Feliza Mirasol is the science editor for 

Feliza Mirasol

Rentschler Biopharma announced a collaboration on Aug. 23, 2023 with Cell and Gene Therapy Catapult (CGT Catapult), a UK-based independent innovation and technology organization specializing in cell and gene therapies, and Refeyn, a UK-based provider of mass photometry instruments and technologies, under which the three organization will develop and apply innovative process analytical technologies (PAT) to improve the manufacturing process for adeno-associated viruses (AAVs) in gene therapy production.

Under this two-year collaboration, the partners aim to develop a digitized and automated AAV gene therapy manufacturing platform. Through a combination of expertise in manufacturing, process analytics, and PAT, the collaborators will develop automated monitoring and control that will then be applied to Rentschler Biopharma’s existing AAV manufacturing process.

Because current analytical methods related to AAV production mainly rely on manual sampling, the production of AAVs has been difficult and time consuming. However, over 65% of gene therapies in development currently rely on AAV vectors.

To address the AAV manufacturing challenges, the teams under this collaboration will carry out high throughput and automated sampling and analysis of AAV material throughout the production process. The data collected from this analysis will be used to create digital twins, which are digital models of the manufacturing process that can be used to further refine and improve the efficiency of the process.

Thus, using the digital twins, the teams can carry out initial tests on any changes to the manufacturing process in a digital environment. Troubleshooting in this fashion would reduce the number of expensive and time-consuming physical tests that otherwise would be needed to be carried out in the laboratory, according to a company press release.

The collaborators will assess any improvements in productivity and AAV yield using automated analytical technologies, which will include Refeyn’s technology to assess the proportion of full AAV capsids produced. Assessing the proportion of full AAV capsids produced is a key measurement for the industry; the quantity of full AAV capsids indicates process efficiency but may also impact clinical efficacy, according to the press release. Refeyn will additionally use this project to test a new current good manufacturing practice-compliant version of its mass photometer.

“With this collaborative project … we seek to unleash the potential of faster viral vector development with multi-parameter driven optimization,” said Christian Schetter, chief scientific officer, Rentschler Biopharma, in the press release. “This promises to translate to higher outputs, robustness, and better process control; ultimately lowering the risk associated with the transition from early to late-stage manufacturing for the benefit of our clients and their patients.”

“The outputs will help us understand the future needs of viral vector manufacturing environments, informing product development to better satisfy these needs,” said Matthias Langhorst, chief product officer, Refeyn, in the release.

The project is being funded through a grant from Innovate UK.

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Rentschler Biopharma, CGT Catapult, and Refeyn aim to use automated and digital technologies to improve AAV manufacturing for gene therapies.

Three-Way Collaboration Between Rentschler Biopharma, CGT Catapult, and Refeyn Aims to Improve PAT for Gene Therapy Manufacturing

On Aug. 28, 2023, Danaher, an innovator of science and technologies, announced that it has entered into a definitive agreement to acquire UK-based Abcam, a supplier of protein consumables, for approximately $5.7 billion ($24.00 per share). Under the agreement, Abcam will operate as a standalone operating company and brand within the life sciences segment of Danaher.

The transaction, which is expected to close in mid-2024, is in line with Danaher's strategy to facilitate the mapping of complex diseases and accelerate the drug discovery process. According to a company press release, Danaher expects to fund the acquisition with cash on hand and proceeds from the issuance of commercial paper.

Headquartered in Cambridge, UK, Abcam supplies validated antibodies, reagents, biomarkers, and assays. The company’s offerings help researchers to address targets in biological pathways that are considered critical for advancing drug discovery as well as life sciences research and diagnostics.

"We couldn't be more excited to have Abcam join Danaher. Abcam's long track record of innovation, … product quality, and breadth of antibody portfolio positions them as a key partner for the scientific community,” said Rainer M. Blair, president and CEO, Danaher, in the company press release. “We look forward to welcoming Abcam's innovative and talented team to Danaher as we continue to help our customers solve some of the world's biggest healthcare challenges."

"Our strategy has transformed Abcam to become a scale innovator and important catalyst in the global life science community. Danaher shares our passion to help life science researchers achieve their mission faster, and [its] operating company model allows us to continue to pursue our strategy, while harnessing the power of the Danaher Business System to ensure we remain the partner of choice for our customers," said Alan Hirzel, CEO, Abcam, in the release.

