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DeepTech in Biomedicine

DeepTech companies are founded on scientific discoveries and engineering innovations

DeepTech companies combine cutting edge science and advanced engineering with the objective of making a profound impact on humanity. Some of the industries most impacted by DeepTech include life sciences, biotech, biomedicine, and Longevity. Companies in these sectors are using advanced technologies such as AI, deep learning and machine learning to tackle the most challenging problems facing humanity.

Companies that apply AI for drug discovery are DeepTech companies. Companies that combine DNA sequencing and bioinformatics are DeepTech companies. Companies that apply AI and Data Science to diagnose disease are DeepTech companies. DeepTech companies are fundamentally different from regular tech companies. Instead of being based on innovative business models, they’re based on cutting edge science and technology that have the potential to cause major disruption across industries. A good example is DeepMind, an AI startup acquired by Google at the unprecedented valuation of $500 million in 2014.

DeepTech companies transform scientific breakthroughs into tangible results. Instead of relying on marketing and PR, they rely on the successful application of their capabilities. DeepTech companies stand solely on the results of their scientific and technical prowess.

The quality standards and barriers to entry for DeepTech companies are quite steep compared to other companies. These companies require very high levels of scientific and technological expertise translated into tangible results within a reasonable time frame. This minimum viable threshold is referred to as the DeepTech Valley of Death, a reference to the significant amount of seed capital ($3-5 million) and time (2-3 years) required to bring proof-of-concept prototypes to the level of practical application to justify further rounds of financing. A conventional startup developing a mobile app typically requires only about $500,000 in seed capital and 6-12 months to deliver a prototype.

The minimum viable threshold required to be a successful DeepTech investment firm is even higher, requiring both advanced levels of science and technology assessment and new approaches to venture capital business models and exit strategies. A significant gap exists between the level of scientific and technical development in the startup world compared to the venture capital industry. As the number of DeepTech companies increases exponentially as a result of the accelerated rate of technological progress (with tens of thousands of companies on the horizon) the business models, investment tactics, exit strategies and even core technical assessment methodologies used by investors lags behind.

This disproportion between the DeepTech startup community and the conventional venture investment community will eventually be adjusted. A combination of technologies including FinTech, Blockchain, AI, and most importantly innovation in InvestTech itself, will help narrow this gap within the next 5 years. This will prompt investment funds to adapt their business models, exit strategies, and underlying technology assessment methodologies to become more relevant.

Longevity companies that prove capable of crossing the threshold of minimum technical viability, and achieving tangible results, will become the next Googles. Investment firms that make smart bets on those companies will become the SoftBanks of tomorrow.

The Longevity Industry, positioned at the forefront of advanced biomedicine, is a good example of a DeepTech sector within the life science industry. The Longevity sphere is far more advanced than traditional biomedicine. In fact, it's considered next generation. Companies working in Longevity require integration of advanced applications of personalized and preventive medicine with many distinct scientific subdomains including AI, digital medicine, and geroscience (the science of aging). Companies in this sector also require advanced methods of diagnostic and prognostic assessment and next generation techniques for conducting trials compared to conventional standards which are largely based on results from in vitro experiments and model organisms (mice). Due to this complexity, the barriers to being a capable and relevant investment fund focusing on this sector are proportionally large, requiring advanced methods of science and technology assessment, and novel ways of fund structuring in order to remain applicable to the dynamics of the industry.

Aging is the biggest risk factor for developing many diseases including Alzheimer’s, osteoporosis, cardiovascular disease, cancer. Few breakthroughs would make as profound an impact on humanity as curing aging.

