On December 5, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that a review of BP1001 data as a treatment for chronic myelogenous leukemia (CML) was presented in a poster at the 58th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place from December 3-6, 2016 in San Diego, CA (Filing, 8-K, Bio-Path Holdings, DEC 6, 2016, View Source [SID1234516978]).

Ana Tari Ashizawa, Ph.D., Bio-Path’s director of research, presented the poster titled "BP1001, a Novel Therapeutic for Chronic Myelogenous Leukemia." The results demonstrated that BP1001 decreased the proliferation of Gleevec (imatinib)-resistant CML cells in a dose-dependent manner. In addition, BP1001 pretreatment enhanced the inhibitory effects of Sprycel (dasatinib) in CML cells, leading to cell death. Five CML blast phase patients were enrolled in the first cohort (5 mg/m2 BP1001) of the Phase 1 BP1001 clinical study. Two CML patients, who had T315I mutation, showed significant reductions in circulating blasts during treatment. One patient’s blasts were reduced from 89% to 12%, while another patient’s blasts were reduced from 24% to 7%.

"These patient data, supported by previous in vivo and in vitro results, suggest that BP1001 has the potential to treat the 33% of CML patients who are resistant to Gleevec, the current standard of care. Sprycel is a second-generation tyrosine kinase inhibitor that is often used for Gleevec resistant patients. We are pleased that our preclinical results showed that BP1001 can enhance Sprycel activity in CML cells. These positive data give us confidence that BP1001 could play a valuable role in treating this patient population and encourage us to move forward with the initiation of our safety segment of the Phase 2 trial in patients with CML," said Peter Nielsen, chief executive officer of Bio-Path Holdings.

About BP1001

BP1001 (Liposomal Grb2 antisense) is Bio-Path’s lead product candidate, a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Grb2 (growth factor receptor bound protein 2). Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 is an adapter protein that bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins. Inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with antibodies or kinase inhibitors. Inhibition of Grb2 has been demonstrated to halt cell proliferation and enhance cell killing by chemotherapeutic agents without added toxicity.

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On December 5, 2016 Acceleron Pharma Inc. (NASDAQ:XLRN) and Celgene Corporation (NASDAQ:CELG), reported preliminary results from an ongoing investigator initiated Phase 2 study with investigational drug sotatercept in patients with myelofibrosis at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California (Press release, Acceleron Pharma, DEC 5, 2016, View Source [SID1234516914]). Sotatercept is being developed as part of the global collaboration between Acceleron and Celgene.

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"These initial and encouraging data support our efforts for further clinical development work with our Acceleron-partnered programs in myelofibrosis," said Michael Pehl, President, Hematology and Oncology for Celgene. "We believe these programs have the potential to address a major unmet need in patients with myelofibrosis."

Highlights of the Sotatercept Myelofibrosis Phase 2 Data Presented at ASH (Free ASH Whitepaper)

Results

19 patients were enrolled and treated with sotatercept (12 patients at 0.75 mg/kg and 7 at 1 mg/kg) and 14 of these patients have received at least 5 doses of sotatercept and are evaluable for response
36% (5/14) of the evaluable patients achieved an anemia response, defined as a composite of RBC-transfusion-independence and hemoglobin response (increase of ≥1.5 g/dL from baseline on every determination consecutively over ≥84 days without RBC transfusions).
Overall Safety

Most adverse events were grades 1 or 2.
Adverse events at least possibly related to study drug that occurred include grade 3 hypertension leading to discontinuation, grade 1 myalgia, bone pain, pain in extremity and injection site reaction.
13 patients have discontinued from the study: 5 due to no response, 2 proceeded to stem cell transplantation, 2 had MF progression, 1 transformed to AML, 1 each withdrew consent, had unrelated medical problems and hypertension
Sotatercept is an investigational product that is not approved for use in any country.

