Gamida Cell Stock

Gamida Cell Ltd. operates as an advanced cell therapy company. The company is committed to finding cures for patients with blood cancers and serious blood diseases. The company develops novel curative treatments using stem cells and Natural Killer (NK) cells.

The company is a cell therapy pioneer working to turn cells into powerful therapeutics. The company applies a proprietary expansion platform leveraging the properties of nicotinamide, or NAM, to allogeneic cell sources, including umbilical cord blood-derived cells and natural killer, or NK, cells to create cell therapy candidates with the potential to redefine standards of care. The company’s primary product candidate is omidubicel, an advanced cell therapy candidate for allogeneic hematopoietic stem cell transplant that, if approved, has the potential to expand access and improve outcomes for patients with blood cancers. Historically, the company had also developed a line of enhanced and engineered NK cells targeted at solid tumors and hematological malignancies.

Omidubicel, the company’s primary product candidate, is designed to address the limitations of donor sources used for HSCT. Omidubicel consists of NAM-expanded and enhanced hematopoietic stem cells and differentiated immune cells, including T cells. The final cell therapy product is cryopreserved until the patient is ready to begin the transplant, when it is thawed and infused. Omidubicel has the potential to be a stem cell donor source in two broad patient groups: patients with high-risk leukemias and lymphomas who require HSCT; and patients with severe hematologic disorders such as severe aplastic anemia. Based on results from the company’s clinical studies, if approved, omidubicel has the potential to improve outcomes as compared to other donor sources and to increase access for patients who cannot find an appropriate donor.

In October 2021, the complete results from the company’s pivotal Phase 3 clinical study of omidubicel in 125 patients with various hematologic malignancies were published in the peer-reviewed medical journal Blood. The trial achieved its primary endpoint of time to neutrophil engraftment, as well as all three of the prespecified secondary endpoints. These secondary endpoints were the proportion of patients who achieved platelet engraftment by day 42, the proportion of patients with grade 2 or grade 3 bacterial or invasive fungal infections in the first 100 days following transplant, and the number of days alive and out of the hospital in the first 100 days following transplant.

In early 2022, the FDA agreed that the initiation of the company’s rolling biologics license application, or BLA, submission for omidubicel was appropriate and it initiated the rolling submission process. The company completed submission of the BLA in June 2022. The FDA accepted the BLA in July 2022. Subsequently, the FDA issued an information request and viewed the data in the company’s response as a major amendment. On November 18, 2022, the company received correspondence from the U.S. Food and Drug Administration, or FDA, that the agency had updated its previous target action date under the Prescription Drug User Fee Act, or PDUFA, from January 30, 2023 to May 1, 2023, for its BLA for omidubicel. In the fourth quarter of 2022, the Israeli Ministry of Health and the FDA completed physical inspections of its Kiryat Gat facility which, to date, has resulted in no FDA 483 observations.

Beginning in March 2023, the company initiated a strategic restructuring of its business to primarily focus on the commercial launch of omidubicel, following FDA approval if granted.

Omidubicel

The company’s clinical trials of omidubicel include an initial safety evaluation of omidubicel in a Phase 1 pilot study at Duke University, a Phase 1/2 clinical trial that enrolled 36 patients in an international, multicenter, open-label, single-arm trial, and a Phase 3 clinical trial that evaluated 125 patients in a pivotal, international, multi-center, randomized trial. All patients in the company’s clinical trials of omidubicel had been previously treated for various hematologic malignancies, including ALL, AML, MDS, CML and lymphoma. These patients were deemed to be in remission and at high risk of subsequent relapse.

Pivotal Phase 3 Trial

In January 2020, the company enrolled the last patient in the pivotal, international, multi-center, randomized Phase 3 trial of omidubicel. Initiated in 2017, the study compared omidubicel to single or double standard, unmanipulated umbilical cord blood transplantation. Randomization was stratified by treatment center, disease risk, age and intent to perform single or double cord blood transplant.

In addition to hematologic malignancies, the company ispursuing the development of omidubicel for the treatment of severe aplastic anemia and other bone marrow failure disorders. Severe aplastic anemia is a rare disease, with an estimated incidence in the United States of 600-900 patients per year.

