Ribo Life Science and Boehringer Ingelheim Forge $2B+ Partnership to Develop siRNA Therapies for NASH/MASH

On January 3, 2024, Suzhou Ribo Life Science Co., Ltd. and Ribocure Pharmaceuticals AB (collectively referred to as "Ribo") reached a collaboration with Boehringer Ingelheim, announcing their joint effort to develop innovative small nucleic acid therapies for the treatment of non-alcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH).

According to the terms of the collaboration, in addition to an upfront payment, Ribo will be eligible to receive milestone payments based on the conduct of clinical studies, regulatory filings, and commercial success, as well as tiered royalties on product sales. The total value of the deal exceeds $2 billion.

This collaboration will closely integrate Ribo's leading experience in early research and clinical development in the siRNA drug field with Boehringer Ingelheim's commitment to improving the quality of life for patients with cardiovascular, renal, and metabolic (CRM) diseases.

Recently, the entire small nucleic acid field has ushered in an unprecedented boom.Just last year, there were four small nucleic acid products that were approved for marketing.They are the ASO drug Tofersen co-developed by Biogen/Ionis, Novo Nordisk's RNAi therapy Nedosiran for PH1, Astellas' aptamer drug Izervay, and the ASO therapy Eplontersen co-developed by AstraZeneca and Ionis.

It is not difficult to see that in the rapidly developing and highly competitive CGT field, small nucleic acids have become a new blue ocean for pharmaceutical companies to vie for due to their vast number of candidate targets and long half-life cycles.

In theory, small nucleic acid drugs are an ideal type of drug that can provide solutions for many challenging diseases in clinical practice.

On one hand, the drug-like properties of these medications are relatively high. Under current technological conditions, small nucleic acid drugs can silence any gene within the liver. Theoretically, as more delivery technologies are developed, small nucleic acid drugs could target every gene in the entire genome, whereas traditional small molecule drugs and antibody drugs can only target about 4% of gene products with marketed drugs available.

On the other hand, small nucleic acid drugs have a relatively long half-life, resulting in a longer dosing cycle. Moreover, compared to gene therapy, small nucleic acid drugs only involve mRNA without affecting the genome, which implies higher safety.

But in reality, small nucleic acid drugs still face many challenges. For example, after injecting small nucleic acid drugs into patients, how can the drugs remain in the body for a sufficient amount of time? Another example is how to enable therapeutic small nucleic acids to precisely enter target cells to exert their therapeutic function while avoiding harm to normal cells as much as possible. This is also the most critical issue faced by small nucleic acid drugs, which requires the development of an appropriate drug delivery system to address.

At this stage, with the continuous exploration of global small nucleic acid drug development companies, scientists have found some drug delivery systems with relatively ideal drug development performance, which has placed small nucleic acid drugs at the turning point of an application explosion.

RIBO-GalSTAR, Ribo Life Science's self-developed GalNAc small nucleic acid drug delivery technology platform^TMAs an example. This technology platform can specifically target pathogenic genes in hepatocytes, selectively inhibit their mRNA, and thereby develop RNA interference (RNAi) therapies. RNAi therapies have the potential to target undruggable targets by traditional drug molecules, achieving the goal of treating corresponding diseases.

Although small nucleic acid therapies have been highly praised in the pharmaceutical market due to the aforementioned advantages, they haven't gained as much commercial success.

In the early days, the indications for small nucleic acid therapies were mostly rare diseases. Therefore, even though there has been nearly 20 years of drug development history and drugs have been continuously coming to market since 2018, leading pharmaceutical companies specializing in the development of small nucleic acid drugs still seem to struggle to establish an overwhelming advantage over their peers in any major disease area.

This dilemma has been changed by Alnylam, a leading small nucleic acid company, which has continuously developed multiple innovative therapies in the ATTR disease field.

