Brazilian startup MirScience Therapeutics is working on reversing muscle loss. I had an illuminating chat with co-founder Milena Peregrino, PhD about the technology and the company’s progress.
Highlights:
Sal Daher Introduces Milena Peregrino
MicroRNAs and What They Do
MirScience Therapeutics
"... Keeping in mind that we're talking about mouse models, it has not gone into human trials yet, but this is very promising..."
"... We are going to need the non-rodent species. For now, we are planning to go with non-human primates, so monkeys..."
How MirScience Was Founded
Milena's Background
"... Most people die from the results from falls. It's not necessarily immediately, it's within six months. If they have a severe fall, old people decline very fast and so this has huge implication for people to age better. The ability to have muscular old people going around instead of frail people who fall over easily..."
Why Milena Chose Biology
Advice to the Audience
ANGEL INVEST BOSTON IS SPONSORED BY:
Transcript of “Reversing Muscle Loss”
Guest: Milena Peregrino, PhD
Sal Daher: Hey, this is Sal Daher. I'm delighted you found the Angel Invest Boston podcast in which I interview people who know a lot about building technology startups. I now have a substack about losing and keeping off 100 pounds of body weight in my 60s. It's called Aging Fit and my goal is to build a community of people interested in keeping fit as they age. Look for Sal Daher on substack.com. Daher, by the way, is spelled Delta, Alpha, Hotel, Echo, Romeo. Enjoy the podcast.
Sal Daher Introduces Milena Peregrino
Welcome to Angel Invest Boston, conversations with Boston's most interesting founders and angels. Today, we are really privileged to have a founder who is in Brazil. Her name is Milena Peregrino, PhD, and she's the co-founder of MirScience Therapeutics. Welcome, Milena.
Milena Peregrino: Thank you, Sal. I'm very pleased to be here.
Sal Daher: Excellent. MirScience is a startup that is located in São Paulo in Brazil. Surprise, surprise, there's a lot of biotech going on in Brazil. Brazil is a country of 220 million people, 216 million, with a very advanced medical system, so a large population, Brazilian doctors are world-class, and so it means that biotech also is very strong in Brazil. An example of this is MirScience Therapeutics. Milena, first tell us what is microRNA and what you're doing with it.
MicroRNAs and What They Do
Milena Peregrino: Perfect. It's a pleasure to be here talking more about MirScience Therapeutics and representing, in a way, biotechnology startups here in Brazil. MicroRNAs, they have an interesting background. In the '90s, 2000, we only look at the DNA and errors at the DNA, the structure of this genetic information. Later on, we learned that the RNAs are not only messengers. They can regulate which gene can be translated and introduced into proteins.
Basically, they are the ones who can pick which gene are going to be activated, in a way, and at what time this will happen. It's really interesting to work with this new class of drugs based on RNAs.
Sal Daher: MicroRNA is controlling the expression of genes for people who are not biotech savvy. Genes are a repository of genetic information. It's like the storage of the blueprints, let's say, for certain actions in the body. In a messenger RNA, that everybody's familiar with, because of the vaccine is the mechanism by which the genetic instructions in the RNA are transmitted and put into action in the cells to produce proteins, which is what does everything in the body. Proteins, they're like the foot soldiers. They go around and do things.
The DNA has the war plans and the foot soldiers, or the protein that goes and does stuff, and the mechanism that delivers this information to the ribosomes or the cells that produce the proteins that go out and do all this stuff, that's the mRNA. Now the microRNA is implicated in triggering the genes, which are sequences of DNA to become active because we have way more genes in our bodies than necessarily ever utilized. We have whole sets of genes for repairing muscle damage, for example, from exercise. Then we have an entirely different set of genes for growing new muscle if we overexert.
That's how abundant genes are, there's a lot of stuff that doesn't get expressed all the time, so you need a mechanism to turn genes on and off. Is that a correct explanation?
Milena Peregrino: Yes, it's correct. It's perfect.
MirScience Therapeutics
Sal Daher: All right. What is it that MirScience is doing that sets itself apart from its competitors?
