underway, we are further increasing our diversified pipeline of potent, highly selective investigational medicines that target specific disease drivers in genomically-defined patient populations."

"RET fusions and mutations are recognized as important drivers in multiple cancers, but existing multi-kinase inhibitors with RET activity do not provide sufficient, durable benefit for patients with RET alterations," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "BLU-667 is being developed to potently inhibit RET, and simultaneously prevent the development of on-target resistance, which we believe will provide more lasting clinical benefit and prevent or delay disease recurrence. We look forward to working with patients and physicians to explore BLU-667’s potential."

BLU-667 is an orally available, potent and selective inhibitor designed to target RET mutations, fusions and predicted resistance mutants. RET activating fusions and mutations are a key disease driver in multiple cancers, including NSCLC and MTC, with RET fusions implicated in approximately 1-2% of patients with NSCLC, and RET mutations implicated in approximately 60% of patients with MTC. In addition, genomic analyses published by scientists at Blueprint Medicines have identified RET fusions at low frequencies in colon and breast cancer. Currently, there are no approved therapies that selectively target RET-driven cancers, though there are several approved multi-kinase inhibitors with RET activity being evaluated in clinical trials. Thus far, clinical activity attributable to RET inhibition has been uncertain for these inhibitors, likely due to insufficient inhibition of RET and off-target toxicities. In preclinical studies using biochemical and cellular assays, and tumor models, BLU-667 was active against RET fusions and mutations, including predicted resistance mutations.

About the Phase 1 Clinical Trial for BLU-667 in RET

Blueprint Medicines’ Phase 1 clinical trial of BLU-667 in RET is designed to evaluate the safety and tolerability of BLU-667 in multiple ascending doses in patients with NSCLC, MTC, and other advanced solid tumors with the goal of establishing a maximum tolerated dose (MTD) or a lower recommended dose if appropriate. Once the MTD is reached, or a recommended dose is established, Blueprint Medicines plans to open expansion cohorts for NSCLC patients with a RET rearrangement, patients with MTC, and patients with RET-altered solid tumors other than NSCLC and MTC. Secondary objectives for this Phase 1 clinical trial include assessing the pharmacokinetic profile of BLU-667, assessing RET gene status in plasma and tumor tissue, characterizing the pharmacodynamic effects of BLU-667 and assessing response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, which are criteria commonly used to measure clinical responses in solid tumors. The Phase 1 clinical trial is designed to enroll approximately 115 patients, including approximately 35 patients during dose escalation and approximately 80 additional patients in expansion cohorts, at multiple sites in the United States and the European Union. Please refer to www.clinicaltrials.gov (NCT03037385) for additional details related to this Phase 1 clinical trial. For more information, contact the study director for this Phase 1 clinical trial at studydirector@blueprintmedicines.com.

Loxo Oncology Announces Larotrectinib Pan-TRK IHC Companion Diagnostic Collaboration with Ventana Medical Systems, Inc., a member of the Roche Group

On March 20, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the Company has entered into a collaboration agreement with Ventana Medical Systems, Inc., a member of the Roche Group (Roche), to develop and commercialize a pan-TRK immunohistochemistry (IHC) test as a companion diagnostic to identify patients across tumor types suitable for treatment with larotrectinib (Press release, Loxo Oncology, MAR 20, 2017, View Source [SID1234518218]).

"We are excited to partner with Roche, the global leader in developing and commercializing IHC assays for cancer diagnostics. Our initial technology assessment suggests that an IHC pan-TRK assay is feasible, which is exciting since Roche has thousands of VENTANA BenchMark instruments installed worldwide," said Josh Bilenker, M.D., Chief Executive Officer of Loxo Oncology. "IHC remains a mainstay of the cancer pathology workup, due in part to its speed, limited tissue requirements, low cost, and established reimbursement paradigms. Diagnostics are a crucial part of our commercial strategy, and we believe IHC will be an important tool, alongside next-generation sequencing, that pathologists can employ in screening for patients who may benefit from larotrectinib."

Loxo Oncology and Roche will utilize an investigational assay piloted by Loxo Oncology that will be further developed by Roche using its flagship OptiView DAB detection technology. Initially, the parties will optimize and validate the assay to ensure it is sufficiently robust to withstand clinical and regulatory scrutiny. The parties plan to first globally commercialize an analytical assay and then develop a Class III assay for pre-market approval (PMA) from the U.S. Food and Drug Administration (FDA). FDA approval will be based on analyses of patient samples collected from ongoing larotrectinib clinical trials to support clinical claims referencing larotrectinib. Roche is responsible for developing, obtaining and maintaining regulatory approvals for the companion diagnostic test in the United States, specified countries in the European Union and other countries that recognize the CE/ in vitro diagnostic registration process, as mutually agreed.

About Larotrectinib (LOXO-101)
Larotrectinib (LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, larotrectinib has demonstrated encouraging preliminary efficacy. Larotrectinib is also being evaluated in the NAVIGATE global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions, and the SCOUT Phase 1/2 trial in pediatric patients, including patients with advanced cancer, TRK gene fusions and infantile fibrosarcoma. Larotrectinib has been granted Breakthrough Therapy Designation and Rare Pediatric Disease Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.