Using senolytics to target a druggable pathway that plays a pivotal role in many age-related diseases.

Over the coming weeks, we will be bringing you extracts from 7 company profiles from our Longevity Senotherapeutics Report. Each profile includes an assessment of Longevity Potential, Pre-Clinical and Clinical Studies, Technology/platform analysis, Safety and Risks, Target Market and Success Factors.

We also study each company’s IP, team, UVP, product efficacy, competitive advantage, runway and inflection point, and much more. Here’s the lowdown on Rockfish Bio.

Rockfish Bio is the latest member of a series of successful start-ups in the field of cellular senescence and aging emerging from the research groups around Regina and Johannes Grillari.

Rockfish Bio is planning to launch in Q2 of 2021 with the mission to develop senolytic therapies. The Rockfish team is convinced that senolytic therapies have an enormous potential for the treatment of age-related diseases and the extension of the human healthspan. Its senolytic compounds are based on a recently discovered druggable pathway that is associated with many age-related diseases and will enable Rockfish Bio to develop senolytics with high efficacy and a favourable safety profile.

The idea for Rockfish Bio was born in 2019 when co-founders Johannes Grillari, Otto Kanzler and Ingo Lämmermann were inspired by the potential of a newly discovered pathway for the development of senolytics. At that time, the enormous potential of senolytics and the concomitant lack of suitable drugs with high efficacy and good safety profiles became obvious.

“We knew that we were on to something big the moment we saw that the pathway we discovered played a pivotal role in so many age-related diseases, and that existing drugs targeting our pathway were associated with only mild side effects,” says Johannes Grillari.

Rockfish Bio will benefit from synergies formed with its two predecessors Evercyte and TAmiRNA. Evercyte provides know-how on cultivation of human cell lines for in vitro screening of senolytic compounds, whereas TAmiRNA is currently developing a blood sample-based method for quantification of the senescent cell load – an essential companion diagnostic, prognostic and treatment monitoring tool for future clinical trials.

Additionally, Johannes Grillari is the director of Ludwig Boltzmann Institute for Experimental and Clinical Traumatology which is located at the AUVA Trauma Center, Vienna thereby providing a close connection with clinicians and real-life patients. He is also an associate Professor at the University of Natural Resources and Life Sciences, Vienna (BOKU).

After clarifying the molecular mechanism of its senolytics, identifying renal epithelial cells as a promising therapeutic target (therapeutic index of ~700) and successfully testing the first generation of self-designed small molecule senolytics, Rockfish Bio now aims to secure sufficient funding from investors to verify the in vivo efficacy of its approach and commence senolytic drug development with chronic kidney disease as its lead indication.

Rockfish Bio projects its exit point in six and a half years from now (clinical Phase 2 completion), where it plans to cooperate with, or out-license its asset to, the pharmaceutical industry. It will then switch focus to its next indication.

The senolytic compounds Rockfish Bio uses are based on the elevated formation rate of arachidonic acid (AA) in senescent cells due to increased enzymatic hydrolysis of membrane lipids by phospholipases. By inhibiting the conversion of AA with its compounds, the team at Rockfish Bio can increase the intracellular content of pro-apoptotic AA selectively in senescent cells, thereby inducing a senolytic effect.

Downstream metabolites of AA and key enzymes involved in their biogenesis are associated with many age-related diseases including chronic kidney disease. Further, inhibition of AA-converting enzymes by existing drugs, such as NSAIDs, is associated with only mild side effects especially when only used for a short period.

This senolytic pathway is protected by Rockfish Bio with a patent (WO2020084105A2) and it is currently in the process of filing an additional patent for the protection of novel small molecules in collaboration with med chem experts (2nd generation molecules are currently synthesised) targeting this pathway.

Besides chronic kidney disease as the first lead indication, Rockfish Bio plans to develop a medical product for the improvement of kidney transplants during normothermic reperfusion. The quality of transplant organs was shown to be closely correlated to the senescent cell load and recent reports suggest that senolytics can be used to improve their performance (Iske et al., 2020).

The team at Rockfish Bio are in contact with leading scientists in the field of normothermic perfusion of kidney transplants who are willing to test its senolytic drugs in human kidney transplants declined by the transplant centres, thereby providing ex vivo data of the efficacy of the chosen senolytic drugs and the feasibility of their use to combat the chronic shortage of kidney transplants.

In parallel, Rockfish Bio are screening its senolytic compounds in several human cell types to identify additional promising lead indications to pursue, thereby mitigating risk of failure.