07. December 2023

LMU spin-off RNhale founded!

The formation of the biotech spinoff RNhale can be traced back to Professor Olivia Merkel’s groundbreaking research on non-viral delivery vectors for siRNA therapeutics, at Wayne State University in Michigan, USA, in 2011. After relocating to Germany and joining Ludwig-Maximilians-University Munich, her work was backed by a €2 million ERC Starting Grant (ERC-2014-StG – 637830 “Novel Asthma Therapy”). Her research then focused on developing siRNA-based drugs for asthma treatment, specifically designed for direct administration to the lungs.

From a pharmaceutical technologist’s perspective, formulation and administration have always been pivotal in drug development. Long before the public was aware of the colloidal stability issues in RNA drugs, highlighted during the development of mRNA-based COVID vaccines, Prof. Merkel recognized that administration and stability were critical challenges in making RNA drugs broadly available.

Years of extensive experimentation and optimization led to a pivotal study published by Prof. Merkel’s group in 2019, which laid the foundation for RNhale’s current commercial endeavors: siRNA-containing dry powders for pulmonary delivery (Keil, Feldmann et al. 2019). Subsequent research examined the influence of different excipient materials, the comparison between crystalline and amorphous formulations, and the stability of these dry powders (Keil, Zimmermann et al. 2021).

In 2022, with the support of an ERC Proof of Concept Grant (ERC-2022-PoC1-101069308 “RNhale”), this strategy was enhanced by incorporating siRNA encapsulated into lipid-based carriers, specifically lipid nanoparticles (LNPs) (Zimmermann, Baldassi et al. 2022). This formulation has demonstrated remarkable stability, maintaining efficacy for 18 months at room temperature (Zimmermann, Deßloch et al. 2023).

Supported by the German Excellence Initiative through LMU’s Knowledge Transfer Fund, an in vivo Proof of Concept study for siRNA dry powder technology in asthma therapy was conducted. This completed the academic research package, leading to the incorporation of RNhale GmbH in September 2023.

RNhale GmbH is now advancing a siRNA-based therapy for treating severe uncontrolled asthma. Current treatments for this condition often rely on systemically administered antibody-based drugs, which suffer from several significant drawbacks. These drugs exhibit low lung bioavailability (Amgen, 2020), are prohibitively expensive, carry substantial immunological risks, and can lead to the development of resistance. In contrast, RNhale’s innovative approach delivers RNA directly to the lungs, precisely targeting the respiratory condition. By focusing the treatment where it’s needed most, RNhale enhances the therapy’s efficacy and reduces potential systemic side effects. This significant advancement allows patients to manage their treatment more efficiently and discreetly, without the constant need for healthcare professionals.

Link to RNhale Homepage