Pharmaceutical Technology Editors

MilliporeSigma, the U.S. and Canadian Life Science business of Merck KGaA, Darmstadt, Germany, announced that they signed an agreement to license their patented clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 (CRISPR-Cas9) technology to Cellecta, a functional genomics products and services provider. Cellecta provides RNA interference (RNAi) and CRISPR technologies for the discovery and characterization of novel therapeutic targets and genetic profiling for drug and biomarker discovery and validation.

According to a Merck press release, Cellecta plans to use the CRISPR patent estate to offer CRISPR-mediated targeted “knock-in.” This method gives scientists more efficient options for complex therapeutic and disease research projects.

“The technology enables us to provide a more comprehensive range of options for cell modification to our customers,” said Paul Diehl, COO of Cellecta, in a MilliporeSigma press release. “More specifically, access to this technology allows us to conduct integrated knock-in which is a key component of our customer’s drug testing.”

“We are committed to advancing research and drug discovery through the development of powerful, unique technologies,” said Angela Myers, head of gene editing and novel modalities, life science, at Merck, in the Merck press release. “This licensing agreement is of paramount importance for researchers and scientists. Our CRISPR-based foundational integration technology is essential for many genome-editing applications and is used to identify future treatments in myriads of cellular and genetic diseases.”

Merck democratized its patented CRISPR technology. Globally, Merck’s life science business holds 40 CRISPR-related patents in methods and composition, including the CRISPR-Cas9 foundational technology for genetic integration in mammalian cells. The company’s experience in genome editing has led to a comprehensive portfolio of CRISPR and other genomics technologies that impact drug development, from basic research to therapeutic delivery.

The life science business of Merck is actively licensing its CRISPR technology for therapeutic and other uses. They are seeking collaboration partners for research and product development.

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MilliporeSigma, the U.S. and Canadian Life Science business of Merck KGaA, Darmstadt, Germany, signed an agreement with Cellecta to license its genome-editing tool.

MilliporeSigma Licenses CRISPR-Cas9 Technology to Cellecta

ChemoCentryx, a biopharmaceutical company targeting the chemokine and chemoattractant systems, announced that FDA approved Tavenos (avacopan), an orally-administered selective complement 5a receptor inhibitor, on Oct. 8th, 2021. Avacopan was approved as an adjunctive treatment for adults with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis, also known as ANCA-associated vasculitis, in combination with standard therapy.

ANCA-associated vasculitis is a systemic autoimmune disease where over-activation of the complement system further activates neutrophils, which leads to inflammation and destruction of small blood vessels. This results in organ damage and failure, often in the kidneys, and is usually fatal if untreated. Avocapan is intended for the two main forms of ANCA-associated vasculitis—granulomatosis with polyangiitis and microscopic polyangiitis.

According to a company press release, avacopan is an orally-administered small molecule that employs a novel, highly-targeted mode of action in complement-driven autoimmune and inflammatory diseases. By blocking the complement 5a receptor (C5aR) for the pro-inflammatory complement system fragment, it can arrest the ability of those cells to do damage in response to C5a activation. This is key because this pathway is known to be the driver of ANCA vasculitis, halting detrimental effects. Additionally, it leaves the beneficial C5a pathway through the C5L2 receptor functioning normally.

“I am excited that our work has helped lead to the first-in-a-decade approval of a medicine for ANCA-associated vasculitis. This is an important step forward in the treatment of this disease,” said Peter A. Merkel, chief of rheumatology at the Perelman School of Medicine at the University of Pennsylvania, director of the international Vasculitis Clinical Research Consortium, and consultant to ChemoCentryx, in the press release. “Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis.”

The approval of ChemoCentryx’s Tavenos (avacopan) provides a new treatment for active anti-neutrophil cytoplasmic autoantibody-associated vasculitis.

FDA Approves ChemoCentryx’s Tavenos

Astrazeneca announced on Oct. 8, 2021that FDA granted its drug, tezepelumab, orphan drug designation for the treatment of eosinophilic esophagitis (EoE). EoE is a rare, chronic, inflammatory disease that has no approved treatments to date.

EoE occurs when eosinophils, a type of white blood cell, accumulate in the esophagus. If left untreated, it can make eating difficult or uncomfortable, leading to chronic pain, difficulty swallowing, poor growth, malnutrition, and weight loss. Other cells, including mast cells, T-cells, and fibroblasts, may also drive injury, inflammation, and detrimental tissue remodeling.

According to a company press release, tezepelumab is a monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades. The intent behind blocking TSLP is to prevent pro-inflammatory cytokines by immune cells, which are implicated in many epithelial disease pathophysiologies.

