Whether you believe human aging is one distinct disease or the result of a combination of degenerative diseases, the race is on to find the ‘fountain of youth’ in biotech laboratories to extend life’s runway. Seattle-based Oisín Biotechnologies is in that race.
Oisín’s researchers believe when cells detect that they have been irreversibly damaged, they enter a non-dividing condition known as cell-cycle arrest, or senescence. It’s believed this occurs to prevent cells from going rogue and turning cancerous. Ideally, they should die by the process known as apoptosis, but as we age, more and more frequently they don’t. They become zombie cells – unable to kill themselves or resume normal function.
Senescent cells secrete molecules that cause inflammation in an effort to attract immune cells that would usually clear them. But for reasons that are not fully known, as we age, persistently senescent cells accumulate, leading to a vast number of age-related diseases.
Oisín is developing a highly precise, patent-pending, DNA-targeted intervention to clear these cells. As a recent study has shown, clearing senescent cells both reduce negative effects of aging pathologies and also extend median lifespan and survival.
Guiding this research is Gary Hudson, Oisín co-founder and acting CEO. Hudson is also active in several non-profits focusing on age-related disease. He provided seed funding for the SENS Research Foundation, which is transforming the way the world researches and treats age-related disease. He is a major donor to and serves as an advisor to the Methuselah Foundation, which is dedicated to extending the healthy human lifespan by advancing tissue engineering and regenerative medicine therapies.
Prior to Oisín, Hudson worked extensively in the field of commercial space, successfully starting and growing several companies. He is best known as the founder of Rotary Rocket, which built a landing test simulator for a reusable rocket that flew three successful flights in 1999.
WuXi AppTec Communications, as part of a new industry series, recently interviewed Hudson about the clinical direction and goals of Oisín, as well as what the future looks like for research extending human life.
WuXi: How do you define aging? Is it an illness itself? Is it a specific group of diseases?
Gary Hudson: I view aging as a progressive loss of function, especially in the ability to respond to stressors, over time. There’s much debate whether it should be called a disease, but for me there is no debate that it should be treated as if it were a disease.
WuXi: What is your anti-aging technology and how are you applying it?
Gary Hudson: Our first anti-aging therapy is to ablate senescent cells. The anti-aging research and translational community is largely agreed that this approach has significant benefit; the debate is how to accomplish it effectively and safely. Most competitors are exploring repurposing conventional drugs, but we have taken a gene-based approach. Using a novel and patented lipid nanoparticle (a liposome with specific and unique ‘decoration’ on its surface) we can transduce cells with a plasmid that contains both a promoter section of DNA that targets senescent cells plus a suicide gene, which will kill only that cell if the promoter is activated. The promoter in question is activated by up-regulation of transcription factors that have been expressed because the cell has determined it has suffered sufficient DNA damage to force itself to stop replicating.
WuXi: What is the goal of your technology? Is it improving quality of life for more years or extending the average life span?
Gary Hudson: We’ve just about reached the limits of extending life in humans who are suffering the ravages of aging-associated disease. No one really wants to perpetuate suffering. Our goal has to be extending healthspan by repairing age-associated damage; if we accomplish this, it is my personal belief that lifespan extension will be an added bonus.
WuXi: What will define success for your anti-aging technology?
Gary Hudson: The ultimate goal is reaching ‘escape velocity,’ which is a hypothetical situation in which life expectancy is being extended longer than the time that is passing.
WuXi: How does your approach differ from other companies in this field?
Gary Hudson: Many of our colleagues and competitors are working in the so-called ‘small molecule’ space. This is the traditional pharma model of drug discovery and testing, which is familiar to investors and regulators but has the disadvantage of off-target effects. We kill senescent cells based on what the cell’s internal gene expression is at any given point in time as enabled by up-regulation of specific transcription factors. Anthropomorphically speaking, we kill cells based on ‘what they are thinking’ rather than on internal metabolism, surface markers or other features.
WuXi: How will anti-aging strategies evolve over the next five to 10 years?
Gary Hudson: We expect that there will be a suite of complementary therapies that will be brought to bear on the root causes of aging, including elimination of senescent cells, repair of mitochondrial dysfunction, and probably stem cell replacement or reprogramming. All we can be sure of is that progress is rapidly accelerating and there will be many surprises and new technology to emerge in the next decade.
WuXi: Do you need a different business model than a traditional biotech or pharma company? If so, what are the differences?
