Interview with Kelsey Moody: How to Build a Company and End Age-Related Pathologies

Original author: Steve Hill
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I recently attended the Longevity Leaders Conference in London and had the opportunity to speak with Kelsey Moody, head of Ichor Therapeutics , a company specializing in the study of aging and the fight against age-related pathologies. I already interviewed him earlier, in 2017, so this was the best moment to find out what happened to his company during all this time.

Steve Hill : For the past year, Ichor and its portfolio companies have been busy, I think it's time for us to catch up and learn about your progress. Tell us how things are going in Ichor group.

Kelsey Moody : 2018 was a good year for Ichor. We have raised more than $ 16 million and expanded the scope of our business. Now we have more than 50 employees, mainly scientists and technical specialists working in the laboratory. Our goal is to be a vertically integrated biopharmaceutical company, and we strive for it.

We want to be able to take any idea - whatever it is, for example, a substance of a certain type or therapy - and quickly carry it through all stages, from a scientific discovery to a study of demand. The capital we received and the infrastructure we build allow us to bring all this together to support the areas of science that deal with longevity.
Each of our programs is fully funded, and that's great! We continue to work with a number of other startups that work with us as partners or clients. We can get the most out of our knowledge about aging and technical expertise with individual types of research models and use this to support other companies working in this field, as well as to promote and further develop our own programs. Last year, we teamed up with Jim Mellon's Juvenescence .

Steve Hill : Yes, you and Juvenescence have created a FoxBio joint project. How are you doing with him?

Kelsey Moody : Unfortunately, I cannot say much about FoxBio's work now, except that I am optimistic and excited about our prospects. We are very pleased with the partnership with Juvenescence. They brought their vast experience and deep understanding of drug development processes and research programs to the research process. They are also well versed in how to create structures and platforms within the company that will greatly increase the capital needed for clinical trials. We enjoyed working with them, and we will be happy to further expand the scope of these relations in the future.

Steve hill: It's really great to see people like Jim Mellon and Juvenescence involved in your research early on, guys. Well, let's hope for a sequel. What news is there about Lysoclear - therapy for age-related blindness?

Kelsey Moody : And again, I can’t tell you all the details, but we closed the next round of financing in December 2018 and are ready to move from our leading test drug, which was used to test the concept, to its clinical version, with which it will be possible to conduct human trials.

We have a plan - get IND status(Investigational New Drug) - and now we are thinking about how to achieve this. In the US, obtaining IND status is the starting point for the first human trials of a drug. To do this, you need all kinds of support - from the production of your product in accordance with GMP (Good Manufacturing Practice) to toxicological studies and more.

Last year, we were lucky to hire a medical director with extensive experience in the development and research of drugs. Among his achievements are 12 drugs and medical devices and about 185 clinical trials in the field of macular degeneration. Thanks to his participation in the DARPin programMolecular Partners managed to close a deal worth $ 500 million plus double-digit royalties with large pharmaceutical company Allergan. We are very enthusiastic about the fact that in our company the management of clinical planning was undertaken by a person with such serious experience. This gives us confidence that when we are ready to release our drug, we will be able to navigate the clinical and regulatory problems that may arise.

Steve hill: This is a serious challenge! But there is another problem area in the past - to conduct research from the initial stages to the point where the product can be brought to the market. A few years ago, you mentioned in an interview about the problem of lack of experience of “dirty work” among specialists engaged in basic research, and that people who are capable of innovations at the broadcast stage are not inclined to think outside the box. Has the situation improved in the last few years?

Kelsey Moody : I think so. Now there are many academic laboratories that understand how to promote a company, especially with regard to new groups that have arisen in this area. Juvenescence licenses various technologies and collaborates with the Tank Institute . Life biosciences- A new player in this market, this company attracts significant finances to help academic laboratories with their programs.

What really impresses me about all this is that when you introduce these drug developers, sophisticated in your lesson, into this area, a certain level of reliability arises, which is not always possible under traditional academic conditions. This allows you to take and combine the best of both worlds.

Steve Hill : Let's talk about one of your parallel projects. In a previous interview, we touched on the topic of Senolitics , then you had some doubts about whether you should do this. You are currently working with the pharmaceutical company Antoxerene, which develops Senolitics. What made you change your mind and start moving in this direction?

Kelsey Moody : We were motivated by a collaboration with James Kirkland of Mayo Clinic. We saw that senolytic therapy has a strong effect, prolonging the life of mammals. Antoxerene is a platform company. The basis of its technologies is attempts to search for medicines, simultaneously addressing the issue of your interest. Suppose there are two proteins, the interaction between which leads to pathology, and you are trying to disrupt it. To produce mass screening of drugs, you need a lot of proteins involved in this way. You will screen drugs and select those samples that can interrupt this interaction.

