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STAT+: Sanofi asks to pull diabetes drug out of FDA voucher program after political appointee interfered with review

WASHINGTON — Sanofi has asked the Food and Drug Administration to pull its type 1 diabetes drug, teplizumab, out of Commissioner Marty Makary’s new speedy drug review program. 

The move comes after acting Center for Drug Evaluation and Research Director Tracy Beth Høeg disagreed with a staff decision to approve the drug, according to sources familiar with the dispute who requested anonymity due to fear of reprisal. The agency has missed its goal date of April 21 to deliver a decision to Sanofi.

Such decisions are typically made by career scientists. It’s rare for a center director to become involved in scientific review of a single drug, and particularly a political appointee like Høeg. Makary recently told CNBC that he stands behind review teams, and that “disaster” occurs whenever political leaders overrule scientific staff. 

Continue to STAT+ to read the full story…

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<![CDATA[Tracy Hicks, DNP, FNP/PMHNP-BC, outlines how personalized, team-based care and shared decision-making can improve schizophrenia outcomes in real-world practice.]]>
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Heavy-Chain BsAbs More Manufacturable than Light-Chains

Bispecific antibodies (BsAb) were first approved in 2014. Since then, a total of 19 have been approved globally, and approximately 250 BsAbs are being developed by some 180 companies, according to a report from Research and Markets. As this therapeutic class moves out of the lab and into clinical and commercial sectors, manufacturing may be its biggest challenge.

These dual-targeting compounds are considered difficult to produce, especially at scale. With low yields, potential chain mispairing, stability and aggregation issues, and analytical characterization challenges, biomanufacturers are eager to find expedient solutions. “There is still significant work to be done in bioprocess engineering to substantially improve the efficiency of bispecific antibody design and manufacturing,” Laura A. Palomares, PhD, senior researcher, Universidad Nacional Autónoma de Mexico (UNAM), tells GEN.

To that point, rather than relying upon transient expression systems or evaluating various antibody sequences, Palomares and her team are identifying manufacturable BsAbs by correlating their architectures to growth, productivity, downstream recovery, production of product-related variants, and in vitro binding to Zika virus and transferrin receptor (TfR). They found BsAb architecture is crucial in terms of those manufacturing criteria.

Structure governs performance

Specifically, as much as a 70% difference in productivity was found between symmetric heavy-chain scFv fusion BsAbs—which performed like the parental antibody—and BsAbs that were designed as light-chain scFv fusion, dual-variable domain immunoglobulin (DVD), or asymmetric antibodies. That’s according to a recent study by Palomares, doctoral student Juan Carlos Rivera-Castro, and senior researcher Octavio T. Ramirez, PhD.

Asymmetric BsAbs had the worst culture performance and productivity of the BsAb architectures tested. Asymmetry created imbalanced chain expression and formed homodimeric and half-antibody by-products, they reported, which dropped purity to approximately 68% after protein A purification. They found that binding to the LC-scFV diminished the binding to Zika virus, and that DVD increases it. Also, binding to TfR varied according to BsAb valency and configuration.

In contrast, “Bivalent heavy-chain scFV formats show[ed] stronger apparent binding than monovalent formats,” they report.

For the best manufacturability, the team says, “Avoid the modification of the light chain and preserve symmetric assembly.” This strategy resulted in higher cell viability, productivity, and final purity.

“The construction and head-to-head comparison of various formats, including the effect of the formats on antigen binding, can guide those planning the design and production of BsAbs,” Palomares says, by understanding the relative tradeoffs of various architectures as they design and clone BsAbs for specific functionalities.

“Format selection should prioritize manufacturability, with complex designs reserved for cases with particular functional requirements,” the scientists conclude.

Next steps, Palomares says, are to “determine the in vivo functionality of the constructed formats to neutralize Zika virus after traversing the blood-brain barrier. The results of those experiments will also be useful to scientists interested in BsAb design.”

