On May 11, 2017 VBL Therapeutics (Nasdaq:VBLT) reported new preclinical data indicating that treatment with ofranergene obadenovec (VB-111) augments the anti-tumor activity of a PD-L1 blocker in lung cancer and melanoma models (Press release, VBL Therapeutics, MAY 11, 2017, View Source [SID1234519057]). The data will be presented tomorrow, May 12, in a poster session at the 20th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper), taking place in Washington, DC.


Immunotherapy with checkpoint inhibitors demonstrates remarkable efficacy in several cancers; yet, only a low percentage of patients seem to benefit from this class of treatment when given as a monotherapy. Several studies have shown that response rates are increased when checkpoint blockade is combined with other anti-cancer treatments. VB-111 is a biologic agent that is being currently studied in a Phase 3 clinical trial for recurrent glioblastoma (rGBM). VB-111 specifically targets angiogenic endothelial cells and promotes antitumor immune response. In the study to be presented at ASGCT (Free ASGCT Whitepaper), VB-111 was evaluated in combination with an anti-PD-L1 checkpoint inhibitor in lung and melanoma cancer models, indications for which PD-1 blockers are already marketed.

VBL’s data show that treatment with either VB-111 or anti-PD-L1 reduced tumor burden in mice induced with Lewis lung carcinoma (LLC), by 42% and 51% versus saline control, respectively; however, the combination of both agents resulted in an amplified effect (67% reduction versus control; p≤0.001), and similar results were seen in a melanoma model. In addition, treatment with VB-111 and anti-PD-L1 enhanced infiltration of CD8+ cells to lung tumors. A copy of the poster will be available on VBL’s website, beginning May 12.

"An important observation from our pre-clinical data in the LLC model was that the combination of VB-111 at a dose of 109 viral particles (VPs)/mouse, which is equivalent to the human therapeutic dose, with a PD-L1 blocker, yielded a tumor burden reduction similar to treatment with 1011 VPs/mouse, a 100-fold higher dose," said Eyal Breitbart, Ph.D., Vice President of Research and Operations at VBL. "Therefore, a combination with a checkpoint inhibitor may achieve much better anti-tumor activity than VB-111 alone," added Dr. Breitbart.

VB-111 is currently studied in the pivotal Phase 3 GLOBE trial in rGBM, comparing VB-111 in combination with Avastin (bevacizumab) to Avastin alone, which is being conducted in the US, Canada and Israel. Enrollment in the study, 256 patients in total, was completed earlier this year, five months ahead of schedule. The study is proceeding under a Special Protocol Assessment (SPA) granted by the FDA, with full endorsement by the Canadian Brain Tumor Consortium (CBTC). The Company expects to report interim data from the GLOBE trial in Q3-2017, with top-line results from the full dataset expected to be available in early 2018.

VBL plans to launch a Phase 3 study for VB-111 in combination with chemotherapy for platinum-resistant ovarian cancer in the second half of 2017. Launch of an exploratory clinical study on VB-111 in combination with a checkpoint inhibitor in lung cancer is also expected by year-end 2017.

About Ofranergene Obadenovec (VB-111)
Ofranergene obadenovec is a unique biologic agent that uses a dual mechanism to target solid tumors. Based on a non-integrating, non-replicating, Adeno 5 vector, ofranergene obadenovec utilizes VBL’s proprietary Vascular Targeting System (VTS) to target the tumor vasculature for cancer therapy. Unlike anti-VEGF or TKIs, ofranergene obadenovec does not aim to block a specific pro-angiogenic pathway; instead, it uses an angiogenesis-specific sensor (VBL’s PPE-1-3x proprietary promoter) to specifically induce cell death in angiogenic endothelial cells in the tumor milieu. This mechanism retains activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor and shows activity even after failure of prior treatment with other anti-angiogenics. Moreover, ofranergene obadenovec induces specific anti-tumor immune response, which is accompanied by recruitment of CD8 T-cells and apoptosis of tumor cells.

Ofranergene obadenovec completed a Phase 2 study in rGBM, which showed a statistically significant improvement in overall survival in patients treated with ofranergene obadenovec through progression, compared to either patients treated with ofranergene obadenovec followed by bevacizumab alone, or to historical bevacizumab data. In a Phase 2 trial for recurrent platinum-resistant ovarian cancer, ofranergene obadenovec demonstrated a statistically significant increase in overall survival and 60% durable response rate (as measured by reduction in CA-125), approximately twice the historical response with bevacizumab plus chemotherapy in ovarian cancer. In a Phase 2 study in recurrent, iodine-resistant differentiated thyroid cancer, ofranergene obadenovec met the primary endpoint demonstrating disease stabilization with a positive safety profile, along with a dose-response and evidence of an overall survival benefit. Ofranergene obadenovec has received Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.

