Amyotrophic Lateral Sclerosis (ALS) research has revealed genetic mutations associated with the motor neuron death characteristics of the disease. According to the researchers, although such studies are producing drug candidates, their scope of influence will be limited. Marginal genomics CEO Zhang Aili. She said the mutations they resolved are very rare, so drugs targeting these targets will still prevent many ALS patients from receiving treatment.
Verge’s artificial intelligence technology has discovered other genes related to ALS, and Zhang believes that these goals may solve a wider range of patients. Eli Lilly saw enough hope in Verge’s work to establish partnerships to discover and develop new ALS drugs.
The alliance announced on Thursday lasted for three years and paid Verge $25 million. This amount is a combination of advance payments, equity investments, and recent payments related to research. The details of these payments were not specified. San Francisco-based Verge will use its technology to validate ALS drug targets; Eli Lilly may advance four of them through clinical development and potential commercialization. According to the progress of ALS drug candidates, Verge can earn up to $694 million in revenue, plus sales royalties.
Zhang said that up to now, Verge has been focusing on the development of small molecule drugs, thanks to Lilly’s ability to solve ALS with new drugs such as antisense oligonucleotides and gene therapy. These genetic drugs will target the disease targets identified by Verge.
“We have this big hammer for gene therapy,” Zhang said. “We can now recognize better nails.”
Verge describes its drug discovery method as “all mankind.” Zhang said that animal models may have played a role in drug discovery, but they do not well predict how drugs will treat complex diseases such as neurodegenerative diseases in humans. Verge has established a large proprietary database containing human brain tissue collected from samples obtained from brain banks and hospitals. These samples come from patients with neurodegenerative diseases, such as ALS, Parkinson’s disease, and Alzheimer’s disease. Verge sequenced these samples to capture the entire expression of the genome, which was then mined by machine learning algorithms. The analytical insights reveal the goals of Verge drugs.
With the support of its AI-driven platform, Verge has established an internal drug candidate pipeline. Zhang said that the most advanced of these is an ALS drug targeting PIKfyve. PIKfyve is a lipid kinase that is the key to the formation of lysosomes, which is a cell processing system that removes old or damaged proteins. Failure to remove protein aggregates can cause cell dysfunction and make cells vulnerable to ALS. Zhang said that the purpose of hitting PIKfyve with drugs is to restore or enhance lysosomal function to normal or close to normal, which is expected to slow down the death of motor neurons. Verge’s PIKfyve targeted small molecules is expected to start clinical trials next year.
Eli Lilly’s neuroscience pipeline includes clinical-stage drugs for the treatment of Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. Zhang said that Lilly contacted Verge and was interested in how the company’s technology led to the discovery and advancement of its PIKfyve targeted drugs in ALS. The molecule will remain in Verge for development. The ALS targets covered by the Eli Lilly partnership will be selected by the two companies. If a goal is best solved by small molecules, Verge will pursue it. But if it is best solved by genomic medicine, Eli Lilly will take over.
Neurodegenerative diseases have been the focus of Verge from the beginning, but the startup’s ALS research has opened up more opportunities. About a year ago, “Nature” Publish Research at the Icahn School of Medicine at Mount Sinai evaluated the activity of approximately 12,000 drugs (experimental and FDA approved) against the new coronavirus. The PIKfyve kinase inhibitor was found to be the most effective. Zhang said that research has found that in addition to its role in lysosomes, PIKfyve is also important for the way SARS-CoV-2 enters cells. Blocking it is thought to prevent the virus’ ability to release its RNA into the cell, thereby preventing virus replication.
Verge is developing a PIKfyve blocking antiviral drug called VRG101, and now it has some preclinical data to support it. On Wednesday, during the European Conference on Clinical Microbiology and Infectious Diseases, Verge Present Some early data on its antiviral drugs. In laboratory tests, the drug showed antiviral activity against the new coronavirus in a variety of cell lines. It also shows activity against other coronaviruses. In a preclinical study on hamsters infected with Covid-19, compared with the control group, the lungs showed “significant improvement” after four days of treatment with Verge antiviral drugs.
Zhang said that the emergence of SARS-CoV-2 variants means that antiviral drugs are needed to supplement the vaccine. The Verge drug will be an oral pill, which is an easier preparation for patients to take compared to the currently available infusion and injection versions.
Recognizing that antiviral drugs are not outside Verge’s neurological focus, Zhang said her company will look for partners to develop the pill. Verge has established three partnerships with undisclosed pharmaceutical companies. Zhang said that these agreements were reached earlier in the history of Verge and mainly involved the application of the company’s artificial intelligence technology to data provided by pharmaceutical companies.
The alliance with Eli Lilly makes Indianapolis-based pharmaceutical giant Verge the first publicly announced partner. Zhang said that Verge will exclusively collaborate with Eli Lilly to research ALS in the next three years. But Verge is not currently seeking other neuroscience partners. Zhang said her vision is to continue to build Verge into a fully integrated treatment company that discovers, develops and ultimately sells its own drugs. She added that Eli Lilly’s deal fits this goal.
“It allows us to focus on projects that we think may be successful, but still get value from these other opportunities, especially if the partners have complementary capabilities,” she said.
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