The post Heavy-Chain BsAbs More Manufacturable than Light-Chains appeared first on GEN – Genetic Engineering and Biotechnology News.

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Researchers’ Spinout Focuses on Simplifying Viral Vector Purification

U.S.-based researchers have developed a portfolio of peptide ligands for purifying viral vectors for gene therapies and have launched a company that develops affinity technologies for biopharmaceutical manufacturers.

ChromaGenix, a spinout from North Carolina State University (NC State), commercializes peptide ligands as an alternative to the traditional protein ligands used in affinity chromatography.

According to Stefano Menegatti, PhD, CSO at ChromaGenix and a professor in the Department of Chemical and Biomolecular Engineering at NC State, the ligands are cheaper and less likely to trigger an immune response in patients than the protein ligands traditionally used.

“Protein ligands have been a fantastic enabler of advanced biological therapies over the past two decades, but they do have shortcomings,” he explains. “Proteins can denature or degrade, potentially releasing immunogenic fragments, which poses a certain level of risk.” As such, Menegatti says, protein ligands have a short lifetime and must be replaced frequently, adding further to production costs. They can also bind too strongly to the product, making it harder to recover it from the chromatographic step.

By contrast, peptide ligands, which are very small proteins, overcome these issues, he says. They can be produced synthetically, making them cheaper than proteins. As they don’t have a complex structure, they can be cleaned under harsh conditions without becoming inactive. They have a longer lifespan and a much lower immunogenicity risk, Menegatti says. Also, as they’re small, he explains,they can be cleared during final product filtration.

This “represents a new frontier of gene therapy manufacturing, says Menegatti, “as it boosts the efficiency of the viral vector manufacturing pipeline.”

Having developed peptide ligands for a wide variety of viral vectors, ChromaGenix is already selling to many companies, Menegatti says. The researchers and the company are now hoping to move beyond gene therapies.

“Our next chapter is going to be developing ligands for the purification of therapeutic cells, starting with CAR [chimeric antigen receptor] T cells,” he says.

The post Researchers’ Spinout Focuses on Simplifying Viral Vector Purification appeared first on GEN – Genetic Engineering and Biotechnology News.

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Moss Powering the Next Drug Frontier

For decades, Chinese hamster ovary (CHO) cells have been the gold standard for producing biologic drugs, from monoclonal antibodies to enzyme therapies. But for some of the most complex and fragile proteins, even CHO systems can fall short. Now, an unlikely contender—moss—is offering a new path forward.

At Germany-based Eleva, researchers are using Physcomitrium patens, a simple moss species, as a suspension cell culture system for producing recombinant human proteins that are difficult and sometimes impossible to manufacture in conventional platforms. According to Andreas Schaaf, PhD, Eleva’s CSO, these include “glycoproteins with complex or sensitive glycosylation requirements,” as well as cytokines, immune-cytokines, complement regulators, enzymes for rare metabolic disorders, and advanced antibody formats such as antibody-toxin conjugates.

The technology has deep academic roots. Plant biotechnologist Ralf Reski, PhD, at the University of Freiburg, helped develop P. patens into a model species for synthetic and systems biology and co-invented the moss bioreactor. His research led to the founding of Greenovation, now known as Eleva, which has since advanced the platform toward clinical-stage drug development.

The company’s first moss-produced drug candidate to enter clinical studies was a recombinant alpha-galactosidase enzyme replacement therapy (ERT) for Fabry disease, a rare lysosomal storage disorder. Current ERT options for Fabry patients are limited by short circulating half-life, inefficient uptake into key affected cell types, and immunogenicity. Eleva believes the more uniform glycosylation achieved through moss production could help overcome these limitations.

A particularly significant demonstration of the platform is Eleva’s recombinant complement Factor H candidate, currently in Phase Ib. Factor H is a large complement-regulatory glycoprotein used to target complement-related renal diseases such as C3 glomerulopathy (C3G), lupus nephritis (LN), and potentially dry age-related macular degeneration (AMD).