Milena Peregrino: Everything you start looking to the genes that RNAs as you were talking in choosing a sequence that can be used as a target. Now we are trying to understand the biology, and we are specifically focused on muscle or skeletal muscle, and how we choose a target. To do that, we look to held data banks of which RNA are upregulated or downregulated in each scenario for each type of disease. We try to extract as much information as we can, and we selected our sequence that now is moving forward.
Sal Daher: Upregulated just means more active.
Milena Peregrino: Exactly. With this platform that we call OAT, which is an acronym for oligonucleotide activating therapeutics, we chose our sequence. We are also improving our platform, so we are able to expand the portfolio of diseases and products as we are growing as a company. Now our first product that is most advanced, it's called MT-29. I am really proud of the efficacy data because it can increase the muscle mass until 20% after one application, which is a dream.
Sal Daher: Cachexic patients who are suffering muscle loss from certain types of diseases like cancer.
Milena Peregrino: Exactly. Everything that I have from data is everything pre-clinical. So everything was done with mice or rats. We also can increase the strength. This is the first thing that set us apart from our competitors, that we can increase the mass and the strength.
Sal Daher: Oh, not just mass but also strength in the muscles?
Milena Peregrino: Exactly.
Sal Daher: It's important to have strong mice.
Milena Peregrino: [laughs] It is.
Sal Daher: Brazil will have the strongest mice because of MirScience.
[laughter]
Milena Peregrino: Yes, exactly.
"... Keeping in mind that we're talking about mouse models, it has not gone into human trials yet, but this is very promising..."
Sal Daher: Joking aside, it's entirely possible for you to prevent muscle loss, but the idea that you're actually causing muscle to grow and that you're causing increased strength. Keeping in mind that we're talking about mouse models, it has not gone into human trials yet, but this is very promising. Now the model, so these are healthy mice that were treated with the compounds, the molecules that you have, so it doesn't matter if someone is suffering from cachexia or from sarcopenia from old age, loss of muscle from old age.
Listeners to this podcast may be familiar with I go on and on and on about the importance of building muscle as you age, because having strong musculature as you age is really important to stave off diabetes, being fit. If you can build additional muscle, that's a big step in the direction of preventing just the worst diseases that you can find, which is diabetes. The number of people getting diabetes is enormous, so this is very promising. Once again, let's keep in mind this is still in a mouse model. What are your plans? Are you heading towards clinical trials, human trials?
Milena Peregrino: Yes, we are. Our goal is to go to clinical trials until 2025. Now we are moving for a really set of experiments looking to the regulatory aspects of it. My job has been reading a lot of guidelines from FDA and organizing these next experiments to get everything they need we have to prove in order for that.
Sal Daher: Milena, are you planning to do these experiments in Brazil or in the US? You mentioned the FDA.
Milena Peregrino: Yes. Everything regarding pre-clinical we are doing here in Brazil. I think it's worth mentioning we are based in São Paulo, as you said, in the incubator of the hospital, Albert Einstein Hospital, which has a biotech programs for biotech companies. Everything regarding pre-clinical studies we are doing here, but we are planning to move forward to the clinical phase one in the States.
Sal Daher: Excellent. Now, Americans may not be familiar with the standard of care in Brazil. Brazil is a developing country and it doesn't have the depth of medical services that exist in the United States. The top medical centers like the Albert Einstein Center in São Paulo, they're world-class. A cousin of mine had some friends who were Canadian and the wife had some problems, she went to a Canadian doctor and was put off. She's now, "Oh, this is just a minor problem, don't worry about it, treat it with pain." She happened to be in Brazil and she got a very acute case. She was seen at Albert Einstein, and they diagnosed a very serious cancer and they removed it, and saved her life.
Let me tell you, if you can have access to care, of course, you're very lucky to be able to have access to care at Albert Einstein, the average Brazilian does not. It's a very different system, but it is top levels in Brazil. People should understand that Brazilian science and Brazilian medical care at the top level is world-class. You're located at the accelerator of the Albert Einstein Hospital, please continue. Your plans for doing clinical trials.