Acceleron ASH (Free ASH Whitepaper) Conference Call Information

Acceleron will host a conference call and live webcast to discuss data presented at the ASH (Free ASH Whitepaper) meeting on December 5, 2016, at 9:00 a.m. EST (6:00 a.m. PST). To participate by teleconference, please dial 877-312-5848 (domestic) or 253-237-1155 (international) and refer to the Acceleron ASH (Free ASH Whitepaper) Review.

To access the live webcast, please select "Events & Presentations" in the Investors section on Acceleron’s website (www.acceleronpharma.com) at least 10 minutes beforehand to ensure time for any downloads that may be required.

An archived webcast recording will be available on the Acceleron website beginning approximately two hours after the event.

About the Phase 2 Study

Data were presented from an ongoing investigator sponsored Phase 2 study of sotatercept in subjects with myelofibrosis at the conference. Subjects enrolled were red blood cell (RBC) transfusion-dependent, have hemoglobin < 10 g/dL on every determination during the 84 days preceding study entry without RBC transfusions, or have hemoglobin < 10 g/dL despite intermittent RBC transfusions without fulfilling the criteria for transfusion dependence. Patients received open-label sotatercept at 0.75 mg/kg or 1 mg/kg, dosed subcutaneously once every three weeks.

The primary outcome measures for the study include anemia response and safety. Anemia response is a composite of RBC-transfusion-independence and hemoglobin response (increase of ≥1.5 g/dL from baseline on every determination consecutively over ≥84 days without RBC transfusions). Subjects must have received ≥5 cycles of sotatercept to be evaluable for response.

About Sotatercept

Sotatercept is an activin receptor type IIA fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in fibrosis and late stage erythropoiesis (red blood cell production). Acceleron and Celgene are jointly developing sotatercept as part of a global collaboration. Sotatercept is currently in multiple Phase 2 investigator initiated trials. For more information, please visit www.clinicaltrials.gov.

On December 5, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported a review of results to date from its multicenter BP-004 clinical trial of BPX-501 in the pediatric setting, and provided an update on the regulatory pathway for product registration in Europe at an investor and analyst event held today (Press release, Bellicum Pharmaceuticals, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227672 [SID1234516942]). Clinical results on BPX-501 in children with hematological malignancies were also presented in a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.

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"We have made significant progress with our BPX-501 program since initiating the BP-004 clinical trial in children two years ago," commented Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "To date, we have treated more than 100 patients at leading pediatric transplant centers in Europe and the U.S. Results thus far have been impressive—including GvHD- and disease-free outcomes in children with a range of blood cancers and genetic diseases, as reported this weekend in several presentations at ASH (Free ASH Whitepaper). We’re also pleased with the progress we’ve made in formalizing an expedient pathway to regulatory approval in Europe with BPX-501 to treat both malignant and nonmalignant diseases. We look forward to providing an update on our U.S. regulatory path in the first half of 2017."

Overall Summary of Results of BP-004 Study with BPX-501 (n=85)

The Company presented a review of results to date of the BP-004 study in pediatric patients with malignant and nonmalignant diseases who underwent a haploidentical hematopoietic stem cell transplant (HSCT) followed by an add-back of genetically modified BPX-501 T cells. Eighty-five patients have been treated with BPX-501 at multiple U.S. and European sites and followed for at least 100 days (out of a total of 105 patients treated to date). Only one case of transplant-related mortality has been reported, unrelated to BPX-501 cells, and none out of 51 patients with nonmalignant disorders. Compared to T-depleted haplo-transplants alone, results have also shown significantly faster immune recoveries, as well as reduced viral infections and reactivation, and reductions in time to hospital discharge and re-hospitalizations due to infection. In five cases where uncontrolled acute GvHD was attributable to BPX-501 cells, rimiducid was administered and symptoms resolved.

Results have been consistent across a range of diseases and disorders where allogeneic HSCT is recognized as curative, including hemoglobinopathies such as Beta Thalassemia Major (β0β0), Sickle Cell Disease and Diamond-Blackfan Anemia; Primary Immune Deficiencies such as Severe Combined Immune Deficiency ("Bubble boy" disease) and Wiskott-Aldrich syndrome; leukemias and lymphomas; and bone marrow failure syndromes. The Company also reported that of six refractory AML patients treated under compassionate use because of their active disease and not included in the BP-004 summary data, 4 remain alive and in remission, including two who are now 11 and 20 months post-transplant.

