Feliza Mirasol is the science editor for 

Feliza Mirasol

On Nov. 14, 2023, Lonza announced the launch of its new cell line, GS Effex, which is intended for the development of therapeutic antibodies with enhanced potency. Derived from the company’s GS Xceed cell line, GS Effex was developed to meet the development needs for more sophisticated therapeutic antibodies. The new cell line combines the characteristics of good cell growth with the ability to produce therapeutic antibodies with increased potency.

GS Effex is a stable, scalable, and productive cell line that produces Fc domains free of fucose, which, according to Lonza, increases the antibody-dependent cellular cytotoxicity (ADCC) function and therapeutic potency of the final antibody. GS Effex is available under license or as a complete service offering.

"Lonza is committed to providing our customers with the right tools to develop their novel therapies. Leveraging more than 35 years of protein expression expertise, more than 75 molecules have been manufactured and brought to the clinic using our expression platforms,” said Ulrich Osswald, vice-president, Licensing, Lonza, in a company press release. “The new GS Effex cell line represents an enhanced solution especially relevant for the oncology field since improved ADCC represents a vital enhancement of the therapeutic success of an antibody product."

“At Lonza, we develop and invest in novel, disruptive technologies with potential to transform the development, analytics, and manufacturing of established and novel biotherapeutics,” said Atul Mohindra, head of Biologics R&D, Lonza, in the press release. “The GS Effex cell line provides a reliable protein expression platform with the needs of our customers in mind. This cell line enables the efficient production of monoclonal antibodies with increased ADCC, while also delivering the required product quality and efficacy profile.”

Articles

Lonza’s new GS Effex cell line can help overcome the challenges of developing therapeutic antibodies with increased potency.

Lonza Launches New Cell Line for Higher Potency Antibody Development

On Nov. 13, 2023, Legend Biotech, a biotechnology company, announced that its wholly owned subsidiary, Legend Biotech Ireland, entered into an exclusive, global license agreement with Novartis for certain Legend Biotech chimeric antigen receptor T-cell (CAR-T) cell therapies targeting Delta-like ligand protein 3 (DLL3). The deal includes Legend Biotech’s autologous CAR-T cell therapy candidate, LB2102 (NCT05680922).

Under the agreement, Legend Biotech will receive a $100 million upfront payment and will be eligible to receive up to $1.01 billion in clinical, regulatory, and commercial milestone payments as well as tiered royalties. Novartis will be granted exclusive worldwide rights to develop, manufacture, and commercialize these cell therapies.

Novartis may also apply its T-Charge CAR-T cell therapy platform to the manufacture of these candidates. The platform is a next-generation CAR-T cell therapy manufacturing platform designed to preserve T cell stemness. It also facilitates CAR-T cell expansion primarily 

. The platform is designed to reduce the need for extensive culture time outside the body and results in T cells with greater proliferative potential as well as fewer exhausted T cells. If applied to the manufacture of LB2102, this would be the first application of the T-Charge platform to a cell therapy candidate targeting solid tumors, according to a company press release.

Legend Biotech will conduct a Phase I clinical trial for LB2102 in the United States, and Novartis will conduct all other development for the licensed products. Clinical development for LB2102 starts with treatment of extensive stage small cell lung cancer and large cell neuroendocrine carcinoma following FDA’s clearance of the therapeutic’s investigational new drug application in 2022. In 2023, FDA granted the candidate orphan drug designation.

“We believe LB2102 has an innovative CAR design and armor mechanism that increases its anti-tumor activity. The preclinical evidence shows that an autologous CAR-T could be a differentiated treatment option for patients with small cell lung cancer,” said Guowei Fang, chief scientific officer and head of Business Development, Legend Biotech, in the press release. “We are excited that a major pharmaceutical company with deep roots in oncology and cell therapy has chosen to further this product candidate in the clinic. We are delighted that a combination of our unique candidate design in LB2102 with the T-Charge platform may potentially offer transformative benefits to small cell lung cancer patients.”

Novartis and Legend Biotech seek to advance certain CAR-T cell therapy candidates targeting Delta-like ligand protein 3.

Novartis and Legend Biotech Sign Exclusive License Agreement for CAR-T Therapies

®, Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, Waters Corporation remarks on how current technologies have enabled oligonucleotide (oligo) development to push forward to the forefont.

“Synthetic oligos just so interesting because it is the world in between the biologically produced, recombinantly produced, drugs and those small-molecule drugs that have been produced through traditional synthetic pharma science,” he states.

Much of the work being conducted on oligo drug development has centered around modifications of the oligo molecule, he emphasizes. “Notice that, even in our mRNA [messenger RNA] vaccines, [which gave us] 

, one of the big things that unlocked mRNA vaccines was a modified nucleotide,” Lauber notes.

“These are the same things … it's a modification of these things that are our genome code—our transcriptome code— that is giving us our opportunity for a new form of science,” Lauber states.

AAPS PharmSci 360 ran Oct. 22–25 in Orlando, Fl.

Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, at Waters Corporation highlights how current technologies are enabling oligonucleotide development.

