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An Interview with Kelsey Moody of Ichor Therapeutics, Bringing a SENS Therapy for Macular Degeneration to the Clinic – Article by Reason

An Interview with Kelsey Moody of Ichor Therapeutics, Bringing a SENS Therapy for Macular Degeneration to the Clinic – Article by Reason

The New Renaissance HatReason
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As I mentioned last week, earlier this year Fight Aging! invested a modest amount in the Ichor Therapeutics initiative to develop a treatment for macular degeneration, joining a number of other amateur and professional investors in helping to get this venture started. The approach taken here is based on the results of research carried out at the Methuselah Foundation and SENS Research Foundation over much of the past decade, funded by philanthropists and the support of our community of longevity science enthusiasts. This is how we succeed in building the future: medical science in the laboratory leads to medical development in startup companies, each new stage bringing treatments capable of repairing specific forms of age-related molecular damage that much closer to the clinic.

Ichor Therapeutics is one of a growing number of success stories to emerge from the SENS rejuvenation research community. Young scientists, advocates, and donors involved in earlier projects – years ago now – have gone on to build their own ventures, while retaining an interest in stepping up to do something meaningful to help bring an end to aging. Back in 2010, Kelsey Moody worked on the LysoSENS project to find ways to break down damaging metabolic waste in old tissues; fast-forward six years, and he is the now the CEO of a successful small biotechnology company with a great team, taking that very same technology and putting it to good use. I recently had the chance to ask Kelsey a few questions about the future of SENS rejuvenation research, as well as how the Ichor scientists intend to construct a new class of therapy for macular degeneration, one based on removing one of the root causes of the condition.

Quote:

Who are the people behind Ichor Therapeutics? How did you meet and decide that this was the thing to do? Why macular degeneration as a target?

People have always been the focus of Ichor. Since day one we have worked to create a positive environment that cultivates a product-oriented research focus and emphasizes autonomy and personal accountability for work. As a result, ambitious self-starters tend to find their way to Ichor and remain here. However, we recognized early on that just filling a lab with a bunch of blue-eyed bushy tailed young up-and-comers is not sufficient to develop a robust, mature, translational pipeline. We have augmented our team with a number of critical staff members who are seasoned pharma operators, including our Quality Assurance Director and General Counsel.

Age-related macular degeneration (AMD) was chosen as a target because we believe it is the closest SENS therapy to the clinic. While we obviously have an interest in providing cures for the patients suffering from AMD and are attracted to the large market opportunities such a treatment could bring, our broader interest is in validating the entire SENS paradigm. We believe that Aubrey de Grey continues to receive excessive criticism because nothing spun out of SENS has ever made it into a legitimate pre-clinical pipeline, much less to the bedside. However, this does not mean he is wrong. Our goal is to be the first group to bring a SENS inspired therapy into the clinic and in doing so, silence critics and generate new energy and capital for this cause.

I understand there’s a lengthy origin story for the approach you are taking to treat AMD; it’d be great to hear some of it.

Our approach to treating AMD is based on the hypothesis that cellular junk that accumulates over the lifespan significantly contributes to the onset and progression of AMD. Our goal is to periodically reduce the burden of the junk so it never accumulates to levels sufficient to induce pathology. The strategy to accomplish this calls for the identification of enzymes that can break down the junk in a physiological setting, and the engineering of these enzymes such that they can break down the target in the correct organelle of the correct cell without appreciable collateral damage to healthy cells or tissue.

Methuselah Foundation and SENS Research Foundation did excellent work in establishing this program nearly a decade ago. They successfully identified a number of candidate enzymes that could break down the molecular junk, but reported that the targeting systems evaluated failed to deliver these enzymes to the appropriate organelles and cells. My group reevaluated these findings, and discovered that these findings were flawed. The delivery failure could be entirely attributed to a subtle, yet highly significant difference between how the target cells behave outside of the body as compared to inside the body. It turned out that the approach was in fact valid, it was the cell based assay that had been used that was flawed. This discovery was striking enough that SENS Research Foundation provided Ichor with funding and a material and technology transfer agreement to reassess the technology, and over $700,000 in directed program investments and grants have been received in the last year or two.

You recently completed a round of funding for the AMD work; what is the plan for the next year or so?

