BioLineRx Ltd (BLRX)

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BioLineRx Announces Publication of Data from Ongoing COMBAT/KEYNOTE-202 Clinical Trial in Nature Medicine

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PR Newswire PR Newswire•May 27, 2020

TEL AVIV, Israel, May 27, 2020 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical Company focused on oncology, today announced that a paper, entitled 'BL-8040, a CXCR4 Antagonist, in Combination with Pembrolizumab and Chemotherapy for Pancreatic Cancer: The COMBAT Trial,' has been published in the peer-reviewed journal Nature Medicine.

The paper highlights previously disclosed biomarker and clinical data from the Company's ongoing COMBAT/KEYNOTE-202 clinical trial, consisting of two cohorts assessing the safety, efficacy and immunobiological effects in patients with metastatic pancreatic ductal adenocarcinoma (metastatic pancreatic cancer, or PDAC).

The first cohort evaluated the combination of motixafortide (BL-8040) and pembrolizumab in 37 patients refractory to 1-4 prior lines of chemotherapy. The primary outcome measure was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. The DCR was 34.5% in the evaluable population (N=29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months. Notably, in the subset of second-line patients (N=16), mOS was 7.5 months. In addition, motixafortide monotherapy, as well as the dual combination, showed increased CD8+ effector T-cell tumor infiltration, decreased myeloid derived suppressor cells in the tumor microenvironment, and a decrease in circulating immuno-suppressive Tregs, thereby confirming the mechanism of action originally hypothesized and previously seen only in animal models.

Based on the clinical and immuno-biological effects observed in the first cohort, as well as preclinical data showing that the combination of chemotherapy with motixafortide and a PD-1 inhibitor results in increased anti-tumor effects, a second study cohort was initiated, incorporating the triple combination of motixafortide, pembrolizumab and chemotherapy. This cohort will include approximately 40 subjects with metastatic PDAC at first diagnosis, and with disease progression following first-line gemcitabine-based treatment. Preliminary data from 22 patients in the second cohort were available at the date of paper submission. This data showed ORR, DCR and median duration of clinical benefit of 32%, 77% and 7.8 months, respectively.

"PDAC is among the most difficult cancers to treat, due to its generally late stage at the time of initial diagnosis, its relative chemoresistance and its highly immunosuppressive microenvironment. In light of this, PDAC has shown a poor response to immunotherapies such as checkpoint inhibitors that have positively impacted patient prognoses in many other cancer types," stated Philip Serlin, Chief Executive Officer of BioLineRx.

"This paper describes that the dual combination of motixafortide and KEYTRUDA® showed encouraging clinical activity, as well as proof-of-mechanism, in one of the coldest tumors. It also presents preliminary data from the triple combination suggesting that CXCR4/PD-1 blockade may enhance the benefit of chemotherapy in patients suffering from PDAC. We look forward to progression free survival and overall survival data later this year. We believe that our findings to date warrant further evaluation of this promising combination via a randomized trial," Mr. Serlin concluded.

The Company completed enrollment in the triple combination arm in January 2020 and anticipates reporting progression-free survival and overall survival data mid-year.

The paper is available online at: https://www.nature.com/articles/s41591-020-0880-x.

About Motixafortide in Cancer Immunotherapy

Motixafortide is targeting CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

Motixafortide is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

n a number of clinical and preclinical studies, motixafortide has been shown to affect multiple modes of action in 'cold' tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor niche, turning 'cold' tumors, such as pancreatic cancer, into "hot" (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

About Pancreatic Cancer

Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. Its incidence rate in the US is estimated at 3.2% of new cancer cases. Each year, about 185,000 individuals globally are diagnosed with this condition, and an estimated 55,000 individuals were diagnosed with pancreatic cancer in the US during 2018. Symptoms are usually non-specific and as a result, pancreatic cancer is often not diagnosed until it reaches an advanced stage. Surgical resection does not offer adequate treatment since only 20% of patients have resectable tumors at the time of diagnosis. Even among patients who undergo resection for pancreatic cancer and have tumor-free margins, the five-year survival rate is only 10%-25%. The overall five-year survival rate among pancreatic cancer patients is 7-8%, which constitutes the highest mortality rate among solid tumor malignancies. The overall median survival is less than one year from diagnosis, highlighting the need for the development of new therapeutic options.

Despite advances in chemotherapeutics and immunotherapy, increases in median and overall survival rates in pancreatic cancer have been modest. Pancreatic cancer remains an area of unmet medical need, with no new approved therapies since the approval of nab-paclitaxel in combination with gemcitabine (Abraxane®) for first-line treatment in 2013 and Onivyde® in combination with fluorouracil and leucovorin for second-line treatment in 2015. The limited clinical benefits demonstrated by these existing standard treatment options reinforce the need for additional approaches.

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