On May 11, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration (AMD) and fibrotic diseases, reported that preclinical data indicating the potential clinical utility of targeting endoglin in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-cell ALL), was published in the May 4, 2017 issue of Blood (Volume 129, Number 19, pages 2526-2536), a weekly medical journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Tracon Pharmaceuticals, MAY 11, 2017, View Source [SID1234519056]).

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Dr. Rita Perlingeiro, Professor of Medicine, and colleagues of the University of Minnesota, along with collaborators at the Federal University of Bahia (Salvador, Brazil) and the Laboratory for the Diagnosis of Onco-Hematological Disorders (Curitiba, Brazil), identified endoglin expression on the majority of blasts from patients with AML and B-cell ALL. These endoglin expressing blasts were shown to have superior leukemogenic activity. Furthermore, the researchers demonstrated that TRACON’s endoglin antibody, TRC105, prevented the engraftment of primary AML blasts, and inhibited leukemic progression following disease establishment in mice. In both AML and B-cell ALL, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis in the mouse model.

"We have been studying the function of endoglin in hematopoiesis for more than a decade, and the consistent expression of this receptor in the majority of acute leukemias was intriguing. Our hypothesis that endoglin expression was linked to leukemia-forming activity was proven to be true, and it was even more rewarding to witness the robust anti-leukemogenic effect of blocking endoglin signalling with TRC105, even when leukemia had already been established in the mouse," said Dr. Perlingeiro. "We are thrilled with the potential of our basic research to contribute to the development of a new line of therapy for patients with AML and B-cell ALL."

"We are pleased to see that this promising research, conducted by Dr. Perlingeiro and her collaborators, has been published in Blood," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "AML and B-cell ALL represent hematologic malignancies with high unmet need and, as this data indicate, the potential utility of directly targeting endoglin may represent an additional development opportunity for TRC105."

About Carotuximab (TRC105)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in one Phase 3 and multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumors in combination with VEGF inhibitors. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the U.S. and EU. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

On May 11, 2017 Peloton Therapeutics, Inc., a drug discovery and development company focused on advancing novel small molecule cancer therapies, reported initiation of patient dosing in a Phase 2 study of PT2385, the Company’s investigational first-in-class small molecule drug targeting hypoxia-inducible factor 2α (HIF-2α), for patients with von Hippel-Lindau (VHL) disease-associated kidney cancer (Press release, Peloton Therapeutics, MAY 11, 2017, View Source [SID1234519055]). The primary objective of the study is to assess the overall response rate (ORR) of VHL disease-associated clear cell renal cell carcinoma (ccRCC) tumors in untreated VHL patients who received PT2385. The study is being conducted in collaboration with the National Cancer Institute (NCI).

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"There is a significant need for new treatment options for VHL disease, a rare disease with serious and life-long consequences for patients, and for which there are no approved systemic therapies," said John A. Josey, Ph.D., Peloton’s Chief Executive Officer. "The current standard of care for patients with VHL disease-associated kidney cancer is surgery, which commonly does not result in a cure for these patients."
At the recent ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium, W. Marston Linehan, M.D., Chief of the Urologic Oncology Branch of the NCI, had noted "We are getting ready to start a trial of a drug targeting the HIF-2 pathway with the Peloton PT2385 drug, which we are very encouraged about."

PT2385 is a selective, orally active agent that blocks HIF-2α with potent anti-cancer activity in preclinical models of ccRCC. This open-label Phase 2 study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of PT2385 in patients with VHL disease who have at least one measurable VHL disease-associated ccRCC tumor (as defined by RECIST 1.1). PT2385 will be administered orally and treatment will be continuous unless there is disease progression. Changes in VHL disease-associated non-ccRCC lesions will also be evaluated.

"Patients with VHL disease-associated kidney cancer look forward to having the opportunity to participate in this first-ever study of a drug in patients with VHL disease that targets the immediate downstream effect of the VHL mutation," said Ilene Sussman of the VHL Alliance, a patient advocacy group for individuals with VHL disease. "If the drug is shown to be effective, it may reduce the number or frequency of surgeries needed. Overall, having an oral medication that could halt or reverse the progression of this disease would greatly benefit patients."
Further information on the clinical trial of PT2385 in VHL disease-associated kidney cancer can be found on clinicaltrials.gov (Study identifier: NCT03108066).

