Medusa Therapeutics: Pioneering the Biomolecular Condensate Drug Discovery Frontier

At this year’s Jinji Lake Entrepreneurship Competition, a “new face” in the biotech sector, Medusa Therapeutics, stood out among more than 1,700 projects, advanced all the way to the finals, and won the Third Prize. The company focuses on developing innovative targeted therapeutics based on liquid–liquid phase separation (LLPS) biomolecular condensates. Medusa Therapeutics was founded in 2021, at the onset of the capital market winter.Behind a “fearless” startup lies an emerging sector on the rise: biomolecular condensates.

Biomolecular condensates, along with numerous emerging technologies such as protein degradation, gene editing, and targeted RNA regulation, share a common application objective: to provide novel drug development strategies for “undruggable” therapeutic targets. Although biomolecular condensates have been known for over a century, their therapeutic potential for disease treatment was only recognized around 2018 due to the inherent challenges in studying them. Currently, there are only five to six startups operating in this field.

Among the handful of “explorer” companies worldwide, Medusa Therapeutics Limited, although the most recently established, was the earliest to validate therapeutic efficacy at the animal level.“We aim to become the first condensate drug company in this sector to enter the clinical stage,” revealed Dr. Ralf Altmeyer, founder of Medusa Therapeutics Limited.How is Medusa Therapeutics exploring the field of biomolecular condensates formed via liquid-liquid phase separation (LLPS)? What progress has been made in its research? Why is it poised to become the first company to advance a condensate-targeting drug into clinical trials? To gain insights into this emerging therapeutic arena and the current status of Medusa Therapeutics, VCBeat New Medicine interviewed Dr. Ralf Altmeyer, Founder, and Xu Danqi, Chief Operating Officer.

Dewpoint Therapeutics, the first company abroad to research phase separation and biomolecular condensates, was founded in 2018. It has cumulatively raised over $287 million in financing. Over the past three years, Dewpoint has entered into collaborations with Bayer, Merck & Co., and Pfizer, with total potential transaction values exceeding $600 million.The rapid development of Dewpoint Therapeutics has led other astute scientists to recognize the vast potential of biomolecular condensates.

In addition to Dewpoint Therapeutics, three other companies—Faze Medicines, Transition Bio, and Neireid Therapeutics—have successively entered the field abroad. In China, two biomolecular condensate companies are competing in this space: one is Yituo Pharma, founded under the leadership of Dr. Jidong Zhu, and the other is Medusa Therapeutics, an innovative drug R&D company established by German virologist Dr. Ralf Altmeyer.

Startups in this field are primarily exploring two directions. One approach is physics-centric, applying concepts such as droplet microfluidics, statistical thermodynamics, and soft condensed matter physics to determine how changes in states of matter drive the formation of liquid-like assemblies. The other approach is grounded in life sciences, leveraging the expertise of their scientific founders in fields such as cell biology, biochemistry, or neurogenetics to pursue therapeutic investigations into observed condensate phenomena. Medusa Therapeutics Limited, a young company focused on biomolecular condensates, falls into the latter category.

Biomolecular condensates offer a solution for many previously undruggable targets by activating protein function through the promotion of biomolecular condensate formation, thereby enabling the modulation of currently “undruggable” targets by targeting phase separation mediated by intrinsically disordered regions.

Currently, the key competitive focus among global condensate-focused companies lies in therapeutic strategies for modulating pathological condensate states. Depending on the specific indications, these approaches can be broadly categorized into two types.The first approach involves dissolving pathological biomolecular condensates. The second approach induces a liquid-to-solid phase transition in pathological condensates, causing them to harden, lose fluidity, and rendering all condensate components nonfunctional. This latter strategy aligns with the development approach adopted by Medusa Therapeutics Limited.

Medusa Therapeutics' Drug Development Strategy: Inducing Pathological Liquid-to-Solid Phase Transition of Condensates

In collaborative research, Dr. Ralf Altmeyer, founder of Medusa Therapeutics Limited, together with the French teams of JF Eléouët and MA Rameix-Welti, discovered thatThe effect of CPM (cyclopamine) on RSV liquid condensates is nearly instantaneous, demonstrating that these molecules act directly on the proteins comprising the condensates via liquid-liquid phase separation.Targeting only one key protein-protein interaction (PPI) within pathological condensates (pathogenic condensates), the compound reduces the mobility of key component molecules, which in turn leads to the hardening of pathological condensates and loss of molecular mobility, thereby resulting in functional impairment of the aggregated components. This effect of abolishing the activity of pathological condensates is highly attractive to drug developers.

On the other hand, they found thatThe action of coacervate-hardening compounds is irreversible, and the hardened coacervates exhibit higher thermodynamic stability.Once the liquid-to-solid phase transition (condensate hardening) occurs and the compounds separate from the extracellular medium, the condensates cannot revert to their original functional liquid state.