“Eosinophilic esophagitis is a rare disease which involves a range of inflammatory cells that contribute to debilitating symptoms for patients, including severe pain and difficulty swallowing food,” said Mene Pangalos, executive vice-president, BioPharmaceuticals R&D, AstraZeneca, in the press release. “We are hopeful that tezepelumab, with its unique mechanism of action that targets the top of the inflammatory cascade, could become a potential new medicine to improve outcomes for these patients.”

AstraZeneca entered into a collaboration agreement with Amgen to develop tezepelumab in 2020. According to the press release, AstraZeneca leads development, while Amgen oversees the manufacturing process.

AstraZeneca’s tezelpelumab was granted orphan drug designation by FDA for the treatment of eosinophilic esophagitis.

FDA Grants AstraZeneca's Tezepelumab Orphan Drug Designation 

Voyager Therapeutics, a gene therapy company, announced on Oct. 6, 2021 that it had entered into a licensing agreement with Pfizer for the use of its tropism redirection of adeno-associated virus (AAV) by cell-type-specific expression of RNA (TRACER) platform. Pfizer will pay Voyager $30 million for transgene-specific access to their novel AAV capsids, with additional payments of up to $600 million available in option exercise fees, milestone payments, and product royalties.

Voyager’s TRACER system is a RNA-based functional screening platform that allows for 

 evolution of AAV capsids with enhanced tropisms and cell- and tissue-specific transduction properties in multiple species. According to a Voyager press release, Pfizer will use this system to investigate potential use of two undisclosed transgenes to treat certain neurological and cardiovascular diseases.

“This transaction highlights the potential of our TRACER platform to identify novel AAV capsids that target desired cells and tissues with greater specificity at lower doses and with fewer off-target risks than conventional AAV serotypes,” said Michael Higgins, interim CEO of Voyager, in the press release. “We believe that our TRACER platform has the ability to produce not only enhanced blood-brain-barrier penetrant capsids, but also novel capsids with enhanced tropisms across a diversity of tissues and cell types, offering promise to unlock the fullest potential of gene therapies for a wide array of diseases with unmet medical need.”

"Our collaboration with Voyager will provide Pfizer with access to additional AAV capsids that may help further advance our industry-leading gene therapy portfolio,” said Seng Cheng, senior vice-president and chief scientific officer of Pfizer's Rare Disease Research Unit, in the press release. “We are impressed with Voyager’s results to date and are enthusiastic about the potential to utilize these novel capsids to help accelerate the development of new therapeutic options for patients living with certain neurologic and cardiovascular diseases.”

Pfizer may pay up to $630 million for access to Voyager’s novel AAV capsids in transgene research.

Pfizer Agrees to License Agreement with Voyager Therapeutics

Pfizer and BioNTech requested an emergency use authorization (EUA) from FDA on Oct. 7th, 2021, for the use of their COVID-19 vaccine on children aged 5 to 11. This would make it the first vaccine to be authorized for use in individuals under the age of 12.

 in a recent clinical vaccine trial of the 5-11 age bracket on Sept. 20, 2021. The study found that, when given a two-dose regimen of 10 µg (selected due to concerns of safety, tolerability, and immunogenicity), children in this age bracket showed comparable results to individuals aged 16-25 who were immunized with 30 µg doses.

“We’re committed to working with the FDA with the ultimate goal of helping protect children against this serious public health threat.” said Pfizer on Twitter.

FDA will review the request with a panel of outside experts on Oct. 26th, 2021. The Pfizer / BioNTech vaccine has currently received an EUA for individuals aged 12 to 15 and is fully approved for individuals aged 16 and older.

Pfizer and BioNTech’s request would make them the first vaccine accessible to individuals under the age of 12.

Pfizer, BioNTech Request EUA for COVID-19 Vaccine in Children Aged 5-11

Moderna announced, in an Oct. 7th, 2021 press release, its intent to build a new $500 million mRNA facility in Africa. Upon completion, the expectation is that the facility will be capable of producing 500 million doses of vaccines each year at the 50 µg dose level.

The facility is expected to not only manufacture drug substance, but also have fill/finish and packaging capabilities at the new site. At this point in time, no site has been selected for the new facility.

“On behalf of our growing team, partners and shareholders, we are determined to extend Moderna’s societal impact through the investment in a state-of-the-art mRNA manufacturing facility in Africa,” said Stephane Bancel, CEO, Moderna, in a company press release. “While we are still working to increase capacity in our current network to deliver vaccines for the ongoing pandemic in 2022, we believe it is important to invest in the future. We expect to manufacture our COVID-19 vaccine as well as additional products within our mRNA vaccine portfolio at this facility.”

To date, Moderna has produced over 500 million doses of its COVID-19 vaccine. According to the press release, the company has 20 prophylactic vaccine candidates in its pipeline. These include vaccines for respiratory viruses, latent viruses, and for “threats to global public health.”

Moderna’s new facility is expected to produce 500 million vaccine doses per year.