GSK Exits Cell and Gene Therapy to Focus on Oligonucleotide-Based Medicines

Recently, Emma Walmsley, CEO of pharmaceutical giant GSK, emphasized during a summary of GSK's vision to investors that GSK has decided to "end its investment in cell and gene therapy." This is also a clear signal released by GSK a few months after canceling its cell therapy collaborations with Lyell and Immatics, indicating that GSK’s drug development direction is going against the industry trend.

GSK believes that, instead of rushing to bring "off-the-shelf"CAR-TPushing towards clinical applications, or fully committing to a cell therapy strategy for solid tumors, may not be as smooth a path to market success as leveraging its specialized technical expertise in the field of genetics.

GSK's R&D head, Dr. John Lepore, stated that currently, about 70% of GSK's entire portfolio has a strong foundation in human genetics. Theoretically, targets validated by genetic evidence are at least twice as likely to succeed in becoming drugs. While this is not a panacea, GSK’s substantial investments in human genetics, functional genomics, and artificial intelligence could double the probability of drug success — a critical advancement for both GSK and the industry as a whole. Significant progress in this area has already been achieved by GSK.

This may sound simple, but not every large pharmaceutical company dares to bet on genetic targets because half of the new potential targets identified through genetics cannot be targeted by small molecules or antibodies.

And this is where oligonucleotides come into play. These synthetically produced short chains of DNA or RNA can reduce, restore, or modulate RNA through several different mechanisms.

Biotech companies like Alynlam and Ionis were early pioneers in this field, with market values exceeding $27 billion and $5 billion respectively. They each have several siRNA or ASO drugs on the market. Today, the oligonucleotide platform is developing rapidly, even surpassing the initial visions of these two companies.

It is precisely due to the optimism about oligonucleotide technology that GSK invested $170 million in a collaboration with Wave Life Sciences last December. Wave is the only company with an oligonucleotide platform that possesses three RNA-targeting modalities: editing, splicing, and silencing. When researching drug targets based on genetics, GSK is interested in all three RNA-targeting modalities. Another aspect that attracts GSK to Wave is that Wave's delivery technology can target organs and tissues beyond the liver (such as the kidneys and lungs), which is expected to address current challenges in extrahepatic targeting.

GSK and Wave's collaboration involves up to 8 co-development pipelines, the most important of which is WVE-006. This is a small nucleic acid drug in the preclinical research stage that restores normal α1-antitrypsin expression by targeting pathogenic RNA, intended for the treatment of α1-antitrypsin deficiency. α1-Antitrypsin deficiency is a hereditary metabolic disorder caused by a lack of α1-antitrypsin, leading to neonatal hepatitis, infantile and adult cirrhosis.Liver CancerAnd emphysema, etc.

Although exciting, WVE-006 remains in a relatively early stage within GSK's small nucleic acid drug pipeline. In contrast, bepirovirsen, an antisense oligonucleotide (ASO) drug co-developed by GSK and Ionis, is much further ahead. Bepirovirsen is currently undergoing two Phase 3 clinical trials, with the potential to achieve a functional cure for hepatitis B.

Nucleoside/nucleoside analogs are first-line treatment drugs for hepatitis B patients, which can inhibit the replication of the hepatitis B virus. However, they cannot eliminate the hepatitis B virus, so lifelong medication is required. Bepirovirsen’s unique design can reduce the replication of the hepatitis B virus and suppress the production of HBsAg, thereby achieving a functional cure and freeing patients from lifelong medication. In June 2022, GSK announced interim data from the Phase 2b clinical trial of bepirovirsen at the 2022 International Liver Congress. The data showed that after 24 weeks of treatment, nearly 30% of hepatitis B patients had undetectable levels of the hepatitis B virus. These data were subsequently published in the New England Journal of Medicine (NEJM).

Oligonucleotide technology has been around for decades, but currently, the dozen or so approved drugs on the market are all concentrated in the field of rare genetic diseases. Bepirovirsen, developed by GSK, is one of the most advanced small nucleic acid drugs targeting major common diseases, and its success will significantly propel small nucleic acid drugs into broader disease areas.

In addition, GSK4532990, a small nucleic acid drug co-developed by GSK and Arrowhead, is about to enter Phase 2 clinical trials for the treatment of the chronic disease nonalcoholic steatohepatitis (NASH).

In fact, the heavy bet on small nucleic acid drugs is not the only move by GSK that goes against the trend of drug development; they are also vigorously developing new types of...Antibiotics。

In November 2022, GSK announced positive results for two new antibiotics, one for the treatment of tuberculosis and the other for urinary tract infections, with the latter expected to be submitted this year.FDA。

Despite the growing issue of antibiotic resistance, the return on investment for developing antibiotics has been too low for decades. In the field of new drug development, there is a "double ten rule" (the average cost of bringing an innovative drug from research to market exceeds $1 billion and takes more than 10 years), while the development of antibiotics averages $1.6 billion. More critically, the lengthy development process means that some antibiotics have developed bacterial resistance even before they are approved for marketing or widely used. This has led even large pharmaceutical companies to shy away from antibiotic development. However, GSK believes this is an area where development must continue; we cannot let antibiotic research disappear.

GSK Executives Believe Abandoning the Popular Field of Cell and Gene Therapy Was the Right Decision