Tag: Biotech

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Novel Targets for Complex Cancer Revealed by Genetic Regulatory Node Mapping

In a new study published in Nature titled, “Mapping convergent regulators of melanoma drug resistance by PerturbFate,” researchers from The Rockefeller University have developed a platform called PerturbFate that can systematically map how diverse disease-associated genetic variations reshape cells. By tracking gene regulation in single cells over time, the team identified regulatory nodes common to diverse variations. Using melanoma drug resistance as a proof-of-concept, results showed that these shared points of control offer a path toward combination therapies that can target disease across many genetic causes. 

“Once you know that a disease is associated with hundreds of genes, how do you design one therapy to target it?” posed Junyue Cao, PhD, head of the Laboratory of Single-Cell Genomics and Population Dynamics at Rockefeller. “We wondered whether all these different genes may be mediated by some shared downstream signaling that we can discover and target instead.” 

Advances in genomic sequencing and genetic screening have allowed researchers to identify hundreds of genetic mutations linked to disease. Yet these genes often span diverse pathways with broad functionalities, from gene regulation to cell signaling, making them difficult to target collectively.  

Cao proposed that if these mutations converge on shared downstream programs, the key challenge is not to target each mutation individually, but to identify the common control points known as regulatory nodes.  

PerturbFate allows researchers to observe how different genetic changes reshape a cell in real time by tracking DNA accessibility, and RNA production and processing. By capturing these changes in the same single cell, the system reveals the networks of genes that control cell behavior and how different genetic variations can have the same effect. 

“This technology lets us perturb hundreds to thousands of genes in parallel and then measure the detailed molecular changes in each individual cell,” says Cao. “That allows us to link many different genetic perturbations to their downstream effects and identify regulatory nodes.” 

To test the platform, the authors focused on melanoma drug resistance. Using PerturbFate, they selected 143 genes linked to resistance to the common melanoma drug, Vemurafenib. PerturbFate then tracked how deactivating each of these genes reshaped the cell. Cao explains the platform captures gene expression, RNA dynamics and chromatin state, all critical components when identifying upstream regulators that drive these disease states. 

After analyzing more than 300,000 cells, the researchers found that diverse genetic perturbations pushed melanoma cells into the same drug-resistant state. Drug resistance dropped significantly when these common control points were targeted, pointing to a promising strategy for combination therapies. 

The platform also revealed an important nuance involving the transcriptional coactivator, Mediator Complex. Disrupting different parts of this same complex could trigger drug resistance through routes that ultimately converged on the same survival signal in melanoma cells, called VEGFC. Resistant cells could no longer proliferate after blocking that signal. 

The team has made both the experimental and computational tools behind PerturbFate openly available, and plans to extend the approach from cultured cells to living systems. Cao and colleagues are currently applying PerturbFate to conditions, such as aging and Alzheimer’s disease, to uncover shared vulnerabilities that can guide more effective treatments. 

“This is just a starting point,” says Cao. “Now that we’ve demonstrated the approach in a simple model, we’re working to extend it into living systems to study even more complex diseases.” 

The post Novel Targets for Complex Cancer Revealed by Genetic Regulatory Node Mapping appeared first on GEN – Genetic Engineering and Biotechnology News.

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STAT+: Novartis CEO joins Anthropic’s board

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Good morning. A reminder that if you’re ever feeling down about a mistake you made, there is always a way to turn it around — like how this delivery robot company has turned the issue of its robot crashing into my local bus stop into a marketing opportunity.

The need-to-know this morning

  • Revolution Medicines raised $2 billion in concurrent stock and debt offerings. The mammoth financings — double what the company intended to raise — come just days after daraxonrasib, its experimental treatment for advanced pancreatic cancer, was shown to double the median overall survival of patients in a Phase 3 clinical trial.

Bain Capital again creates a startup with older pharma drugs

After Bain Capital last summer said it licensed five immunology drugs from Bristol Myers Squibb, it’s now unveiling the company to take those treatments forward: a startup called Beeline Medicines.