Milena Peregrino: Maybe it's worth mentioning when they started the biotech core program, they chose the best startups in Brazil and we were selected as the best one in Brazil and they gave us this opportunity to be here, which I'm very proud and very happy to be here at Albert Einstein with all the help they can provide us and using all this structure that is amazing. Our plans to move forward is to focus on the safety because we have great results above the efficacy. What I have so far regarding safety is so good. Every hepatic function, kidney function, we are looking to everything and everything is working good.
Sal Daher: Of course, before trying out a new molecule in human beings you have to do a lot of safety studies. These safety studies, are there going to be studies done on larger animals than mice?
"... We are going to need the non-rodent species. For now, we are planning to go with non-human primates, so monkeys..."
Milena Peregrino: Yes. We are going to need the non-rodent species. For now, we are planning to go with non-human primates, so monkeys. They have the immune system more similar to human systems. It's a very good model for us to test everything and have all safety aspects very crystal clear to convince the regulatory agencies that we are safe enough to move forward to humans.
Sal Daher: Are there non-human primates that suffer from cachexia or muscle loss the same way that we do?
Milena Peregrino: It's very similar. Usually, the experiments they are with healthy animals because the cause of putting the animal through a disease sometimes is harder, sometimes is easier depending on the indication.
Sal Daher: Basically, you're going to be seeing if your compounds are able to cause muscle growth and increase strength in a non-human primate with a good safety profile and that should be a very good indication that if it's safe on non-human primates, it'll be safe for humans. Very, very similar physiology.
Milena Peregrino: Exactly, that.
Sal Daher: That is really interesting. Tell me a little bit of the founding story of MirScience. That's M-I-R for microRNA, M-I-R for MirScience Therapeutics. Tell me how you and Lucas came to start the company. Lucas Fernandes is your co-founder.
How MirScience Was Founded
Milena Peregrino: It all started with my two other partners here. It is Lucas and William and they were doing their PhD in Universidade de São Paulo, São Paulo University here. They came about these microRNAs and skeletal muscle diseases. During their academic experience, they decide to join effort and to found a company and to fight against all odds that is related to being an entrepreneur in a developing country. They invited me to join the team in the very early days.
My background is more related to drug delivery systems, which is the biggest challenge in the RNA therapies. How we deliver these molecules to the target without side effects and with the biggest precision you can possibly make. After that, we started doing some proof of concept work at the university and after that, we moved to the Einstein accelerator where we continued the development.
Sal Daher: What is your role in MirScience? What is your function?
Milena Peregrino: My main role is head of pre-clinical studies. Everything related to mice, rats, non-human primates, organizing, setting the experiments, and talking with the regulatory agencies is what is under my row of responsibilities. We are a small team. We are now about 10 people, so it's very easy. What I really like about working in a small company, is very easy to talk. Everybody knows more or less where everybody is in their functions and helping everybody.
Sal Daher: Excellent. How have you been funded so far?
Milena Peregrino: Our first round of funding, we have a family officer from Brazil called Green Rock that is related to Salomão Zoppi Diagnosis Company. They were our first investors with a couple of angel investors that--
Sal Daher: Can you spell that name?
Milena Peregrino: Green, G-R-E-E-N, like the color, and Rock.
Sal Daher: Oh, Green Rock?
Milena Peregrino: They are great. They help us a lot throughout all the challenge that we always have. We also have non-diluted grants from agencies here in Brazil. As we are in São Paulo, we are very privileged to have a lot of lines of grants that help startups to build. Now we have a funding round open, so we are getting prepared to really move forward to these bigger steps regarding regulatory.
Sal Daher: Excellent. The plans that you have, you say you're studying FDA regulations for clinical trials, so are you thinking of doing clinical trials in the US, or are they going to be done in Brazil under FDA standards?
Milena Peregrino: We are planning to go to the FDA. This is strategic because we really want to position ourselves as a company that is started in Brazil but is now moving forward to the US scenario.
Sal Daher: If I understand then, you're thinking of repatriating to the United States, moving presumably the patent portfolio, and so forth. Is your patent portfolio also filed in the United States in addition to Brazil?
Milena Peregrino: Yes, our patent portfolio is entirely in the US PTO.
Sal Daher: Excellent. Do you feel at ease discussing the particular intellectual property that sets your science apart from other players?
