First in Human Episode #22 featuring Kristian Reich

For episode 22 we connect with Dr. Kristian Reich, Founder & Chief Scientific Officer of MoonLake Immunotherapeutics. Find out the key things that have contributed to Dr. Reich’s success in raising capital and having to tell his story 521 times. First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder & guest host Co-Founder, Andrew Brackin. Episodes launch weekly on Tuesdays & Thursdays.

Simon Burns: Thank you for joining us today on First in Human, Dr. Kristian Reich.

Kristian Reich: Simon, thank you for allowing me to be here. Maybe a quick introduction. Kristian Reich. I actually live in Hamburg, Germany, originally. Now, working a lot from Switzerland. I’m an MD-PhD. I was actually trained as an immunologist, and dermatologist. I spent most of my life doing research on inflammatory skin diseases.

I’ve contributed quite a bit to developing, especially the new targeted antibody therapies. Just imagine, Simon, when I started, we were putting tar on our psoriasis patients and giving them some phototherapy. The severely affected were in the hospitals for months every year. And today, you inject one ml of an antibody once every two or three months and 90% of the patients clear.

 I can proudly say that we have seen an absolute revolution in the way we can treat not only inflammatory skin, but actually, quite a number of inflammatory conditions in rheumatology, in dermatology, in other indications. This progress has indeed been driven by two factors. That sums up my professional career also quite a bit. It’s A: research, identifying where this inflammation is coming from, what are the factors that work together to give a patient a disease. Secondly, to be able to create antibodies that specifically target these cytokines normalizing an exaggerated immune response. 

If you have a disease where there’s too much TNF or IL-17, you give an antibody against TNF 17. So, you specifically normalize, I use this word on purpose, I don’t think we can speak here about general immunosuppressive effect. This is the beauty of these targeted therapies, but by antagonizing, normalizing these cytokines, seeing fantastic responses. I’ve been lucky, obviously, left all of this behind to become Chief Scientific Officer of MoonLake, recently.

Why is this Simon? After all these years, almost decades now, with the antibodies, MoonLake is developing a nanobody. A molecule that has the potential to do things that antibodies do probably just better. Also, again, as an immunologist, after this first big wave of TNF-driven inflammatory diseases, how many indications did HUMIRA have in the end? [00:05:00] 18? 19? 

 IBD, rheumatological indications, dermatological indications, what we currently see is a similar development for the IL-17 pathway. There is a growing number of diseases where this pathway is the driving force behind the disease. Obviously this Nanobody Sonelokimab that Moonlake is developing does not only have these unique molecule characteristics, but also optimizes the way we can inhibit this pathway by blocking not only IL-17A, but also this other IL-17 family member, IL-17F.

Simon Burns: That was a power intro. You’ve had several careers within there, Kristian. you’re a PI, a teacher, an academic and now a founder of a biotech company. These are radically different in scope. What’s changed in what’s been required of you? How have you adapted to now being a CSO and founder?

Kristian Reich: You have to sleep less, right? No, but, honestly, in my previous life, I saw thousands and thousands of patients. This gives you the authenticity you really need to understand what patients and prescribers want. I did a lot of research. I have a passion for this understanding of disease processes. Taking it also to the translational level, how can we use this knowledge to optimize therapies? Again, I did so many clinical trials. I was not only a professor seeing patients, I had my own clinical trials aside and hundreds of these trials.

 In the end, you suddenly see this molecule, this nanobody. Now you have to put it into the test be brave, right? Let’s go out there, create clinical trials, and try to give birth to a new therapeutic molecule. Indications and hidradenitis suppurativa, psoriatic arthritis, psoriasis– where I felt relatively familiar with. It was a huge step. I still wake up every morning and say, “God, what have you done?”

What drives me, the excitement comes from the idea, maybe indeed, we are able to bring a new therapy to patients. It’s not the simple humanitarian aspect. I’ve seen patients with hidradenitis suppurativa. There’s a single biologic that is approved for this condition right now, which is adalimumab. It gives 50% of the patients a 50% improvement. I know that this term “unmet need” is overused. But here, you have a disease where there is a lot of unmet need. My excitement, my passion comes from this hope, this wish, that, yes, indeed, we can bring a new therapy to patients. We can contribute that some of the diseases that still cannot be well managed today can be managed better in the future.

