Interview with Kelsey Moody: How to build a company and do away with age-related pathologies

I recently visited the Longevity Leaders Conference in London and there had the opportunity to talk with Kelsey Moody, the head of Ichor Therapeutics , a company specializing in the study of aging processes and the fight against age-related pathologies. I already interviewed him earlier, in 2017, so it was the best time to find out what happened to his company during all this time.

Steve Hill : All last year Ichor and her portfolio companies were busy, I think it's time for us to catch up and learn about your progress. Tell us how things are going in the Ichor group.

Kelsey Moody : 2018 was a good year for Ichor . We raised over $ 16 million and expanded our entire operations. Now we have more than 50 employees, mostly scientists and technicians working in the laboratory. Our goal is to be a vertically integrated biopharmaceutical company, and we are committed to it.
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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 scientific discovery to the study of demand. The capital we received and the infrastructure we build allow us to put it all together to support the longevity science.

Each of our programs is fully funded, and this is great! We continue to cooperate with a number of other startups who work with us as partners or customers. We can get the most out of our knowledge of aging and technical expertise with individual types of research models and use this to support other companies operating in this area, as well as to promote and further develop our own programs. Last year, we teamed up with Jim Mellon Juvenescence .

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

Kelsey Moody : Unfortunately, I can’t say a lot about the work of FoxBio right now, except that I’m optimistic and excited about our prospects. We are very pleased with the partnership with Juvenescence. They brought to the research process their vast experience and in-depth understanding of drug development processes and research programs. 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 this relationship in the future.

Steve Hill : It's really great to see people like Jim Mellon and Juvenescence involved in your early studies, guys. Well, let's hope to continue. And what is the news about Lysoclear - the treatment of age blindness?

Kelsey Moody : Again, I can’t tell you all the details, but we closed the next round of funding in December 2018 and are ready to move on from our lead test drug, which was used in the concept test, to its clinical version, with which we can conduct human trials.

We have a plan - to get the status of IND (Investigational New Drug) - and now we are thinking about how to achieve this. In the United States, obtaining IND status is the starting point for the onset of the first human drug trials. All types of support are needed for this - from the production of your product in accordance with good manufacturing practice of GMP (Good Manufacturing Practice) to toxicological research and so on.

Last year, we were fortunate enough to hire a medical officer with extensive experience in drug development and research. 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 program , Molecular Partners managed to conclude a deal worth $ 500 million plus double-digit royalties with a large pharmaceutical company Allergan. We are very enthusiastic about the fact that in our company a person with such serious experience took over the management of clinical planning. 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 area of ​​concern in the past - to conduct research from the initial stages to the point where the product can be put on the market. A few years ago, you mentioned in an interview about the problem of the lack of “dirty work” experience among specialists involved in basic research and that people who are capable of innovations at the translational 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 for new groups that have emerged in this area. Juvenescence licenses various technologies and collaborates with the Baka Institute . Life Biosciences is a new player in this market, this company attracts significant funds to help academic laboratories with their programs.

What really impresses me about this is that when you introduce these sophisticated drug developers to your business in this area, a certain level of reliability arises, which is not always possible in traditional academic settings. It 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 the senolithic , then you had certain doubts about whether you should do this. You are currently working with the pharmaceutical company Antoxerene , which develops senolithics. What made you change your mind and start moving in that direction?

Kelsey Moody : We were motivated by the collaboration with James Kirkland of Mayo Clinic. We have seen that senolithic therapy has a strong effect, prolonging the life of mammals. Antoxerene is a platform company. The basis of its technology - is trying to look for drugs, along the way engaged in the issue of interest to you. Suppose there are two proteins, the interaction between which leads to pathology, and you try to break it. To produce a mass screening of drugs, you need a lot of proteins involved in this path. You will conduct a screening of drugs and highlight 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 protected by a gigantic variety of proteins, and people cannot create them on such a scale for drug screening. 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 implement many screening projects related to oncology, senolitic therapy and so on. Together with Juvenescence and FoxBio, we created a risky project dedicated to some of these senolithic programs, but this is not all that is being done on the Antoxerene platform. We are actively looking for pharmaceutical companies that would be interested in becoming our partners and using these technologies to solve the technical problems they have with their own platforms.

We hope to expand and develop this direction in the future. In the pharmaceutical and biopharmaceuticals, there is a situation - at least we have the feeling - when the basics on which all these clinical programs are built are not given enough attention. Ichor has now hypothesized that an excessively high level of drug failure in clinical practice is associated with poor selection of model organisms or with unsatisfactory preclinical studies.