Regulatory Update for BPX-501 in the European Union

The Company also announced today that the protocol assistance provided by the European Medicines Agency (EMA) for the registration study of BPX-501 in Europe is complete, and the Company is finalizing plans for the BP-004 trial extension. The Company will continue enrolling up to 40 additional patients with malignant and nonmalignant diseases in the trial. Concurrent with this study, the Company will initiate a comparator trial of malignant and nonmalignant patients receiving a matched unrelated donor (MUD) HSCT. This trial will include both retrospective patients and up to 40 prospective patients. The primary endpoint will be event-free survival (death, GvHD and infection) at 6 months.

Bellicum anticipates that it could pursue approval in the EU under the "exceptional circumstances" provision. Exceptional circumstances may be granted for medicines that treat very rare diseases, or where controlled studies are impractical or not consistent with accepted principles of medical ethics. The Company continues to discuss the regulatory path to approval in the U.S. with FDA and expects to provide an update in the first half of 2017.

Also today at the ASH (Free ASH Whitepaper) 2016 annual meeting, updated results were presented in patients with acute myeloid leukemia (AML).

AML Highlights (Abstract #4683)

"T-cell depleted HLA-haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) followed by donor lymphocyte infusion with T cells transduced with the inducible caspase 9 (iC9) suicide gene in children with hematological malignancies"

In a poster session, investigators presented data in 33 children with AML who received an α/β TCR-depleted haplo-HSCT and BPX-501 cells. The data indicate that infusion of BPX-501 results in low non-relapse mortality, and low rates of acute and chronic Graft versus Host Disease. Median follow-up was 8 months (range: 1–19 months). All 33 patients were high-risk CR1 (6/33) or CR2 (27/33). Study outcomes include:

All 33 patients engrafted with no secondary graft failure
One patient with steroid-resistant Grade II skin acute GvHD received rimiducid with complete resolution of disease in 24 hours
One treatment-related mortality from chronic GvHD was determined to be allograft-related and not from BPX-501 T cells
3 of 33 patients have relapsed; the probability of disease-free survival at 15 months is 83.6%
A replay of the investor and analyst meeting held today can be accessed from the News & Events section of the Bellicum website. An archived version of the webcast will be available for at least two weeks following the event.

About BPX-501

BPX-501 is an adjunct T-cell therapy administered after allogeneic HSCT, comprising genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by adding back BPX-501 engineered T cells to speed immune reconstitution and provide control over viral infections, without unacceptable risk of uncontrollable GvHD. The ongoing BP-004 Phase 1/2 clinical study of BPX-501 is being conducted at transplant centers in the U.S. and Europe.

On December 5, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported positive Phase 2a correlative data, as well as detailed mechanism-of-action data, for BL-8040, the Company’s leading oncology platform at the ongoing 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exhibition in San Diego, California (Press release, BioLineRx, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227400 [SID1234516915]).

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As previously announced, in an oral presentation at 10:30am PST today, entitled, "The High Affinity CXCR4 Inhibitor, BL-8040, Induces Apoptosis of AML Blasts and their Terminal Differentiation by Blocking AKT/ERK Survival Signals and Downregulating BCL-2, MCL-1 and Cyclin-D1 through Regulation of miR-15a/16-1 Expression," BioLineRx reports detailed data on the mechanism-of-action by which BL-8040 directly induces apoptosis of AML cells. The data, presented by Prof. Amnon Peled, are from in vitro studies using human AML cell lines and human primary AML samples, as well as in vivo studies using human primary AML cells engrafted in NOD scid gamma (NSG) mice.

