Tag: Biotech

Posted on

T-Cell Synapse Formation Is Restrained by PTPN22–PSTPIP1 Signaling

T cells don’t simply switch on—they reshape themselves. When these immune sentinels recognize a target, they rapidly reorganize their internal scaffolding to build an immunological synapse, a nanoscale interface that determines how strongly they respond. But that architectural overhaul needs brakes. Without them, T cells risk becoming hypersensitive, reacting to weak cues, and drifting toward autoimmunity. Now, new work reveals that one of those brakes—PTPN22 (proline-serine-threonine phosphatase–interacting protein 1)—acts not only on signaling molecules but also on the cytoskeletal machinery that sculpts the synapse itself.

In a study published in Science Signaling, lead author Megan Joseph, PhD, of University College London and colleagues uncover how PTPN22 interacts with the cytoskeletal adaptor protein PSTPIP1 to restrain actin remodeling at the T‑cell synapse. Their paper, “PTPN22 regulates T-cell synapse formation through PSTPIP1-dependent actin remodeling,” shows that this phosphatase plays a previously unappreciated role at the plasma membrane, shaping how T cells respond to antigens of varying affinity. As the authors wrote, “These findings uncover a PTPN22–PSTPIP1 signaling axis that is critical for regulating cytoskeletal remodeling and receptor organization, providing insights into T-cell hyperactivation that may be relevant to autoimmune disease.”

PTPN22 is already well known as a negative regulator of early T‑cell activation. Variants in the gene, including the autoimmune‑associated R620W allele, have been linked to diseases ranging from lupus to rheumatoid arthritis. Using super‑resolution DNA‑PAINT imaging, Joseph et al. visualized how T cells reorganize their actin networks as they engage activating ligands. In wild‑type Jurkat cells, PTPN22 helped maintain orderly actin dynamics. In its absence, however, PSTPIP1 accumulated at T cell receptors (TCRs), disrupting Arp2/3‑dependent actin polymerization and generating dense central F‑actin foci, as well as enhanced Ca2+ signaling, especially under low-affinity stimulation of the TCR, according to the paper.

This hyper‑remodeling had functional consequences. PTPN22‑deficient cells became unusually sensitive to low‑affinity antigens, responding more vigorously than their wild‑type counterparts. “Autoimmunity is inherently linked to immune tolerance mechanisms normally associated with low-affinity TCR responses to self, which, when breeched lead to inappropriate immune reactions. To better understand how PTPN22 contributes to these processes, we used WT and PTPN22 KO TCR−/− Jurkat cells engineered to express a transgenic TCR with high affinity for the pTax peptide and low affinity for the pHuD peptide,” the authors wrote.

Joseph and colleagues suggest that understanding this axis could inform both autoimmune research and efforts to modulate T‑cell activation in cancer immunotherapy. By mapping how PTPN22 and PSTPIP1 coordinate actin remodeling, the study provides a mechanistic foothold for exploring how synapse architecture shapes immune outcomes.

The post T-Cell Synapse Formation Is Restrained by PTPN22–PSTPIP1 Signaling appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Incyte to Acquire Vega Therapeutics for Up-to-$2B, Growing Hematology Pipeline with Phase III VWD Candidate

Incyte has agreed to acquire Vega Therapeutics for up to $2 billion, the companies said, in a deal designed to bolster the buyer’s hematology pipeline with antibody assets led by VGA039, a Phase III candidate for von Willebrand disease (VWD).

Vega, a wholly owned subsidiary of privately held Star Therapeutics, focuses on developing treatments for bleeding disorders. Vega’s lead candidate VGA039 could, if approved, be the first subcutaneous prophylactic therapy with a more convenient once-monthly, self-administered dosing regimen for patients with VWD, compared with current therapies requiring more frequent (2-3x/week) intravenous infusions.

VGA039 is a monoclonal antibody designed to modulate Protein S with the aim of improving hemostasis, potentially improving the body’s ability to control bleeding in numerous bleeding disorders. VGA039 is under study in the Phase III VIVID-6 trial (NCT07115004), a global single arm crossover study designed to investigate the safety and efficacy of subcutaneous administration of VGA039 as prophylaxis for bleeding in patients with every type of VWD, including those with a high disease burden.

VIVID-6’s estimated completion date is October 2028, with data expected to be read out in early 2029.

“VGA039 fits directly into our strategy of building a top-tier growth company for the future,” Incyte CEO Bill Meury said in a statement. “It is a first-in-class, Phase III asset with compelling early data, a manageable development path and the potential to become an important new growth driver in one of our core therapeutic areas, hematology. The transaction has all of the attributes we look for in business development opportunities.”

