HONG KONG – South Korean company Alteogen Inc.
is working with its U.S. partner, Lynkogen Inc.
, of New Jersey, to develop novel GLP-1 mimetic and alpha-1 antitrypsin (A1AT) fusion proteins for the treatment of nonalcoholic steatohepatitis (NASH) and metabolic diseases. Clinical trials could begin in two years' time.
Under the agreement, Lynkogen has the exclusive rights to develop and commercialize the fusion proteins worldwide, except for South Korea and emerging markets. Both firms will receive cross-royalties on sales of the licensed products from their respective territories.
"A1AT fusion proteins are in proof-of-concept stage, and Alteogen plans to advance them into clinical trials in the U.S. in two years," Soon Jae Park, CEO at Alteogen, told BioWorld
Arun Swaminathan, CEO at Lynkogen, told BioWorld
that the firm will first focus on major markets such as the U.S. and Europe. "Advancing the lead candidate to investigational new drug [IND] application and initiating clinical trials will be our priority.
"Complex metabolic diseases like NASH and type 1 diabetes are caused by more than one trigger," he explained. "There is a need for therapies that can address more than one trigger."
The GLP-1/A1AT fusion proteins have that potential. "This is a differentiated approach compared to other single trigger-targeted therapies in development," Swaminathan added.
"Lynkogen will be responsible for development of the GLP-1/A1AT fusion proteins. However, the two companies will continue to collaborate on the global development plans," he added. "Lynkogen will also leverage Alteogen's expertise in production and scale-up of the fusion proteins using their NexP technology."
The GLP-1/A1AT fusion protein therapies are developed with Alteogen's in-house NexP Fusion Technology, which is a platform technology for developing next-generation long-acting therapeutics.
It uses DNA recombination and human A1AT protein as the protein carrier. That way, it can increase the half-life of biologics and eliminate intrinsic activity in order to use as a safe carrier.
"The original protease inhibitor activity of A1AT is maintained in these GLP-1/A1AT fusion proteins. It is because the A1AT's role in this fusion protein is important for the treatment of NASH or type 1 diabetes," said Park.
According to Alteogen, NexP Fusion Technology can be fused at either C- or N-terminus of proteins or peptides. The therapeutic proteins or peptides fused show long-acting properties without causing any loss of activity as medicines. In preclinical studies, the experimental drugs demonstrated longer in vivo half-life and improved potency. The drugs could come with less frequent dosing, fewer side effects and better clinical efficacy.
"Early preclinical mouse data for GLP-1/A1AT fusion proteins suggest strong potential for improved efficacy in fatty liver disease, type 1 diabetes and other metabolic diseases," said Swaminathan.
The two biotech firms said they believe there is an enormous unmet need for NASH treatment, pointing out that NASH will become a leading cause of liver transplants by 2020, and the market is projected to reach more than $20 billion by 2025.
Meanwhile, the market for diabetes and related metabolic diseases, which the fusion proteins aim to target, is also expected to reach $58 million by 2025, given that the incidence rate is rising globally.
Park said partner company Lynkogen's focus on complex metabolic diseases would help Alteogen introduce new treatment options for such diseases.
Alteogen also has another proprietary technology known as the NexMab ADC Technology for developing multiple cancer drugs. It is for conjugating the cancer chemical drugs to an antibody protein, enhancing antibody-drug conjugate (ADC) clinical efficacy by increasing in vivo half-life.
Included in its pipeline is ALT-P7, an ADC targeting HER2 for treating HER2-positive breast cancer. With the NexMab ADC technology, the firm plans to further expand the indications of ALT-P7 to gastric cancer.
Apart from those, Alteogen is also working on two biosimilars ALT-L2 and ALT-L9, which reference Herceptin (trastuzumab/Roche Holding AG) and Eylea (aflibercept/Regeneron Pharmaceuticals Inc.) for the treatment of breast and gastric cancers, and age-related macular degeneration, respectively.
ALT-L2 has completed phase I trials in Canada and will soon enter phase III studies in the country. Alteogen is collaborating with Dutch firm Linxis BV to get the supply of the biosimilar candidate, and China's Qilu Pharmaceutical Co. Ltd. for joint development and commercialization.
Alteogen's ALT-L9 could be the world's first biosimilar of Eylea. The company plans to file an IND application with the U.S. FDA this year after the preclinical studies in the U.S. showed similarity and efficacy of its ALT-L9 compared to the original. It also plans to launch the follow-on version in Japan and China in 2022 when the Eylea's patents expire.