Feliza Mirasol is the science editor for 

Feliza Mirasol

Charles River Laboratories International announced the launch of its off-the-shelf replication/capsid (rep/cap) plasmids for the manufacture of adeno-associated virus (AAV) vectors during Advanced Therapies Week, held Jan. 16–19, 2024 in Miami Beach, Fla. These plasmids are designed to streamline AAV-based gene therapy programs, according to a company press release.

The addition of AAV rep/cap (RC2, 5, 6, 8, 9) follows a previously announced launch of the company’s lentiviral packaging and AAV helper plasmid products. According to Charles River, the ready-to-use plasmid products are produced and released according to batch production records. The products include chemistry, manufacturing, and controls guidance and a certificate of analysis to support investigational new drug and clinical trial application filing.

Standard off-the-shelf plasmids, such as helper and rep/cap plasmids required for AAV production, are immediately available, which can lower development costs, risks, and timelines for gene therapy developers, according to the press release. Charles River’s rep/cap plasmids have been used to support the production of AAV serotypes carrying various therapeutic transgenes at multiple development and good manufacturing practice production scales.

“The reduction in production time and improved efficacy of the supply chain will help accomplish our ultimate goal of delivering safe, effective therapies to patients, faster,” said Kerstin Dolph, senior vice-president, Manufacturing, Charles River, in the release.

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Charles River’s off-the-shelf rep/cap plasmids are intended to simplify gene therapy supply chains.

Charles River Launches Off-the-Shelf Rep/Cap Plasmids for AAV Vector Manufacturing

Merck, known as MSD outside of the United States and Canada, and Harpoon Therapeutics, a US-based clinical-stage immuno-oncology company, announced on Jan. 8, 2024 that they have entered into a definitive agreement for Merck to acquire Harpoon via a Merck subsidiary. Merck will acquire Harpoon for $23.00 per share in cash, or a total equity value of approximately $680 million. The transaction is expected to close in the first half of 2024.

Under the agreement, Merck will gain Harpoon’s lead candidate, HPN328, a T-cell engager targeting delta-like ligand 3 (DLL3). DLL3 is an inhibitory canonical Notch ligand that has been shown to be expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors. HPN328 is currently being studied in a Phase I/II clinical trial as a monotherapy in patients with advanced cancers associated with the expression of DLL3. It is also being studied in combination with atezolizumab in patients with SCLC. Harpoon announced positive interim tolerability and response data in certain patients with SCLC and neuroendocrine tumors last October 2023.

Harpoon has developed a portfolio of novel T-cell engagers using the company’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform. The TriTAC platform is an engineered protein technology that has been designed to direct a patient’s own immune cells to kill tumor cells. In addition, the company’s ProTriTAC platform involves the application of a prodrug concept to the TriTAC platform to create a therapeutic T-cell engager that is designed to remain inactive until it reaches the tumor.

Additional candidates in the company’s pipeline include HPN217, which targets B-cell maturation antigen (BCMA). HPN217 is currently in Phase I clinical development for treating patients with relapsed/refractory multiple myeloma. The company also has several preclinical-stage candidates, including HPN601, which is a conditionally activated targeting epithelial cell adhesion molecule (EpCAM) for treating certain patients with EpCAM-expressing tumors.

“At Merck, we continue to enhance our oncology pipeline through strategic acquisitions that complement our current portfolio and advance breakthrough science to help address the needs of people with cancer worldwide,” said Dean Y. Li, president, Merck Research Laboratories, in a company press release. “This agreement reflects the creativity and commitment of scientists and clinical development teams at Harpoon. We look forward to further evaluating HPN328 in innovative combinations with other pipeline candidates.”

“At Harpoon, we have always been committed to advancing our cancer immunotherapy candidates to improve the lives of patients. With Merck’s recognized leadership in oncology clinical development and global commercial footprint, our lead candidate, HPN328, is well positioned moving forward,” said Julie Eastland, president and chief executive officer, Harpoon Therapeutics, in the press release.

Through the acquisition of Harpoon Therapeutics, Merck will gain an investigational delta-like ligand 3-targeting T-cell engager under development for cancer treatment.

