GSK (NYSE:GSK) is advancing a respiratory and immunology pipeline centered on longer-acting biologics, more targeted patient selection and combination approaches, according to Kaivan Khavandi, the company’s senior vice president and global head of Translational and Development Sciences.
Speaking at a Bernstein event, Khavandi said his organization has end-to-end research and development responsibility across respiratory, immunology and inflammation, from target selection through clinical development and product approval. The unit also oversees translational development capabilities spanning Asia R&D, genetics and genomics, and real-world evidence.
Respiratory strategy shifts toward disease segmentation
In asthma, treatments targeting Th2-driven inflammation have demonstrated effectiveness, he said. Yet patient persistence on shorter-acting biologics remains a challenge, with many patients discontinuing treatment within a year despite the drugs’ safety and efficacy profiles.
GSK’s response is to pursue ultra-long-acting medicines that reduce treatment burden. Khavandi said the company believes a biologic administered twice a year could help improve both uptake and persistence.
For COPD, GSK is studying several mechanisms alongside IL-5, including an ultra-long-acting thymic stromal lymphopoietin, or TSLP, treatment; a long-acting IL-33 program; an inhaled PDE3/4 approach; and an siRNA program that is in Phase 1b.
Khavandi said COPD affects approximately 300 million patients globally and remains a life-threatening condition. He noted that Dupixent and Nucala are the only two approved advanced therapies in the disease and are limited to particular patient segments.
- IL-4/13 treatment effects have been associated with patients whose eosinophil levels exceed 300.
- Nucala has shown clinically meaningful effects at eosinophil levels above 150, with enhanced effects above 300, Khavandi said.
- TSLP is being evaluated in pivotal studies and appears to be active in patients with eosinophils above 150, according to Khavandi.
He said the field is developing a more nuanced view of how different mechanisms may affect lung function, symptoms, exacerbations and survival. That could ultimately support combination treatment approaches.
IL-33 and TSLP programs move into pivotal development
Khavandi outlined GSK’s view that its IL-33 program differs from therapies that block the ST2 receptor. He said GSK’s approach is designed to neutralize the IL-33 ligand itself, potentially addressing signaling pathways beyond ST2, and is intended for dosing every three months.
GSK has used internal clinical, genetic and genomic data, as well as readouts from competing programs, to identify patients most likely to respond to IL-33 treatment, he said. The company plans to initiate a third pivotal IL-33 study next year evaluating cardiovascular hospitalizations, respiratory hospitalizations and mortality in COPD patients.
The company’s long-acting TSLP program is designed for twice-yearly dosing. Khavandi said a Phase 2 asthma study, called NAZARE, showed the pharmacology needed to support that schedule, with results expected to be shared next year. GSK has also reviewed data from partners in China and Hungary that evaluated the same molecule in nasal polyps.
GSK is running one more conventional pivotal asthma study in patients who had two exacerbations during the prior year, along with another study requiring one previous exacerbation and additional criteria intended to support a sufficient event rate. Khavandi said the latter design could enable treatment earlier in a patient’s disease course.
Pulmonary hypertension and liver disease opportunities
Khavandi also discussed HS235, an earlier-stage activin-trap program for pulmonary arterial hypertension. He said the asset was designed to inhibit activin A and B while sparing BMP9, which GSK believes could preserve efficacy while avoiding adverse events associated with BMP9 inhibition.
The company acquired the program through 35Pharma. Khavandi said multiple ascending-dose data through 20 weeks had shown none of the adverse events of concern cited in connection with other treatments in the class. He said the approach may also have potential metabolic and anti-inflammatory benefits because of its activity involving GDF8, or myostatin.
In metabolic dysfunction-associated steatohepatitis, or MASH, GSK’s FGF21 analog program came through its acquisition of Boston Pharmaceuticals. Khavandi said the class has shown the potential to reverse cirrhotic F4 MASH to non-cirrhotic disease by improving fibrosis, an outcome he described as particularly important because other mechanisms have not demonstrated comparable efficacy in that setting.
He said GSK sees its monthly-dosed program as potentially complementary to GLP-1 medicines and resmetirom. He cited clinical data in which an FGF21 analog’s benefits were additive to those of stable GLP-1 therapy. The company also sees a potential opportunity in alcohol-related liver disease, based on its view that the mechanism could work across steatotic liver disease regardless of cause or stage.
China partnerships and AI-enabled development
Khavandi said GSK is increasingly using external innovation and partnerships to shorten the path from biological insight to clinical testing. The company has established what it calls the Global China Translational Hub, working with companies including Hengrui to apply its human disease data and translational insights to trial design.
Artificial intelligence is already being used at GSK for operational activities including trial-enrollment intelligence, competitive insights, regulatory document preparation and medicine design, he said. Khavandi added that GSK has 150 AI engineers in a dedicated R&D group and has built proprietary tools.
He said GSK’s larger goal is to use AI to identify “target-trait pairings” by integrating genetics, genomics, imaging, clinical trial and other human data. In COPD, he said GSK used an AI-enabled multimodal-data approach to identify a TSLP/IL-33 combination as potentially additive or synergistic. The company has started a Phase 2 study co-administering its two monospecific antibodies and is using its China presence to accelerate the program.
About GSK (NYSE:GSK)
GSK plc is a global biopharmaceutical company headquartered in Brentford, England. The company researches, develops and manufactures medicines and vaccines for the prevention and treatment of disease, serving patients and healthcare providers in markets around the world.
GSK focuses on specialty medicines and vaccines in areas including infectious diseases, HIV, respiratory disease, immunology and oncology. Its products include prescription medicines, long-acting treatments and vaccines designed to protect against diseases such as shingles, meningitis, influenza and respiratory syncytial virus (RSV).
The company was formed in 2000 through the merger of Glaxo Wellcome and SmithKline Beecham.