The new funds will allow us to develop a portfolio of enzyme therapy candidates to treat AMD. We will obtain critical data necessary to secure follow-on investment including in vitro studies (cell culture studies to confirm mechanism of action and cytotoxicity) and pivotal proof-of-concept in vivo studies, such as toxicity, PK/PD (how long the enzyme stays in the body and where), and efficacy. We will also be restructuring the company (reincorporating an IP holding company in Delaware, ensuring all contracts are up to date and audited) and ensuring our IP position is on solid footing (licensing in several related patents from existing collaborators, and filing several provisional patents from our intramural work). Collectively, we believe these efforts will position us to obtain series A for investigational new drug (IND) enabling pre-clinical studies.

You’ve been involved in the rejuvenation research community for quite some time now. What is your take on the bigger picture of SENS and the goal of ending aging?

This is a loaded question. What I can say is that the medical establishment has made great progress in the treatment of infectious disease through the development of antibiotics, vaccines, and hygiene programs. However, similar progress has not been realized for the diseases of old age, despite exorbitant expenditures. I have chosen to work in this space because I think a different approach is necessary, and it is here that I believe my companies and I can be the most impactful. I think SENS provides a good framework within which to ask and answer questions.

What do you see as the best approach to getting nascent SENS technologies like this one out of the laboratory and into the clinic?

We need more people who fully understand, in a highly detailed way, what a real translational path looks like. To take on projects like this, being a good scientist is not enough. We need people who can speak business, science, medicine, and legal, and apply these diverse disciplines to a well articulated, focused product or problem. There is no shortage of people who partially understand some of these, but the details are not somewhat important – they are all that matter for success in this space.

Another area is for investors. Some of the projects that come across my desk for review are truly abysmal, yet I have seen projects that are clearly elaborate hoaxes or outright scams (to anyone who has stepped foot in a laboratory) get funded to the tune of hundreds of thousands of dollars or more. While it is perfectly reasonable for high net worth individuals to gamble on moon shots in the anti-aging space (and I am ever grateful for the investors who have taken such a gamble on us) even aggressive development strategies should have some basis in reality. This is especially true as more and more high tech and internet investors move into the space.

If this works stupendously well, what comes next for Ichor Therapeutics?

I really want to get back into stem-cell research, but I basically need a blank check and a strong knowledge of the regulatory path to clinic before I feel comfortable moving into the space. A successful AMD exit would accomplish both of these goals, and position us to pivot to cell-based therapies.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
Free Your Talent and the Rest Will Follow – Article by Orly Lobel

Free Your Talent and the Rest Will Follow – Article by Orly Lobel

The New Renaissance Hat
Orly Lobel
October 17, 2013
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Imagine two great cities. Both are blessed with world-class universities, high-tech companies, and a concentration of highly educated professionals. Which will grow faster? Which will become the envy and aspiration for industrial hubs all around the world?

Such was the reality for two emerging regions in the 1970s: California’s Silicon Valley and the high-tech hub of Massachusetts Route 128. Each region benefited from established cities (San Francisco and Boston), strong nearby universities (University of California-Berkeley/Stanford and Harvard/MIT), and large pools of talented people.

We’ve all heard about Silicon Valley, but not so much Route 128. Despite their similarities, and despite the Bostonian hub having three times more jobs than Silicon Valley in the 1970s, Silicon Valley eventually overtook Route 128 in number of start-ups, number of jobs, salaries per capita, and invention rates.

The distinguishing factor for Silicon Valley was an economic environment of openness and mobility. For more than a century, dating back to 1872, California has banned post-employment restrictions. The California Business and Professions Code voids every contract that restrains someone from engaging in a lawful profession, trade, or business. This means that unlike most other states, California’s policy favors open competition and the right to move from job to job without constraint. California courts have repeatedly explained that this ban is about freeing up talent, allowing skilled people to move among ventures for the overall gain of California’s economy.

The data confirm this intuition: Silicon Valley is legendary for the success of employees leaving stable jobs to work out of their garages, starting new ventures that make them millionaires overnight. Stories are abundant of entire teams leaving a large corporation to start a competitive firm. Despite these risks, California employers don’t run away. On the contrary, they seek out the Valley as a prime location to do business. Despite not having the ability to require non-compete clauses from their employees, California companies compete lucratively on a global scale. These businesses think of the talent wars as a repeat game and find other ways to retain the talent they need most.

