About Cleveland BioLabs

Cleveland BioLabs, Inc., a biopharmaceutical company, develops approaches to activate the immune system and address serious medical needs. The company’s proprietary platform of Toll-like immune receptor activators has applications in mitigation of radiation injury and immuno-oncology. Entolimod Entolimod, a Toll-like receptor 5 (TLR5) agonist, which the company is developing as a medical radiation countermeasure (MRC) for reducing the risk of death following exposure to potentially lethal irradiation Acute Radiation Syndrome (ARS) is its advanced product candidate. Other indications, including immunotherapy for oncology, have been or are being investigated as well. Entolimod as an MRC is being developed under the U.S. Food & Drug Administration’s (FDA’s) Animal Efficacy Rule for the indication of reducing the risk of death following exposure to potentially lethal irradiation occurring as a result of a radiation disaster. The company has completed two Good Clinical Practices clinical studies designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of entolimod in a total of 150 healthy subjects. It has completed a Good Laboratory Practices (GLP), randomized, blinded, placebo-controlled, pivotal study designed to evaluate the dose-dependent effect of entolimod on survival and biomarker induction in 179 non-human primates exposed to 7.2 Gy total body irradiation when entolimod or a placebo was administered at 25 hours after radiation exposure. The company has also completed a GLP, randomized, open-label, placebo-controlled, pivotal study designed to evaluate the dose-dependent effect of entolimod on biomarker induction in 160 non-irradiated non-human primates. In 2015, following confirmation from the FDA on the sufficiency of the company’s existing efficacy and safety data and animal-to-human dose conversion, it submitted to the FDA an application for pre-Emergency Use Authorization (pre-EUA), a form of authorization granted by the FDA under certain circumstances In addition, the company submitted a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for entolimod as an MRC in Europe. The MAA was validated by the EMA in the fourth quarter of 2017 but was withdrawn in August 2018 because a complete response to certain questions posed by the EMA could not be prepared in the time frame required by the EMA's review process as a result of the delay in its receipt of the results of the bio-comparability study. The MAA application remains in a withdrawn state and the company continues to evaluate its next steps with the EMA in parallel with progress on review of the pre-EUA application. In addition to development work on the MRC for reducing the risk of death from ARS indication, the company has completed a Phase 1 open-label, dose-escalation trial of entolimod in 26 patients with advanced cancer in the United States (U.S.). The data for the U.S. study were presented at the 2015 annual meeting of the American Society of Clinical Oncology. Seven additional patients have been dosed with the entolimod drug formulation proposed for commercialization under the pre-EUA and MAA in an extension of this study performed in Russia. In 2018, the company created a joint venture called Genome Protection, Inc. (GPI) with Everon Biosciences, Inc. (Everon). GPI, which is 50% owned by the company and 50% owned by Everon, is undertaking a research and development program aimed at clinical testing of entolimod and GP532 (a variant of its entolimod drug candidate) and the development of medications with anti-aging and other indications associated with genome damage. Mobilan Mobilan is a recombinant non-replicating adenovirus that directs expression of TLR5 and its agonistic ligand, a secretory non-glycosylated version of entolimod the company is also developing through its subsidiary, Panacela Labs, Inc. (Panacela). Two randomized, placebo-controlled, dose-ranging studies of Mobilan in men with prostate cancer are ongoing in Russia. In 2016, Panacela completed enrollment of patients in a Phase 1 multicenter, randomized, placebo-controlled, single-blinded study in Russia evaluating single injections of ascending doses of Mobilan administered directly into the prostate of patients with prostate cancer. Panacela holds exclusive worldwide development and commercialization rights to Mobilan. As of December 31, 2020, the company owned 67.57% of Panacela. CBL0137 CBL0137 is a small molecule with a multi-targeted mechanism of action that may be broadly useful for the treatment of many different types of cancer and is being developed by Incuron LLC (Incuron). During 2015, the company sold its remaining equity interest in Incuron but retain a 2% royalty on product sales of CBL0137, consideration received by Incuron from a licensee or sublicensee, and consideration received in connection with the first change of control of Incuron. Incuron’s royalty obligations continue until April 29, 2025. CBL0137 may offer efficacy and substantially lower risk for the development of drug resistance than conventional chemotherapeutic agents. CBL0137 inhibits MYC protein, Nuclear Factor kappa-B, Heat Shock Factor Protein-1, and Hypoxia-inducible factor 1-alpha, which are transcription factors that are important for the viability of many types of tumors. The drug also activates tumor suppressor protein p53 by modulating intracellular localization and activity of chromatin remodeling complex facilitates chromatin transcription. CBL0137 has been shown to be efficacious in animal models of colon, lung, breast, renal, pancreatic, head and neck and prostate cancers; melanoma; glioblastoma; and neuroblastoma. It has also been shown to be efficacious in animal models of hematological cancers, including lymphoma, leukemia, and multiple myeloma. Incuron holds worldwide development and commercialization rights to CBL0137. Strategic Partnerships The company has licensed rights in each of its technologies from The Cleveland Clinic (CCF) and Roswell Park Cancer Institute (RPCI). Through these partnerships the company has collaborated with scientists from other countries to develop its novel technologies and accessed non-traditional funding sources, including the U.S. federal and foreign government contracts and project-oriented funding. CCF In 2004, the company entered into an exclusive license agreement with CCF (‘The Cleveland Clinic License’) pursuant to which it was granted an exclusive license to CCF’s research base underlying