About VHL Disease
Von Hippel-Lindau disease is a hereditary cancer syndrome caused by a germline mutation in or deletion of the VHL gene, and patients are at risk for developing tumors and fluid-filled sacs (cysts) in a number of organs. Renal cell carcinoma occurs in about 70 percent of individuals with VHL disease and is the leading cause of mortality. Approximately 6,000 people have VHL disease in the U.S.

On May 11, 2017 TESARO Inc. (NASDAQ:TSRO) and Clinigen Group plc’s (AIM:CLIN) (‘Clinigen’) Idis Managed Access division reported that they have partnered to launch a Managed Access Program (also known as an Early Access Program) in Europe for the investigational PARP 1/2 inhibitor, niraparib, for patients with recurrent ovarian cancer (Press release, TESARO, MAY 11, 2017, View Source [SID1234519052]).

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Niraparib is currently an investigational agent in Europe and as such has not been granted approval by the European Commission. The niraparib marketing authorization application is under review by the European Medicines Agency.

Niraparib was recently approved by the United States (U.S.) Food and Drug Administration under the brand name ZEJULA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Approximately 65,000 women are diagnosed with ovarian cancer in Europe every year. Ovarian cancer is the fifth-most frequent cause of cancer death among women. Despite high initial response rates to platinum-based chemotherapy, 85% of women with advanced ovarian cancer will see a recurrence of the disease after first line treatment. The efficacy of chemotherapy also diminishes over time.

Steve Glass, Chief Commercial Officer, North America and Europe for Clinigen said, "Following the successful delivery of the niraparib Managed Access Program in the US, we are pleased to be partnering with TESARO once again, providing eligible women in Europe the opportunity to gain access to this important investigational therapy."

Martin Huber, M.D., Senior Vice President, Chief Medical Officer for TESARO said, "We are proud to partner with Clinigen on this important Managed Access Program for women bravely facing ovarian cancer. The team at Clinigen has proven to be a partner of choice for TESARO as we look to address the needs of the ovarian cancer community."

About Niraparib
In Europe, niraparib is an investigational oral, once-daily poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, niraparib concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

On May 11, 2017 Atossa Genetics, Inc. (NASDAQ: ATOS) reported First Quarter ended March 31, 2017 financial results and provided an update on recent company developments (Press release, Atossa Genetics, MAY 11, 2017, View Source [SID1234519037]).

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Steve Quay, President and CEO, commented, "We are encouraged by our positive progress in advancing the endoxifen program with our ongoing Phase 1 endoxifen study and pleased that our fulvestrant microcatheter study is proceeding at Montefiore Medical Center. We look forward to completing our endoxifen Phase 1 study in the next quarter and commencing a Phase 2 study in the second half of 2017."

Recent Corporate Developments

Atossa’s important recent developments include the following:

May 2017 – Atossa received second positive safety decision in Phase 1 topical endoxifen study.
May 2017 – Institutional Review Board approved continuation of fulvestrant microcatheter Phase 2 study at Montefiore Medical Center.
April 2017 – Atossa received positive interim review from independent safety committee in Phase 1 topical endoxifen study.
April 2017 – Atossa enrolled first cohort of eight subjects in endoxifen study.
March 2017 – Atossa raised approximately $4.4 million in gross proceeds in a public offering.
March 2017 – Atossa opened its endoxifen Phase 1 clinical study.
Atossa plans to commence a Phase 2 clinical study of endoxifen in the second half of 2017.

Q1 2017 Financial Results

We are in the research and development phase and do not generate revenue.

Operating expenses: Total operating expenses were approximately $1.7 million for the three months ended March 31, 2017, consisting of general and administrative (G&A) expenses of approximately $1.1 million and R&D expenses of approximately $544,000. Operating expenses for the three months ended March 31, 2017 decreased approximately $641,000, or 27.5%, from approximately $2.3 million for the three months ended March 31, 2016, which consisted of G&A expenses of approximately $2.2 million, and R&D expenses of approximately $150,000.

The Company recorded a net loss of $1.7 million, for the three months ended March 31, 2017, as compared to a net loss of $2.3 million for the three months ended March 31, 2016.