Although a niche market, cell and gene therapy development and manufacturing is an active area of investment by select bio/pharmaceutical majors, CDMOs/CMOs and smaller bio/pharmaceuticals. Which companies are expanding? DCAT Value Chain Insights rounds up the latest developments.

By Patricia Van Arnum, Editorial Director, DCAT, pvanarnum@dcat.org

Big Pharma’s play in cell and gene therapies
In addition to organic expansions, the large pharma bio/pharma companies gain manufacturing capabilities for cell and gene therapies either from manufacturing agreements with CDMOs/CMOs or by gaining access to a smaller company’s manufacturing capabilities as part of a drug-development deal or acquisition. Some noteworthy deals thus far in 2024 are noted below.

Bristol-Myers Squibb and Gilead Sciences. In April (April 2024), Bristol Myers Squibb (BMS) and Cellares, a South San Francisco, California-based CDMO of cell therapies, announced a worldwide capacity reservation and supply agreement for the manufacture of BMS’ CAR-T cell therapies in a deal worth up to $380 million in upfront and milestone payments. BMS will use Cellares’ proprietary Cell Shuttle platform, an end-to-end, automated cell-therapy manufacturing platform, for the clinical and commercial-scale manufacturing of select CAR-T cell therapies.

As part of the agreement, Cellares will optimize, automate, and tech-transfer select BMS CAR-T cell therapies onto its manufacturing platform. Cellares will dedicate multiple systems for BMS’ exclusive use. The systems will be deployed in Cellares’ facilities in the US, the European Union, and Japan. The agreement expands upon existing collaborations between BMS and Cellares. In August 2023, BMS participated in a financing round that launched the CDMO. That same month, BMS joined Cellares’ technology adoption partnership program to evaluate the Cell Shuttle’s automated manufacturing capabilities.

In June (June 2024), Cellares also announced that Kite, part of Gilead Sciences, will evaluate Cellares’ automated manufacturing platform, the Cell Shuttle. The data generated in this proof-of-concept evaluation will be utilized to assess viability of the Cell Shuttle as a future manufacturing option for Kite.

Earlier this year (2024), Cellares secured $255 million in funding for the launch of an 118,000-square-foot development and commercial-scale manufacturing facility in Bridgewater, New Jersey. The new facility will be capable of producing 40,000 cell-therapy batches per year and is slated to be cGMP-ready in the second half of 2024 and is Cellares’ third manufacturing facility in the US. It operates two facilities in the US. Cellares’ first facility in South San Francisco, California, is used for preclinical process development and tech transfer of manual processes and another South San Francisco facility was slated to be cGMP-ready in the first half of 2024. The company will also break ground on another industrial-scale facility in Europe in 2024.

AstraZeneca. In February (February 2024), AstraZeneca announced plans to invest $300 million in a new cell-therapy manufacturing facility in Rockville, Maryland, for clinical and commercial supply. The facility will initially focus on manufacturing T-cell therapies for clinical supply. The Rockville facility will join AstraZeneca’s global manufacturing and supply network of nearly 30 manufacturing and supply sites in 16 countries, which are either currently operational or under development, In the US, AstraZeneca’s manufacturing sites focus on the production of small molecules and biologics.

AstraZeneca also advanced its position in cell- and gene-therapy manufacturing with two other deals this year. In May (May 2024), AstraZeneca completed an equity investment in Cellectis, a Paris-based bio/pharmaceutical company, in a deal worth up to $840 million ($140 million equity stake and $700 million in milestone payments), relating to cell- and gene-therapy assets. The equity investment and a research collaboration agreement, first announced in November 2023, will use the Cellectis’ gene-editing technologies and manufacturing capabilities to design up to 10 cell- and gene-therapy products for areas, including oncology, immunology and rare diseases. AstraZeneca retains an option for a worldwide exclusive license for the candidate products developed under the research agreement, to be exercised before investigational new drug application filing.

In February (February 2024), AstraZeneca completed its acquisition of Gracell Biotechnologies, a Jiangsu, China-based clinical-stage bio/pharmaceutical company focused on cell-therapies, in a deal worth up to $1.2 billion ($1.0 billion upfront and $234 million in milestone and contingency rights payments). Gracell’s lead asset is GC012F, a CAR-T therapy for treating multiple myeloma, as well as other hematologic malignancies and autoimmune diseases, including systemic lupus erythematosus. Gracell has initiated a Phase Ib/II trial evaluating GC012F for the treatment of relapsed or refractory multiple myeloma in the US.  With the acquisition, AstraZeneca gained Gracell’s proprietary autologous CAR-T-cell therapy manufacturing platform (FasTCART) and an allogeneic CAR-T cell-therapy manufacturing platform (TruUCART).