Schaaf notes that Factor H “had long resisted reliable expression in conventional systems such as yeast or CHO cells.” For patients with C3G—many of whom are young and face a 50% rate of kidney failure within ten years—the ability to restore natural Factor H activity could represent a major therapeutic shift. Current treatments often rely on broader complement suppression and carry boxed warnings for serious infections.

So why moss?

Unlike mammalian cells, which often generate heterogeneous glycan mixtures, moss produces more uniform glycosylation profiles due to its simplified glycan-processing pathway. This matters because glycosylation can directly affect a drug’s stability, efficacy, and immunogenicity.

Moss cells are also largely unaffected by toxic cytokine feedback, which in mammalian systems can inhibit growth or trigger apoptosis, limiting secretion efficiency and yields. Plant-specific chaperones and folding assistants, including protein disulfide isomerases, also help prevent protein aggregation and support the correct assembly of complex multimeric proteins.

“Moss offers clear advantages over other expression systems for certain protein classes that are difficult or impossible to manufacture otherwise,” Schaaf says, adding that such therapies might otherwise be “deprioritized or abandoned.”

There are practical manufacturing advantages, too. Moss requires no animal-derived media supplements, eliminating mammalian virus risk and removing the need for costly viral filtration in downstream processing. It is also less sensitive to fluctuations in temperature and pH, giving manufacturers greater process flexibility and potentially lowering production costs.

Still, Eleva is careful not to position moss as a replacement for CHO. Björn Cochlovius, PhD, CEO of Eleva, says standard proteins will continue to be best served by established systems. “The goal is not to replace CHO or other systems with moss when those other systems deliver well,” he explains.

Instead, the aim is to ensure that the range of therapeutic candidates in development is not defined by the limits of existing manufacturing platforms. Yields for large-scale GMP production and improving predictability remain ongoing challenges, but commercially viable titers are already being achieved through continuous optimization.

Cochlovius believes regulatory precedent and growing CDMO partnerships will further strengthen adoption. “A moss-based platform capable of reliably producing this category of proteins at scale would open a pipeline of programs that are currently inaccessible,” he says.

For biotech developers—and for patients with limited treatment options—that could make all the difference. Sometimes, the future of medicine grows in the smallest places.

The post Moss Powering the Next Drug Frontier appeared first on GEN – Genetic Engineering and Biotechnology News.

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Regulators Should Rely on Peers’ GMP Audits to Cut Inspection Burden

Biopharma is a global industry with drug firms routinely supplying medicines to multiple markets from the same manufacturing plant. But while globalization has helped expand revenues, it has also increased the number of GMP inspections developers undergo.

The average biopharmaceutical production facility has 2.68 good manufacturing practices (GMP) inspections a year, with auditors spending up to nine days on site per visit, according to recent analysis.

Preparing for an inspection typically involves GAP analysis to determine how current practices measure up to regulations, followed by corrective actions.

Companies also need to ensure they have the correct documentation for all operations. How long these preparatory steps take varies for each company. However, according to the U.S. Center for Professional Innovation and Education, getting set up for an audit can take anywhere from six months to a year.

Down with duplication

But drug companies should not have to undergo multiple GMP visits, according to the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), which says regulators can cut the number they carry out through collaboration.

Sérgio Cavalheiro Filho, IFPMA’s regulatory affairs manager, tells GEN, “The most pressing compliance challenge relating to good manufacturing practice today is the inefficiency created by duplicative inspections.

“In an increasingly complex and globalized manufacturing landscape, it is critical that we look to reduce unnecessary duplication through greater inspection reliance amongst those national regulatory agencies that belong to the Pharmaceutical Inspection Co-operation Scheme.”

For the uninitiated, the Pharmaceutical Inspection Co-operation Scheme is an informal arrangement between regulators focused on GMP. Its key aims are to harmonize inspections and promote information sharing between regulators.