In addition, yesterday, in a poster titled, "The Selective Anti Leukemic Effect of BL-8040, a Peptidic CXCR4 Antagonist, is Mediated by Induction of Leukemic Blast Mobilization, Differentiation and Apoptosis: Results of Correlative Studies from a Ph2a Trial in Acute Myeloid Leukemia," BioLineRx reported the final correlative results from its Phase 2a trial in acute myeloid leukemia (AML). The trial consisted of 45 AML patients receiving BL-8040 monotherapy on days 1-2, followed by the same dose of BL-8040 plus chemotherapy (Cytarabine) on days 3-7. All patients had poor-risk disease and had been heavily pretreated, with 19% having relapsed after a short first remission (≤12 months), 17% having 2 or more relapses, while 45% were refractory to 1-2 induction treatments. The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving BL-8040 dose ≥1.0 mg/kg (n=39). These response rates are superior to the historical response rate of approximately 20% reported for high-risk AML patients treated with Cytarabine alone.

Philip Serlin, CEO of BioLineRx, commented, "We are excited to take part in the world’s premier event in malignant and non-malignant hematology, with over 20,000 hematology professionals from every subspecialty in attendance. At this event, we are pleased to present additional positive results about BL-8040. This includes clinical data that supports the rational for incorporation of BL-8040 in front-line AML treatment settings, such as AML consolidation and maintenance. In this regard, we are currently running a large Phase 2b study in consolidation AML, and we expect to initiate a Phase 1b study in maintenance AML under our collaboration with Genentech in mid-2017. We are also pleased to see pre-clinical data that support the mechanism of action of BL-8040 and show synergistic effects of BL-8040 with drugs that are also being investigated as AML treatments. We continue to anticipate that BL-8040, in combination with a growing repertoire of drugs, will be able to offer hope in this difficult to treat condition."

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. Furthermore, scientific findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with immune checkpoint inhibitors, BL-8040 has the potential to enable activated T cells to better reach tumor cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On December 5, 2016 Dynavax Technologies Corporation (NASDAQ: DVAX) reported clinical data from an ongoing Phase 1/2, two-part clinical trial evaluating intratumoral administration of SD-101 in the treatment of low-grade lymphoma (Press release, Dynavax Technologies, DEC 5, 2016, View Source [SID1234516916]). The combination of intratumoral SD-101 and low-dose irradiation resulted in tumor regression in untreated tumor sites as well as in the treated tumors. Treatment was well-tolerated and changes in T cell populations consistent with stimulation of anti-tumor immunity were observed in the treated lesions. These data were presented in a poster session on Sunday at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California.

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Data from the dose escalation and expansion phase of the study were reported from 28 evaluable patients. None of the patients had received prior treatment for their low-grade lymphoma. The primary endpoints of the trial are maximum tolerated dose (MTD) and evaluation of the safety of intratumoral SD-101 in combination with low dose radiotherapy. In addition, the trial is evaluating anti-tumor activity, pharmacodynamics, and duration of response. Doses ranged from 1 mg to 8 mg per injection in successive cohorts.

Key findings presented include:

Of the 28 evaluable patients treated across all dose levels, 3 had a partial response (PR) and1 had a complete response (CR) as measured by Cheson criteria.
Durable abscopal tumor shrinkage was observed in the majority of patients.
Confirming observations in the dose escalation phase, the most common treatment-related treatment emergent adverse events (TEAEs) in the expansion phase were flu-like symptoms, consistent with the engagement of TLR9 and the induction of interferon-alpha.
Increases in CD8+ cells were observed in the injected tumor, and correlated with an increased abscopal tumor shrinkage
"The clinical data emerging from our SD-101 program continues to be encouraging. We look forward to providing updates from our ongoing clinical trials," stated Eddie Gray, chief executive officer of Dynavax Technologies. "We will discuss this program and our oncology pipeline in our cancer R&D Day which will be webcast live on December 9th at 8:30 a.m. EST."

About SD-101

SD-101 is Dynavax’s proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 is being studied for its multiple anti-tumor activities in innate immune cells and activation of plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.