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Heat Biologics Reports Positive Interim Phase 2 Lung Cancer Results in Patients Treated with HS-110 in Combination with a Checkpoint Inhibitor

On March 21, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), a leader in the development of immunotherapies designed to activate a patient’s immune system against cancer, reported the latest results of its ongoing Phase 2 clinical trial of HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), for the treatment of non-small cell lung cancer (NSCLC) (Press release, Heat Biologics, MAR 21, 2017, View Source [SID1234518225]). Fifteen patients have completed the HS-110/nivolumab combination treatment to-date and 12 of these 15 patients were evaluable for ELISPOT analysis. Researchers reported a strong correlation between T cell activation, tumor reductions and increased overall survival in these 12 patients. These data reinforce preliminary results seen in the first eight patients as reported last December at the International Association for the Study of Lung Cancer Annual Meeting.

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Key findings:

Immune responses to HS-110 were observed in all 5 patients that exhibited tumor reductions.

No tumor reductions were observed in patients that did not mount an immune response to HS-110.

The timing of immune responses to HS-110 corresponded to the timing of observed clinical responses, and those responses appear to be sustained.

To-date, 5 patients have been enrolled in the low tumor infiltrating lymphocytes (TIL) cohort (patients with "cold" tumors). Three of these 5 patients (60%) have experienced significant tumor reduction, which is higher than the 10% response rate of low TIL patients reported for existing data on nivolumab alone.1
Researchers reported continued indications that patients are mounting a vaccine-mediated immune response to the vaccine lysate, as well as to peptides derived from cancer-specific antigens in their peripheral blood cells via ELISPOT analysis. ELISPOT analysis is the most widely used method for monitoring cellular immune responses in humans. This suggests that the HS-110 vaccine is making a measurable contribution to the desired cancer-specific immune response.

Of the 15 patients who have completed the HS-110/nivolumab combination treatment to-date, 12 were evaluable for ELISPOT analysis. Six of the 12 evaluable patients met the criteria for a positive ELISPOT response to vaccine lysate, and 5 of these 6 patients experienced tumor reductions and increased overall survival. All 5 patients who exhibited a clinical response also saw an immune response to HS-110. Of the 6 patients who did not respond by ELISPOT analysis, 5 patients saw tumor progression and 1 patient discontinued treatment due to a non-serious adverse event.

These data suggest that the 5 tumor reductions seen thus far in the 15 evaluated patients are the result of synergistic activity between HS-110 and anti-PD-1 therapy. Researchers also reported that the safety profile continues to be favorable in the HS-110/nivolumab combination, with no evidence of additional toxicities seen as compared to existing data on nivolumab alone.

"Checkpoint inhibitors, such as nivolumab, are currently effective in treating approximately 10% of lung cancer patients with low TIL and about 20% of patients overall in the 2nd line setting," said Jeff Hutchins, Ph.D., Heat’s Chief Scientific Officer and Senior Vice President of Preclinical Development. "Our results appear to further validate the expected mechanism of action of our approach in combination with checkpoint inhibitors, with a continuing trend towards early and sustained T cell activation in the peripheral blood cells. All patients who mounted a sustained immune response to HS-110 exhibited substantial tumor reductions. We do not see any tumor reduction in patients who did not mount a response to the vaccine. Furthermore, if ELISPOT assay results continue to correlate with clinical results, the combination of HS-110 and nivolumab may become an attractive therapeutic approach for the approximately 80% of patients that do not respond well to nivolumab alone, particularly with the positive safety profile of this combination seen to-date."

1Teng et al, Cancer Research 75(11) June 1, 2015

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Syros Pharmaceuticals has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Syros Pharmaceuticals, 2017, MAR 20, 2017, View Source [SID1234521276]).

Checkpoint Therapeutics to Present Preclinical Data at the American Association for Cancer Research Annual Meeting 2017

On March 20, 2017 Checkpoint Therapeutics, Inc. ("Checkpoint") (OTCQX: CKPT), a Fortress Biotech (NASDAQ: FBIO) company, reported that preclinical data on its anti-PD-L1 antibody and EGFR inhibitor programs will be presented in poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017, to be held April 1-5, at the Walter E. Washington Convention Center in Washington, D.C (Press release, Fortress Biotech, MAR 20, 2017, View Source;FID=1001221494 [SID1234518214]).

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Details on the poster presentations are as follows:

Title: CK-101 (RX518), a mutant-selective inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC
When: Monday, April 3, 1 – 5 p.m. ET
Session Title: Growth Factor and Hormone Receptors as Therapeutic Targets
Location: Halls A-C, Poster Section 4
Abstract Number: 2078
Poster Number: 5

Title: Preclinical characterization of a novel fully human IgG1 anti-PD-L1 mAb CK-301
When: Tuesday, April 4, 1 – 5 p.m. ET
Session Title: Immunoconjugates and Antibodies
Location: Halls A-C, Poster Section 26
Abstract Number: 4606
Poster Number: 21

For additional information, please visit the AACR (Free AACR Whitepaper) website: www.aacr.org.

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]).

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.