Milena Peregrino: Yes. In our patent, we have the sequence of oligonucleotide that we have developed in the lead one and the drug delivery system that we have been working on.
Sal Daher: [chuckles] So it's pretty fun and pretty basic?
Milena Peregrino: Yes. It's basic, the secret sauce.
Sal Daher: It's a pretty strong patent of that pieces.
Milena Peregrino: The method and the use in muscle diseases and everything related to muscle.
Sal Daher: Very interesting. Milena, I would like to do a very brief promo for the podcast, and then would I invite people to give ratings and reviews of the podcast. Then after that, I want to get a little bit into, how did a smart Brazilian scientist like you decide to go into entrepreneurship. I want you to talk about your entrepreneurial journey. First to pitch for the podcast. This is the Angel Invest Boston podcast. We talk to brilliant founders. Very, very smart and supportive angel investors to try to understand better how to support startups in building new technology companies.
If you find this conversation valuable, you could upvote us by going to wherever platform you listen to podcasts and do a new rating, five-star rating, and also leaving a written review. It doesn't have to be much. Milena Peregrino, PhD rocks. That's just enough, not a lot of writing. What that does is the algorithm, we all dance to the tune of algorithms, sees that someone went to the trouble of doing a review, and then features that episode, more prominently. This podcast has lots and lots of compelling stories that deserve greater attention. Anyway, Milena, tell us the story. Where are you from? Are you from São Paulo?
Milena's Background
Milena Peregrino: Yes, I'm from São Paulo, Brazil. Born and bred here.
Sal Daher: You studied the high school there and the university?
Milena Peregrino: Yes.
Sal Daher: You've been USP all the time?
Milena Peregrino: Yes. Actually, my undergraduation was in biology in Federal University of San Paolo. Later I did my master's and my PhD. During my PhD, I stayed a little while in the Scotland in the Edinburgh University, which was very important for my academic background and formation.
Sal Daher: A word about universities in Brazil. Brazil has some really, really great universities. Generally, the Federal University is the top university. I remember my father when he was a professor of engineering at the University of Goiás. It was not the Federal University, it was University of Goiás. I remember very well the day, right at the end of the term of Juscelino Kubitschek, that they were publishing the law that made the Universidade de Goiás, the Federal University of Goiás.
I was there early in the morning, at five in the morning in Brasilia, outside the printing press for the official diary, where all the laws were published. Because my father and the president of the university, his friend Colemar, they wanted to see that the law had been passed because Juscelino Kubitschek was leaving. What that meant was it became a federal university and the salaries would get paid on time as being a state university in Goiás. [laughs]
In 1960, Goiás was a very poor state. Now it's very rich from rice and all that. In the State of São Paulo, USP is a state university of the State of São Paulo, and the Federal University is a federal university, so they're both well funded and so forth, because São Paulo's a very rich state. It's not like in the old days. I think of my father being, "Oh, now the professors will get paid on time because it's a federal university". This is Brasil, circa 1960. Anyway, you studied at the Federal University, studied biology, and then you did your PhD at the University of São Paulo, the state university, USP, very famous, this broad versus top university.
You focused on drug delivery, but then what made you think about doing this crazy thing because someone with your skills could go into industry and earn very well and have a very normal life and not be worrying crazy things going on and so forth. What made you do this really crazy and risky thing?
Milena Peregrino: That's such a great question that I think made every entrepreneur ask themselves at a point because it's quite risky. If you are in a developing country as we are, the risk curves sometimes are bigger because of funding. It's harder to find people willing to invest in biotech companies. I think for me, what really drove me to do that and drives every day because every day is a choice, is I really believe our drug can help a lot of people. I really think that this is a drug that people today they need it and that we need to move forward as fast as we can, of course, taking responsibility every step of the way but I really believe that we have something that could benefit multiple lives.
"... Most people die from the results from falls. It's not necessarily immediately, it's within six months. If they have a severe fall, old people decline very fast and so this has huge implication for people to age better. The ability to have muscular old people going around instead of frail people who fall over easily..."