Five Prime Examples of DeepTech in Advanced Biomedicine and Longevity

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1. The Buck Institute for Research on Aging

The Buck Institute for Research on Aging is the epicenter of Longevity research. The Buck, located 30 minutes north of San Francisco, was designed by eminent architect I.M. Pei. Inside these stunning buildings with 75 foot ceilings and massive skylights, scientists are conducting the most advanced Longevity research on the planet. Their mission is to end the threat of age-related disease for this and future generations. They seek a comprehensive understanding of the biology of aging itself. At the Buck, top scientists from around the world are researching many diseases including Alzheimer's, Parkinson's, cancer, osteoporosis, and cardiovascular disease.

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What sets the Buck apart from other research organizations is that this was the first institution that was founded with the goal of expanding human health span by understanding aging and how aging contributes to disease. All of the scientists at the Buck are focused on understanding aging and they work collaboratively with a common goal. Even if a group is working primarily on Alzheimer's disease, they are interested in what it is about aging that gives rise to Alzheimer's. Since aging is the single most important risk factor in many diseases, if we can slow aging, we can prevent many diseases and keep people much more functional as they age.

"Science is showing that while chronological aging is inevitable, biological aging is malleable. There's a part of it that you can fight, and we are getting closer and closer to winning that fight."

Eric Verdin, MD, President and CEO, The Buck Institute for Research on Aging

The first demonstration that a small molecule could increase lifespan was done by Gordon Lithgow at The Buck Institute. Out of this came a whole series of discoveries. Today we’re at a point where people are considering starting clinical trials. This is why there is so much excitement and interest. Now that we know some of the pathways that are the primary drivers of aging, scientists are developing novel strategies to treat diseases of aging.

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The Buck has over 250 scientists and 19 labs, each run by a principal investigator. AI is quickly becoming a driver of progress and is galvanizing a rapid paradigm shift. AI for aging research in particular is recognized as a highly convergent approach on the forefront of practical applications in the Longevity space. The Buck’s AI and Computational Biology Center will use AI to exploit the full value of research data and expertise in the pursuit of new interventions and diagnostic tools to enable the extension of the human health span. AI has the potential to create a portfolio of new findings that will generate new grant resources and partnerships to enhance Buck research.

In July 2018, The Buck announced the establishment of the world’s first Center for Female Reproductive Longevity and Equality with a $6 million gift from Nicole Shanahan. The Buck’s commitment to prioritize AI research combined with their position as a leading institute for research on aging, makes them the epicenter of AI for Longevity. The convergence of AI and Longevity research will lead to accelerating important medical breakthroughs that will benefit all of humanity. @BuckInstitute

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2. Leucadia Therapeutics

Over 40 million people are living with Alzheimer’s disease worldwide. More people die from Alzheimer’s disease than breast cancer and prostate cancer combined. Since 2000, deaths from Alzheimer’s disease have increased by 89% while deaths from heart disease have decreased. By 2050, the annual cost of caring for Alzheimer’s patients will surpass $1 trillion in the US, and China’s economy could become crippled caring for half a billion seniors. Total worldwide costs for Alzheimer’s could approach $4 trillion per year. Pharmaceutical companies have invested over $30 billion dollars in a series of high-profile clinical trials for Alzheimer’s disease. Even after all of this money and effort, not a single drug has been developed that can halt or even slow its relentless progression.

Leucadia Therapeutics is taking a new approach to combating Alzheimer’s Disease. Their research suggests that the plaques and tangles found in the brains of Alzheimer’s patients are not the root cause of Alzheimer’s, but pathological effects of a more serious underlying condition. They are using deep learning to develop a non-invasive method to predict who will get Alzheimer’s years before cognitive impairment develops. Leucadia has also developed a treatment to correct this condition at the cribriform plate, a porous bony structure that becomes occluded as we age. An implantable device, called Arethusta®, fixes the root cause of this pathology and clears toxic metabolites from intercellular spaces in the brain—similar to the way the lymphatic system clears toxins from the rest of the body. This unique and compelling approach could potentially predict, halt, and cure Alzheimer's Disease before it even begins. @LeucadiaT

