novartis institutes for biomedical research

Working together, we can reimagine medicine to improve and extend people’s lives.

Oncology research at Novartis

Fighting cancer with next-generation therapeutics.

Cancer is a formidable enemy that uses molecular tricks to evade drugs and the human immune systems. Efforts to fight it are advancing rapidly, and more patients are living longer with cancer than ever before. But cancer death rates are still too high, particularly for patients with advanced malignancies.

The oncology team is developing a robust portfolio of treatments that destroy tumors selectively and strip away their defenses. They include:

• Chimeric antigen receptor T (CAR-T) cell therapies : CAR-T cell therapies train T-cells from the patient's own immune system to attack and kill tumors.
• Targeted Radioligand (RLT) therapies : RLT therapies attach radioactive isotopes to proteins that home in on cancer cell targets with high precision, thereby sparing healthy tissues.
• Novel small molecules : We are developing novel small molecules against targets that were previously considered undruggable.

Our researchers leverage fundamental knowledge of cancer biology and bring new chemistry to bear on the most difficult therapeutic challenges.

Importantly, our work is not limited to pioneering discoveries in the laboratory. We also collaborate and test hypotheses in early-phase clinical trials, so we learn directly from patients.

Reimagine medicine with Novartis

Related links, addtoany buttons, printable links block (content).

• Health Tech
• Health Insurance
• Medical Devices
• Gene Therapy
• Neuroscience
• H5N1 Bird Flu
• Health Disparities
• Infectious Disease
• Mental Health
• Cardiovascular Disease
• Chronic Disease
• Alzheimer's
• Coercive Care
• The Obesity Revolution
• The War on Recovery
• Adam Feuerstein
• Matthew Herper
• Jennifer Adaeze Okwerekwu
• Ed Silverman
• CRISPR Tracker
• Breakthrough Device Tracker
• Generative AI Tracker
• Obesity Drug Tracker
• 2024 STAT Summit
• Wunderkinds Nomination
• STAT Madness
• STAT Brand Studio

Don't miss out

Subscribe to STAT+ today, for the best life sciences journalism in the industry

Why Novartis is changing the name of its research labs

By Jonathan Wosen Sept. 8, 2023

S wiss drugmaker Novartis’ research and development hub has a new name — and a new guiding strategy.

The hub, which is headquartered in Cambridge, Mass., and for years has been known as Novartis Institutes for BioMedical Research, or NIBR, will soon simply be known as Novartis Biomedical Research.

advertisement

But that’s not the only thing that’s changing, Fiona Marshall, the hub’s president, told a virtual audience Thursday during the 2023 STAT Future Summit . The new name reflects a larger shift by the pharma giant to retool its research strategy — from one driven by the pure pursuit of scientific discovery to a tighter focus on projects likely to yield commercially successful drugs.

STAT+ Exclusive Story

Already have an account? Log in

This article is exclusive to STAT+ subscribers

Unlock this article — plus daily coverage and analysis of the pharma industry — by subscribing to stat+..

Totals $468 per year

for 3 months, then $39/month

Then $39/month

Savings start at 25%!

Annually per user

$300 Annually per user

Get unlimited access to award-winning journalism and exclusive events.

About the Author Reprints

Jonathan wosen.

West Coast Biotech & Life Sciences Reporter

Jonathan Wosen is STAT’s West Coast biotech & life sciences reporter.

drug development

STAT Future Summit

STAT encourages you to share your voice. We welcome your commentary, criticism, and expertise on our subscriber-only platform, STAT+ Connect

To submit a correction request, please visit our Contact Us page .

Recommended

Recommended Stories

STAT Plus: Biopharma layoffs are leaving the industry’s scientists reeling — and in search of scarce opportunities

STAT Plus: Ascension is racing to unload hospitals as execs work to stem losses

STAT Plus: The inside story of how Lykos’ MDMA research went awry

STAT Plus: GLP-1s associated with lower risk of 10 obesity-related cancers, study shows

STAT Plus: Troubled for-profit chains are stealthily operating dozens of psychiatric hospitals under nonprofits’ names

Careers in Research

Our researchers combine imagination with the rigor of collaborative science to find better treatments for disease.

