Bayer and NextRNA Therapeutics Announce $547M Collaboration to Develop Two lncRNA-Targeting Small Molecule Therapies

On August 28 local time, Bayer and NextRNA Therapeutics announced that they had reached a collaboration and licensing agreement to jointly develop two small-molecule therapies targeting long non-coding RNA (lncRNA), further enhancing Bayer's precision oncology R&D pipeline.

According to the terms of the agreement, NextRNA Therapeutics will receive up to $547 million (approximately RMB 3.888 billion) from the two programs, including upfront payments, near-term milestone payments, research funding, development and commercial milestone payments, as well as tiered royalties on net sales.

NextRNA Therapeutics, founded in January 2021 and headquartered in Massachusetts, is a biotechnology company focused on developing transformative drugs to address diseases driven by long non-coding RNA (lncRNA), with a primary focus on oncology and neuroscience.

The company's therapeutic approach mainly focuses on inhibiting the function of lncRNA by disrupting the interaction between lncRNA, RBP, and small molecules. NextRNA Therapeutics has a unique advantage in the field of non-coding RNA-guided drugs, having built a robust target and drug discovery engine called NextMap, which systematically identifies disease-associated long non-coding RNAs and their interacting proteins.

In fact, the origin of NextRNA Therapeutics came from a research project at the Dana-Farber Cancer Institute. Therefore, its founders include Dr. Carl Novina from the Dana-Farber Cancer Institute at Harvard Medical School, Dr. Kenneth Anderson from the Dana-Farber Cancer Institute at Harvard Medical School, and Dr. Robert Langer from the Massachusetts Institute of Technology, among others.

Among them, everyone must be familiar with co-founder Robert Langer. Robert Langer is regarded as one of the most important scientists in the biotechnology field who can change the future. He is also a great inventor and entrepreneur. He is one of the most cited researchers in the world and a highly productive entrepreneur, having participated in the founding of more than 40 biotech companies. Langer's research laboratory at MIT is the largest biomedical engineering laboratory in the world.

Robert Langer is a distinguished figure who embodies multiple roles as a professor, scientist, entrepreneur, and inventor. In the scientific community, he is renowned for his cutting-edge research in drug delivery systems, biomaterials, nanotechnology, tissue engineering, and regenerative medicine, earning him the title of the "Edison of Medicine." His primary research focuses on targeted drug delivery systems and tissue engineering, and he is acclaimed as the "Father of Tissue Engineering and Drug Delivery."

In the industry, he founded Flagship VentureLabs, a venture capital firm focused on incubating small biotechnology companies, and successfully incubated over 40 companies, including Moderna, one of the top three global mRNA vaccine giants, Sigilon Therapeutics, a rising company in encapsulated cell therapy, and Immunai, a biotechnology company specializing in immunotherapy.

Enterprises co-founded by Robert Langer naturally attract attention. NextRNA Therapeutics not only gained recognition and attention from Bayer this time but also received favor from numerous foreign investors previously. In March 2022, the company announced it had completed $9.3 million in seed funding and $46.8 million in Series A financing, led by Cobro Ventures and Lightchain Capital, with participation from Circle Alternative Investments, Evans Capital, Jefferies, Rivas Capital, and Willett Advisors.

In this collaboration, Bayer and NextRNA Therapeutics will jointly advance two oncology programs targeting indications with high unmet medical needs. The first program is a small-molecule therapy targeting lncRNA, currently in the early preclinical development stage. Details of the second collaborative program have not been disclosed yet. According to the press release, NextRNA Therapeutics will continue researching lncRNA targets already identified by its platform, while Bayer will have the option to select one of these targets for co-development. Under the agreement, Bayer can utilize NextRNA's differentiated approach to inhibit lncRNA function by disrupting interactions between lncRNA, RBP, and small molecules.

In the field of nucleic acid drugs, lncRNA seems to receive less attention, and its related mechanisms and functions have even been controversial in the scientific community for a period of time.

It was not until 2008, when Science, Nature, and Cell published reviews on lncRNA, that the related mechanisms of lncRNA gained widespread recognition, and this field began to gradually become popular. The number of lncRNA projects approved by the National Natural Science Foundation of China also surged from 1 in 2007 to 717 in 2018.

In 2021, a study published in *Signal Transduction and Targeted Therapy* revealed the important role of the interaction between lncRNA SNHG1 and vesicle transport protein VPS13D in immune function, while also suggesting that lncRNA SNHG1 may serve as a potential immune function marker.

In 2023, a study on potential targets for myocardial fibrosis was published in Circulation. Through high-throughput single-cell sequencing analysis, it was found that lncRNA FIXER is a potential therapeutic target for myocardial fibrosis.

In the same year, a study on the regulation of human germ cell development was published in *eLife*. Through single-cell lncRNA analysis, it was discovered that LNC1845 cis-regulates the neighboring transcription factor gene LHX8, thereby controlling germ cell development and meiosis. This approach can be applied to fields involving cell development and differentiation, such as developmental biology, stem cell research, and cancer cell studies, using a combination of single-cell analysis and in vitro experimental validation to further explore the regulatory mechanisms of lncRNAs.

In February this year, Nature published a study on the whole-genome deep analysis of hepatocellular carcinoma in the Chinese population. The study analyzed non-coding tumor drivers and identified 31 non-coding drivers, including lncRNAs, 90.3% of which were discovered for the first time, providing new insights into the mechanisms of hepatocellular carcinoma development.

A large number of studies have shown that lncRNA regulates gene expression at multiple levels, including epigenetics, gene transcription, and protein translation. It is widely involved in physiological processes such as cell differentiation and individual development. lncRNA is closely related to the pathological processes of major human diseases such as cancer. Whether in mechanism exploration, biomarker discovery, or drug target development, there is broad research space.

In addition, compared with other nucleic acid drugs, lncRNA drugs have better stability and are not limited by the type or location of the target molecule. Extracellular, membrane-bound, and intracellular molecules are all potential targets for lncRNA drugs, and DNA, RNA, and proteins are all potential target molecules for lncRNA drugs.

lncRNA is becoming a hotspot of continuous attention in both basic and applied biomedical research, and a large number of studies on the functions and mechanisms of lncRNA have brought opportunities for the development of lncRNA drugs.

In this context, in recent years, globally, leading incubators, investment institutions, and large multinational pharmaceutical companies such as Flagship Pioneering, Sanofi Ventures, Takeda Ventures, BMS, Inkef Capital, Broadview Ventures, Brandon Capital, and Cobro Ventures have successively entered the lncRNA field.

Outside of China, in addition to NextRNA Therapeutics, companies such as Transine Therapeutics, Laronde, Haya Therapeutics, Amaroq Therapeutics, Cardior Pharmaceuticals, and ROME Therapeutics are also active in this field.

In China, there is already a company named Lingtaikr focused on lncRNA drug development. Other companies such as RiboBio, Hanheng Bio, OBiO Technology, and Novogene have also established services related to lncRNA. Notably, Song Xu, the founder of Lingtaikr, is one of the pioneers in the lncRNA field and was among the first to report internationally on the interaction between lncRNA and proteins in the mechanisms of tumor development and progression.

Overall, companies targeting lncRNA only began to emerge after 2021. Both domestic and international companies are startups, still in the early stages, with projects running neck and neck. However, frequent academic breakthroughs and institutional investments indicate that this blue ocean is about to be tapped, and the era of lncRNA drugs is approaching.

Reference: M20 Genomics "National Natural Science Foundation Hotspot | How to Approach lncRNA Research?"