Continue to STAT+ to read the full story…

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STAT+: New Bain biotech startup, building on BMS drugs, gets a name and a CEO

Last summer, Bain Capital Life Sciences announced that it would form a new biotech startup, created with $300 million and five drugs licensed from Bristol Myers Squibb.

Now that company has a name, a CEO, and a mission.

The venture, Beeline Medicines, will continue development of five inflammatory and immune disorder drugs, starting with a potential daily pill for lupus. Beeline plans to report data from a Phase 2 trial of that drug later this year. 

Continue to STAT+ to read the full story…

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Engineered Miniature CRISPR Boosts Gene‑Editing Efficiency in Human Cells

One of the biggest obstacles in targeting CRISPR therapy deliveries directly into the body isn’t the editing chemistry, it’s the size of the editors themselves. The field’s workhorse nucleases, including Cas9 and Cas12a, are considerably large (exceeding 1,300 amino acids) to fit inside adeno‑associated virus (AAV) vectors, the most widely used delivery vehicle for in vivo gene therapy. That size mismatch has forced most clinical applications to rely on ex vivo editing of blood or bone‑marrow‑derived cells, leaving many tissues out of reach. A smaller CRISPR system that can be packaged into AAV without sacrificing efficiency has long been a key missing piece.

A new study published in Nature Structural & Molecular Biology takes a major step toward that goal. Researchers at the University of Texas at Austin and collaborators report the discovery and engineering of a compact Cas12f nuclease that performs robustly in human cells, a notable advance for a class of miniature enzymes that have historically shown lower efficiencies in mammalian cells compared to larger systems. The paper is titled, “Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency.”

The team began by mining metagenomic datasets for naturally small CRISPR enzymes and identified a previously uncharacterized ortholog, Alistipes sp. Cas12f (Al3Cas12f). Despite its compact size—roughly one‑third that of Cas9—the nuclease showed unexpectedly strong activity in human cells. In initial screens, Al3Cas12f produced more than 50% editing at many genomic sites and exceeded 90% at several targets. The authors wrote, “Results from a gRNA screen targeting intron 1 of the ALB gene, exon 3 of the APOA1 gene and the AAVS1 site within PPP1R12C intron 1 showed that 27 target sites displayed >10% editing, 19 sites displayed >50% editing and 10 sites displayed >90% editing across AAVS1 and APOA1.”

Cryo‑EM structures revealed why this miniature enzyme punches above its weight. Compared with other Cas12f orthologs, Al3Cas12f forms a more extensive and interlocking dimer interface, creating a stable, preassembled complex that supports efficient R‑loop formation. The guide RNA scaffold also appears naturally streamlined: unlike other Cas12f gRNAs, it lacks an extraneous stem‑loop and adopts a compact conformation that docks cleanly into the protein. As the authors noted, Al3Cas12f achieves “efficient R‑loop formation through a stable dimer interface and a naturally optimized gRNA.”

Using these structural insights, the team engineered an enhanced variant, Al3Cas12f RKK, that dramatically boosts editing efficiency across genomic loci. In human cells, the variant increased editing from below 10% to more than 80% at many targets, with some sites reaching 90%. The researchers tested the system in a leukemia‑derived human cell line, focusing on genes implicated in cancer, atherosclerosis, and ALS.

The mechanistic comparisons were equally revealing. By solving the structures of two additional Cas12f orthologs—Oscillibacter sp. Cas12f and Ruminiclostridium herbifermentans Cas12f—the team noted “divergent architectures and regulatory features governing protospacer-adjacent motif recognition, gRNA binding, dimerization, and DNA cleavage.” Al3Cas12f’s extended helices and mortise‑and‑tenon‑like interactions appear to be lineage‑specific adaptations that stabilize the nuclease and support high activity.