In fact, the competitive talent policy is also supported by a market spirit of openness and collaboration. Even when restrictions are legally possible—for example, in trade secret disputes—Silicon Valley firms frequently choose to look the other way. Sociologist Annalee Saxenian, who studied the industrial cultures of both Silicon Valley and Route 128 in Massachusetts, found that while Boston’s Route 128 developed a culture of secrecy, hierarchy, and a conservative attitude that feared exchanges and viewed every new company as a threat, Silicon Valley developed an opposing ethos of fluidity and networked collaborations. These exchanges of the Valley gave it an edge over the autarkic environment that developed on the East Coast. In Massachusetts, firms are more likely to be vertically integrated—or to have internalized most production functions—and employee movement among firms occurs less frequently.

New research considering these different attitudes and policy approaches toward the talent wars supports California’s modus operandi.

A recent study by the Federal Reserve and the National Bureau of Economic Research examined job mobility in the nation’s top 20 metropolitan areas and found that high-tech communities throughout California—not only Silicon Valley—have greater job mobility than equivalent communities in other states. Network mapping of connections between inventors also reveals that Silicon Valley has rapidly developed denser inventor networks than other high-tech hubs have.

Researching over two million inventors and almost three million patents over three decades, a 2007 Harvard Business School study by Lee Fleming and Keon Frenken observes a dramatic aggregation of the Silicon Valley regional networks at the beginning of the 1990s. Comparing Boston to Northern California, the study finds that Silicon Valley mushroomed into a giant inventor network and a dense superstructure of connectivity, as small isolated networks came together. By the new century, almost half of all inventors in the area were part of the super-network. By contrast, the transition in Boston occurred much later and much less dramatically.

Michigan provides a natural experiment for understanding the consequences of constraining talent mobility. Until the mid-1980s, Michigan, like California, had banned non-competes. In 1985, as part of an overarching antitrust reform, Michigan began allowing non-competes, like most other states. Several new studies led by MIT Sloan professor Matt Marx look at the effects of this change on the Michigan talent pool. The studies find that not only did mobility drop, but that also once non-competes became prevalent, the region experienced a continuous brain drain: Its star inventors became more likely to move elsewhere, mainly to California. In other words, California gained twice: once from its intra-regional mobility supported by a strong policy that favors such flows, and once from its comparative advantage over regions that suppress mobility.

A virtuous cycle can be put into motion geographically where talent mobility supports professional networks, which in turn enhance regional innovation. Firms can learn to love these environments of high risk and even higher gain. Rather than thinking of every employee who leaves the company as a threat and an enemy, smart companies are beginning to think of their former employees as assets, just as universities wish for the success of their alumni. Companies like Microsoft and Capital One have established networks of alumni. They showcase their former employees’ achievements and practicing rehiring of their best talent, hoping that at least some of those who leave will soon realize that the grass is not always greener elsewhere.

Most importantly, motivation and performance are triggered by commitment and positive incentives to stay, rather than threats and legal restrictions against leaving. In behavioral research I’ve conducted with my co-author On Amir, we find that restrictions over mobility can suppress performance and cause people to feel less committed to the task. Cognitive controls over skill, knowledge, and ideas are worse than controls over other forms of intellectual property because they prevent people from using their creative capacities, they don’t just prevent firms from using inventions that are already out there. So instead of requiring non-competes or threatening litigation over intellectual property, California companies use rewards systems, creating the kind of corporate cultures where employees want to work and do well. Again, a double victory.

Unsurprisingly, when Forbes recently looked at the most inventive cities in the country for 2013 using OECD data, the two top cities were in California: bio-tech haven San Diego, and the legendary home of Silicon Valley, San Francisco. Boston, still vibrant and highly innovative despite its most restrictive attitudes, came in third. Competition is the lifeblood of any economy, and fierce competition over people is the essence of the knowledge economy.

Orly Lobel is the Don Weckstein Professor of Law at the University of San Diego and founding faculty member of the Center for Intellectual Property and Markets. Her latest book is Talent Wants to be Free: Why We Should Learn to Love Leaks, Raids, and Free-Riding (Yale University Press, September 2013).

This article was originally published by The Foundation for Economic Education.