its therapeutic platform. The company amended The Cleveland Clinic License, effective as of September 22, 2011, pursuant to which it was granted an exclusive license to CCF’s research base underlying certain product candidates in development by Panacela (‘Panacela Products’), including Mobilan and several earlier-stage compounds that are not material to its business. RPCI The company has entered into a number of agreements with RPCI relating to the licensure and development of its product candidates, including two exclusive license and option agreements effective December 2007 and September 2011; various sponsored research agreements entered into between January 2007 to present; and clinical trial agreements for conducting its Phase 1 entolimod oncology study and Incuron’s Phase 1 CBL0137 intravenous administration study. In 2007, the company entered into an agreement with RPCI pursuant to which CBLI has an option to exclusively license any technological improvements to its foundational technology developed by RPCI for the term of the agreement. In 2011, Panacela entered into an agreement with RPCI (the ‘Panacela-RPCI License’) to exclusively license from RPCI certain rights to the Panacela Products, including Mobilan and several earlier-stage compounds that are not material to its business, and to non-exclusively license from RPCI certain know-how relating to the aforementioned product candidates for the limited purposes of research and development and regulatory, export and other government filings. Additionally, under the Panacela-RPCI License, Panacela has a right to exclusively license from RPCI any technological improvements to the Panacela Products developed by RPCI before September 2016; and any technology jointly developed by Panacela and RPCI. Intellectual Property The company’s patent portfolio includes patents and patent applications with claims directed to compositions of matter, pharmaceutical formulations, and methods of use. In the U.S., the company has 25 issued patents or allowed patent applications relating to our clinical-stage programs expiring on various dates between 2024 and 2032, as well as numerous pending patent applications and foreign counterpart patent filings, which relate to its proprietary technologies. These patents and patent applications include claims directed to compositions of matter and methods of use. The company has 22 issued or allowed U.S. patents covering entolimod, which expire between 2024 and 2032. These patents include composition of matter claims, as well as method of use claims relating to its biodefense and oncology indications, reducing effects of chemotherapy, and treatment of reperfusion injuries. In addition, it has pending U.S. patent applications related to compositions of matter, oncology methods of use, and others biodefense methods, which if issued, will expire between 2025 and 2035. The company has 2 issued or allowed U.S. patents covering CBLB612 and related agents, which expire between 2026 and 2027. These patents include composition of matter and methods of use claims. The company has one issued U.S. patent covering compositions of matter for various vectors, including Mobilan, which expires in 2032. It also has issued or allowed patents covering Mobilan and related agents, which expire in 2030 that cover a broad list of international territories, including the European Union, Australia, Japan, and Russia. These patents include composition of matter and methods of use claims. In addition, as of December 31, 2020, the company had approximately 35 additional patents and patent applications filed worldwide. Any patents that may issue from its pending patent applications would expire between 2024 and 2035, excluding patent term extensions. These patents and patent applications disclose compositions of matter and methods of use. Suppliers The company relies on third-party manufacturers, and in most cases only one third-party, Wacker Biotech B.V., to manufacture critical raw materials, drug substance and final drug product for its research, preclinical development, and clinical trial activities. Research and Development As of December 31, 2020, the company’s research and development expenses were $0.7 million. Regulation In the U.S., the FDA regulates drugs and drug testing under the Federal Food, Drug, and Cosmetic Act and in the case of biologics, also under the Public Health Service Act. The company’s product candidates must follow processes consistent with these laws before they may be marketed in the U.S. The company must submit to the FDA the results of nonclinical studies, which may include laboratory evaluations and animal studies, together with manufacturing information and analytical data, and the proposed clinical protocol for the first clinical trial of the drug as part of an Investigational New Drug application. Entolimod has been granted Fast Track designation by the FDA for reducing the risk of death following total body irradiation. Entolimod has been granted Orphan Drug designation by the FDA for prevention of death following a potentially lethal dose of total body irradiation. The company’s Russian activities are regulated by the Ministry of Health of the Russian Federation (Minzdrav). The principal statute that governs the company’s activities in Russia is the Federal Law No. 61-FZ ‘On Medicine Circulation’ of April 12, 2010 (as amended). In particular, the incorporation, corporate governance, shareholders' rights, and contractual matters related to its Russian subsidiaries and joint ventures are governed by the Civil Code of the Russian Federation and the Federal Law No. 14-FZ ‘On Limited Liability Companies’ of February 8, 1998 (as amended). Also, pursuant to the Russian Labor Code, the company’s Russian subsidiaries and joint ventures must enter into employment contracts with each employee, afford them at least 28 days paid vacation period, limit the working week to 40 hours per week and follow the code’s specific procedures in case of employment termination. Competition The company competes with various companies developing radiation countermeasures to treat the effects of ARS, including Aeolus Pharmaceuticals; Araim Pharmaceuticals, Inc.; Cellerant Therapeutics, Inc.; Humanetics Corporation; Neumedicines, Inc.; Pluristem Therapeutics, Inc; RxBio, Inc.; and Soligenix, Inc. History Cleveland BioLabs, Inc. was founded in 2003. The company was incorporated under the laws of the state of Delaware in 2003.