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

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

Kelsey Moody : In many different ways. Companies such as 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 spending on the construction of new infrastructure and other things that are typical. They appreciate it, and it is very good for us.

It is very beneficial to have the opportunity to cooperate with other companies engaged in the development of new technologies in this field. If everything looks promising, we can communicate with them, provide them with strategic support and so on - to help them make progress with their programs faster.

If you have not yet encountered research and drug development, you do not know about the pitfalls that are waiting for you. There are many unobvious ways to stumble along the way. We share the philosophy and goals that this movement is trying to achieve. Contributing to other startups is in itself valuable to us, and we are going to continue to do so.

We want to increase the scope of our contract work and optimize it. To this end, we are going to allocate all contractual research services 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 one 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, New York, I studied the area and realized that this is the perfect place to create a real company. Mostly startups working in the field of biomedical sciences tend to remain virtual companies. To do their job, they collaborate with academic laboratories and research organizations working on a contract basis.

The problem is that the sphere is very new. Take, for example, the senolithic. We have already talked about a number of companies specializing in analytics or drugs designed to destroy the senescent cells that provoke the development of age-related pathologies. If you want to develop any product, you could not give it away to an outsourced research contract organization right now, because this is a completely new field. Contract-based research organizations have not yet commercialized these models and services so that they can be simply ordered under the thumbnails. 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 in Silicon Valley or Boston would cost a year and a half. The value proposition is huge. There is an airport here, and we have no problems with obtaining 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 whole hurricane of opportunities in terms of intellectual capital and finance. I also want to note that during World War II, Bristol Myers Squibb produced about half of all penicillin in the world in Syracuse. And Bristol Myers still has actively working production facilities in Syracuse. Ichor is closely monitoring PLP-compatible animal studies and GMP, production and others to support our own development. We were able to recruit talented quality control professionals, as well as technicians and research scientists 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 precision 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 man behind all this. How did you build your career and turned from a guy who was involved in sports in school and college, and then worked at McDonalds - who you are now?

Kelsey Moody : Like many other people trying to start a company and do something in this area, I started with Aubrey de Gray's book Ending Aging , which was published a little more than 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 along this line until I could be sure that Aubrey was wrong.

But, despite all my efforts, I could not reach any final conclusion on this issue. Many have 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, it seems to me, is underestimated, the central element of our approach to structuring companies is an approach aimed at eliminating damage. Many people like the Aubrey’s proposed approach to eliminating damage (SENS), because this is something that we can easily understand - all these arguments about workarounds, lack of understanding of metabolism, etc.

Many people involved in drug development underestimate the fact that the types of therapy that can emerge from this approach are therapies that will be used periodically, and from a development point of view it is very beneficial. Let's think about problems 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 medicine every day. The safety and efficacy of such drugs should 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 whole life, to deal with them you can create drugs with a less favorable toxicological profile. They are less effective in terms of the impact on the target, but in a clinical setting they are potentially better because the injuries take a long time to accumulate.

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 medication with which we are now familiar.

Steve Hill : People in the community often ask us this. If we perceive aging as a pathology, then we cannot 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 to start treating it or to look for ways to get around this problem?

Kelsey Moody : Not at all, at least not in the problems that we deal with, although there are other areas where this 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 deal with senescent cells - and this is a completely new, little-developed sphere - we are not going to introduce new methods of treatment. We will use small molecules - an approach that pharmaceuticals used to combat pathologies at the dawn of time. In the case of our program to combat macular degeneration, where enzyme therapy is applied, which we are developing to remove unwanted "garbage" from the eye, which, we believe, causes the development of pathology, we follow the same translational path as other companies involved in lysosomal accumulation diseases - Genzyme, Sanofi, Biomarin and others that have been successfully operating since the late 80s - early 90s of the last century.

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

Our second guiding principle concerns ideas about aging as a pathology. In order to check all of our programs, we try to select specific diseases, but we also have the opportunity to precisely target using the programs that we develop with the basic damage that occurs during the aging process. As for our senolysis program, we are going to deal with diseases that other companies may be engaged in, 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, discreet approach — looking at incidence and hospitalization rates in patients they treat with mTOR inhibitors. We see that, although they work with specific diseases, there should 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 to focus on programs that suggest conservative paths to clinical practice, and have certain advantages in terms of anti-aging that can be developed in the future.

Steve Hill : The Senolithic is a classic example of this approach. You can start practicing them with one goal, 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 true.

Steve Hill : So we don’t need to classify aging as a pathology. Yes, it would be good, but it 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, then aging is something that we must work seriously on. And here 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 to us.

Translated by Irina Abramidze , SENS Volunteers Group