Simon Burns: I’d love to dig in there on an unmet need. If you were an immunologist, or giving advice to a young immunologist going into the field, lots of very hot topics of research there, generalized priorities of unknown origin, sarcoidosis, PN, still facing. What are the unmet needs that MoonLake with all its capital and team can go address that you would want to see more attention given to?

Kristian Reich: I have a son that studied medicine at Imperial College. We had conversations, obviously, and I said, “Yeah, immunology, damn immunology. But you have discovered it all, right? what’s left?” I said, “We have not even discovered 2%.” I cannot help myself, Simon. I’m an immunology man. Obviously, if you think about it, many other specialties like oncology, how much immunology is there in oncology? Many of the modern oncology treatments are immunologic treatments. They manipulate the immune system with the hope they activated immune system defends the cancer better.

Definitely, all surface diseases, the mucosa, the skin (even the liver, immunologically is a surface to a certain degree) all this chronic inflammatory diseases. They are all hot boiled immunologic diseases.

If you add up the prevalences of these diseases, Simon, you have 20%, right? Psoriasis is two. Atopic dermatitis is another three. A PsA is 05. HS, probably 1%. Rheumatoid is 1% And so on, and so on, right? We talk about things that can go wrong immunologically that give human beings a plethora of diseases. The underlying pathways are overlapping. There is so much left to be discovered.

 Vitiligo, alopecia areata, vasculitis, prurigo nodularis, hepatitis, many kidney diseases. There are so many diseases. Systemic lupus, right? Do we really have good drugs to treat systemic lupus? And what is even systemic lupus? Is it a kidney disease? Is it a skin disease? What is it?

 Would I still advise a young researcher today that go into immunology? It’s fantastic. Absolutely, yes. Is it a door opener to multiple specialties? A very large group of diseases across different specialties? Absolutely, yes. Do I continue to believe that many new therapies now in the future will come from an improved understanding and also therapeutic manipulation of the disease pathways? Absolutely, yes. If you ask me, would you do it again? I would say, yes. If a young doctor asked me, is it worth going into immunology? I would loud and proud say yes.

Simon Burns: I’m going to give you three back-to-back questions. Take them in the order you want. The first is, we had Frank Watanabe on the podcast not too long ago, a peer of yours, CEO of Arcutis who said, under-investment in dermatology therapeutic areas, relative to others, thinks there should be more therapeutic area investment [00:10:00] in dermatology. I’m curious to hear your thoughts there. 

The second is you guys are pioneering. You’re up against big pharma competitors. Some biotechs are doing that. Not as many as some would hope are going late stages clinical trials competing directly with pharma. I’m curious, where do you think the balance is? Is innovation being driven by biotech pharma? Where is the future there?

Lastly, next generation modality, nanobodies, biospecific antibodies, Krystal doing some work in cell and gene therapy. Is the future of derm more of these next generation modalities? And where do you see that taking forward?

Kristian Reich: Do we need more drugs in dermatology? Are there still unmet needs? Quite a bit. This includes injectables, like bodies, antibodies, nanobodies, other molecules. This may also include some oral therapies if they give patients an advantage and have an acceptable benefit/risk profile. Will we continue to see a development in the space of immunology? Absolutely, yes. 

There are so many chronic inflammatory conditions. We still talk about treatments that make patients better as long as they take it. We have evidence that some of the treatments may have some disease modifying effects. But of course, ultimately, the dream, the vision, the hope would be, do we find immunologic vaccinations that allow us to cure some of these diseases? It’s complicated. Not many of them are straightforward autoimmune diseases. So, number one, I think a loud and clear yes.

Number two, biotech was large pharma. A lot of innovation comes from biotech. A lot of innovation still comes from academia. The poor professors stumble their first steps into forming a company. It takes ages. What is more complex than clinical development? For good reasons, you need a big apparatus to run clinical trials. You need to interact with CROs that overwhelm you if you’re a small company, all of this. You need a lot of money.

