An Update on Senolytics Company Cleara Biotech

Senescent cells accumulate with age, and that accumulation is responsible for a meaningful fraction of degenerative aging. Many groups are working on ways to remove these cells and thereby reverse aspects of aging. Among their number, Cleara Biotech was founded four years ago on to advance initially promising work on the FOXO4-p53 interaction in cellular senescence, a possible targeted way to destroy senescent cells. This approach will join the numerous other mechanisms already being exploited as the basis for potential rejuvenation therapies.

A couple of companies have been looking into FOXO4 biochemistry in the context of cellular senescence, with very little new information emerging in recent years. Four years isn't that long in the biotech field, in which every aspect of development is challenging, but silence suggests that making something of the early FOXO4-related research has proved to be harder than expected.

Still, the Cleara principals appear confident enough in their present approach to be gearing up to prepare for clinical development. Certainly, there will be room for many different approaches and specializations in the clearance of senescent cells; it is coming to be a crowded field of many biotech startups and other entities pursing a diverse set of approaches and development programs.

Cleara Biotech Raises $2.5 Million in Seed Financing to Advance FOXO4-Therapeutics Pipeline for Treating Cancer and Chronic Diseases

Cleara Biotech B.V., a preclinical-stage biotechnology company focused on developing innovative, proprietary therapies for treating different pathologies of "scarred cellular" senescence, including late-stage cancer and chronic diseases, today announced that it closed a $2.5 million seed financing round earlier in the year, led by Apollo Health Ventures, with participation from Curie Capital B.V., ROM Utrecht Region, and Longevity Tech Fund.

Cleara has optimized two lead developmental candidates, CL04177 and CL04183, that can eliminate scarred cancer cells found in several late-stage cancers and chronic diseases in humans. The company is aiming to develop precision medicine tools that treat specific diseases with clear niche-directed, anti-senescent lead candidates, accompanied with associated biomarkers, around its FOXO4-based D-amino acid peptides and pipeline against subtypes of senescence.

Designed and optimized based on an extensive (3D) structural, molecular and cellular understanding of cell scarring's mechanism of action and how FOXO4 restrains this particular form of the cell guardian p53, both lead compounds potently counter viability of scarred cancer cells in 2D culture and 3D organoids, as well as strongly reduce the metastatic burden and infiltration in mouse in vivo models for metastatic colon cancer and triple-negative breast cancer. Furthermore, they show favorable pharmacokinetics and tissue distribution in mice, with an maximum tolerable dose that is well above their efficacious dose.

Comments

Indiscriminately destroying senescent cells seems to have some downside:

"In their studies of lung tissue, Peng's team observed green glowing senescent cells lying next to stem cells on the basement membrane that serves as a barrier preventing foreign cells and harmful chemicals from entering the body and also allows oxygen to diffuse from air in the lungs into underlying tissues. Damage can occur at this dynamic interface. The team saw senescent cells in similar positions in other barrier organs such as small intestine, colon, and skin, and their experiments confirmed that if senescent cells were killed with senolytics, lung stem cells were not able to properly repair the barrier surface."

https://medicalxpress.com/news/2022-10-scientists-reappraise-role-zombie-cells.html

Posted by: erasmus at October 17th, 2022 2:30 PM
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