Pharmaceutical Technology Editors

Vectura, a contract development and manufacturing organization announced an agreement with Incannex Healthcare Limited, an Australian cannabinoid medicines development company, to provide preclinical development services for IHL-216A, an inhaled drug product for the treatment of traumatic brain injury (TBI).

IHL-216A a combination of cannabidiol with the anesthetic isoflurane, has been found in studies by Incannex to reduce neuronal damage, neuroinflammation, and behavioral deficits resulting from TBI. The combination drug is designed to be administered soon after head trauma, thereby reducing secondary brain injuries.

Vectura will conduct studies for formulation screening manufacturing process optimization, stability assessments, and manufacturing a laboratory-scale batch of IHL-216A for toxicological studies.

Incannex is partnering with the Monash Trauma Group at Monash University’s Department of Neuroscience in Australia to conduct an 

 study on the protective effect of IHL-216A in sports concussion, based on a model of TBI developed with the National Football League (NFL). Vectura reports it will further develop the IHL-216A formulation in parallel with the 

 experiments in advance of clinical trials.

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Vectura will provide preclinical development services for Incannex’s inhaled drug product for the treatment of traumatic brain injury.

Vectura Partners with Cannabinoid Medicines Company 

The first patients in a Phase II/III trial have received doses of AstraZeneca’s AZD2816—a COVID-19 variant vaccine—to assess the safety and immunogenicity of the vaccine against the SARS-CoV-2 virus, the company announced in a press statement on June 27, 2021.

Both previously vaccinated and unvaccinated adults will participate in the trial, which will recruit approximately 2250 participants across the United Kingdom, South Africa, Brazil, and Poland.

Individuals who have been fully vaccinated with Vaxzevria or an mRNA vaccine will receive AZD2816 at least three months after their last injection. Non-vaccinated individuals will receive two doses, four or 12 weeks apart; or the variant vaccine will be given as a second dose following a first dose of Vaxzevriafour weeks apart, the company reported in a statement.

AZD2816 was developed using the same adenoviral vector platform as Vaxzevria. In addition, the spike protein had minor genetic alterations based on the Beta (B.1.351, South African) variant, the company reports.

“It is important we continue to stay ahead of genetically distinct variants of the coronavirus,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D in a press statement. “AZD2816 should help broaden individuals’ immune response against emerging variants of concern.”

Initial findings for the trial are expected later in 2021. AZD2816 will be assessed in an expedited regulatory pathway as a potential next-generation booster, the company reported.

The first participants, both previously vaccinated and unvaccinated, receive AstraZeneca’s new COVID-19 variant vaccine AZD2816. 

AstraZeneca Doses Patients in COVID-19 Variant Vaccine in Trial

WuXi STA, a contract development and manufacturing organization, and Delaware Prosperity Partnership announced plans for a pharmaceutical manufacturing campus in Middletown, Del.

Expected to open in 2024, the 190-acre campus in Middletown will be WuXi STA’s second site in the United States and will house pharmaceutical clinical and commercial manufacturing. The location will be the company’s eighth global manufacturing facility.

The company aims to bring 500 full-time positions to the Delaware complex by 2026, which has the potential to expand to a total workforce exceeding 1000 employees.

WuXi STA provides pharmaceutical development and manufacturing for more than 470 partners worldwide, covering small molecules and novel molecular modalities such as oligonucleotide, peptide, and complex conjugates.

WuXi STA’s Delaware campus will contain clinical and commercial manufacturing capabilities for small molecules and novel molecular modalities.

WuXi STA to Build New Manufacturing Campus

Celularity Inc., a clinical-stage biotechnology company developing cell therapies and biomaterial products derived from the postpartum human placenta to treat cancer, infectious, and degenerative diseases, and Arthrex, Inc., a global leader in minimally invasive orthopedic technology, announced on July 1, 2021, that the companies have entered into an exclusive partnership to distribute and commercialize Celularity’s biomaterial products for orthopedic surgery and sports medicine.

Under the terms of the agreement, Celularity will provide Arthrex with exclusive commercial distribution rights for orthopedic surgery and sports medicine and will continue to be responsible for product manufacturing and supply.

“We are tremendously excited to have Arthrex, a global leader in minimally invasive orthopedics, as a commercial partner to distribute our placental-derived biomaterial products,” said Robert J. Hariri, founder, chairperson and chief executive officer of Celularity in a press release. “Each of our regenerative products leverages the unique properties of the placenta to augment the body’s innate ability to heal across a variety of clinical conditions. We look forward to working closely with Arthrex to increase the availability of these innovative products in orthopedic surgery and sports medicine, and to improve the lives of patients.”

"Arthrex is proud to support Celularity's innovative technology that leverages the unique biology of the placenta. Partnering with Celularity positions us to explore new opportunities in the Orthobiologics space while continuing our mission of helping surgeons better treat their patients," David Shepard, Arthrex senior director of orthobiologics commented in the press statement.

Stephen A. Brigido, president of Celularity’s Degenerative Diseases Division, noted in the statement “Arthrex is highly innovative, progressive, and committed to new product development. Our shared commitment to medical and surgical education creates important cultural synergies between the two companies. The Arthrex partnership will broaden the platform for using Celularity’s regenerative products in the setting of orthopedic surgery, the market for which by one estimate is $1.5 billion in the U.S. alone.”

Arthrex to receive exclusive rights to distribute and commercialize Celularity’s placental-derived biomaterial products for orthopedics and sport medicine in the United States.