 I’m terribly oversimplifying here. But, I think it takes great courage and great effort for a small company to really do advanced steps in clinical development. I’m very proud that MoonLake will finish its third global phase two program by the end of this year. This says something, but as an idea generator, I think biotech is hard to beat.

 If you see which drugs have the big pharma companies brought to market successfully in recent years, not many of them were actually developed in house. They were developed by small biotech companies. But, of course these big well oiled machines, do they know better how to run phase three trials? Do they have a center of excellence for regulatory where you have 25 people? Of course. When it comes to ideas and innovations, biotech is big. When it comes to executing clinical development, and, obviously, bringing drugs to market, this is where big pharma, obviously scored.

Your last question, the nanobodies. 

Simon Burns: Yeah, it’s the future of derm, yeah, next generation.

Kristian Reich: It seems to be and, again, I’m terribly oversimplifying here. But, not all sites of inflammation that can be affected by inflammatory diseases are easy to reach for an antibody that you give systemically. We call them “difficult to reach” sites of inflammation. I wouldn’t think that a psoriatic plaque for example is “difficult to reach” site of inflammation, but I would think that a deep nodule in HS surrounded by scar tissue, a tunnel, an emphasis in PSA are difficult to reach sites of inflammation.

We have evidence that the smaller your targeting molecule is, the better is your tissue penetration. Some of these molecules including our Nanobody Sonelokimab, they have an albumin binding piece. The original idea is that you prolong the half life to the two weeks, for example, that we have, but patients have a swollen joint if they have arthritis, because there’s an accumulation of albumin-rich fluid. That’s not rocket science, Simon, but suddenly we discover that having an albumin binding path also helps your molecule to specifically enrich at sites of inflammation because these sites have more albumin than healthy tissue.

There’s also this idea that why evolution has produced nanobodies is because they wanted to have targeted therapies that find the functionally relevant epitopes better. One example, some cancers are being treated by blocking their growth receptor with an antibody. These cancers have a little mutation in the receptor. And the antibody because of steric hindrance no longer binds. The tumor escapes the inhibitory effect. Now, the nanobody that binds the same growth type of receptor still binds and still has an inhibitory effect.

 There is some hypothesis involved in what I said. But if I look into the field of cancer, into the field of virology, you know that nanobodies against SARS-CoV-2 just to give you another example, they bind much better than antibodies against SARS-CoV-2. In the field of inflammation, where we need tissue penetration, we need albumin binding. I have the idea that at least in multiple areas, the nanobodies will take over. They are antibodies 2.0.

Simon Burns: You’ve been quite successful raising capital. It is no easy feat as a biotech company, certainly within a bear market like we’ve been in. What are the lessons learned in [00:15:00] storytelling, investor relations? [Kristian laughs] How have you been so successful?

Kristian Reich: I like your word storytelling. Yes, you have to be able to tell your story 521 times. Of course, you need to have a solid idea, solid preclinical data. You need to have good science. You need to be able to tell a story. It helps if you have a first phase one data in disease patients. That would be general advice. You go into the disease as quickly as possible. Then, you have to run around and put it all together and hopefully convince investors that what you have makes a lot of sense.

Now, if you ask me as a scientist, do I necessarily think that all the investments I see left and right, are based on evidence, and on rock solid data? Or, they’re sometimes based on six patients treated in the phase one for some weeks, and no one knows what’s really going on. But it’s all driven by hope, and so, yes. But Simon, without money, these things do not fly. As a responsible sponsor, as a responsible biotech, you have to get your things right from the get go. 

Do your work properly. Do your study designs properly. Put the right scientific experiments in place. Do your preclinical work properly. There is no alternative to this. And when, at some point, big pharma will look into what you have been doing, then everybody will be glad if they see, “Oh, this has been done very properly. This has been done like, we would have been doing this.” Unfortunately, being a biotech, Simon, is no excuse. You still have to do your things very properly. You have to go around and you convince investors that what you do make sense, and you actually have a potential to develop something new that is relevant.