It also aims to foster trust between regulatory agencies, with the idea being to encourage them to rely on GMP inspections carried out by fellow regulators rather than re-auditing sites themselves each time certification is sought.

“Greater inspection reliance would allow both regulators and companies to focus resources where they matter most: patient safety and product development,” Filho says.

IFPMA made the case for greater inspection reliance in a position paper, arguing that while pilot mutual recognition efforts have shown promise, regulators have yet to fully embrace the approach.

Filho tells GEN, “Regulators have made meaningful progress on GMP harmonization through frameworks such as PIC/S and ICH, but more consistent use of inspection reliance is needed to translate alignment on paper into real efficiency.”

Part of the problem is that advanced modalities, such as mAbs and cell and gene therapies, are often perceived as being higher risk, which means, despite the various mutual recognition agreements, regulators still tend to carry out their own inspections.

However, in such cases, trusting others’ audits is a more efficient option, according to Filho, who says, “Relying on trusted regulatory partners where appropriate is a well‑tested and effective strategy that enables regulators to focus on higher‑risk activities. And, any steps to reduce the incidence of the GMP audits they face would be welcomed by biopharma, Filho adds.

“Industry supports moving from pilots to routine reliance, underpinned by sound legal and data‑sharing frameworks. GMP challenges are also increasingly addressed through collaboration between manufacturers and technology suppliers, and through digitalization, automation, and AI‑enabled tools that strengthen monitoring and quality oversight within robust quality systems,” he says.

The post Regulators Should Rely on Peers’ GMP Audits to Cut Inspection Burden appeared first on GEN – Genetic Engineering and Biotechnology News.

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STAT+: Color Health moving deeper into cancer services, complete with virtual ‘tumor boards’

The way Color Health’s CEO Othman Laraki sees it, cancer has a scaling problem. New science regularly sets new standards of care, increasing the intricacy of managing an already complex illness. Cancer patients are multiplying faster than oncologists, Laraki said, and costs, too, are exploding. All this makes it difficult for everyone to receive the best possible therapy. The solution that the Silicon Valley executive sees is inevitable.

“In our mind, the only way this is going to be addressed and solved is in a virtual first, AI-driven manner,” Laraki said. “In the coming years, the biggest cancer centers will be virtual first.”

Virtual care for cancer may sound like an oxymoron. After all, the pillars of cancer treatment are almost all hands-on: surgery, radiation, infusions, and the like. But Color Health has been building out a virtual cancer clinic — including a virtual “tumor board” of multidisciplinary experts —  that the company says can deliver and manage care at a high quality. The company just received a certification from the American Society of Clinical Oncology to back it up.

Continue to STAT+ to read the full story…

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CoCoGraph AI Model Generates Molecules that Comply with Rules of Chemistry

Developing new molecular compounds is crucial to address pressing challenges, from drug discovery to sustainable materials. However, discovering viable new molecules is challenging due to the vastness of the search space. 

In a new paper published in Nature Machine Intelligence titled, “A collaborative constrained graph diffusion model for the generation of realistic synthetic molecules,” researchers from Universitat Rovira i Virgili (URV) have developed an AI tool capable of generating molecules that are guaranteed to comply with the rules of chemistry. The model, named CoCoGraph, operates similarly to generative AI tools for text or images, such as ChatGPT or Dall-E.  

“These models create new content that looks very much like the real thing. Our algorithm does the same, but with molecules,” said Roger Guimerà, PhD, ICREA research professor in the department of chemical engineering at URV and co-corresponding author of the study. He explains that the number of possible chemical molecules could be up to 10⁶⁰ variants, which is more than the number of water molecules in the ocean.  

CoCoGraph uses a diffusion model, a technique common in image generation, which progressively “disorders” a real molecule and trains the system to learn how to reconstruct it. 