Oligonucleotide-Enabling Technology Pushes Oligos to the Forefront (AAPS PharmSci 360)

®, Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, Waters Corporation, had this to say when asked his thoughts on whether oligonucleotides (oligos) may be the next wave of biotherapeutics on the market in the near future: “The market for synthetic oligonucleotides is happening right now,” as he pointed out that oligos historically got their start in the late 1990s.

“What's interesting,” he notes, “is that the delivery mechanisms have been improving as of late.” Lauber points to some of the earliest oligo drugs using lipid nanoparticles as a delivery mechanism, sharing that “the basis of that technology is what [also] gave the formulation for the [messenger RNA] vaccines.”

However, he adds, today, the synthetic oligo market has moved on and is not using these nanoparticles anymore, which he characterizes as an amazing technology in and of themselves. Rather, he explains, whatever is needed for drug delivery is being put directly onto the synthetic oligo, so that, as in the case of a lipid modification, a direct conjugate is added directly onto the oligo molecule that helps the drug be internalized.

“All of this [new technology] has given [the] basis for this resurgence, and there are hundreds of new synthetic oligos in the market right now. It's an interesting subsegment to the overall wave coming up nucleic acid-based medicine,” Lauber states.

 industry’s focus on oligonucleotide therapeutics

Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, at Waters Corporation, considers that status of oligonucleotides on the market.

Oligonucleotides: The Next Therapeutic Wave on the Market? (AAPS PharmSci 360)

“You might be familiar with Waters. Waters is a specialty instrument company focused on making analytical measurements, and with this analytical science, our team has been studying what would be needed to help improve the quantitation reliability and robustness quantitation of synthetic oligonucleotides from biofluids,” says Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, Waters Corporation in an exclusive interview with 

Traditionally, Lauber says, improving such analytical techniques has been done by liquid–liquid extraction, which is often involved in the use of toxic chemicals such as chloroform and phenol, which are iteratively used for liquid–liquid extraction. These techniques involve laborious procedures, but, today, people in labs are wanting to have a safer environment and to move toward greener chemistries, he emphasizes.

“What we've devised here [with Waters’ new bioanalysis kit] is an approach that takes advantage of enzyme technology, or recombinant proteinase K, that will act upon the protein composition of any biofluid or tissue sample. So, this rapidly degrades protein composition, and this helps us work against what was designed in the oligonucleotide for its pharmacology effects,” Lauber states. He further explains that oligonucleotides with lipid modifications and backbone modifications are designed to bind to proteins, but that action is essentially an interference on the quantitation assay.

“Secondly, after a rapid digestion of all the proteome, we can take the sample and load to a mixed-mode SPE (solid phase extraction) procedure, and this is a specially tuned type of chemistry, where we bind the washing of the glue and the resulting sample; we produce something that gives high recovery, high yield of the oligonucleotide drugs and their metabolites,” Lauber continues. “This facilitates, directly, a direct injection into an LC–MS [liquid chromatography–mass spectrometry] experiment where triple quad mass spectrometry can be used for very sensitive analysis of the sample. This produces a PK/PD [pharmacokinetic/pharmacodynamic] curve. You can also give information on, of course, half-lives and the metabolites of disease,” he concludes.

nd the industry’s focus on oligonucleotide therapeutics

Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, at Waters Corporation highlights the company’s motivation behind their new bioanalysis kit for oligonucleotides.

The Need for New Bioanalysis Technology (AAPS PharmSci 360)

® at AAPS PharmSci 360, Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, Waters Corporation, discusses the analytical and downstream purification challenges of working with oligonucleotides (oligos). He notes that the pharmaceutical landscape is changing—diversifying into more types of molecules.

Of oligos, he says, “Synthetic oligonucleotide therapies represent a type of molecule that's a little bit in between both worlds, being that they’re synthetically produced, yet they are really large molecules in a way —they're 15- to 30-mer residue long oligonucleotides. But being that they're chemically synthesized, what is occurring right now in the landscape—in the pipeline—is they're being modified extensively with phosphorothioate backbones, with methyl group modifications, and, on top of this, they're being conjugated with new saccharide and lipid moieties so that they can be very carefully controlled for their absorption.”

Meanwhile, commenting on some key challenges in the downstream purification of oligo molecules, Lauber explains that “because they are so exquisitely modified, these chemically synthesized oligonucleotides also need to be carefully purified, and this is usually done through anion exchange or first-phase preparative chromatography.”

“With this,” he continues, “the impurities have to be analyzed to at least 0.1% relative abundances and thoroughly understood. Many companies are working very hard on characterizing those impurities.”

Lauber goes on to explain that, even with a purified drug substance, however, there is another type of analysis—quantitative bioanalysis—that is important. This quantitative bioanalysis enables researchers to “see what happens with the drug once it's dosed to an animal model, or first studied in 

 cell analysis, or later on in clinical study as the first-in-humans study.”

View Lauber’s video interviews about the 

industry’s focus on oligonucleotide therapeutics

Matthew Lauber, senior director—Cell and Gene Therapy, Consumables & Lab Automation, at Waters Corporation discusses the analytical and downstream purification challenges of oligonucleotides.