Simon Burns: Well, your enthusiasm for the sciences is palpable. The fervor is real. I can see where investors got some level of attraction. Tell us a little bit more about clinical trials. You’ve run quite a few of them. If a small biotech company were approaching you saying, “We’ve got a clinical trial coming up. How should we think about CRO selection, site selection, protocol design, endpoint selection?” All of these key questions that these teams have. Many of them are really struggling. How would you advise them?

Kristian Reich: Simon, very good point. It depends a little bit on how your personnel is composed, If you have people on board that have a lot of experience in clinical development. But, let’s say the classical, a few professors found something super interesting, a new target. They looked at this in an animal model, great promise. They’ve never designed a clinical trial. They don’t know what a CRO is. Boy, do they face a high hurdle?

If you have 15, 20 people, any collaboration with a big CRO will likely overwhelm. You don’t even have enough staff to supervise what they’re doing. This would be the minimum requirement for any sponsor. We all know the names. You have huge CROs that have done this a million times. But, they have a huge apparatus. It’s like you’re against a whale. It’s a small Volkswagen against a jumbo jet.

It’s super-hard to find a way to optimally interact. As a small biotech, what you would wish is, you get a customized CRO who helps you in different areas. Who brings the expertise for a study design to you, that require some therapeutic expertise. Do you use PASI 75 or PASI 90? Do you use high score of 50? There are many delicate questions that help you to address the regulatory questions that you have. 

You need to exchange with the EMA, and with the FDA. There’s this whole regulatory world. Then, of course, you need to execute the clinical trials. Which countries do you select? Which sites do you select? How do you train the site? There are multiple questions. Ideally, of course, you have a partner that can do this all.

 I’m not sure that any partner could bring this to all indications. Maybe one solution is that you say, “Look, we are only dermatology but we do everything in dermatology. We even have our own KOL network. We do everything. Just give us a trial. We can give you advice on preclinical, this is how we would do the phase one, SAD, the first disease patient. So that they take you by the hand and walk with you all the way. 

And they do this in a way that you don’t have to worry about quality. Again, this oversight, if you do a global phase two program. Just one global phase two program, this, can already be overwhelming for a very small company that has to use their brains and their time for other things.

This is a little bit of a dilemma. If you want to do a global phase two, you go to one of the big CROs, but, then you have this disproportional relationship. You are small and they are huge. You just have to pray that it works out. I do see room for specialized CROs. Specialized doesn’t mean they only sit in the US or Poland or Germany or what have you. But small means that they are focused. But in one area, this vertical approach, they know everything. They can offer full service package.

Simon Burns: I like jumbo jet and Volkswagen, it’s very evocative. It’s still in my mind’s eye. Last question for you. At Vial, we think a lot about applications where technology can drive clinical trials to be more efficient. In your experience, where have you seen room where you really thought technology could have had an impact in preventive outcomes?

Kristian Reich: You have to do things that [00:20:00] regulatory authorities approved. That says something. They’re not the most innovative folks out there. But the Corona crisis, which was a big crisis for clinical development, has taught us, the hard way, we need to think about alternative ways of doing clinical trials remote for example. Patients don’t have to come every week. That’s even more complex. And again, I’m using dermatology here as an example, even more complex skin course can be assessed at home, both photography, tailored dermatology, some really new ways of, doing this.

We all do electronic data entering nowadays. But to really optimize this, to take this to a different level, while having all the data protection in place, that’s a huge thing in IT. And primarily sits in the US. But here in Europe, GDPR is wow, you hear this and you freeze. Your hairs go up. I want to see progress being made IT solutions, definitely. This has to be a joint activity with regulatory authorities. They need to have trust in what you’re doing. Otherwise, you will not use it. It needs to fulfill all these formulas, data protection elements. But, there is also patient recruitment, right? I see enormous room for going to social media more cleverly addressed patients that really would benefit from participation in a clinical trial.

Not only new CROs that are smaller, probably vertical, but also CROs that are really innovative. But, that get this right from the first place. There’s nothing worse than using an electronic system, and you find out that the cool stylus allows investigators to enter numbers that make no sense. And there’s no control of the system.

Simon Burns: I very much agree there. Well, with that, Dr. Reich, it was a total thrill chatting. Thank you so much for joining me.

Kristian Reich: Simon, absolute pleasure.

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