Omidubicel has also been tested in patients with sickle cell disease, or SCD, for which HSCT is the only clinically established cure. The results of the company’s Phase 1/2 clinical trial were published in Blood. Overall, 16 patients with severe SCD were treated, 13 patients with omidubicel in conjunction with a standard unit of cord blood, and three patients with standalone omidubicel. All patients initially engrafted at a median of seven days for double cord and eight days for single cord. Two of the patients died, one due to chronic GvHD and the other due to secondary graft failure.

NK Cell Product Candidates

The company’s pipeline of NK cell-based cancer immunotherapies consists of GDA-201 and three additional preclinical programs that involve modifications intended to direct NK cells against specific tumor markers to improve their cancer killing capabilities in both hematological and solid tumors.

GDA-201 is the company’s lead investigational NK cell-based cancer immunotherapy product candidate. GDA-201 addresses a key limitation in the therapeutic potential of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture conditions. GDA-201 was evaluated in an investigator-sponsored Phase 1/2 trial for the treatment of NHL and MM.

In May 2022, the company announced the dosing of its first patient in a Phase 1/2 clinical trial of GDA-201 for the treatment of patients with follicular and diffuse large B-cell lymphomas, and patient enrollment in this study is ongoing.

GDA-201

The company has developed GDA-201, a cell therapy product candidate generated by expansion of healthy donor NK cells using the company’s NAM technology. GDA-201 has potential application in boosting the innate immune response to cancer. Functional studies have shown that the company’s GDA-201 cells expanded in culture with its NAM technology and the cytokine IL-15 display increased tumor killing activity over NK cells expanded with IL-15 but without NAM. The company has also demonstrated ADCC with GDA-201 in combination with antibodies, including rituximab.

Additional NK Cell Product Candidates

The company has developed other NAM-enabled genetically modified NK cell product candidates, which utilize CAR, membrane bound- and CRISPR-mediated strategies to increase targeting, potency and persistence against hematologic malignancies and solid tumors. As part of its strategic restructuring, in March 2023, the company discontinued development of this preclinical pipeline.

GDA-301: Knockout of CISH, or cytokine inducible SH2 containing protein, in NK cells using CRISPR/Cas9 in combination with a membrane-bound IL-15/IL-15Ra. Designed to improve tumor killing by promoting activation of NK cells and inhibiting negative feedback signals. Potential applications exist across a range of solid tumors and hematologic malignancies. Data presented at the International Society for Cell & Gene Therapy, or ISCT, 2022 meeting demonstrated that after six hours of co-culture with a chronic myelogenous leukemia (K562) or multiple myeloma (RPMI) cell line, GDA-301, a combined genetic manipulation of CISH gene editing and the engineered expression of mb IL-15, showed increased cytotoxicity compared with control NAM-NK cells. Additional in vitro assays showed elevation of degranulation marker CD107alpha, intracellular proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha, suggesting increased potency of GDA-301 compared with control cells. The potency and cytotoxicity data suggest that GDA-301 represents a novel potential immunotherapeutic targeting hematologic malignancies, as well as solid tumors.

GDA-501: CAR-engineered NK cells to target HER2+ solid tumors with the potential to enhance homing and activation against cancers with HER2 overexpression, including breast, ovarian, lung, bladder, and gastric cancers.

GDA-601: Knockout of CD38 on NK cells to avoid fratricide by CD38-targeting antibodies in combination treatment of multiple myeloma, combined with a CD38 CAR designed to enhance killing of multiple myeloma cells.

Marketing, Sales and Distribution

The company’s strategy is to ensure omidubicel is made available to appropriate patients upon FDA approval. While the BLA for omidubicel is under review by the FDA, the company is preparing for a commercial launch of omidubicel in the United States that will require a more limited investment resulting in a slower ramp of sales.

Strategy

The key elements of the company’s strategy are to obtain regulatory approval for omidubicel in hematologic malignancies; and initial commercial launch of omidubicel in the United States, if approved.

Intellectual Property

As of December 31, 2022, the company owned 33 issued patents and 61 pending patent applications worldwide, including five U.S. issued patents, six pending U.S. non-provisional patent applications and three pending PCT applications.