$1B+ opportunity

In a presentation to analysts Monday morning, Incyte quantified that potential market opportunity as “$1B+ global net sales opportunity.”—an estimate with which three analysts concur:

“VGA039 has the potential to address a clear unmet need for a practical, targeted therapy for von Willebrand disease, and even with conservative assumptions around pricing and market penetration, VGA039 has a clear path to a more than $1 billion market opportunity,” Matt Phipps, PhD, partner and group head of biotechnology equity research with William Blair, wrote Monday in a research note.

“Overall, we believe the deal for VGA039 fits well into Incyte’s current hematology franchise and capabilities and offers a relatively de-risked Phase III asset with blockbuster commercial potential in the 2030s,” Phipps added.

Jessica Fye, a managing director and senior equity research analyst with J.P. Morgan, was also bullish on VGA039’s commercial potential: “We think mgmt [management] framing VGA039 as a potential $1bn+ global sales opportunity is credible and think it should be able to leverage some of INCY’s existing presence with hematology centers.”

Faisal Khurshid, equity analyst with Jefferies, agreed that VGA039 “could have blockbuster potential” assuming it is priced at about $500,000/year compared with the $0.5 to $1 million range of current prophylactic therapies, and assuming ~2,000 patients at hemophilia treatment centers receive frequent IV prophylaxis out of 7,000-10,000 patients who have severe or recurrent bleeds.

“We feel that VGA039 largely fits INCY’s strategic goals and is well-positioned to succeed in Ph[ase III],” Khurshid wrote in a research note.

Despite the positive comments from analysts, Incyte shares dipped 1.7% Monday, from $102.38 to $100.64, though the stock rebounded Tuesday in early trading, rising nearly 3% to $103.31 as of 10:25 a.m. ET.

Eligible for voucher

VGA039 has received the FDA’s Fast Track, Orphan Drug, Breakthrough Therapy, and Rare Pediatric Disease (RPD) designations. The RPD designation made Star Therapeutics eligible to receive a Rare Pediatric Disease Priority Review Voucher (PRV) upon approval of a Biologics License Application for VGA039—eligibility that would transfer to Incyte if its acquisition of Vega occurs as planned. The voucher may be redeemed to obtain priority review for a subsequent marketing application or transferred or sold to another sponsor.

The Breakthrough Therapy designation was supported by interim data from the Phase I/II multidose study (NCT05776069) of VGA039 in adult and adolescent patients with VWD, showing substantial bleed reductions across all types of VWD and all types of bleeds. The data was presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025.

Vega’s pipeline includes two other programs, both preclinical—a complement therapy program, and an undisclosed program.

Looking beyond Jakafi®

Acquiring Vega and its pipeline is among moves Incyte has undertaken in recent months under Meury to recoup the billions of dollars in sales that it stands to lose once its aging blockbuster Jakafi® (ruxolitinib) loses patent exclusivity in 2028—one of the Top 20 Drugs Heading for the Patent Cliff through 2029, according to a recent GEN A-List.

Jakafi, marketed outside the U.S, as Jakavi®, generated $3.093 billion in net product revenues last year, up 11% from $2.792 billion in 2024. Jakafi finished the first quarter with $757.755 million in net product revenues, up 7% from $709,412 in Q1 2025.

Incyte has agreed to pay Star $1.25 billion upfront for Vega, plus up to $750 million in payments tied to achieving sales milestones.

The boards of Incyte and Star have approved the acquisition deal, through which Incyte will acquire all of Vega’s outstanding shares through a stock purchase agreement. The deal is subject to expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions.

Incyte expects to incur an R&D charge of approximately $1.25 billion, to be included in third quarter and full year 2026 GAAP and non-GAAP results, as a result of the acquisition.

However, the benefits of an acquisition by Incyte outweigh its costs, Vega and parent Star Therapeutics reason.

“This milestone reflects our team’s deep commitment to innovation and underscores our strategy to develop first-in-class and best-in-class therapies for serious conditions with high unmet need,” stated Adam Rosenthal, PhD, Star’s founder and CEO.

The post Incyte to Acquire Vega Therapeutics for Up-to-$2B, Growing Hematology Pipeline with Phase III VWD Candidate appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Fifteenth In Vivo Lentiviral Vector-Based Therapeutic Technology Added to VIVEbiotech’s CGT Platform

Spain-based CDMO VIVEbiotech added its 15th in vivo lentiviral vector-based therapeutic program using its platform. These programs, several of which have already received regulatory clearance for clinical trials, including from the FDA, span a range of applications such as in vivo CAR T, rare diseases, gene editing, and vaccines, according to the company.