Doug Ethell, PhD, Founder and CEO of Leucadia Therapeutics

3. Oisín Biotechnologies

As we age, our bodies accumulate damage. Over time this damage leads to disease. The process starts with the natural activity of cell replication. After several replications, certain cells lose their ability to divide, but remain viable. This is known as cellular senescence. In the human body, the number of senescent cells in many tissues increases with age. Senescent cells are found in the tissues of age-related pathologies such as osteoporosis. Aging researchers theorize that the accumulation senescent cells in healthy tissue in the body may promote aging. 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 understood, as we age, senescent cells accumulate persistently, leading to a vast number of age-related diseases.

Oisin Biotechnologies is a platform drug development company focused on creating drugs to combat a variety of age related diseases by reducing senescent cells to slow down aging. Oisin is developing a highly precise, patent-pending, DNA-targeted intervention to clear senescent cells. Oisin’s technology allows for the targeting of senescent cells with precision without harming undamaged cells. Oisin has applied their technology to oncology applications. In a study on mice, they reduced tumor mass by 90% in 24-48 hours. Oisin Biotechnologies differs from other companies that develop senolytic therapies. Oisin’s technology can be programmed to kill any class of cell with a distinct internal marker in the expressing a specific protein, and can effectively target cancer cells with p16 and p53 markers. The technology is designed to be adapted to attack any type of cell that is undesirable by targeting its distinctive chemistry. There are many possible targets.

John Lewis, Co-founder of Oisín Biotechnologies

4. Elevian

Studies show that when old animals are transfused with the blood of young animals, they experience regeneration across many tissues and organs. And, when young animals are transfused with the blood of old animals, they experience premature aging. Elevian is a biotech company working to discover novel candidates and pathways for therapeutic intervention of aging.

Elevian is a preclinical stage therapeutics company founded by professors leading three labs at Harvard University. They are developing new medicines to restore regenerative capacity, with the potential to prevent and treat many age-related diseases. Their mission is to help people age without developing the diseases of aging.

Research has identified specific circulating factors responsible for regenerative and degenerative effects, including GDF11. When provided to aging animals, GDF11 stimulates stem cells to repair tissue damaged by aging and degeneration. Animal studies have demonstrated a reduction in age-related cardiac hypertrophy, youthful skeletal muscle repair, improved brain function, improved metabolism, reversal of renal and pulmonary disease, and tumor suppression.

Elevian is developing therapeutics that regulate GDF11 and other circulating factors, in order to stimulate and replenish our body’s natural regenerative capacity. Unlike current therapeutics with limited, disease-specific benefits, Elevian’s therapeutics have broad benefits, with the potential to treat and prevent many age-related diseases. Therapeutic candidates have shown efficacy in preclinical models of cardiovascular, metabolic, neurodegenerative, and musculoskeletal disease. Additionally, human epidemiological evidence in nearly 2,000 patients shows that lower levels of a measure of GDF11 predicts a 7-fold higher risk of death, along with higher risk of strokes, heart attacks and heart failure hospitalizations. @ElevianInc

Dr. Mark Allen, Co-founder & CEO Elevian

5. Insilico Medicine

Although there are about 125 AI companies working in the AI for drug discovery space, very few are capable of building end to end solutions. Insilico Medicine is a leader in this area. Insilico Medicine’s drug discovery engine is involved in the drug discovery and in silico validation stages of the drug development cycle. The company focuses on the generation of novel drug candidates with specified molecular properties for precise disease targets. Traditional pharmaceutical companies screen through many possible leads, testing each one and hoping that one works. Insilico Medicine starts with molecular leads that have been specifically designed, in terms of their pharmacokinetic and pharmacodynamic properties, and therefore have a higher probability of being effective for specific disease targets.