Gary Hudson: Most start-up biotech firms quickly identify a particular indication or group of indications that they wish to target, based on the action of their small molecule drug. They then staff their management team to address the regulatory path to market, first conducting toxicity studies and then human clinical trails. Once they go down this path, they are locked into their course and can’t easily make corrections. If the clinical trial fails, and 90% of them do fail, then the company is doomed.
Alternatively, Oisín Bio is structured as a discovery and IP company, which also produces the platform therapeutics we intend to employ against many different aging and oncology indications. Each indication or group of indications is then spun out as a separate wholly owned subsidiary, joint venture, or is offered as a licensing opportunity to conventional pharmas. This way each indication can raise capital as needed, staff their clinical approach as required, and succeed or fail independently of the ‘mothership’ – Oisín Bio.
WuXi: What are the major challenges you face in developing and marketing your anti-aging technology?
Gary Hudson: Since we can’t currently take an anti-aging therapy though the FDA regulatory process, we have to target one or more indications (currently approved diseases). Accordingly, the regulatory process becomes no different for us than any other therapy of comparable type.
Wuxi: What kinds of collaborations are essential for your company?
Gary Hudson: Oisín Bio is principally a discovery-focused venture, exploring and perfecting several related therapeutics based around a common platform. We depend on collaborations with existing pharmas as well as other smaller biotechs to partner with us to take individual treatments to market. We can’t develop the regulatory and marketing expertise for all the disparate indications we could potentially treat – so partnerships are the only way to maximize the availability of the platform’s potential.
WuXi: What kinds of global partnerships do you have or plan to pursue?
Gary Hudson: We’ve been in talks with both US-based pharmas as well as a few Asian and European biotechs. Our approach is “first come, first served” meaning that we’ll partner with foreign entities as the opportunities emerge. And if any of those companies wanted to emphasize anti-aging as a treatment strategy over specific individual diseases, based on a perhaps more favorable regulatory climate in their homeland, we’d be very interested in having a conversation.
Wuxi: What challenges do you face in structuring clinical trials to evaluate your technology?
Gary Hudson: For individual disease indications – which is the only path to market under FDA rules as this time – the challenges are essentially identical to any novel gene therapy approach. The real challenge will come when the FDA starts developing guidelines for using therapies such as Oisín’s for treatment of ‘aging’ as the indication. This may not happen for some time but there are signs that the FDA is moving in this direction. Until they draft rules and regulations it is impossible to say what the risks are, beyond noting that finding ‘endpoints’ in clinical trials for aging will itself be challenging. Unlike many diseases, where the endpoint of the trial is a cure or moderation/amelioration of the disease state, we have to select biomarkers of aging that tell us we are having a beneficial effect of mortality and morbidity. The research community hasn’t settled on such biomarkers as yet.
WuXi: What regulatory challenges do you anticipate?
Gary Hudson: Ours is a first-in-man type of genetic therapy, so will face the normal problems such an approach might see. But unlike most other genetic therapies, our plasmid doesn’t integrate with the cell’s genome, avoiding many of the issues that confronted early gene therapy approaches. So we expect to be treated similarly to viral based therapies but without some of the specific concerns that have been expressed for such treatments.
WuXi: How soon will an anti-aging medicine be available?
Gary Hudson: We’re hopeful that the first indications may reach the market in 5-10 years, but those will be specifically disease-focused. The question of when this platform will be approved for more general anti-aging treatment is a question only regulatory agencies can answer.
WuXi: How will your anti-aging technology change medical care?
Gary Hudson: In the U.S. we spend about $1T each year on diseases of aging (cancer, type II diabetes, dementia and such). If instead of providing mostly palliative care for a patient – which after age 50 or so means everyone – we should be able to eliminate or greatly delay the onset of these diseases. That can’t help but have a salutatory effect on both patient wellbeing and the national debt.
WuXi: Are there any ethical considerations involving your approach or the whole concept of anti-aging strategies?
Gary Hudson: Personally, I don’t view anti-aging strategies as different in any respect from normal medical care. If a treatment is available that extends both health and lifespan, I’d use the same metric to evaluate its application for anti-aging as I would for any disease condition.
WuXi: What are the societal implications of extending the average life span by 10 or 20 years?
Gary Hudson: I expect they are not much different than the implications we already faced in the past fifty years, as average lifespans grew by that amount over the past half century. It’s useful to remind ourselves that at the time of the U.S. Civil War, the average lifespan was only half of what it is today – we survived that doubling of average lifespan and created a prosperous society as a result of increased productivity. Doubling human average lifespan over the next 100 years would have similar effects, I believe.