Novartis Institutes for BioMedical Research (NIBR)

NIBR is the global pharmaceutical research organization of Novartis. With approximately 6,000 scientists and physicians around the world, our research is focused on discovering innovative new drugs that will change the practice of medicine. We have an open and entrepreneurial culture, encouraging collaboration to make effective therapies. We have an open and entrepreneurial culture, encouraging collaboration internally and externally to make effective therapies. Today, our research benefits from an external network of more than 300 academic and 100 industry alliances focused on areas of mutual scientific interest.

Academic Alliances

Industry alliances.

At NIBR, you will have the opportunity to work alongside an extraordinarily talented and diverse group of people from around the globe, all committed to making a difference for our patients and customers.

We have opportunities globally in the following research areas:

• Autoimmunity, Transplantation and Inflammation
• Cardiovascular, Renal and Metabolism
• Musculoskeletal Diseases
• Ophthalmology
• Analytical and Imaging Sciences
• Global Discovery Chemistry
• Developmental & Molecular Pathways
• Center for Proteomic Chemistry
• Epigenetics
• Translational Medicine
• Preclinical Safety
• DMPK and Biomarker Development

Novartis Institute for Tropical Diseases (NITD)

NITD  is an established organization that is striving to help end the burden of tropical disease in developing countries. With more than 100 researchers and support staff, NITD focuses its research activities on dengue, tuberculosis and malaria. We will make our treatments readily available without profit to poor patients in developing countries where these diseases are endemic.

NITD recruits the best scientific experts in the world. As a major center of excellence, NITD offers teaching and training opportunities for:

• Post-doctoral fellows
• Graduate students
• Undergraduates

Find your Career in Research and impact the lives of millions.

Addtoany buttons, printable links block (content).

• Featured News
• Artificial Intelligence
• Bioprocessing
• Drug Discovery
• Genome Editing
• Infectious Diseases
• Translational Medicine
• Browse Issues
• Learning Labs
• eBooks/Perspectives
• GEN Biotechnology
• Re:Gen Open
• New Products
• Conference Calendar
• Get GEN Magazine
• Get GEN eNewsletters

Gee WIZ: Novartis’ “Glue Degrader” Drug Candidate for Sickle Cell Shows Promise in Animal Studies

By Kevin Davies, PhD

Credit: EzumeImages / iStock / Getty Images Plus

Identifying a small-molecule drug that can effectively treat (or potentially cure) patients with sickle cell disease (SCD) around the world is something of a Holy Grail in hematology research and drug discovery more broadly. After more than a decade of effort, researchers at the Novartis Biomedical Research report the identification and extensive testing of a small-molecule drug candidate that has the potential to treat SCD patients by boosting the levels of fetal hemoglobin (HbF).  

The research, published today in Science in a report entitled “ A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction ,” was led by Pamela Ting, PhD, associate director of hematology at Novartis Biomedical Research. Ting leads a team of 40 co-authors, including Jay Bradner, MD, PhD, the former president of Novartis Institutes for BioMedical Research, who left the company in 2022 and joined Amgen late last year. Developing small-molecule drugs for SCD has been a long-standing interest of Bradner’s, dating back almost 15 years to research he performed on histone deacetylase inhibitors in collaboration with Stuart Schreiber, PhD, and colleagues at the Broad Institute.   

Over the past decade or more, predating her own arrival at the company in 2015, Ting estimates that Novartis has screened some two million compounds in the search for a promising compound to take to the clinic. Along the way, the company briefly pursued its own CRISPR gene editing strategy, following a similar path to the approach that Vertex Pharmaceuticals took in developing Casgevy by boosting HbF production. (Although Novartis and collaborators published promising initial clinical data last year, the company decided to shelve the gene editing program.)  

Despite the remarkable clinical success of the CRISPR ex vivo approach—the first American patient in the Vertex trial, Victoria Gray, celebrated the fifth anniversary of her stem cell transfusion earlier this week—it is clear that this demanding (and expensive) ex vivo strategy will not help the millions of patients in Africa and beyond—a point that Ting and colleagues hit home in their report in Science .  

