With fresh $40M, Rubedo outlines senescent roadmap

22 Apr 2024
firstwordpharma.com
Phase 1Cell Therapy
Rubedo Life Sciences is taking a tactical approach to the emerging field of senolytics: drugs that target ageing-associated senescent cells, which have stopped dividing but don’t die, instead secreting pro-inflammatory cytokines that can cause fibrosis and tissue degeneration.
Since its formation in 2018, the biotech has been doing its biological due diligence to characterise different senescent cellular subgroups, identify potential targets, and select the most strategic indications – and it seems that strategy has paid off. On Monday, Rubedo announced a $40-million Series A round led by Khosla Ventures and Ahren Innovation Capital that will bring lead candidate RLS-1496 into the clinic for chronic skin diseases by year-end.
The fundraising comes nearly four years after a clinical failure in osteoarthritis from senolytics poster child Unity Biotechnology somewhat cooled investors on the space, but Rubedo co-founder and CEO Marco Quarta told FirstWord those results have still proven valuable – and weren’t altogether surprising.
The trial “was extremely informative for [Unity] and for the field to progress and move forward,” Quarta said. “I mean, how many trials failed in oncology before we started to see the first successes? I think that's a natural course of development for a new field like this one.”
Combining AI with multiomics
The infancy of senolytics is, in part, why Rubedo has put in the time to build out its drug discovery technologies and map out its clinical strategy before moving to in-human studies.
Its AI-powered Alembic platform uses single-cell multiomics to profile clinical samples, triangulating which subpopulation of senescent cells is driving disease progression, and what vulnerabilities could be therapeutically targeted.
“We think that until recently there were not the tools to find the right senescent cells, to find the right targets, to pretty much fish in the right pond,” Quarta said.
After experimentally validating Alembic’s findings, the next stop on Rubedo’s discovery workflow is the SenTech platform, which engineers small molecules that are highly selective for the specific disease-associated type of senescent cells.
Starting with skin
According to Quarta, another time-intensive challenge has been narrowing down which indications to explore first, given that senescent cells are essentially a “master regulator of degenerative biological processes” and play a role in many diseases.
Rubedo is first testing the senescent waters with a Phase I basket trial of RLS-1496 in chronic atopic dermatitis and psoriasis, before potentially branching into other diseases.
“We really wanted to take the time to… build a pipeline with a very strategic view of the entry point where we can validate our platform, strategy, and targets, and from there, move beyond the skin to other tissues,” he explained. “And that took time, right? We didn't want to rush, we wanted to make sure that we were solid before embarking into clinical development. And now we are ready.”
Rubedo chose to start with chronic skin conditions because between the shortcomings of steroids and biologics, there’s still unmet patient need, and because it's easier to measure whether the senolytic is working as intended – as biomarkers measuring senescent cell populations can be finicky.
“It's easier to track and monitor a tissue that is exposed and visible, since you can do punch biopsies, tape stripping, and visual observations,” Quarta said. He added that Rubedo is designing an extensive biomarker panel it plans to incorporate into the trial.
Plus, because senolytics are intended to eradicate a disease-driving cell population, the hope is that RLS-1496 could be given as an intermittent topical, rather than a constant injectable.
“We thought that [atopic dermatitis and psoriasis] was a great entry point to validate this target and actually introduce what could be a disease modifying intervention to really treat this persistence of skin lesions across many diseases,” he said.
Rubedo - which secured $12 million in seed financing in 2020 - also has preclinical programmes for idiopathic pulmonary fibrosis, metabolic dysfunction-associated steatohepatitis (MASH), sarcopenia, and non-small-cell lung cancer.
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