Danaher intends to acquire Abcam, a provider of life sciences assays and reagents, for $5.7 billion.

Danaher to Acquire Abcam in $5.7 Billion Deal

On Aug. 18, 2023, Regeneron Pharmaceuticals announced that FDA has approved Veopoz (pozelimab-bbfg), a monoclonal antibody, for treating adult and pediatric patients one year and older with CHAPLE disease, or CD55-deficient protein-losing enteropathy. The company also announced that FDA has approved Eylea HD (aflibercept) Injection 8 mg, a high-dose version of Eylea, for treating wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and diabetic retinopathy.

According to a company press release, the pozelimab approval marks the first and only treatment indicated specifically for CHAPLE. This approval also signals that pre-approval inspection issues related to the aflibercept 8 mg biologics license application (BLA) have been addressed and that FDA action on the aflibercept 8 mg BLA is expected in the next few weeks.

CHAPLE is a rare, hereditary life-threatening immune disease that is driven by an overactivation of the complement system. Normally, the complement system in healthy individuals is a mechanism for destroying microbes. For those living with CHAPLE, however, individuals are unable to regulate complement activity because of mutations in their CD55 gene, and without proper CD55 regulation, the complement system may attack normal cells. This can cause damage to blood and lymph vessels along the upper digestive tract and lead to loss of circulating proteins. According to the press release, fewer than 10 patients have been identified in the United States who have the disease.

“Most patients with CHAPLE disease are children who face severely debilitating symptoms and often life-threatening complications that begin in infancy,” said Michael Lenardo, chief, Molecular Development of the Immune System Section and co-director, Clinical Genomics Program, National Institute of Allergy and Infectious Disease, National Institutes of Health, in the company press release. “As an investigator in this pivotal trial and one of the discoverers of this disease, I saw first-hand the transformational clinical improvement that pozelimab achieves in those suffering from CHAPLE. The approval of pozelimab is a milestone to celebrate, providing a new medicine that can help these long-suffering patients.”

“Beyond CHAPLE, we believe [pozelimab] has promise in a variety of complement-mediated diseases and are driving forward several clinical programs to explore its broader potential,” said George D. Yancopoulos, board co-chair, president, and chief scientific officer, Regeneron, in the release.

Meanwhile, the approval of Eylea HD Injection 8 mg was based on the 48-week results of two double-masked, active-controlled pivotal trials (PULSAR in wAMD and PHOTON in DME) which evaluated Eylea HD compared to Eylea Injection 2 mg. Both trials met their primary endpoint. Eylea HD demonstrated non-inferior and clinically equivalent vision gains at 48 weeks (with both 12- and 16-week dosing regimens following three initial monthly doses), compared to an Eylea 8-week dosing regimen after initial monthly doses. According to a company press release, the vast majority of patients randomized at baseline to Eylea HD 12- or 16-week dosing regimens (following the three initial monthly doses) were able to maintain these dosing intervals throughout the 48 weeks.

“The FDA approval of Eylea HD is an important advancement in retinal care,” said Peter Kaiser, Chaney Family endowed chair in Ophthalmology Research at the Cole Eye Institute and professor of Ophthalmology at Cleveland Clinic Lerner College of Medicine, in the release. “With Eylea HD, patients with wet age-related macular degeneration or diabetic retinal disease can now receive less frequent injections after their initial monthly doses and still experience the similar visual gains, anatomic improvements, and safety profile of Eylea.”

FDA has approved a new mAb therapy from Regeneron Pharmaceuticals as well as a higher dose version of Eylea, the company’s eye disease therapeutic.

Regeneron Gets FDA Approvals on New Biologic and New High Dose for Eye Disease Therapy

On Aug. 21, 2023, Gilead Sciences announced that FDA has placed a partial clinical hold on the company initiating new patients into US studies for magrolimab, an investigational anti-CD47 immunotherapy, to treat acute myeloid leukemia (AML). FDA’s decision follows a previous announcement in which a Phase III clinical study was discontinued that was studying magrolimab in higher-risk myelodysplastic syndromes (1).

According to a Gilead company press release, screening and enrollment of new study participants under US investigational new drug application (IND) 147229 and a US expanded access program will be paused, effective immediately. However, patients who are already enrolled in AML clinical studies may continue to be treated and monitored, according to study protocol. Meanwhile, studies of magrolimab in solid tumors may continue and are not impactd by this FDA action.