Sal Daher: If it works, this could be tremendous. You take an injection and you don't lose muscle mass. The loss of muscle mass is related to, as I said, diabetes, but it's also related to loss of balance and falls. Most people die from the results from falls. It's not necessarily immediately, it's within six months. If they have a severe fall, old people decline very fast and so this has huge implication for people to age better. The ability to have muscular old people going around instead of frail people who fall over easily.
Milena Peregrino: There are so many studies showing that when you have great muscle mass, you live longer, you have more quality of life. Even if you stay in the ICU, you have more chances to getting away with good health. I'm really passionate about that. I really believe in this and I really believe this will work. Sometimes it's very satisfying to build something from the ground up and to share this with entrepreneurs that we know and share the ups and downs, so this is also very satisfying.
Sal Daher: Now did you have a model in your family? Any of your parents entrepreneurs or they're scientists? What do they do?
Milena Peregrino: Actually not. My parents are employees in companies. [laughs] They like the safety of that and I understand the side of this.
Sal Daher: Are they scientists?
Milena Peregrino: My mom, she works with literature. She's also a professor in a university here. She's around the academia but in another field.
Sal Daher: Another field? Okay. What prompted you to look at biology? What got you excited about biology?
Why Milena Chose Biology
Milena Peregrino: I think I always loved to understand how the body works and the biomolecular of it. It really makes sense for me, really it's easy for me to see the word and understand it through the lens of biology. I think that was my favorite subject at school. [chuckles]
Sal Daher: That is really tremendous.
Milena Peregrino: Drug development, for me it's quite interesting because a drug can change so many lives. Another day I was reading about when they launched the starting drugs which is for lowering blood pressure and cholesterol.
Sal Daher: Not blood pressure, blood lipids.
Milena Peregrino: Yes, exactly and it really changed a generation of people who has it so you have a potential to reach so many people. I think now after the effects of the COVID vaccine, everybody can see the impact that a new drug can have in our really daily lives and I'm really passionate about that.
Sal Daher: Milena, I'll tell you, when I was a boy growing up in Brazil, my father, when he came to the US to do his PhD in math, he was 41 years old. He had friends who died of heart attacks in Brazil. In the mid-1960s, relatively young Brazilian men would die of heart attacks and these are professionals. These are not people who are drunks or so forth or alcoholics and so on. They're just working professionals but they had bad blood lipids and they were working too hard and they would have heart attacks.
The second drugs that control blood lipids or cholesterol, certain types of blood lipids that are very distructive. I had open heart surgery about 11 years ago because of a heart valve. It was a genetic condition or something that I heard was a birth defect of a heart valve eventually became very stiff and wasn't functioning well. I had open heart surgery and the surgeon who did it, she said to me, "I used to do coronary artery bypass surgery which is a surgeon you could do when someone has a heart attack. Meaning that an artery or one of the blood vessels in the heart gets obstructed, and then the heart doesn't get enough oxygen supply, and part of the heart muscle dies.
What they do is they would take a graft of a vein somewhere else in the body, the saphenous vein in the leg, and then they would put that in the heart, and that's the coronary artery bypass surgery. He used to do this, that was his living. He says, "Because of saphenous, I couldn't make a living doing what they call CABG, coronary artery bypass, and I had to go and retrain to do heart valves because people's heart valves give out when they're 80-something years old, like clockwork. It's a good business."
This is a real testament to the power of one of these really good drugs, effective drugs. Today, I listen to the podcast of Peter Attia, MD. He's a doctor who focuses on treating patients, aiming towards longevity in Austin, Texas. He wrote a book about this, Outlive. Basically, he says, heart disease, for most people, is optional. If you manage your blood lipids early on, you don't get heart disease. Cancer, you can't avoid, but heart disease, for most people, can be prevented if they use the right statins. That is his view. I agree with him entirely.
Perhaps the compounds that neuroscience is developing will have that effect. Perhaps muscle loss, sarcopenia, people getting diabetes because they've lost muscle mass, or falling because their muscles are weak and they can't balance when they're old. Maybe that'll become history, and we're going to have old people who are much healthier and can enjoy their grandkids and great-grandkids.
