BioLineRx Stock

BioLineRx Ltd. operates as a pre-commercial-stage biopharmaceutical development company focuses on oncology.

The company's development and commercialization pipeline consist of two clinical-stage therapeutic candidates - motixafortide (BL-8040), a novel peptide for the treatment of stem-cell mobilization and solid tumors, and AGI-134, an immuno-oncology agent in development for solid tumors. In addition, it has an off-strategy, legacy therapeutic product called BL-5010 for the treatment of skin lesions. The company has generated its pipeline by systematically identifying, rigorously validating and in-licensing therapeutic candidates that it exhibits a high probability of therapeutic and commercial success. To date, except for BL-5010, none of its therapeutic candidates have been approved for marketing or sold commercially. In this regard, the company is executing on an independent commercialization plan for motixafortide in stem cell mobilization for autologous bone marrow transplantation in multiple myeloma patients.

The company seeks to develop a pipeline of promising therapeutic candidates that exhibit distinct advantages over available therapies or address unmet medical needs. The company focuses on advancing its therapeutic candidates through development and toward commercialization. The company's drug development pipeline consists of two clinical-stage therapeutic candidates.

Product Pipeline

Motixafortide

Motixafortide, is a novel, short peptide that functions as a high-affinity antagonist for CXCR4, which the company is developing for the treatment of stem cell mobilization and solid tumors. CXCR4 is expressed by normal hematopoietic cells and overexpressed in various human cancers where its expression correlates with disease severity.

In October 2021, the company received World Health Organization, or WHO approval of the United States Adopted Name, or USAN, 'motixafortide'.

Stem cell mobilization

In March 2015, the company reported successful top-line results from a Phase 1 safety and efficacy trial for the use of motixafortide as a novel stem cell mobilization treatment for allogeneic bone marrow transplantation at Hadassah Medical Center in Jerusalem.

In March 2016, the company initiated a Phase 2 trial for motixafortide in allogeneic stem cell transplantation, conducted in collaboration with the Washington University School of Medicine, Division of Oncology and Hematology. In May 2018, the company announced positive top-line results of this study showing, among other things, that a single injection of motixafortide mobilized sufficient amounts of CD34+ 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.

In December 2017, the company commenced a randomized, placebo-controlled Phase 3 registrational trial for motixafortide, known as the GENESIS trial, for the mobilization of HSCs, for autologous transplantation in patients with multiple myeloma.

In August 2020, the company announced a decision to perform an interim analysis on approximately 65% of the original study sample size, primarily based on a significantly lower-than-anticipated patient-dropout rate in the study. In October 2020, the company announced positive results from the interim analysis. In May 2021, the company announced positive top-line results from the Phase 3 trial.

The company continues to follow-up on the GENESIS study patients for relapse-free and overall survival. In addition, it continues to perform detailed analyses of the data according to the statistical analysis plan agreed-upon with the U.S. Food and Drug Administration (FDA), as well as certain post hoc analyses. In December 2021, the company held a pre-NDA meeting with the FDA. In September 2022, the company submitted a New Drug Application (NDA) to the FDA for motixafortide in stem cell mobilization for autologous bone marrow transplantation for multiple myeloma patients and in November 2022, the FDA accepted for review the NDA and assigned the NDA a PDUFA target action date of September 9, 2023.

In October 2021, the company announced positive results from a pharmacoeconomic study evaluating the cost-effectiveness of using investigational drug motixafortide as a primary stem cell mobilization agent on top of granulocyte colony stimulating factor (G-CSF), versus G-CSF alone, in multiple myeloma patients undergoing autologous stem-cell transplantation (ASCT).

In March 2022, the company announced results from a follow-on pharmacoeconomic study performed by the HEOR team of IQVIA.

In September 2022, the company announced its U.S. commercialization plan for APHEXDA (motixafortide) in stem cell mobilization for autologous bone marrow transplantation for multiple myeloma patients.

In March 2023, the company entered into a clinical collaboration with Washington University School of Medicine in St. Louis to advance a Phase 1 clinical trial in which motixafortide will be tested as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene therapies in Sickle Cell Disease (SCD). The study will enroll five adults with a diagnosis of SCD who are receiving automated red blood cell exchanges via apheresis.

Solid tumors

In January 2016, the company entered into a clinical collaboration with MSD (a tradename of Merck & Co., Inc., Kenilworth, New Jersey) in the field of cancer immunotherapy. Based on this collaboration, in September 2016, the company initiated a Phase 2a study, known as the COMBAT/KEYNOTE-202 study, focusing on evaluating the safety and efficacy of motixafortide in combination with KEYTRUDA (pembrolizumab), MSD's anti-PD-1 therapy, in 37 patients with metastatic pancreatic adenocarcinoma, or PDAC.