Global regulatory authorities and clinical trial investigators involved in the studies have been informed of FDA’s decision. Gilead is working with regulatory authorities to determine the next steps needed to release the partial clinical hold.

Magrolimab is an investigational molecule that has not been approved anywhere globally, and Its safety and efficacy have not yet been established. In addition to AML, magrolimab is being developed as a potential treatment for myeloid malignancies, lymphoma, myeloma, head and neck cancer, colorectal cancer, lung cancer, and breast cancer.

1. Gilead Sciences, Gilead To Discontinue Phase 3 ENHANCE Study of Magrolimab Plus Azacitidine in Higher-Risk MDS. Press Release, July 21, 2023.

FDA has halted enrollment in clinical studies for Gilead Sciences’ magrolimab, a biologic treatment in development for acute myeloid leukemia.

FDA Halts Clinical Trial Enrollment for Gilead’s Magrolimab in AML Studies

On Aug. 15, 2023, US-based Chiesi Global Rare Diseases, a business unit of the Chiesi Group, announced that it has entered into a co-development agreement with Aliada Therapeutics, a US-based biotechnology company focused on developing a novel blood-brain barrier (BBB)-crossing platform technology. Under the collaboration, the companies will focus on multiple enzyme cargoes that have been modified using Aliada's Modular Delivery (MODEL) platform. The goal is to establish drug delivery systems that will allow large-molecule therapeutics to cross the BBB, particularly for the treatment of lysosomal storage disorders (LSDs).

Aliada’s MODEL platform harnesses the endogenous cell transport mechanisms in brain endothelial cells to efficiently move large-molecule therapeutics across the BBB. The technology enables high therapeutic exposure in the brain, according to a company press release. According to the release, the MODEL platform demonstrates advantages over competing approaches as it offers a broad design landscape that confers an ability to optimize therapeutics for both central nervous system (CNS) delivery and downstream functionality.

"Our commitment to the development of new treatment options for people living with [LSDs] is global, as evidenced by recent regulatory approvals," said Giacomo Chiesi, head of Chiesi Global Rare Diseases, in the press release. "Many LSDs have CNS involvement. With this collaboration, we are expanding our strategy and presence in BBB-crossing technologies and hope to leverage our know-how in LSDs to support the development of an effective and differentiated drug delivery platform. We are especially proud to advance this important research with Aliada, a partner with vast experience in neuro drug development and biologics delivery."

"We are excited to partner with Chiesi to develop improved therapeutics for patients living with LSDs, who currently lack treatments that can readily access the brain," said Adam Rosenberg, CEO, Aliada Therapeutics, in the release. "We admire Chiesi's continued commitment to patients, exemplified by their two recent FDA approvals. This collaboration will allow Aliada to demonstrate the diverse capabilities of our MODEL platform, which enables us to efficiently transport a diverse range of therapeutic cargoes into the brain."

With this agreement, Chiesi Global Rare Diseases will co-develop drug delivery systems with Aliada Therapeutics for large-molecule therapeutics that can cross the blood-brain barrier.

Chiesi Global Rare Diseases and Aliada Therapeutics Partner to Advance Blood-Brain Barrier-Crossing Platform Technology for Drug Delivery

China-based HitGen, a drug discovery technology platform company, announced on Aug. 10, 2023 that it has entered into a research service agreement with Nested Therapeutics (Nested), a US-based biotechnology company specializing in a next-generation precision medicine platform for hard-to-treat cancers. Under the agreement, HitGen will use its DNA-encoded library (DEL) technology platform to identify hits against targets in which Nested is interested.

HitGen’s technology platform is centered around the design, synthesis, and screening of DELs. The company applies its technology to early stage small-molecule drug discovery. Its platform includes more than 1.2 trillion small molecules generated by its DEL technology, which streamlines the screening process.

“We look forward to working with the research teams at Nested to generate novel starting points for their research programs to help address the unmet needs of patients with cancer. As one of HitGen’s four core technology platforms, our … DEL platform is an efficient ‘engine’ to advance drug discovery and has enabled hit identification and lead generation for many innovative discovery programs by our customers and partners. We look forward to delivering useful outcome[s ]for Nested’s research programs,” said Jin Li, chairman of the board and CEO of HitGen, in the press release.

HitGen has entered into a research service agreement with Nested Therapeutics for use of HitGen’s DNA-encoded library for drug discovery.