Growing interest in in vivo cell and gene therapies is driving significant investment, given their potential to address some of the manufacturing and commercialization challenges associated with current ex vivo approaches. However, the direct administration of lentiviral vectors imposes significantly more stringent requirements on the quality attributes of the final product, notes Jon Alberdi, CEO of VIVEbiotech. Accordingly, process control must be optimized to improve both yield and purity. As manufacturing becomes increasingly complex, the scope of analytical characterization is also expanding.

“In vivo lentiviral vectors have the potential to transform treatment paradigms through faster administration and direct therapeutic delivery,” says Alberdi. “However, these advantages come with more stringent manufacturing requirements—from achieving the required purity profile to ensuring consistent performance at scale.”

“As interest in in vivo delivery continues to grow, we are witnessing a fundamental shift in how gene therapies are developed and brought to patients,” adds Marie Fertin, chief custom solution and process development officer at VIVEbiotech. “Our continued investment in capabilities reflects both our confidence in this field and our commitment to enabling our partners.”

The company’s platform has been specifically designed to preserve lentiviral vector integrity throughout the manufacturing process by minimizing shear stress and maintaining cell health, thereby ensuring high vector functionality, continues Fertin. By integrating process intensification strategies with optimized transfection conditions, reduced reagent usage, and improved productivity, the upstream setup contributes to enhanced yields and a significant reduction in cost of goods, she maintains.

Beyond manufacturing, VIVEbiotech reports that it has developed a fully customized analytical framework tailored to in vivo lentiviral vectors, specializing in advanced vector characterization, including potency assay development. A full testing panel is proposed following regulatory feedback received for direct in vivo administration.

A company spokesperson points out that VIVEbiotech also supports large-scale manufacturing of in vivo programs. With more than 3,000 sqm of GMP facilities and seven cleanrooms, VIVEbiotech says it works to ensure timely delivery across development stages. An ongoing expansion plan will further increase manufacturing capacity by 2028, supporting the growing demand for in vivo therapies.

 

The post Fifteenth <i>In Vivo</i> Lentiviral Vector-Based Therapeutic Technology Added to VIVEbiotech’s CGT Platform appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Complete Connectome of Fruit Fly Central Nervous System Now Open-Source

A new study published in Nature titled, “Distributed control circuits across a brain-and-cord connectome”, describes a complete wiring diagram of all the connections between neurons in the central nervous system of an adult fruit fly for translational applications.

The work was completed by an international team led by multiple labs at Harvard Medical School (HMS) and Princeton University. The team has made the entire connectome accessible online to propel research into complex behaviors and other fundamentals of the nervous system. 

The fruit fly, Drosophila melanogaster, offers an effective model as they are easy to breed and maintain in the lab. Despite having a relatively simple nervous system made up of around 160,000 neurons, they exhibit complex behaviors such as navigation, social interaction, learning, and responding to sensory cues. 

To build the connectome, the team used electron microscopy to produce millions of images of neurons and neural connections. AI tools aligned the images into a cohesive 3D map. 

“It is really important to have a central nervous system connectome that is as complete as possible so we can link up the brain and body and start thinking about behavior holistically,” said Wei-Chung Allen Lee, PhD, associate professor of neurobiology at HMS and co-corresponding author on the study. 

The connectome shows how each neuron connects in the brain and nerve cord at the synapse level. While the map doesn’t span the fly’s entire body, the team used identifiable neurons and literature review to connect the central nervous system to neurons in appendages and sensory organs. 

The authors have already used the connectome to explore motor control. While a longstanding idea in neuroscience is for a centralized controller in the brain to make decisions about actions, the authors discovered that motor control in the fruit fly mostly occurs at a local level. For example, movement of a fly’s leg is primarily controlled by the neural circuits for that leg. The local circuits for one leg then communicates with other appendages to carry out complex coordinated movements, such as walking. 

“The brain and nerve cord connectomes are each useful on their own, but until you can bridge the two, it’s hard to understand how information moves between the brain and the body,” said co-first author Helen Yang, PhD, a research fellow in neurobiology at HMS. 

Looking ahead, the researchers plan to add more information to the connectome, including data describing neuropeptides, molecules that support neuron communication. Insights from the connectome may reveal fundamental principles about how nervous systems operate across species, including in humans. 

The post Complete Connectome of Fruit Fly Central Nervous System Now Open-Source appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Single-cell spatial pharmacobiology for imaging antibody-based therapies in solid tumors

Nature Biotechnology, Published online: 08 June 2026; doi:10.1038/s41587-026-03171-8

We have developed single-cell spatial pharmacobiology (SSP), which combines in situ imaging of a systemically infused fluorescent therapeutic antibody with high-plex spatial proteomics. Applied to head and neck and pancreatic tumors from patients treated in phase 1 trials, SSP revealed marked spatial heterogeneity in antibody delivery and target engagement, which was shaped by conserved stromal barriers.