“Regrettably,” Ting and her co-authors write, “substantial challenges exist for [hematopoietic stem and progenitor cell] therapies to reach most SCD patients, who live in medically underserved communities and low and middle-income countries. Safe, efficacious, and globally accessible HbF-inducing medicines therefore remain an important unmet need.”  

Fyodor Urnov, PhD, director of technology and translation at the Innovative Genomics Institute, told GEN that the 2023 approval of Casgevy provided definitive clinical evidence that the strategy of upregulating HbF is “a safe and effective approach to resolve major symptoms of sickle cell disease.” The new work builds on the theme of modulating a transcription factor to upregulate HbF, but this time using a small molecule. “Even people who live and breathe CRISPR will agree that, on balance, such a small molecule could have a wider global reach than gene editing,” Urnov said.  

“There is a pressing need for oral agents that can more effectively induce fetal hemoglobin,” agreed hematologist Vijay Sankaran, MD, PhD, professor of pediatrics at Harvard Medical School. (Sankaran played a key role in cementing the HbF upregulation strategy to treat SCD 15 years ago.) He called the new Novartis report impressive and “exciting work and identifies a promising new target for fetal hemoglobin induction.”  

Screen time 

The Novartis study falls into a category known as “molecular glue pharmacology.” The researchers recognized that very small modifications to the chemical structure of a class of drug compounds that mediate targeted protein degradation (TPD) could profoundly affect the choice of protein for degradation. (A good example was work published by Novartis colleagues last year on the discovery of selective glue degraders for cancer immunotherapy ).

“This was a big conceptual leap,” Ting explained. “You could do just a little bit of work around a fundamental structure and then broadly look for changes to the substrate selectivity.”

She added: “We decided, if this [chemical] library is capable of drugging a new class of transcription factors, then we should think about how we can apply it to an age-old problem that, at the root, is really a question of how do we regulate genes? And can we target transcription factors to regulate gene expression?”  

Ting’s team embarked on a screen of a library of almost 3,000 compounds that target cereblon, a component of the E3 ubiquitin ligase complex that is involved in targeted protein degradation. Using a cellular assay that detected the upregulation of HbF) in erythroblasts, Novartis researchers identified scores of candidate molecules before whittling down the list and focusing on “compound C” for further study.   

After mass spectrometry experiments showed that this chemical targeted the WIZ transcription factor, Ting’s group renamed the drug candidate dWIZ-1. The WIZ target was emphatically confirmed by CRISPR gene knock-out experiments. All told, these results suggested that WIZ was a previously unrecognized repressor of HbF expression. dWIZ-1 could recruit WIZ to the cereblon-ubiquitin ligase complex to trigger targeted protein degradation. The Novartis researchers continued experiments with a modified molecule termed dWIZ-2.  

The Science report is packed with multiple types of experiments—molecular assays, mouse and non-human primate models, protein modeling using AlphaFold, and X-ray crystallography. Part of the rationale, Ting says, “was to convince ourselves that by every measurement that we could think of, we could see a reproducible effect.”  

Some of the most important data in the report are results administering dWIZ-2 in a trio of cynomolgus monkeys. This in vivo study monitored the animals for 28 days and showed robust up-regulation of the γ-globin gene and HbF production in virtually all peripheral reticulocytes. “We saw almost pan-cellular HbF expression, which is very promising,” Ting said, and no signs of cytotoxicity. Curiously, one of the three animals was termed a non-responder. Ting calls it “the coolest monkey, because I feel like it must be telling us something and I don’t know what it is!”  

The Novartis team found evidence for WIZ binding directly at the β-globin locus, which was unexpected. “Seeing WIZ for the first time is quite surprising for such a deeply studied locus,” Ting said. “For whatever reason, the globin locus seems to be highly sensitive to the loss of WIZ.” What is striking, she adds, is that “there is relatively strong overlap with binding sites for BCL11A,” the transcription factor that Vertex successfully targets in its Casgevy cell therapy.