The next step is to test whether the enzyme maintains its performance when packaged into AAV vectors. If successful, the system could offer a blueprint for engineering future generations of compact CRISPR tools.

The post Engineered Miniature CRISPR Boosts Gene‑Editing Efficiency in Human Cells appeared first on GEN – Genetic Engineering and Biotechnology News.

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CAR T Cell Therapy Biomanufactured by Cellares Infused Into First Two Patients

Cellares reported that the first two patients have been dosed with Cabaletta Bio’s investigational CAR T cell therapy rese-cel (resecabtagene autoleucel) manufactured on Cellares’ Cell Shuttle™ instrument. The administration of an autologous cell therapy, which met all release criteria and was manufactured on an automated manufacturing platform, represents an important step on the journey to realizing a future where scalable manufacturing of autologous products to supply thousands of patients per year can be achieved with minimal capital investment and a low cost of goods, according to a Cellares spokesperson.

While the transformative clinical benefits of autologous CAR T cell therapy are well established in oncology, the high manufacturing costs, lack of scalability, process inconsistency, and operational inflexibility associated with the current highly manual way of manufacturing have created meaningful barriers to patient access, reducing patient accessibility to these therapies.

“This is an important milestone that reflects three years of focused collaboration between the teams at Cabaletta and Cellares,” said Steven Nichtberger, MD, co-founder, chairman, and CEO of Cabaletta Bio. “The dosing of these first two patients is an important demonstration of Cellares’ GMP manufacturing and supply chain capabilities with their automated manufacturing platform and thus represents a significant achievement toward our goal of securing high-capacity flexible supply with minimal capital investment and a low cost of goods.”

“This milestone is a transformative moment for the field of autologous cell therapy,” added Fabian Gerlinghaus, co-founder and CEO of Cellares. “For years, the promise of autologous CAR T has been constrained by manufacturing models that were never designed to scale.”

Rese-cel (formerly referred to as CABA-201) is an investigational, autologous CAR T cell therapy engineered with a fully human CD19 binder and a 4-1BB co-stimulatory domain, designed specifically for the treatment of autoimmune diseases. Administered as a single, weight-based infusion, rese-cel is intended to transiently and deeply deplete CD19-positive cells, with the goal of resetting the immune system and achieving durable clinical responses without the need for chronic therapy.

Cabaletta is evaluating rese-cel in the RESET™ (REstoring SElf-Tolerance) clinical development program, which includes multiple ongoing company-sponsored trials across a diverse and growing range of autoimmune diseases in rheumatology, neurology, and dermatology.

The post CAR T Cell Therapy Biomanufactured by Cellares Infused Into First Two Patients appeared first on GEN – Genetic Engineering and Biotechnology News.

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Regeneron, Telix Launch Up-to-$4.3B Cancer-Focused Radiopharma Drug, Diagnostic Collaboration

Regeneron Pharmaceuticals plans to expand its pipeline into radiopharmaceutical therapies through an up to $4.3 billion collaboration with Telix Pharmaceuticals to co-develop and co-commercialize precision oncology treatments and companion diagnostics.

The companies have agreed to partner on next-generation radiopharmaceutical therapies aimed at up to eight solid tumor targets from Regeneron’s portfolio of antibodies, generated from VelocImmune® technology, which uses the company’s own mouse platform engineered with a genetically humanized immune system.

Regeneron and Telix also said they plan to develop radio-diagnostics designed to support patient selection and treatment response assessment.

The collaboration is intended to combine the biologics expertise of Tarrytown, NY-based Regeneron, including bispecific antibody discovery, with the radiopharmaceutical development platform, global manufacturing capabilities, and supply chain infrastructure of Telix, which is headquartered in Melbourne, Australia.

“Regeneron is excited to enter the targeted radiopharmaceuticals space and explore the utility of these agents either as monotherapy or rationally combined with our immunotherapy platform, particularly in areas of high unmet patient need such as lung cancer, where our PD-1 inhibitor is a global standard of care,” Israel Lowy, MD, PhD, Regeneron’s senior vice president and clinical development unit head, oncology, said in a statement.