AbbVie. In January (January 2024), AbbVie and Umoja Biopharma, a Seattle, Washington-based bio/pharmaceutical company, entered two exclusive option and license agreements to develop multiple in-situ generated CAR-T cell therapy candidates in oncology using Umoja’s VivoVec platform, in deals worth up to $1.44 billion.  Umoja’s VivoVec gene-delivery platform combines lentiviral vector gene delivery with a novel T-cell targeting and activation surface complex. This enables T cells in the body to manufacture their own cancer-fighting CAR-T cells in vivo. This has the potential to eliminate a number of challenges associated with traditional CAR-T approaches, including reliance on gathering a patient’s own or donor cells that are modified externally before being delivered back to the patient, the associated time lag and manufacturing challenges of ex vivo cell modification, and the need for patient’s lymphodepletion, according to information from AbbVie. 

Other bio/pharma companies’ moves
Vertex Pharmaceuticals. In April (April 2024), Vertex Pharmaceuticals, a Boston-based bio/pharmaceutical company, and TreeFrog Therapeutics, a Bordeaux, France-based bio/pharmaceutical company, formed a collaboration under which Vertex obtained an exclusive license to TreeFrog’s proprietary cell-manufacturing technology, C-Stem, to optimize production of Vertex’s cell therapies for Type 1 diabetes, in a deal worth up to $780 million ($25 million upfront and $755 million in milestone payments). TreeFrog’s technology platform, C-Stem, is designed to mimic the natural microenvironment by allowing cells to grow exponentially in 3D. The technology will enhance Vertex’s ability to generate large amounts of fully differentiated cells for its portfolio of cell therapies for treating Type 1 diabetes. Under the agreement, TreeFrog receives a $25-million upfront payment, an equity investment from Vertex, and up to $215 million in milestones paid in connection with the development of a scaled-up process for fully differentiated islet cells. TreeFrog is also eligible to receive an additional $540 million in clinical, regulatory, and commercial milestones on up to two future products and tiered single-digit royalties. Vertex is funding all research and development costs related to the collaboration and is responsible for all development and commercialization of its cell therapies.

In addition, last August (August 2023), Vertex Pharmaceuticals and the CDMO Lonza broke ground on a cell-therapy manufacturing facility in Portsmouth, New Hampshire. The new facility is being built adjacent to Lonza’s existing campus in Portsmouth and is a co-investment project between the two companies. Operated by Lonza, the facility will span more than 130,000 square feet. The large-scale manufacturing facility will support the commercial production of Vertex’s Type 1 diabetes cell-therapy portfolio.

BioNTech. In February (February 2024), BioNTech, a Mainz, Germany-based bio/pharmaceutical company, and Autolus Therapeutics, a London-based bio/pharmaceutical company, entered a strategic collaboration to advance both companies’ autologous CAR-T programs, in a deal worth up to $250 million ($50 million upfront and a $200-million equity stake in Autolus by BioNTech). In connection with the strategic collaboration, the companies entered into a license and option agreement and a securities purchase agreement. BioNTech is eligible to receive an up to mid-single digit royalties on net sales of obe-cel, Autolus’ lead CAR-T therapy for treating adult acute lymphoblastic leukemia. Autolus will retain full rights to and control of the development and commercialization of obe-cel. In addition, BioNTech has the option to access Autolus’ commercial and clinical site network, manufacturing capacities in the UK, and commercial supply infrastructure for the development of BioNTech’s BNT211, BioNTech’s most advanced cell-therapy development program, in additional CLDN6+ tumor types. BioNTech says it plans to have 10 or more ongoing potentially registrational clinical trials in the pipeline by the end of 2024, including its fully owned CLDN6 CAR-T program BNT211 in relapsed or refractory germ-cell tumors.

CDMOs expand cell- and gene-therapy manufacturing
Fujifilm Diosynth Biotechnologies. Fujifilm Diosynth Biotechnologies is expanding its site in Thousand Oaks, California, with a new development lab and two new independent manufacturing cleanrooms for producing cell and gene therapies. The added capacity is slated to be operational in early 2025.