Celularity and Arthrex Announce Distribution Agreement

Corbus Pharmaceuticals Holdings has expanded its therapeutics pipeline with the addition of two new monoclonal antibodies (mAbs), CRB-601 and CRB-602, that target integrins to inhibit activation of transforming growth factor β (TGFβ). This new integrin program, acquired under two exclusive licensing agreements and added to the company’s existing endocannabinoid system program, expands Corbus’ immunology pipeline for inflammatory, fibrotic, and metabolic diseases as well as cancer. Corbus expects to have four compounds in addition to lenabasum in Phase I testing in 2022.

Under the combined terms of the licensing agreements, Corbus will pay $2 million upfront and will make potential development and sales milestone payments totaling up to $206 million as well as pay low single-digit royalties on sales, the company stated in a June 1, 2021 press release.

CRB-601 was rationally designed by Stephen Nishimura and his colleagues at the University of California San Francisco. It is potent at picomolar concentrations in inhibiting activation of TGFβ. The parent mAb of CRB-601, C6D4, has single agent activity as well as synergistic activity when combined with an anti-programmed death-1 (PD-1) mAb in syngeneic mouse tumor models. Corbus plans to develop CRB-601 for treatment of solid tumors in combination with existing therapies, including checkpoint inhibitors.

CRB-602 was developed by Panorama Research, a privately-owned biomedical research and development holding company, to specifically inhibit both avb6 and avb8, integrins that have been implicated in fibrotic diseases and in cancers of epithelial cell origin. Corbus believes that targeting both integrins at once is a rational approach to treating fibrotic diseases and carcinomas, the company stated the press release.

“We look forward to a strong partnership with Corbus and hope to see our mAb make a positive impact on the lives of cancer patients all over the world,” said Anthony Francis, executive director of Technology Management at UCSF Innovation Ventures, in the press release.

“Corbus is committed to developing new medicines to improve the lives of people who need them,” stated Yuval Cohen, PhD, CEO of Corbus, in the press release. “We believe these two new integrin-targeting mAbs offer a promising approach to inhibiting TGFβ, fit well with our expertise in immunology, and diversify and expand our pipeline. We plan to advance up to four new programs into the clinic next year and have the capital and resources to do so.”

Corbus Pharmaceuticals has licensed two integrin-targeting mAbs, expanding its therapeutics pipeline into inflammatory, fibrotic, and metabolic diseases as well as cancer.

Corbus Pharmaceuticals Expands Pipeline with Two New mAbs

Researchers at Chalmers University of Technology, Sweden, announced on June 30, 2021 that they have succeeded in developing a fluorescence method to label messenger RNA (mRNA) molecules, allowing them to track, in real time, the path of the mRNA molecules through cells with the use of a microscope while not affecting the molecules’ properties or subsequent activity. The breakthrough could be of great importance in facilitating the development of new RNA-based medicines, according to a university press release.

While RNA-based therapeutics offer a range of new opportunities to prevent, treat, and potentially cure diseases, the delivery of such therapeutics into the cell is currently inefficient. Therefore, for new therapeutics to fulfill their potential, the delivery methods need to be optimized.

The research behind the RNA tracking method developed by Chalmers researchers was conducted in collaboration with chemists and biologists at Chalmers and AstraZeneca via their joint research center, FoRmulaEx, as well as a research group at the Pasteur Institute, Paris, France. The method involves replacing one of the RNA building blocks with a fluorescent variant, which, apart from that feature, maintains the natural properties of the original base. The fluorescent units were developed with the help of a special chemistry technique (?), and the researchers have shown that it can be used to produce mRNA without affecting the mRNA’s ability to be translated into a protein at natural speed.

The method represents a breakthrough that has not been done successfully before, according to the press release. The fluorescence furthermore allows researchers to follow functional mRNA molecules in real time with a microscope and observe how they are taken up into cells.

mRNA molecules are challenging to work with because of their large size and the fact that they are charged and, at the same time, fragile. They cannot enter cells directly and must be packaged. The method for mRNA uptake that has proven most successful to date uses lipid nanoparticles to encapsulate the mRNA. However, there still exists the need to develop new and more efficient lipid nanoparticles, which the Chalmers researchers are also working on. The ability to monitor, in real time, how lipid nanoparticles and mRNA are distributed through the cell is an important tool.

"Since our method can help solve one of the biggest problems for drug discovery and development, we see that this research can facilitate a paradigm shift from traditional drugs to RNA-based therapeutics," said Marcus Wilhelmsson, professor at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology, in the press release.

“The great benefit of this method is that we can now easily see where in the cell the delivered mRNA goes, and in which cells the protein is formed, without losing RNA's natural protein-translating ability,” said Elin Esbjörner, associate professor at the Department for Biology and Biotechnology, Chalmers University of Technology, in the press release.

Researchers working in the area of RNA studies can use this fluorescent tracking method to gain greater knowledge of how the uptake process works, which can accelerate and streamline (?) the discovery process for new therapeutics.

“Until now, it has not been possible to measure the natural rate and efficiency with which RNA acts in the cell. This means that you get the wrong answers to the questions you ask when trying to develop a new drug. For example, if you want an answer to what rate a process takes place at, and your method gives you an answer that is a fifth of the correct, drug discovery becomes difficult,” explained Wilhelmsson in the press release.

Chalmers University researchers have developed a method to label and track mRNA molecules.