In July 2018, the company announced the expansion of the COMBAT/KEYNOTE-202 study under the collaboration to include a triple combination arm investigating the safety, tolerability and efficacy of motixafortide, KEYTRUDA and chemotherapy. In December 2019, the company announced that preliminary data from the study indicated that the triple combination therapy showed a high level of disease control, including seven partial responders and 10 patients with stable disease out of 22 evaluable patients. In February 2020, the company completed recruiting a total of 43 patients for the study and in December 2020, it announced the final results of the study.

In August 2016, the company entered into an additional collaboration for the investigation of motixafortide in combination with KEYTRUDA in pancreatic cancer. The focus of this study, in addition to assessing clinical response, was the mechanism of action by which both drugs might synergize, as well as multiple assessments to evaluate the biological anti-tumor effects induced by the combination. The company supplied motixafortide for this Phase 2b study, which commenced in January 2017.

In October 2020, the company announced that motixafortide will be tested in combination with the anti-PD-1 cemiplimab (LIBTAYO) and standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) in first-line PDAC.

In June 2022, the company entered into a collaboration agreement with GenFleet Therapeutics, or GenFleet, an immuno-oncology focused biopharmaceutical company based in China, to advance motixafortide through a randomized Phase 2b clinical trial in PDAC. Under the terms of the agreement, GenFleet will fully fund, design and execute a randomized Phase 2b clinical trial that will enroll approximately 200 first-line metastatic PDAC patients in China.

The company is conducting, or planning to conduct, a number of investigator-initiated, open-label studies in a variety of indications to support the interest of the scientific and medical communities in exploring additional uses for motixafortide.

Motixafortide has been granted three Orphan Drug Designations by the FDA: for use to mobilize HSCs from the bone marrow to peripheral blood for collection in autologous or allogeneic transplantation; for the treatment of AML; and for the treatment of pancreatic cancer. In January 2020, the European Medicines Agency, or EMA, granted Orphan Drug Designation to motixafortide for the treatment of pancreatic cancer.

In September 2022, the FDA approved APHEXDA as motixafortide's trade name.

AGI-134

AGI-134, a clinical therapeutic candidate in-licensed by the company's subsidiary, Agalimmune Ltd., is a synthetic alpha-Gal glycolipid immunotherapy in development for solid tumors. AGI-134 harnesses the body's pre-existing, highly abundant, anti-alpha-Gal antibodies to induce a hyper-acute, systemic, specific anti-tumor response to the patient's own tumor neo-antigens. In August 2018, the company initiated a Phase 1/2a clinical study for AGI-134 that is primarily designed to evaluate the safety and tolerability of AGI-134 in unresectable metastatic solid tumors and to validate AGI-134's mechanism of action using a wide array of biomarkers. In August 2020, the company renewed study enrollment, and in January 2022, it completed enrollment. In December 2022, the company announced results from the study. The study met its primary endpoint of AGI-134's safety and tolerability.

BL-5010

The company's commercialized, legacy therapeutic product, BL-5010, is a customized, proprietary pen-like applicator containing a novel, acidic, aqueous solution for the non-surgical removal of skin lesions. In December 2014, the company entered into an exclusive out-licensing arrangement with Perrigo Company plc, or Perrigo, for the rights to BL-5010 for over-the-counter, or OTC, indications in Europe, Australia and additional selected countries. In March 2016, Perrigo received CE Mark approval for BL-5010 as a novel OTC treatment for the non-surgical removal of warts. In March 2020, the company agreed that Perrigo could relinquish its license rights for certain countries that had been included in its territory according to the original license agreement and was also no longer obligated to develop, obtain regulatory approval for and commercialize products for a second OTC indication. In turn, in March 2020, the company agreed with its licensor of the rights to BL-5010, Innovative Pharmaceutical Concepts (IPC) Inc., or IPC, to return to IPC those license rights no longer out-licensed to Perrigo as a result of the agreement described in the preceding sentence, in consideration of the payment to it of royalties or fees on sublicense receipts.

Strategy

The company's strategy includes commercializing its therapeutic candidates through out-licensing arrangements with biotechnology and pharmaceutical companies and evaluating, on a case-by-case basis, the commercialization of its therapeutic candidates independently.

In-Licensing Agreements

In 2012, the company in-licensed the rights to motixafortide under a license agreement with Biokine Therapeutics Ltd. (Biokine). Pursuant to the agreement, Biokine granted the company an exclusive, worldwide, sublicensable license to develop, manufacture, market and sell certain technology relating to a short peptide that functions as a high-affinity antagonist for CXCR4 and the uses thereof.

In 2017, the company acquired substantially all of the outstanding shares of Agalimmune and entered into the Agalimmune Development Agreement with the selling shareholders.