The problem is that many types of proteins are very difficult to create, such as, for example, p53 protein . The genome is guarded by a gigantic variety of proteins, and people cannot create them on such a scale for screening drugs. Unless you use hyperstable mutants or small fragments instead of whole proteins.
The Antoxerene platform allows us to create these impossible complex proteins at the scale required for drug screening. Thanks to this platform, we were able to carry out many screening projects related to oncology, senolytic therapy and more. Together with Juvenescence and FoxBio, we created a risky project dedicated to some of these senolithic programs, but this is not all that is done on the Antoxerene platform. We are actively looking for pharmaceutical companies that would be interested in becoming our partners and use these technologies to solve technical problems that arise with their own platforms.
We hope to expand and develop this direction in the future. There is a situation in pharmaceuticals and biopharmaceuticals - at least we have a feeling - when not enough attention is paid to the fundamentals on which all these clinical programs are based. Ichor has now hypothesized that an excessively high level of failure with drugs in clinical practice is associated with poor selection of model organisms or with unsatisfactory preclinical studies.

Perhaps in a couple of years I will take back these words, but this is what we are still observing now. While everyone else is in a hurry to bring the matter to clinical practice as soon as possible, we do not strive to be among the first with any specific method or solution, but we do not want to be the last. We want to do everything right and maintain a balance - to have time to timely implement our developments in clinical practice, but be sure that our programs are built on a very reliable basis.

Steve Hill : Let's talk a little bit about how you developed the company. You not only conduct your research focused on aging, but also work on a contract for other laboratories. How do these side projects help your company grow?

Kelsey Moody: In many different ways. Companies like ours rarely work for profit, they have no income. The fact that our company generates income allows us to grow. If we tried to do this only by financing investors, it would be very difficult. Our investors pay only for projects, they do not need to bear the burden of the cost of building new infrastructure and other things, which is typical. They appreciate that, and that’s very good for us.

It is very beneficial to be able to collaborate with other companies involved in the development of new technologies in this area. If everything looks promising, we can talk to them, provide them with strategic support and more - to help them make faster progress with their programs.

If you have not yet encountered the research and development of drugs, you do not know about the pitfalls that await you. There are many unobvious ways to stumble along the way. We share the philosophy and goals that this movement is trying to achieve. To do our part by supporting other startups is valuable to us in itself, and we are going to do this further.
We want to expand the scope of our contract work and optimize it. To this end, we are going to separate all the research services provided under the contract this year into a separate corporate unit - Ikaria Life Sciences. We plan to develop this area as the main one in 2019.

Steve Hill : You continue to grow, soon you will become the main in Lafayette. Some people are surprised that you settled in Lafayette. Why did you choose this city to build a company here?

Kelsey Moody : When I attended SUNY Downstate Medical University Medical School in Syracuse, NY, I explored the area and realized that it was the perfect place to create a real company. Basically, startups working in the biomedical sciences tend to remain virtual companies. To do their job, they collaborate with academic laboratories and contract research organizations.

The problem is that the scope is very new. Take, for example, Senolitics. We have already spoken about a number of companies specializing in analytics or drugs designed to destroy senescent cells that provoke the development of age-related pathologies. If you want to develop a product, you would not be able to outsource it to a research organization working under a contract right now, because this is a completely new field. Contracted research organizations have not yet commercialized these models and services so much that they can simply be ordered on the thumb. It turned out that in order to provide support for research and development, it is very important to establish a physical infrastructure - and the Syracuse area is unique in this sense.

There is a slight economic depression here, especially in the real estate market, so I managed to buy buildings for the same price that would cost a year and a half to rent in Silicon Valley or in Boston. The value proposition is huge. There is an airport here, and yet we have no problems getting high-quality intellectual capital, because there is a medical school here - Upstate Medical , Syracuse University . In the near future, Ichor will have a PhD program with SUNY ESF and Cornell University.

This creates a hurricane of opportunities in terms of intellectual capital and finance. I also want to note that during World War II, Bristol Myers Squibb produced in Syracuse something about half of the total amount of penicillin in the world. And Bristol Myers still has active production facilities in Syracuse. Ichor closely monitors PLP-compatible animal research and GMP, production and more - to support our own developments. We were able to attract talented quality control professionals, as well as technical specialists and research scientists who are accustomed to working in a regulated pharmaceutical environment. This creates an effective balance in the research work of our teams, adding a certain level of industrial accuracy and thoroughness to our creative processes.

