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TEL AVIV, Israel—The first quarter of 2018 has been a positive one so far for biopharmaceutical company BioLineRx Ltd., which debuted encouraging data from two of its oncology programs at this year’s ASCO-SITC Clinical Immuno-Oncology Symposium. The symposium was held in late January in San Francisco.
 
One of the featured candidates was BL-8040, BioLineRx’s lead oncology platform. The study found that BL-8040 boosts the immune system’s ability to fight cancer by increasing the flow of antitumor-specific T cells into the tumor microenvironment. Specifically, the poster abstract noted that the amount of antigen-specific CD8+ T cells in the microenvironment increased significantly. In a mouse model of cancer, this led to a drop in tumor growth and longer survival times: 35 days after tumor implantation, 80 percent of mice in the BL-8040 + vaccine group had survived, compared to none in the BL-8040 or vaccine treatment groups.
 
According to the presentation, the combination group consisted of BL-8040 administered along with “tumor-specific antigen priming using E7 peptide vaccine (3 doses, one week apart),” a vaccine meant to “prime” the immune system against tumors.
 
“I am highly encouraged by the data generated in this preclinical study, which further demonstrates the therapeutic potential of BL-8040,” said Dr. Samir Khleif, professor of oncology and director of the Loop Immunology-Oncology Laboratory at Georgetown Lombardi Comprehensive Cancer Center. “The results provide further evidence that BL-8040 promotes the infiltration of cytotoxic T cells into tumors, which is seen as a key objective to improve responsiveness to checkpoint therapy. I look forward to seeing the results from the clinical studies in which BL-8040 is being combined with checkpoint blockade.”
 
BL-8040 is a short peptide being advanced as a treatment for solid tumors, acute myeloid leukemia and stem cell mobilization. The compound is a high-affinity antagonist of CXCR4, a chemokine receptor that plays a role in tumor progression, angiogenesis, metastasis and cell survival. This chemokine receptor is over-expressed in more than 70 percent of human cancers, with its expression commonly linked to disease severity.
 
As noted by BioLineRx, “In a number of clinical and preclinical studies, BL-8040 has shown robust mobilization of cancer cells and immune cells from the bone marrow, thereby sensitizing cancer cells to chemo- and bio-based anticancer therapy, as well as a direct anticancer effect by inducing cell death (apoptosis) and mobilizing immune cells. In addition, BL-8040 has also demonstrated robust stem cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells.”
 
BioLineRx CEO Philip Serlin commented in a press release that the company is evaluating BL-8040 in eight ongoing clinical trials in multiple indications, ranging from solid tumors to blood cancers.
 
The other program highlighted in a poster presentation was AGI-134, an immunotherapy treatment being developed against multiple solid tumors. The presentation, “Intratumoral Administration of the Alpha-Gal Glycolipid AGI-134 to Induce Tumor Regression in a Mouse Model of Melanoma,” covered data from a pair of preclinical studies of AGI-134 in melanoma.
 
AGI-134, a synthetic alpha-Gal immunotherapy, is presently being developed against solid tumors. As noted by BioLineRx, “AGI-134 harnesses the body’s pre-existing, highly abundant anti-alpha-Gal antibodies to induce a systemic, specific antitumor response to the patient’s own tumor neoantigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on, anti-metastatic immune response.” The company has completed several preclinical studies of AGI-134, in which it has shown strong protection against the development of secondary tumors in a melanoma model after just a single dose. AGI-134 also demonstrated some synergy when combined with a PD-1 immune checkpoint inhibitor.
 
The ASCO-SITC presentation looked at the results of AGI-134 in two mouse models: B16.F10 and B16.OVA. In the B16.F10 model, nearly 50 percent of AGI-134-treated tumors fully regressed, compared to 24 percent in the PBS controls. AGI-134 also improved survival, with only 23 percent of mice treated with AGI-134 dying or requiring euthanasia due to tumors by day 27 post-treatment, compared to 43 percent in the control groups. In addition, examining C5a levels two hours after treatment with either AGI-134 or PBS showed that the former triggered significant activation of the complement system in injected tumors. Such activation is believed to destroy tumor cells and encourage a pro-inflammatory tumor microenvironment that will attract and activate other immune cells, thereby leading to adaptive antitumor immunity. In the B16.OVA model, 67 percent of mice treated with AGI-134 saw their tumors fully regress vs. 0 percent in control mice in two assays.
 
Serlin said in a press release that “Previous studies have demonstrated that intratumoral administration of AGI-134 induces a systemic antitumor response that protects mice from the development of distant tumors. These new studies now show direct regression of established primary tumors after injection with AGI-134, and that this regression is associated with activation of the innate immune system. These compelling preclinical data support investigating this approach in a Phase 1/2a study, and we are excited and on track to commence a first-in-man study with this promising novel oncology asset in patients with solid tumors in the first half of 2018.”

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Volume 14 - Issue 3 | March 2018

March 2018

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