In early August 2022, Alnylam announced that its siRNA drug Patisiran had achieved positive results in the Phase III clinical trial APOLLO-B. Data showed that Patisiran significantly improved symptoms in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), enhanced the 6-minute walk test metrics and quality of life, and also demonstrated good safety. It is expected to be launched within the year. Following the announcement, Alnylam's long-depressed stock price surged nearly 48%, with its market value reaching $25.5 billion.

Small nucleic acid drugs, which have been floating in the global clinical market for many years, are finally on the eve of commercial explosion by leveraging their advantages in compliance to enter the chronic disease market.

In today's cooperation deal, Ribo Life Science and Boehringer Ingelheim are targeting another vast chronic disease market, non-alcoholic steatohepatitis (NASH).

It is estimated that more than 440 million people worldwide suffer from NASH, an inflammatory liver disease caused by the accumulation of fat in the liver. Over time, NASH can lead to liver fibrosis and tissue scarring, and many patients may further develop cirrhosis and related severe complications, including liver failure or liver cancer. According to Sullivan's data, the global NASH drug market size is expected to reach $10.7 billion by 2025 and is projected to grow to $32.2 billion by 2030, with a compound annual growth rate (CAGR) of 41.8% and 24.6%, respectively.

Despite having hundreds of millions of patients and a market worth tens of billions, NASH is one of the few common diseases without any standard treatment. Its pathogenesis is complex, involving multiple aspects such as glucose metabolism and lipid metabolism. For the development of new NASH drugs, most pharmaceutical companies currently rely on the "two-hit hypothesis" for pathological explanations, focusing on four key areas: steatosis, inflammation, ballooning, and fibrosis.

Facing this billion-dollar blue ocean, there is currently no FDA-approved NASH drug on the market. NASH patients urgently need new effective treatment options to prevent the progression of NASH and maintain and restore liver function.

Søren Tullin, Ph.D., Senior Vice President of Boehringer Ingelheim and Global Head of Cardiovascular Metabolic Diseases Research"We look forward to collaborating with the scientists at Ribo Life Science to develop groundbreaking new drugs for NASH patients. This new collaboration is part of our commitment to working with top global peers to address interconnected CRM diseases. Our goal is to develop a new generation of innovative drugs that bring comprehensive health benefits to patients."

Dr. Zicai Liang, Founder and CEO of Ribo Life ScienceSaid: "This collaboration is a high recognition of Ribo Life Science's small nucleic acid drug research and development platform and the scientific research strength of the team. We are very pleased to have the opportunity to collaborate with Boehringer Ingelheim to provide new treatment options for NASH patients."

Dr. Gan Liming, CEO of Ribo Life Science"We look forward to collaborating with Boehringer Ingelheim, leveraging its outstanding experience and deep understanding in the CRM disease field, to continue innovating and introducing breakthrough treatments for CRM diseases."

Boehringer Ingelheim is committed to researching breakthrough therapies aimed at transforming lives and safeguarding the health of generations to come. As a globally leading biopharmaceutical company driven by innovation, Boehringer Ingelheim demonstrates its value through innovation in areas with high unmet medical needs. Since its founding in 1885, Boehringer Ingelheim has remained an independent, family-owned business with a long-term perspective. The company employs over 53,000 people across its human pharmaceuticals and animal health divisions, serving more than 130 regions worldwide.

Suzhou Ribo Life Science Co., Ltd. is an innovative clinical-stage company dedicated to developing small nucleic acid-based drugs using RNA interference (RNAi) technology. With its strong research and development capabilities and an integrated technology platform, Ribo Life Science has built a robust product pipeline aimed at addressing unmet clinical needs for serious diseases. As a subsidiary of Ribo Life Science, Ribocure Pharmaceuticals is committed to the global development of life-saving oligonucleotide therapies. Leveraging extensive experience in translational medicine and clinical development, Ribocure focuses on addressing significant unmet medical needs for major diseases in the liver, cardiovascular system, kidneys, and oncology, as well as rare diseases on a global scale.