In 2013, Agalimmune entered into an exclusive license agreement with the University of Massachusetts, which was amended and restated in February 2017, for rights to intellectual property related to AGI-134. Pursuant to the agreement, Agalimmune has an exclusive, worldwide, royalty-bearing, sublicensable license to develop, manufacture, use, import and sell licensed products. Agalimmune is obligated to use diligent efforts to develop the licensed products and to introduce them into the commercial market.

In 2015, Agalimmune entered into an evaluation license and option agreement with Kode Biotech Limited (Kode Biotech) for the rights to intellectual property related to certain water dispersible glycan-lipid conjugates (the 'KODE Constructs'), including AGI-134. Pursuant to the agreement, Agalimmune had an exclusive license to pursue preclinical assessment of the use of the KODE Constructs in Agalimmune's method of promoting tumor anticancer therapy, and the exclusive right to require Kode Biotech to grant Agalimmune an exploitation license to pursue clinical development and commercialization of the use of the KODE Constructs in its method.

In 2017, Agalimmune exercised its option to enter into the exploitation license agreement with Kode Biotech that grants Agalimmune a worldwide, exclusive, royalty-bearing transferable license to develop, manufacture, use, import and sell licensed products, including AGI-134. Agalimmune is obligated to use reasonable, diligent efforts to develop licensed products and to introduce licensed products into the commercial market.

In 2007, the company in-licensed the rights to develop and commercialize BL-5010 under a license agreement with IPC. Under the agreement, IPC granted it an exclusive, worldwide, sublicensable license to develop, manufacture, market and sell certain technology relating to an acid-based formulation for the non-surgical removal of skin lesions and the uses thereof.

Intellectual Property

Patents

As of March 21, 2023, the company owned or exclusively licensed for uses within its field of business 33 patent families that collectively contain 129 issued patents, 10 allowed patent applications and over 80 pending patent applications relating to the three candidates. It is also pursuing patent protection for other drug candidates in its pipeline.

The motixafortide drug product candidate is covered as a composition of matter by a provisional patent application. Corresponding patents, if granted, would expire in December 2041, not including any applicable patent term extension, which might add an additional term of approximately five years on the patent. It also has an exclusive license to a patent family that covers the active ingredient molecule per se. Patents of this family have been granted in the U.S., Europe, Japan, and Canada. The patents would expire in August 2023, not including any applicable patent term extension. It has an exclusive license to a patent family that covers motixafortide combined with a PD1 antagonist for the treatment of cancer. Four patents of this family has been granted in the U.S., and member patent applications are pending in the U.S., Europe, Japan, China, Canada, Australia, India, Korea, Mexico, Brazil and Israel. The granted U.S. patent and patents to issue in the future based on pending patent applications in this family would expire in 2036, not including any applicable patent term extension. In addition, the company has an exclusive license to nineteen other patent families pending or granted worldwide directed to methods of synthesis of motixafortide and methods of use of motixafortide either alone or in combination with other drugs for the treatment of certain types of cancer and other indications. Furthermore, the company has Orphan Drug status for AML, pancreatic cancer and stem cell mobilization, as well as data exclusivity protection afforded to motixafortide as a new chemical entity (NCE).

With respect to AGI-134, Agalimmune owns or has an exclusive license to three patent families that cover the AGI-134 compound and its use for treating cancer. The use of AGI-134 for treating solid tumors is covered by patents granted in the U.S., Europe, China, Japan, and other countries. The patents would expire in 2035, not including any applicable patent term extensions. The compound AGI-134 is covered by patents granted in the United States, Europe, Japan, and other countries. The patents would expire in 2025, not including any applicable patent term extensions. In addition, the future drug product is eligible for obtaining regulatory Biological Product exclusivity (12 years of market exclusivity in the U.S.).

With respect to BL-5010, the company has an exclusive license to a patent family directed to a novel applicator configured for applying the BL-5010 composition to targeted skin tissue safely and effectively. Patents in this family have been granted in the U.S., Europe, Israel, Japan, and China. The patents would expire in 2034.

Trademarks

As of March 21, 2023, the company has registered trademarks for 'APHEXDA' in Israel and also has the same pending trademarks in the EU and Australia and in the United Kingdom, the U.S., Brazil, Canada, China, Japan, and Republic of Korea jurisdictions.

Research and Development

For the year ended December 31, 2022, the company's research and development expenses included $17.6 million.

Regulation

The company's laboratories are in part compliant with FDA regulations setting forth current good laboratory practices (GLP). Its contract manufacturers must ensure that all of the processes, methods and equipment are compliant with cGMP on an ongoing basis, mandated by the FDA and other regulatory authorities, and conduct audits of vendors, contract laboratories and suppliers. The company outsources certain preclinical and clinical development activities to CROs, which meet FDA or European Medicines Agency regulatory standards.

History

BioLineRx Ltd. was founded in 2003 under the laws of the state of Israel. The company was incorporated in 2003.