“That’s where we leave it in the paper, as a bit of a teaser, something that we hope that we can further study in the future and that others will be inspired to study.”   

Dealbreaker  

As Ting readily acknowledges, there are still many unanswered questions, including the specificity of the inhibition. WIZ naturally binds at many spots in the genome, including a dozen or more in the β-globin gene cluster. “For whatever reason, when we modulate WIZ, the effects are fairly moderate and fairly mild,” Ting said. And the results in the non-human primates bode well. “We hope with these new chemical probes that this is something that we can continue to study and understand in the long run,” Ting says.   

“I think the [Novartis] approach is promising, but with the current data it’s difficult to know what degree of HbF induction a human would experience,” said Vivien Sheehan, MD, PhD, associate professor and director of Sickle Cell Translational Research at Emory University School of Medicine in Atlanta. Sheehan, who first heard these results presented at the American Society of Hematology conference late last year, would like to see additional quantification data including HbF measurements using high-performance liquid chromatography. She also observes that “the lack of myelosuppression is promising for a potential combined therapy with hydroxyurea.”  

Sankaran cautions that the non-specific effects of targeting WIZ lead to expression changes of hundreds of genes in erythroblasts. “More studies are needed before and during human clinical studies,” he said. A rigorous assessment of the safety of systemic WIZ degradation will be needed. “That could be a dealbreaker,” Sheehan says.  

Understandably, Ting would not be drawn on a timeline for progress into the clinic, but her closing comments underlined her team’s belief in the program. “What we’re really focused on now is making sure that we’ve found a molecule that can really go all the way to patients,” she said. “We are highly committed to sickle cell patients around the world. We see the unmet need,” she said. “We’re progressing as quickly as possible, and we really have our eye on a medicine that will reach patients where they are.”  

Nevertheless, while a small-molecule drug should prove both more affordable and accessible in the countries where most SCD live, IGI’s Urnov cautions that access to drug therapies outside the U.S. is by no means guaranteed. For example, a decade ago, Gilead slashed the price of its drug Solvadi by almost 99 percent in order to provide meaningful access to hepatitis patients in Egypt. The Novartis study, Urnov says, offers “an important opportunity to think ahead to how to solve this challenge when and if a medicine based on this work is approved in the U.S.”  

Related Content

Metabolic Proteins “Deorphanized” with Gene-Metabolite Association Prediction Tool

Small-Molecule “Unsilencers” Show Promise against Angelman Syndrome

Lilly to Acquire Morphic for $3.2B, Adding Phase II IBD Programs

Aiming High: 10x, NanoString Launch Large-Scale Panels

Dead at age 28, ascendance biomedical ceo remembered for pushing boundaries, synthego eyes product, platform expansions with latest $110m financing.

Massachusetts Biotechnology Council

Member Directory

Novartis institutes for biomedical research.

Novartis Institutes for BioMedical Research is Novartis global research organization and is committed to discovering innovative medicines that cure disease and improve human health. By conducting more relevant and predictable drug discovery that can yield new and better medicines for patients, Novartis Institutes for BioMedical Research is redefining drug discovery in the post-genomic era. Over the past four years, Novartis Pharmaceuticals has had the greatest number of new molecular entities approved by the US FDA. With its broad focus on diseases for which there is a need for better medical therapies, and with 3,000 talented, dedicated research scientists worldwide, Novartis Institutes for BioMedical Research is well-positioned to ensure Novartis maintains its strong pipeline and highly successful track record in new drug discovery.> Novartis Institutes has sites in Cambridge, Massachusetts (headquarters); Basel, Switzerland; Horsham, UK; East Hanover, NJ; Vienna, Austria; and Tsukuba, Japan. Novartis Institutes Cambridge facilities encompass 750,000 square feet of laboratory and office space. Research in cardiovascular disease, oncology, infectious disease, diabetes, ophthalmology and skeletal muscle disease is headquartered in Cambridge. In addition, Cambridge is home to the following platform technologies: Global Discovery Chemistry, Functional Genomics, Developmental & Molecular Pathways, and Models of Disease Center.

See all Members