Overview

Bellicum Pharmaceuticals (BLCM) is a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for various forms of cancer, including both hematological cancers and solid tumors, as well as orphan inherited blood disorders. Bellicum Pharmaceuticals is using its proprietary Chemical Induction of Dimerization, or CID technology platform to engineer its product candidates with switch technologies that are designed to control components of the immune system in real time. By incorporating its CID platform, its product candidates may offer better safety and efficacy outcomes than are seen with current cellular immunotherapies.

Bellicum Pharmaceuticals is developing next-generation product candidates in some of the most important areas of cellular immunotherapy, including hematopoietic stem cell transplantation, or HSCT, chimeric antigen receptor T cell therapy, or CAR T, and T cell receptors, or TCRs. HSCT, also known as bone marrow transplantation, has for decades been curative for many patients with hematological cancers or orphan inherited blood disorders. However, adoption of HSCT to date has been limited by the risks of transplant-related morbidity and mortality from graft-versus-host-disease, or GvHD, and the potential for serious infections due to the lack of an effective immune system following a transplant. CAR T and TCR cell therapies are an innovative approach in which a patient’s T cells are genetically modified to carry chimeric antigen receptors, or CARs, or TCRs which redirect the T cells against cancer cells. While high objective response rates have been reported in some hematological malignancies, serious and sometimes fatal toxicities have arisen in patients treated with CAR T cell therapies. These toxicities include instances in which the CAR T cells have caused high levels of cytokines due to over-activation, referred to as “cytokine release syndrome,” or CRS, neurologic toxicities and cases in which they have attacked healthy organs. In each case, these toxicities have sometimes resulted in death. In solid tumors, where the behavior of CAR T cells is particularly unpredictable and results have been inconsistent, enhanced CAR T cell approaches are being developed that raise even greater safety concerns.

The company's proprietary CID platform is designed to address these challenges. Events inside a cell are controlled by cascades of specialized signaling proteins. CID consists of molecular switches, modified forms of these signaling proteins, which are triggered inside the patient by infusion of a small molecule, rimiducid, instead of by natural upstream signals. The company include these molecular switches in the appropriate immune cells and deliver the cells to the patient in the manner of conventional cellular immunotherapy. Bellicum Pharmaceuticals has developed two such switches: a “safety switch,” designed to initiate programmed cell death, or apoptosis, of the immunotherapy cells, and an “activation switch,” designed to stimulate activation and in some cases proliferation and/or persistence of the immunotherapy cells. Each of its product candidates incorporates one of these switches, for enhanced, real time control of safety and efficacy:

  • CaspaCIDe is its safety switch, incorporated into its HSCT and TCR product candidates, where it is inactive unless the patient experiences a serious side effect. In that event, rimiducid is administered to induce Caspase-9, or iCaspase, switch activation to fully or partially eliminate the cells, with the goal of terminating or attenuating the therapy and resolving the serious side effect.
  • The company's “Go” switch incorporated into its GoCAR-T product candidates contains its proprietary inducible MyD88/CD40 or iMC activation switch and is designed to allow control of the activation and proliferation of the T cells through the scheduled administration of a course of rimiducid infusions that may continue until the desired patient outcome is achieved. In the event of emergence of side effects, the level of activation of the GoCAR-T cells is designed to be attenuated by extending the interval between rimiducid doses, reducing the dosage per infusion, or suspending further rimiducid administration.

In addition, Bellicum Pharmaceuticals has an active research effort to develop other advanced molecular switch approaches, including a “dual-switch” that is designed to provide a system for managing persistence and safety of tumor antigen-specific CAR T cells.

By incorporating its novel switch technologies, Bellicum Pharmaceuticals is developing product candidates with the potential to elicit positive clinical outcomes and ultimately change the treatment paradigm in various areas of cellular immunotherapy. The company's lead clinical product candidate is described below.