Thermo Fisher Scientific. In 2023, Thermo Fisher expanded its cell-therapy network to include a new 44,000-square-foot cell-therapy development and cGMP manufacturing center adjacent to the University of California, San Francisco (UCSF) Medical Center’s Mission Bay campus. In this facility, Thermo Fisher provides UCSF and other customers process and analytical development capabilities, as well as clinical and commercial manufacturing services, for advanced therapies derived from either a patient’s cells or from a donor source. Also, in 2023, Thermo Fisher expanded its Carlsbad, California, plasmids facility to expand process development and GMP operations, specifically at the 30-L and 300-L scales. 

Siegfried. In 2023, Siegfried, a CDMO of drug substances and drug products, acquired a 95% majority stake in Dinamiqs, a Swiss biotechnology company focused on the development and manufacturing of viral vectors for cell and gene therapies. Siegfried intends to bring Dinamiqs’ capabilities to commercial scale and to create a biotech CDMO in that space. This will include the investment in a GMP manufacturing facility, which is on course to go live in 2025. 

Seqens. In December 2023, Seqens, a CDMO of small-molecule active pharmaceutical ingredients (APIs), intermediates, and specialty ingredients, entered the cell- and gene-therapy market via its acquisition of CELLforCURE, a Les Ulis, France-based CDMO of cell and gene therapies, from Novartis. Inaugurated 10 years ago in September 2013, the CELLforCURE site was one of the first modular units in Europe to enable large-scale industrial production of advanced therapy medicinal products.

Other smaller CDMOs expand and new CDMOs enter the market
Bionova Scientific. In June (June 2024), Bionova Scientific, a CDMO of biologics, announced plans to expand into plasmid DNA (pDNA) production with a new development and manufacturing facility in The Woodlands, Texas (near Houston). When the new facility begins operation (planned for the first quarter of 2025), Bionova Scientific will offer pDNA development services and production of pDNA. GMP manufacturing is planned for later in 2025. The expansion is part of a previously announced long-term strategic initiative by the company to broaden its services portfolio to cover a wider range of technical capabilities and therapeutic modalities.

Genezen. In July (July 2024), Genezen, an Indianapolis, Indiana-based CDMO of cell and gene therapies, acquired a gene-therapy manufacturing facility from uniQure, a Lexington, Massachusetts-based bio/pharma company specializing in cell and gene therapies, for $25 million. Genezen acquired the manufacturing equipment and related manufacturing operations along with certain other assets associated with the Lexington facility. The new facility adds to Genezen’s existing clinical manufacturing operations in Indianapolis, Indiana.

ProBio. ProBio, a Hopewell, New Jersey-based CDMO, expanded its plasmid DNA and viral vector manufacturing capabilities with the opening of a new facility in Hopewell, New Jersey, in June (June 2024).  The facility spans approximately 128,000 square feet and encompasses office, laboratory, and manufacturing spaces outfitted with equipment and technology for process development and cGMP production of plasmid DNA and viral vectors, including adeno-associated virus, lentivirus, and retrovirus. The site supports tech transfer, method and analytical development, process development, drug-substance and drug-product manufacturing for both clinical and commercial-grade plasmid DNA and viral vector-based therapies.

Kincell Bio. In April (April 2024), Kincell Bio, a Gainesville, Florida-based CDMO of cell-therapies, and Imugene, a Sydney, Australia-based bio/pharmaceutical company, formed a strategic manufacturing and process development partnership, which included the sale of Imugene’s North Carolina cGMP manufacturing facility and the transfer of process and analytical development activities to Kincell in a deal worth up to $6 million. The 32,800-square-foot facility is designed with the flexibility to expand in capacity and scope to support the manufacture of cell-based therapies. Kincell intends to evolve the site capabilities to manufacture autologous and allogeneic products.

Advanced Medicine Partners. In January (January 2024), Advanced Medicine Partners launched as a new CDMO of advanced therapy products and analytical services, following its spin-off from Jaguar Gene Therapy, a Lake Forest, Illinois-headquartered gene-therapy company. Jaguar launched the CDMO with funding led by Deerfield Management Company, with additional investors, including ARCH Venture Partners, Nolan Capital, and others. Advanced Medicine Partners has more than 33,000 square feet of lab, office and warehouse space in Cary and Durham, North Carolina. The company is in the process of building out a 174,000-square-foot GMP manufacturing facility in Durham.

PluriCDMO. In January (January 2024), Pluri, a Haifa, Israel-based bio/pharmaceutical company, launched a new business division offering cell-therapy manufacturing services as a CDMO: PluriCDMO. PluriCDMO provides services relating to early preclinical development, through late-stage clinical trials and commercialization. The CDMO has a 47,000-square foot GMP cell-therapy production facility.