Insilico Medicine screens potential drug candidates using generative adversarial networks (GANs). GANs create synthetic datasets that are indistinguishable from real datasets by having two neural networks compete against each other. One neural network generates the data and the other compares it to a real data set in iterative cycles so that the degree of error in the synthetic data set is gradually decreased. Rather than using trial and error when looking for molecular leads, requests are made to the network to generate specific leads and leads are generated on demand.

Recently there’s been a big increase in the number of papers published on GANs. Insilico Medicine was the first company to apply GANs to the generation of new molecular structures with specified parameters. The company has developed adversarial neural networks that compete with each other to generate and evaluate novel drug candidates with specific molecular properties. Insilico Medicine has established itself as a pioneer in the most advanced AI methods for drug discovery.

Insilico's drug discovery engine is trained on massive amounts of structural, functional, and phenotypic data in order to predict the biological activity of compounds. Insilico Medicine has published seminal papers in Oncotarget and Molecular Pharmaceutics. Another paper, published in Molecular Pharmaceutics in 2016, demonstrated the proof of concept of the application of deep neural networks for predicting the therapeutic class of the molecule using the transcriptional response data.

Frost & Sullivan recently awarded Insilico Medicine the North American AI for Aging Research & Drug Development Innovation Award as part of their 2018 Best Practices Awards. The fact that Frost & Sullivan created a new award category for this specific area of research and development is indicative of the interest and support that AI for drug discovery is garnering from the drug development community.@InSilicoMeds

"It’s great to see the Napa Therapeutics NAD Longevity project take off. NAD boosters are the safest and most advanced Longevity medicine in development."

David Sinclair, PhD, Professor and Co-Director, Paul F. Glenn Center, Harvard University

Notable DeepTech Collaborations

Dr. Eric Verdin, CEO of the Buck Institute, is one of the top figures in aging research and is a leading expert in the NAD+ space.The Buck is collaborating with Juvenescence and Insilico Medicine on a joint venture called Napa Therapeutics to develop small molecule drugs against a novel aging-related target for the treatment of age-related diseases. It draws the best from three areas: great science from the Buck, funding and drug hunting and development expertise from Juvenescence and AI prowess and expertise in advanced bioinformatics from Insilico Medicine.

Insilico Medicine and Elevian are collaborating on a small molecule discovery program to discover drugs that target aging. The have entered into a research and development partnership to develop oral medications targeting the GDF11 pathway and associated targets.

Insilico Medicine and A2A Pharmaceuticals, Inc., a biotechnology company focused on novel drug development for oncology, are collaborating on a joint venture called Consortium.AI, which will apply advances in AI to discovery of novel small molecules for the treatment of Duchenne Muscular Dystrophy and other rare diseases.

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This article was written by Margaretta Colangelo and Dmitry Kaminskiy. We're interested in your feedback - please leave your comments in the comments section. Click the subscribe button at the top of this article to have our articles delivered directly to you.

Margaretta Colangelo, Managing Partner at Deep Knowledge Ventures, is based in San Francisco. Margaretta serves on the Advisory Board of the AI Precision Health Institute at the University of Hawai‘i Cancer Center.

Dmitry Kaminskiy, General Partner at Deep Knowledge Ventures, is based in London. Dmitry is Managing Trustee of the Biogerontology Research Foundation.

Deep Knowledge Ventures is an investment fund focused on DeepTech. Investment sectors include AI, Precision Medicine, Longevity, and Neurotech. Deep Knowledge Ventures led Insilico Medicine’s seed funding round in 2014 and has remained a close advisor in the company’s journey towards becoming a global leader in the application of advanced AI, particularly deep learning and GANs.

Deep Knowledge Ventures has two subsidiaries. Deep Knowledge Analytics produces analytical reports on topics related to DeepTech including AI in Drug Discovery and AI in Healthcare. Aging Analytics Agency produces analytical reports on the topics of Longevity, personalized medicine, and preventive medicine. Aging Analytics Agency is the only analytics company focused exclusively on Aging, Geroscience, and Longevity @DeepTech_VC

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