Lowy referred to Libtayo® (cemiplimab-rwlc), a programmed death receptor-1 blocking antibody approved for multiple oncology indications including forms of non-small cell lung cancer (NSCLC), as well as cutaneous squamous cell carcinoma, and basal cell carcinoma. Libtayo finished 2025 with $1.453 billion in worldwide net product sales, up 19% from $1.217 billion in 2024. Figures include $425 million in Q4 2025 global net product sales, up 16% from $367 million in the year-ago quarter.

‘An ideal partner’

“In our view, the deal with Regeneron validates Telix’s differentiated capabilities in radiopharmaceutical development and handling of complex supply chain logistics,” Andy T. Hsieh, PhD, a partner and biotechnology analyst with William Blair, wrote Monday in a research note. “Furthermore, given Regeneron’s track record of developing successful commercial therapeutics, we believe it is an ideal partner in bringing forth antibody-based theranostic assets.”

Telix investors appeared to somewhat agree with that analysis. The company’s ordinary shares traded on the Australian Stock Exchange climbed nearly 8% from A$14.64 ($10.34) to A$15.77 ($11.13). Telix’s American depositary shares traded on NASDAQ rose about 7%, from $10.56 to $11.24.

Hsieh reiterated William Blair’s “Outperform” rating for Telix shares based on several potential value-creating inflection points, including:

  • Continuing gains in market share gains within the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) diagnostic imaging market, based on rising sales and price stability as payers have offered clarity on reimbursement—factors he said enable Telix to expand its precision medicine franchise “from a position of strength.”
  • Therapeutic franchise potential, as supported by recent positive preliminary data from part 1 of the ongoing Phase III ProstACT GLOBAL trial (NCT06520345) assessing TLX591 in metastatic androgen pathway modulation resistant prostate cancer.
  • Potential approvals of two PET imaging agents—TLX250-CDx (Zircaix®, 89Zr-DFO-girentuximab), designed to non-invasively detect and characterize clear cell renal cell carcinoma (ccRCC); and TLX101-Px (Pixclara®, Floretyrosine F 18 or 18F-FET), designed to image glioma. Both could “meaningfully” contribute to Telix’s profit-and-loss statement next year, the analyst predicted.

The FDA rejected both Zircaix and Pixclara last year via separate complete response letters. The agency held in April 2025 that Zircaix required additional confirmatory clinical evidence, which the company agreed to provide. On Friday, Telix said the FDA accepted its resubmitted New Drug Application (NDA) for Pixcara, assigning a target decision date of September 12 under the Prescription Drug User Fee Act (PDUFA).

In August 2025, the FDA rejected Zircaix via complete response letter, alleging deficiencies relating to its chemistry, manufacturing, and controls (CMC) package—deficiencies the company said were “readily addressable.”

“We look forward to additional updates pertaining to efficacy parameters, such as progression-free survival, an approvable endpoint, likely later this year,” Hsieh added.

Growth through acquisitions

Telix has built up its radiopharma infrastructure in recent years through acquisitions, spending $13.6 million to purchase IsoTherapeutics, a contract development and manufacturing organization (CDMO) focused on providing services to Telix and other radiopharmaceutical companies—followed by an up to $82 million buyout of radioisotope production technology firm ARTMS, which stands for alternative radioisotope technologies for medical science.

In September 2024, Telix expanded its manufacturing footprint by acquiring RLS Radiopharmacies for up to $250 million, part of an investment strategy focused around creating vertically integrated supply chain, manufacturing, and distribution.

The global radiopharmaceuticals market is predicted to grow at a compound annual growth rate of 10.1%, more than doubling from $14.2 billion this year to $31 billion in 2032, then soaring again to $54.6 billion by 2040, according to a Roots Analysis report issued in January.

