Oisín on aging as a disease and raising $5m seed

Co-founder Gary Hudson talks cell senescence, trials, spin-outs and the dilemma of treating age as a disease.

Every entrepreneur in Longevity has a different story for how they arrived in the field – some have worked in it their entire careers, while others come to it later and from a multitude of other sectors. Gary Hudson, co-founder of Oisín Biotechnologies, falls under the latter category, having had a successful career in the commercial space industry before moving into anti-aging.

Longevity.Technology: Hudson is a speaker during next Tuesday’s Rejuvenation therapies session at Longevity 2020, where he’ll share the results of recent studies relating to the DNA-targeted cell senescence intervention developed by Oisín (pronounced oh-sheen, in case your Irish is rusty).

Rejuvenation therapies

Hudson attributes his first interest in the role senescent cells (SnCs) play in human aging to a lecture given by Buck Institute scientist Judy Campisi in 2003.

“She made a convincing case that SnCs impact on human health was significant, and hinted that removing them would help to ameliorate several aged-associated illnesses,” he recalls. “The key question was: how? Nearly ten years later the Mayo Clinic demonstrated that removal was possible – in a transgenic model, this is important to note – and that removal would improve median survival, or healthspan, by more than 25%.”

Hudson and co-founder Matt Scholz were sitting together when the results of the Mayo study were presented by Campisi in 2013, where she noted that the transgenic mouse model was not translatable to the human clinic, but was a proof of concept that clearing SnCs was beneficial.


 

“Matt leaned over to me and said ‘I believe I know how to do that therapeutically’ and Oisín Bio was born that night.”

 


 

“Matt leaned over to me and said ‘I believe I know how to do that therapeutically’ and Oisín Bio was born that night,” says Hudson, who went on to lead the company as acting CEO for the next four years, seeking to develop a business model that would address “the dilemma faced by any company that wishes to attack aging as a disease.”

“As we all know, the FDA doesn’t yet accept that premise, and requires biotechs to identify an indication – a specific disease – to be treated by any new investigational drug,” says Hudson. “While we can accommodate the FDA rules by picking a specific indication, the normal pressures of business will inevitably require that whatever indication is first chosen will dictate the path for the company into the far future. An aging-focused start-up will thus become a cancer or heart or kidney disease company, and lose its ability to attack the basis for most age-associated maladies. I wanted to avoid that trap at all costs.”

This led Hudson to adopt model where Oisín is the platform company, providing the technology to use its unique DNA-plasmid and nanoparticle approach to kill cells based on their internal state.


 

“Oisín controls the platform technology and manufactures the therapeutics to maintain quality control, while following the FDA-mandated path to clinical for new drugs.”

 


 

“Once the platform is proven scientifically and pre-clinically demonstrated, our plan was that Oisín would spin out specific indications or classes of indications, either via a conventional out-license to other biotechs or big pharmas, or as partially or wholly-owned subsidiary ventures,” says Hudson, pointing to the company’s oncology spinout, OncoSenX as an example of this. “In this way, Oisín controls the platform technology and manufactures the therapeutics to maintain quality control, while following the FDA-mandated path to clinical for new drugs. Additionally, since some investors will be more comfortable with conventional indication-focused ventures, this model opens up new avenues for funding, partnerships and collaborations with other companies, broadening the market appeal of our technology.”

Initial funding for Oisín was supplied by the Methuselah Foundation, the SENS Foundation and Kizoo Technology Ventures, in addition to Hudson himself and other angel investors.


 

“Oisín’s funding will be used for additional preclinical studies prior to an IND for an aging-related disease indication while OncoSenX’s will be used for the Phase 1 and 2 oncology trials in humans.”

 


 

“We’ve raised over $8m to date for both Oisín and OncoSenX,” he says, adding that both entities are currently in the process of raising new funding rounds. “Oisín has a Series Seed round underway for up to $5m while OncoSenX is raising a Series A of up to $30m. Oisín’s funding will be used for additional preclinical studies prior to an IND for an aging-related disease indication while OncoSenX’s will be used for the Phase 1 and 2 oncology trials in humans.”

The company’s next goal is to conduct a pre-clinical trial application meeting for OncoSenX to clear the path to a Phase 1 safety and efficacy trial against human solid tumors to be conducted in Canada within a year.

“Completion of this milestone allows us to initiate our last GLP safety trial in non-human primates and to begin the production run for the GMP therapeutics required to conduct the oncology trial,” says Hudson. “Once full funding is secured we can proceed to initiate a second clinical trial for Oisín in a to-be-announced indication.”

Longevity2020

About Oisín’s platform technology

The Oisín platform has two parts – the first is a software program the company has written in DNA.

“Is the cell senescent, or not?” explains Hudson. “If senescent, then kill. If not, then ignore. We have been able to write a computer program in DNA that is executed in cells based on if/then logic.”

The second is the transfection technology itself, which Oisín has licensed from its partner Entos Pharmaceuticals – a lipid-based nanoparticle (LNP or ‘fat bubble’) that carries the DNA program until it reaches a cell membrane. The nanoparticle then fuses with the cell and delivers its payload directly into the cytoplasm.

Hudson points out that lipid nanoparticles have been proposed before, and a few have even entered clinical trials, but have generally failed due to cytotoxicity.

“This is due in large part to their need to depend upon charge chemistry in order to activate the endocytotic pathway (to be taken up into cells),” he says. “The Entos Fusogenix LNP doesn’t require a charge and so is neutral in the body, preventing unwanted cell death.”

So how do these new nanoparticles gain admittance to the cell’s inner workings?

“They use a novel fusion protein derived from a reptilian orthoreovirus,” explains Hudson. “This fusion protein is very small (actually, the smallest one known in nature) and can be incorporated into the lipid bubble when it is manufactured in our high-volume microfluidic production facility. Unlike previous LNPs, the Entos nanoparticle will simply fuse with the cell membrane to deliver its contents, just like a virus.”

Oisín has already completed extensive safety testing of its therapeutic in mice, rats and non-human primates. Results to date demonstrate that the nanoparticles do not raise an immune response in the body, and are both tolerable and non-toxic even at high doses. So does Oisín have some specific disease targets in mind for further preclinical exploration?

“Our challenge is that we actually have too many – since SnCs are implicated now in perhaps 100 different diseases of aging – so choosing which to pursue is difficult,” says Hudson. “After the evident success of our initial aged mouse study conducted between 2018 and 2019, we have decided to perform a much bigger study – about 5 times larger – to further demonstrate benefits of the therapy in new indications, such as frailty and cognition.”

Rejuvenation therapies

Image courtesy of Oisín Biotechnologies
Danny Sullivan
Contributing Editor Danny has worked in technology communications for more than 15 years, spanning Europe and North America. From bionics and lasers to software and pharmaceuticals – and everything in between – he’s covered it all. Danny has wide experience of technology publishing and technical writing and has specific interest in the transfer from idea to market.

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