Merck to Acquire Harpoon Therapeutics in Deal Valued at $680 Million

On Jan. 11, 2024, Boehringer Ingelheim announced that it is investing €120 million (US$131 million) to further expand and upgrade its production facility in Koropi, Greece. With the investment, the company plans to increase manufacturing capacity of new and existing medications, some of which are in late-stage development in the company’s pipeline. The company is investigating several main disease areas, including cardio-renal-metabolic diseases, mental health, and pulmonary fibrosis.

According to a company press release, the expansion will boost medicine exports from Greece, in particular Jardiance (empagliflozin) for treating type 2 diabetes, chronic (long-term) heart failure, and chronic kidney disease, to the US market. The expansion will also create 110 additional jobs. The company had originally announced multi-year investments in 2020 to expand the Koropi site and its production capacity.

The expansion falls in line with the company’s goal of implementing innovative production technologies to support its R&D activities, the company stated in its press release. In 2022, the company spent €4.6 billion (US$5 billion) for its Human Pharma R&D unit, with 25% of Human Pharma net sales being reinvested to advance science and cutting-edge research for innovative therapeutics.

“This expansion investment will bring some of our most innovative therapies to an increasing number of patients globally,” said Hubertus von Baumbach, chairman of the board of managing directors at Boehringer Ingelheim, in the press release.

Boehringer Ingelheim is investing €120 million (US$131 million) into its Koropi, Greece site to expand production for new therapeutics.

Boehringer Ingelheim Expands Facility in Greece for Production of New Therapeutics

On Jan. 8, 2024, Pluri, an Israel-based biotech company, announced it launched a new business division named PluriCDMO that will offer cell therapy manufacturing services as a contract development and manufacturing organization (CDMO). The new division includes a 47,000-ft2 good manufacturing practice (GMP) cell therapy production facility.

Through this new division, Pluri will offer services relating to early preclinical development through late-stage clinical trials and commercialization. The company has expanded its experience over the past two decades to include process and analytical development, process scale-up, validation, logistics, automation, and regulatory approved comparability studies, according to a company press release.

The company operates a proprietary, patented bioreactor system that enables 3D cell expansion, allowing it to produce high-quality cells in mass quantities via an automated, fully controlled, and validated process. In addition, the company’s PluriMatrix technology enables industrial-scale production of cell-based products.

Pluri’s technology supports large-scale growth of cells and provides batch-to-batch consistency. It is also scalable, cost-effective, GMP-compliant, and has been used to support late-stage clinical trials in key jurisdictions, including FDA, the European Medicines Agency, Israeli’s Ministry of Health, Japan’s Pharmaceuticals and Medical Devices Agency, and the Ministry of Food and Drug Safety of the Republic of Korea, the company stated in its press release.

“Opening the CDMO division is a strategic move that we expect will boost revenues and cash flow utilizing our … technology and manufacturing facility,” said Yaky Yanay, Pluri’s CEO and president, in the press release. “PluriCDMO’s vision is to provide our clients with … access to valuable knowledge in cell therapy development that has been generated over the [past] two decades. PluriCDMO … can accelerate the development efforts of our partners and provide better control of the risks.”

“Pluri has an established track record of development and manufacturing in this arena and has solved many of the challenges that confront innovative companies in the cell therapy market,” said Andy Lewin, who was appointed as chief commercial officer at Pluri to lead the CDMO division, in the press release. “The [c]ompany has developed innovative production technologies, which allow it to offer large scale (and further scalable) production of cell-based products in GMP grade. Pluri’s technology, long-standing collaborations, and extensive experience enable the manufacturing of a wide range of products, including [m]esenchymal

[s]tem [c]ells (MSCs), [i]nduced [p]luripotent [s]tem Cells (iPSCs), [e]xtracellular [v]esicles (EVs) and gene-modified cells, including CAR-T [chimeric antigen receptor T] cells.”

Pluri has launched PluriCDMO, a new contract development and manufacturing organization business that will offer cell therapy manufacturing services.