Steve Hill : This is an interesting look at the company from the inside. Now let's talk about the person who is behind all this. How did you build your career and turn from a guy who went in for sports at school and college, and then worked at McDonald's - who you are now?

Kelsey Moody : Like many other people trying to found a company and do something in this area, I started with Aubrey de Gray 's book “ Ending Aging ”, which was published a little over 10 years ago, in 2007, if I remember correctly and I really liked the concepts outlined in it. I decided to switch to biochemistry as the main course, and I planned to continue working on this line until I could make sure that Aubrey was wrong.

But, in spite of all my efforts, I still could not make any final conclusion on this issue. Many tried to prove him wrong, and his views may still be wrong, but the trend is in his favor. This led me to work with Aubrey as part of the SENS Research Foundation and to collaborate with various startups in Silicon Valley, in the end I came to Syracuse as a medical student, and here I am.

There is one very interesting thing in the SENS paradigm, which, I think, is underestimated, the central element of our approach to company structuring is the approach aimed at eliminating damage. Many people like Aubrey's proposed approach to damage management (SENS), because this is something we can easily understand - all these arguments about workarounds, misunderstanding metabolism and more
Many drug development people underestimate the fact that the types of therapies that may appear with this approach are therapies that will be used periodically, and from a developmental point of view it is very beneficial. Let's think about issues like high cholesterol or cardiovascular disease. What happens to these patients? They "sit" on statins all their lives, this is a "chronic" treatment, you take medications every day. The safety and efficacy of such drugs must be very high so that they retain clinical benefits. But in order to accumulate all these different classes of damage associated with aging, you need a lifetime, to combat them you can create drugs with a less favorable toxicological profile. They are less effective in terms of the impact on the target,
This creates an excellent opportunity for drug developers to create a completely new class of drugs that can mitigate the manifestations of many age-related pathologies in an unprecedented way that challenges the model of continuous drug use that we are now familiar with.

Steve Hill : People in the community often ask us this. If we perceive aging as a pathology, then we can not do anything about it until the FDA, EMA and others classify it as a pathology. Do you personally think that the classification of aging as a pathology is necessary in order to start treating it or to look for ways to get around this problem?

Kelsey Moody: Not at all, in any case - not in the problems that we are dealing with, although there are other areas where it would certainly be useful. There are two guiding principles with which we approach the implementation of our programs. The first is to do one new thing at a time. So, if we are engaged in senescent cells - and this is a completely new, poorly developed area - we are not going to introduce new methods of treatment. We will use small molecules - the approach that pharmaceuticals used to combat pathologies at the dawn of time. In the case of our program for combating macular degeneration, where enzyme therapy is used, which we are developing to remove unwanted “garbage” from our eyes, which, we believe, causes the development of pathology, we follow the same translational path as other companies

The only change is that we use non-human enzymes to try to renew the lysosomes, instead of restoring the “broken ones”. Whatever we do, we try to do it step by step.

Our second guiding principle concerns the concept of aging as a pathology. In order to check all our programs, we try to choose specific diseases, but we also have the opportunity to fight with the help of the programs that we develop with the basic damage that occurs during aging. As for our senolithic program, we are going to deal with diseases that other companies may deal with, but it will have a side effect in the treatment of chronic inflammation.

I also had the honor of listening to the resTORbio Medical Director, who presented their clinical results at the conference. They use a very similar low-key approach - they look at the incidence and hospitalization rates in patients they treat with mTOR inhibitors. We see that, although they work with specific diseases, there must be a global systemic rejuvenation if the mechanisms underlying their preparations work as we expect.

Our approach has always been to change one thing - and only one thing at a time, and focus on programs that suggest conservative paths to clinical practice, and have certain anti-aging benefits that can be developed in the future.

Steve hill: Senolitics is a classic example of this approach. You can begin to deal with them for one purpose, but when the drug is received and tested, it can potentially be used to achieve many goals - not for its intended purpose.

Kelsey Moody : Yes, absolutely.

Steve Hill : So we do not need to classify aging as a pathology. Yes, that would be good, but that is not necessary.

Kelsey Moody : From a developer's point of view, this is probably not necessary. What really matters is public opinion. Do people understand that aging is something that can be influenced and treated. If so, aging is something we must work seriously on. And here the recognition of aging as a pathology would be potentially useful.

Steve hill: Well, we got first-hand information. Thank you very much Kelsey for taking the time to talk with us.

Translated by Irina Abramidze , SENS Volunteers

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