  • BPX-501 is a CaspaCIDe product candidate designed as an adjunct T cell therapy administered after allogeneic HSCT. BPX-501 is designed to improve transplant outcomes by enhancing the recovery of the immune system following an HSCT procedure. BPX-501 addresses the risk of infusing donor T cells by enabling the elimination of donor T cells through the activation of the CaspaCIDe safety switch if there is an emergence of uncontrolled GvHD.

The European Commission has granted orphan drug designations to BPX-501 for treatment in HSCT, and for activator agent rimiducid for the treatment of GvHD. Additionally, BPX-501 and rimiducid have received orphan drug status from the U.S. Food and Drug Administration, or the FDA, as a combination replacement T-cell therapy for the treatment of immunodeficiency and GvHD after allogeneic HSCT. During 2016, the company discussed with the European Medicines Agency, or the EMA, clinical and regulatory plans to support the filing of Marketing Authorization Applications, or MAAs, for BPX-501 and rimiducid in Europe, initially for pediatric patients with certain orphan inherited blood disorders or treatment-refractory hematological cancers. Based on the regulatory discussions, the company believe that data from the European arm of its BP-004 trial, expanded to enroll additional patients, with a primary endpoint of event-free survival, (with events defined as transplant-related or non-relapse mortality, severe GvHD, and serious infection) at six months, could form the basis of MAAs for BPX-501 and rimiducid. In addition, the EMA’s Committee for Medicinal Products for Human Use, or the CHMP, has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric haploidentical hematopoietic stem cell transplant setting. Exceptional circumstances may be granted for medicines that treat very rare diseases, or where controlled studies are impractical or not consistent with accepted principles of medical ethics. In place of a randomized trial, Bellicum Pharmaceuticals is collecting data from a concurrent observational study in the pediatric matched unrelated donor hematopoietic stem cell transplant setting, which will include both retrospective patients and prospective patients.

Bellicum Pharmaceuticals is working on plans and assessing feasibility for future U.S. clinical trials of BPX-501. The company expect to pursue one or more clinical trials with the intent of an eventual filing for regulatory approval in the U.S., partially supported by a $16.9 million award from the Cancer Prevention and Research Institute of Texas, or CPRIT.

In addition to BPX-501, its clinical stage product candidates which are designed to overcome limitations of CAR T and TCR therapies, include the following:

  • BPX-701 is a CaspaCIDe-enabled natural high affinity TCR product candidate designed to target malignant cells expressing the preferentially-expressed antigen in melanoma, or PRAME. Initial planned indications for BPX-701 development are refractory or relapsed acute myeloid leukemia, or AML, and myelodysplastic syndromes, or MDS, and are considering studies in additional indications. Each of these is an orphan indication where PRAME is highly expressed and for which current treatment options are limited. A Phase 1 dose finding clinical trial in patients with relapsed or refractory myeloid neoplasms is being conducted at the Oregon Health & Science University Hospital in Portland, Oregon.
  • BPX-601 is a GoCAR-T product candidate designed to treat solid tumors expressing prostate stem cell antigen, or PSCA. Preclinical data shows enhanced T cell proliferation, persistence and in vivo anti-tumor activity compared to traditional CAR T therapies. A Phase 1 clinical trial in patients with non-resectable pancreatic cancer is being conducted at the Baylor Sammons Cancer Center in Dallas, Texas.
  • CD19 CAR-T Program - Bellicum Pharmaceuticals is working with academic collaborators to establish clinical proof of concept for CaspaCIDe ® in the CD19 setting. The company believe that this strategy allows a cost-effective approach for clinical evaluation of differentiated product candidates in the highly competitive landscape of CD19-targeted therapies. As part of this strategy, in November 2016 the company announced an expanded collaboration with Ospedale Pediatrico Bambino Gesù, a leading European pediatric research center and hospital, and expect a CaspaCIDe-enabled CD19 CAR-T cell therapy to enter clinical development in the fourth quarter of 2017.