Pluri Launches New Cell Therapy CDMO Division

On Jan. 9, 2024, GSK and Aiolos Bio, a clinical-stage biopharmaceutical company specializing in the treatment of respiratory and inflammatory conditions, announced that they have entered into an agreement for GSK to acquire Aiolos for $1 billion upfront and up to $400 million in certain success-based regulatory milestone payments.

Through the acquisition, GSK will gain access to Aiolos’ AIO-001, a long-acting anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody (mAb) that is ready to enter Phase II clinical development. The mAb is being evaluated for the treatment of adult patients with asthma. Other potential indications include chronic rhinosinusitis with nasal polyps. Aiolos has an exclusive license to AIO-001 outside of Greater China, which was granted by Jiangsu Hengrui Pharmaceuticals (Hengrui).

By targeting the TSLP pathway, one can address a key driver of the inflammatory response in major allergic and inflammatory diseases, according to GSK in a company press release. GSK also confirmed in the release that “TSLP is a clinically validated target in the treatment of asthma regardless of biomarker status.”

AIO-001 has shown initial safety, tolerability, pharmacokinetics, and biological activity in healthy volunteers and asthma patients in early studies. The mAb also has the potential to be administered every six months because of its enhanced potency and half-life extension technology.

“Adding AIO-001, a potentially best-in-class medicine targeting the TSLP pathway, could expand the reach of our current respiratory biologics portfolio, including to the 40% of severe asthma patients with low T2 [type 2] inflammation where treatment options are still needed,” said Tony Wood, chief scientific officer, GSK, in the press release.

“We believe that this transaction speaks to the high potential of our long-acting anti-TSLP monoclonal antibody, AIO-001. By uniting with GSK … we’re confident that we can rapidly advance this therapy in the hopes of significantly reducing the treatment burden for patients,” said Khurem Farooq, CEO, Aiolos Bio, in the release.

In a deal worth up to $1.4 billion, GSK aims to acquire Aiolos Bio and gain an expanded pipeline of biologic-based respiratory therapeutic candidates. 

GSK to Acquire Aiolos Bio, Expands Respiratory Portfolio

MediWound, an Israel-based biopharmaceutical company focused on next-generation enzymatic therapeutics for tissue repair, announced on Dec. 28, 2023 that the US Department of Defense, through the Medical Technology Enterprise Consortium, a biomedical technology consortium focused on developing medical solutions for US military personnel, has awarded MediWound an additional $6.7 million to develop NexoBrid as a non-surgical solution for field-care burn treatment for the US Army.

The additional funding brings MediWound’s R&D budget up to $14.4 million, which the company will use to advance the development and production of a new, temperature-stable formulation of NexoBrid. Doing so will position NexoBrid as the first-line non-surgical solution for treating severe burn injuries in pre-hospital settings, according to a company press release.

NexoBrid is a bromelain-based biological product containing a sterile mix of proteolytic enzymes that selectively removes eschar in patients with deep partial and full-thickness thermal burns (1,2). It is administered topically. The product is currently approved in the United States, European Union, and other international markets (1).

Under an agreement worth potentially $150 million, Vericel, a US-based company specializing in sports medicine and severe burn care, holds an exclusive license for the commercial and development rights to NexoBrid in North America. MediWound retains commercial rights in all non-North American territories (2).

"We are delighted to further solidify our partnership with the US Department of Defense. The additional funding will enhance our CMC [chemistry, manufacturing, and controls] activities, expedite preclinical development, and facilitate the establishment of a GMP [good manufacturing practice]-compliant aseptic production line for the temperature-stable formulation of NexoBrid," said Ofer Gonen, CEO, MediWound, in the press release. "This new award underscores our shared commitment to ensuring NexoBrid's availability for military use and its potential to significantly change the early treatment approach for severe burns."

1. MediWound. Next Generation Enzymatic Therapeutics Focused on Non-Surgical Tissue Repair. 

 (accessed Jan. 5, 2024).
2. MediWound. MediWound Enters into Exclusive License Agreement with Vericel for Commercial Rights to NexoBrid in North America. Press Release, May 7, 2019.

MediWound has been granted an additional $6.7 million by the DoD to advance NexoBrid as a non-surgical field care solution for the US military.