Telix briefly pursued a U.S. initial public offering, which it withdrew in June 2024. The company cited market conditions as biotech IPOs met with chilly receptions on Wall Street and asserted that the offering was not predicated on the need to raise capital.

Regeneron has agreed to pay Telix $40 million in upfront cash for access to its radiopharmaceutical manufacturing platform for four initial therapeutic programs, with Regeneron holding an option to expand the collaboration to include four additional programs with additional upfront payments.

Telix and Regeneron have agreed to share equally their global commercialization costs and potential profits, with Telix retaining the option to co-promote certain potential products. However, if Telix were instead to opt out of the co-funding model for any of the original four programs, it would then be eligible to receive up to $535 million in development and commercial milestone payments, plus low double-digit royalties on future net sales, for that program.

If Telix opts out of co-funding for all four, company could achieve $2.14 billion in payments tied to achieving milestones.

For the diagnostics to be covered by the collaboration, Telix and Regeneron have agreed to jointly develop diagnostic assets, with Telix leading commercialization and Regeneron receiving a set percentage of profits.

“The collaboration with Regeneron reflects a highly complementary set of capabilities and a unique opportunity to explore what true ‘next gen’ biologics-based radiopharmaceuticals can potentially do for patients,” added Christian Behrenbruch, DPhil, managing director and group CEO at Telix. “We are well positioned to work toward the shared goal of advancing next-generation precision radiopharmaceuticals for patients with hard-to-treat cancers.”

The post Regeneron, Telix Launch Up-to-$4.3B Cancer-Focused Radiopharma Drug, Diagnostic Collaboration appeared first on GEN – Genetic Engineering and Biotechnology News.

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AWS Launches Amazon Bio Discovery Agentic AI to Accelerate Drug Development

AWS has now unveiled Amazon Bio Discovery, an AI platform that grants researchers direct access to a broad library of biological foundation models that can be fine-tuned for specific use cases in drug discovery. Announced at the AWS Life Sciences Symposium at the Javits Center in New York, the platform is supported by an AI agent that can select models for research goals, and evaluate candidates for synthesis and testing to enable a rapid lab-in-the-loop experimentation cycle.  

While rising AI models show promise, they require coding skills and the ability to manage computing infrastructure. Additionally, diverse models face benchmarking challenges and moving candidates from computational design to physical synthesis remains a multi-step process. Given that data live in disconnected systems, scientists must manage multiple lab partners and manually coordinate timelines and execution.

Amazon Bio Discovery addresses these challenges with three capabilities: a benchmarked library of AI models and analysis packages, an AI agent that supports experimental lab, and integrated lab partners that test top antibody candidates and route results back to the researchers. This feedback loop improves the next round of design. 

“AI agents make powerful scientific capabilities accessible to all drug researchers, not just those with computational expertise,” said Rajiv Chopra, PhD, vice president of AWS Healthcare AI and Life Sciences.  

Currently, 19 of the top 20 global pharmaceutical companies use AWS to power research workloads. Amazon Bio Discovery will bring enterprise-grade scale, privacy, and security to researchers across pharmaceutical, biotech, and academic research organizations. MSK, Bayer, the Broad Institute, and Voyager Therapeutics are among early adopters of Amazon Bio Discovery. 

Among the Amazon Bio Discovery broad catalog includes open-source and commercial models from Apheris and Boltz. Biohub and Profluent are expected to join the platform. 

Amazon Bio Discovery enables scientists to fine-tune the model by feeding prior experimental data from their organization’s lab results into the application without complex training pipelines or custom code. In-house models can also easily be deployed and hosted within Amazon Bio Discovery.  

To support model selection, an antibody benchmark dataset is available to evaluate the likelihood of a drug candidate to have favorable biological properties, such as manufacturability and stability. 

Candidates selected for experimental validation can be directly sent to Amazon Bio Discovery’s integrated network of laboratory partners, including Twist Bioscience, Ginkgo Bioworks. A-Alpha Bio is also anticipated to join the network. 

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