Bellicum Pharmaceuticals has developed an efficient and scalable process to manufacture genetically modified T cells of high quality, which T cells are currently being manufactured in-house and by third-party contract manufacturers in Europe to produce BPX-501 for its clinical trials. Bellicum Pharmaceuticals is leveraging this process, as well as its resources, capabilities and expertise for the manufacture of its CAR T and TCR product candidates.

Pipeline

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Recent development

Feb. 23, 2018 - Bellicum Pharmaceuticals, Inc., a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, today announced it has received notification from the U.S. Food and Drug Administration (FDA) outlining the criteria required for lifting the clinical hold on U.S. studies of BPX-501. To address the FDA requirements, the Company plans to implement revisions to the U.S. study protocols, including the addition of more comprehensive monitoring and management of neurotoxicity. In addition, the Company will revise the Investigator Brochure and Informed Consent Documents to inform healthcare providers, patients and caregivers of the changes. The Company expects to provide a full response to the FDA within a few weeks.

The clinical hold does not affect the Company’s BP-004 registration trial in Europe.

About BPX-501

BPX-501 is an adjunct T cell therapy administered after allogeneic hematopoietic stem cell transplant (HSCT) to improve outcomes in patients who lack a matched donor. It is comprised of genetically modified donor T cells incorporating Bellicum’s CaspaCIDe® safety switch. BPX-501 is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections and enhance Graft-versus-leukemic effect without unacceptable GvHD risk.

Feb. 21, 2018 (GLOBE NEWSWIRE) -- Bellicum Pharmaceuticals, Inc. announced the appointment of Edmund Harrigan, M.D. to its Board of Directors. Dr. Harrigan has 28 years of pharmaceutical industry experience serving in various executive leadership positions across Business Development, Clinical, Drug Safety, and Regulatory affairs, most recently as Senior Vice President, Worldwide Safety and Regulatory at Pfizer Inc.

Throughout his career, Dr. Harrigan has held multiple executive leadership roles at Pfizer, spanning 18 years. Most recently, as Senior Vice President of Worldwide Safety and Regulatory for Pfizer from 2012 to 2015, he led a 3,500-person team in 80 countries that was responsible for collecting, interpreting and reporting clinical safety data for more than 600 marketed products, and managing regulatory interactions with global health agencies. Previously at Pfizer, he also served as Senior Vice President, Head of Worldwide Business Development and Senior Vice President, Head of Worldwide Regulatory Affairs and Quality Assurance. In addition to his experience at Pfizer, Dr. Harrigan previously served as President & CEO of Karuna Pharmaceuticals, and in senior clinical leadership positions at Neurogen Corp. and Sepracor, Inc.

Feb. 05, 2018 - Bellicum Pharmaceuticals, Inc. , a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, today announced the appointment of William Grossman, M.D., Ph.D., as Chief Medical Officer, effective February 5. Dr. Grossman joins Bellicum from Genentech/Roche.

In his most recent role at Genentech, Dr. Grossman served as the Group Medical Director, Cancer Immunotherapy, where he led the global clinical development of TECENTRIQ® in gastrointestinal cancers and of cancer immunotherapy combinations across all solid tumor types. Among other accomplishments in this role, Dr. Grossman conceived and led the development of the Phase 1b/2 MORPHEUS platform to evaluate cancer immunotherapy combinations more rapidly and efficiently. Previously, he served as Senior Vice President, Research & Clinical Development at Biothera, where he oversaw all discovery and clinical development efforts in oncology and immunology. Dr. Grossman has also held leadership positions in research, clinical development, and medical affairs at AbbVie, Baxter Healthcare, and Merck & Co., where he was involved in the development and clinical study of cancer vaccines, immunomodulatory agents, and small molecules/biologics in oncology.

Tags: US:BLCM
Created by Asif Farooqui on 2019/09/30 06:47
     
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