Marta Sales-Pardo, PhD, professor in the department of chemical engineering at URV and co-corresponding author of the study, explains that the model begins with a real molecule, breaks the bonds, and then creates new bonds at random. The model then learns to reverse this process to reconstruct coherent structures. 

Notably, CoCoGraph directly incorporates the basic rules of chemistry, such as maintaining the correct number of bonds, to guarantee that generated molecules are chemically valid. The system is also more efficient, uses fewer parameters, and requires less computing power to generate molecules more quickly. 

The research team has compared the performance of CoCoGraph with other state-of-the-art models and analyzed 36 physicochemical properties, such as solubility and structural complexity. For two-thirds of these properties, the CoCoGraph generated molecules are chemically more realistic than those from other models. 

Although the model cannot yet design molecules with a specific function, researchers have identified molecules with properties similar to the drug, paracetamol. They have also explored techniques to partially modify an existing molecule to create new variants with similar characteristics, which are useful for optimizing drugs or developing new materials. 

The next step is to design molecules with specific properties, such as solubility and low toxicity. If successful, the technology could accelerate the discovery of new solutions across pharmacology and materials science in a chemical universe that is still practically unexplored. 

The post CoCoGraph AI Model Generates Molecules that Comply with Rules of Chemistry appeared first on GEN – Genetic Engineering and Biotechnology News.

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Next Generation CRISPR Gene Editing Could Help Target Cancer Cells

A CRISPR gene editing protein called Cas12a2 can be turned into a kind of programmable self‑destruct switch for cells, which researchers think could be a new way to treat conditions like cancer if the technique is validated.

Cas12a2 eliminates eukaryotic cells based purely on which RNA transcripts they express, and the investigators showed this can be used to selectively destroy virus‑infected cells, unedited cells, and cancer cells bearing a single‑nucleotide mutation.

“Common molecular and cell-based interventions, such as small-molecule inhibitors, toxins, antibodies, lytic viruses or programmed immune cells, eliminate cells through specific proteins or survival pathways; however, these methods cannot be tailored to arbitrary genetic or transcriptional states as well as difficult-to-drug scenarios such as mutations in non-coding sequences or complex etiologies,” write co-lead author Yang Liu, PhD, assistant professor in biochemistry at University of Utah Health, and colleagues in Nature.

“A cell-killing approach triggered directly by the specific recognition of prescribed DNA or RNA sequences could greatly broaden the range of targetable conditions, creating new means to counter select against specific cells in a variety of situations and applications.”

In this study, the researchers first tested the technology in yeast and human cell lines against a harmless target. They found that the guided Cas12a2 destroyed the cells carrying the marker by effectively shredding their DNA. When they checked for off-target effects they were rare and weak.

They then tested the technology on cancer cells carrying the HPV virus by targeting viral RNA. The method killed cells containing the virus, but not cells negative for HPV. The team also used the Cas12a2 method to “clean up” after gene editing by killing unedited cells and enriching edited ones. Finally, they tested if Cas12a2 could recognize a single mutation in the cancer gene KRAS and showed it could destroy cells with this mutation while leaving cells with a non-mutant version of KRAS alone. This worked even when those cells were resistant to an approved KRAS drug.

“The enzyme that we’re working with is extremely specific,” Liu says. “It does not touch the healthy cells. So if we’re thinking about a cancer therapy, you’re treating cancer with no side effects. That was striking to us. We did not know that was possible.”

This research is early stage, and it will take some time to enter the clinic, as testing in animal models is needed first, but the research team say the results are promising. The technology is being developed commercially by German biotech Akribion Therapeutics, a biotech spin-off from BRAIN Biotech launched in 2024.

The post Next Generation CRISPR Gene Editing Could Help Target Cancer Cells appeared first on Inside Precision Medicine.

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<![CDATA[Explore how neuromelanin-sensitive MRI noninvasively tracks long-term dopamine and noradrenaline system changes.]]>