The company owns two issued patents in the United States and 17 issued foreign patents related to its omidubicel product candidate. The patents that the company owns outside of the United States are granted in Australia, Canada, Europe, Hong Kong, Israel, Japan, Singapore, and South Africa. In addition, the company owns two pending U.S. non-provisional patent applications and 16 pending foreign patent applications related to its omidubicel product candidate. These patents and pending patent applications contain composition-of-matter claims to the company’s omidubicel product candidate, and claims to methods of producing and methods of treatment using omidubicel. Not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, these patents, and if granted, these patent applications, will expire from 2023 to 2038. In particular, U.S. Patent No. 7,955,852, EP Patent No. 1576089, EP Patent No. 2206773, JP Patent No. 4738738, and IL Patent No. 163180, which relate to methods of expanding a population of hematopoietic stem cells by culturing the cells with nicotinamide or nicotinamide analogs, and transplantable cell populations produced by these methods, expire in 2023, not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely and U.S. Patent No. 8,846,393, EP Patent No. 1974012, JP Patent No. 5102773 and IL Patent No. 191669, which relate to methods of enhancing cell homing and engraftment potential of hematopoietic stem cells by expansion in the presence of nicotinamide, expire in 2026, not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely.

The company owns 11 issued foreign patents related to GDA-201. The patents that the company owns outside of the United States are granted in Australia, Canada, Europe, Hong Kong, Israel, Canada, and Japan. In addition, the company owns four pending U.S. non-provisional patent applications, one pending PCT patent application and 36 pending foreign patent applications related to its GDA-201 product candidate. These patents and pending patent applications contain composition-of-matter claims to the company’s GDA-201 product candidate, and claims to methods of producing and methods of treatment using its GDA-201 product candidate. Not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, these patents, and if granted, the U.S. non-provisional patent applications and foreign patent applications, will expire from 2030 to 2040, and patents, and if granted, patent applications claiming priority to the PCT application will expire in 2042. In particular, EP Patent No. 2519239, EP Patent No. 3184109, JP Patent No. 5943843, JP Patent No. 6215394, IL Patent No. 220660, IL Patent No. 259642, CA Patent No. 2,785,627 and CN Patent No. ZL201710426660.X, which relate to methods of expanding a population of natural killer cells by culturing the cells with nicotinamide or nicotinamide analogs, and transplantable cell populations produced by these methods, expire in 2030, not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely.

The company owns PCT application related to GDA-301 and GDA-601. This pending PCT application contains composition-of-matter claims to the company’s GDA-301 and GDA-601 product candidates, and claims to methods of producing and methods of treatment using its GDA-301 and GDA-601 product candidates. Not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, patent applications claiming priority to this U.S. PCT, if granted, would expire in 2042.

The company owns two PCT applications related to GDA-501. These PCT applications contain composition-of-matter claims to the company’s GDA-501 product candidate, and claims to methods of producing and methods of treatment using its GDA-501 product candidate. Not accounting for any patent term adjustment, regulatory extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, patent applications claiming priority to these PCT applications, if granted, would expire in 2042.

In addition, the company filed for and obtained trademark registration in the China, Europe, Hong Kong, Mexico, Canada, Brazil, Russian Federation, Israel, Great Britain and WIPO (International) for Gamida Cell, and in Israel for Symrepliq, Gamida-Cell Assist, Nampluri, Namrepli, Namtypic, Omisirge and Omplusto.

Research and Development

The company’s research and development expenses, net, were approximately $42.7 million in the year ended December 31, 2022.

Government Regulation

The FDA and other regulatory authorities at federal, state, and local levels, as well as in non-U.S. countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics, such as those the company is developing.

Biologic manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP (current Good Manufacturing Practices), which impose certain procedural and documentation requirements upon the company and its third-party manufacturers.

Environmental, Health and Safety Matters

The company’s operations use chemicals and produce waste materials and sewage and require permits from various governmental authorities, including local municipal authorities, the Ministry of Environmental Protection, and the Ministry of Health.

History

Gamida Cell Ltd. was founded in 1998. The company was incorporated in 1998.