These two key properties inspired Dr. Ralf Altmeyer to apply this approach to the treatment of respiratory syncytial virus (RSV) infection, leading to the discovery of the first small molecule that inhibits pathological condensate formation and demonstrates therapeutic efficacy in an RSV animal model (Risso-Ballester, Nature, 2021). This breakthrough opens up the possibility of developing ultra-fast, highly effective single-dose therapies for acute RSV respiratory infections.

Recently, the lead compound in the RSV pipeline has completed studies on its efficacy and mechanism of action both in vitro and in vivo. The data and results have been published in Nature (Bailly, SciRep, 2016; Risso-Ballester, Nature, 2021), and relevant structural compound patents have been granted in China, the United States, Japan, and Europe. Dr. Ralf Altmeyer’s team has communicated with the FDA regarding the experimental protocol for bovine pathological models. After optimizing the Preclinical Candidate Compound (PCC), they will commission a CRO to conduct preclinical studies. They plan to submit an Investigational New Drug (IND) application in both China and the United States in 2024 or 2025, and will also collaborate with the UK-based company Hvivo to conduct human challenge trials.

Meanwhile, leveraging the broad applicability of this novel mechanism, Medusa Therapeutics has strategically initiated projects targeting indications for a second viral infection as well as oncology, continuously refining its R&D platform throughout the research process.

Analysis suggests that Medusa Therapeutics leverages the property of condensates formed via liquid-liquid phase separation (LLPS) to gradually harden upon small-molecule drug treatment, thereby inhibiting RNA replication following viral infection in vivo. Targeting proteins critical to condensate formation and viral replication may hold significant value for the development of broad-spectrum antiviral agents. Furthermore, recent studies have preliminarily confirmed the roles of biomolecular condensates in embryonic development, cellular stress responses, and neurodegenerative diseases. Consequently, modulating biomolecular LLPS activity may emerge as a key therapeutic target for future drug development.

Ralf Altmeyer, the founder of Medusa Therapeutics Limited, is a German virologist who has spent much of his career at France’s renowned Institut Pasteur and in collaboration with partner institutions in China. In 2003, while preparing his postdoctoral thesis on HIV infection, he traveled to Hong Kong, China for the first time to collect more diverse research samples.

Over the past 19 years, he has traveled extensively across Asia. Initially, he served as CEO of the Pasteur Research Centre at the University of Hong Kong, where he oversaw research and management operations. After 2006, he moved to Singapore to serve as President of CombinatoRx (NASDAQ: CRXX) Singapore and Vice President of its global headquarters. Four years later, he returned to China to assume the position of French Director at the Institut Pasteur of Shanghai, Chinese Academy of Sciences.

Dr. Ralf Altmeyer has long been engaged in research on CPM molecules. After a decade of dedicated study, he published his latest findings in Nature in 2021, marking the first time this work gained recognition within the scientific community. Subsequently, Dr. Altmeyer sought to translate these achievements into commercial applications. With the support of multiple scientific advisors specializing in immunology, virology, and cell biology, Medusa Therapeutics was established.

In addition to a robust scientific research team, strong government relations are also driving the development of Medusa Therapeutics Limited.After spending 19 years in Asia, German scientist Dr. Ralf Altmeyer received the Pearl River Talent Introduction Award and the Shandong Province Friendship Award. In 2014, he also presented a work report to the President of China as an expert representative. He chose to launch his startup in July 2021, with financial support from the Hong Kong Government’s Incu-Bio program providing Medusa Therapeutics Limited with greater confidence.

Based on his understanding of the scientific research environments both domestically and internationally, Dr. Ralf Altmeyer stated that China’s research infrastructure has developed rapidly. In terms of hardware alone, China has basically caught up with the United States and Europe. However, there remains a gap between China and foreign countries in academic exchange and collaboration, and the overall state of scientific research still relies heavily on government guidance.

Based on a profound insight into the scientific research and industrial environment,Medusa Therapeutics Limited has adopted a more open development strategy compared to domestic biotech companies, engaging in extensive exchanges and collaborations with pharmaceutical enterprises both in China and abroad. Meanwhile, Dr. Ralf Altmeyer maintains a proactive stance toward pipeline rights transfers, pipeline divestitures, and potential acquisitions.Prior to this entrepreneurial venture, Dr. Ralf Altmeyer’s team had already successfully licensed the patented technology for “active ingredients and methods for treating viral diseases” to Hainan Hongzhi Pharmaceutical, with the aim of developing the world’s first therapeutic drug for hand, foot, and mouth disease—Suramin Sodium for Injection. The project has now entered Phase II clinical trials, marking one of the most notable achievements in Dr. Altmeyer’s scientific career.