Milena Peregrino: We always talk here, as the healthspan, as the lifespan really increased on the last decades, the healthspan did not increase as the same. We are living longer, but not as healthier as we possibly can. If we can provide a better quality of life for people 80 plus, you can have maybe more 10 lives of traveling, of doing what you like, of maybe starting new business. You really gave people options, and I like that.
Sal Daher: Let's just expand on the concept. Everybody knows about lifespan, it's just how long you live. Healthspan is that time in your life when you're healthy and you're able to do things without having to be in and out of the hospital all the time. From my experience, having lost significant weight, a lot of it is behavioral, changing eating habits, changing exercise habits, and so forth. A lot of it, I think, also is going to be medical interventions, therapies, and other types of things, which will become necessary. Because even if you exercise a lot and so forth, as you age, you will lose muscle. If you exercise a lot, you will lose bone even if you do that.
This is a problem for women. Men have a problem of heart disease as they age. Women have a problem of osteoporosis as they age and maintaining strong skeletal muscles implies stronger bones.
Milena Peregrino: The bone health and the muscle healthy are really a crosstalk. They are related. When we increase one, the other one also increases. I came about statistics that when we exercise after 60 or 70, we can gain 2% to 3% of muscle mass. 2% or 3% of your body weight. If we can even decrease the time, if you could get one shot and increase your muscle mass like 10% and continue your training, continue your good habits because this is good for everything, sleeping cycle, and all the other practice.
If you could help this rehabilitation, I think, and shrink the time you need to get in this state of feeling good and moving and being able to walk around by yourself and sitting and standing and being dependent in the house, I think this could really reach a lot of people.
Sal Daher: That is wonderful. Milena Peregrino, PhD, as we think about wrapping up this conversation, take a moment and think what you would like to communicate to our listeners who are angel investors and other founders. Whatever you want to say to them. It could be about what MirScience is doing. It could be other things. Whatever message you want to communicate.
Advice to the Audience
Milena Peregrino: I think I want to invite people to join our efforts to sharing this message of how important is to build muscle mass for your aging for you to age as healthy as possible and to join our efforts to build this drug and taking this from the stage we are on to the market. It can be by investing in us, but it can also be by sharing our project with other people and sharing our social media and really helping us build that dream that is for us and this medicine that I believe will help so many people.
Sal Daher: Please give us where you can be found on social media and also your website.
Milena Peregrino: Everything is MirScience Therapeutics. You can find us on Linked-In.
Sal Daher: Mirsciencetherapeutics.com or MirScience Therapeutics on LinkedIn. What are the other social media that you're on?
Milena Peregrino: We also are on Instagram. I think there is MirScience, M-I-R Science T-X. This is our handle there.
Sal Daher: MirScience TX. Very good. I am so proud of my Brazilian compatriot for doing this splendid effort in an environment that is really, really hard. Believe me, being a founder in Brazil is like living on the planet Krypton, where the gravity is very, very heavy. When people like that go to places with normal gravity, they are like supermen and superwomen. They have superpowers because everything is so hard, so complicated, and so forth. Being an entrepreneur in Europe is hard. Being an entrepreneur in Brazil is even harder. At the same time, I think about Brazilians as this tremendous optimism, tremendous attitude that we can do this, and so forth.
I applaud that, applaud you and Lucas and your team.
Melina Pellegrino: Thank you. Thanks so much, Sal. Thank you very much for this opportunity. I am a really big podcast listener, and I will for sure listen to other episodes of your podcast. That was such a great opportunity.
Sal Daher: I appreciate that. Some very inspiring ones. We have a lot of immigrant founders in biotech in the US. I'm on the board of Sabran Technologies, founded by a professor of Purdue University, which is a sponsor of this podcast. Shari Sabran has a technology that is just amazing. It's a microfluidics technology for capturing or counting extremely rare cells. You mentioned talking about Dr. Alexandra Sakatos with her platform for virus-resistant microorganisms for microbiome therapies. You are joining this team of just amazing founders. So I'm very, very, very happy to have this conversation.
Melina Pellegrino: Thank you.
Sal Daher: This has been a conversation with Milena Peregrino PhD, co-founder of MirScience Therapeutics. This is the Angel Invest Boston podcast. I'm Sal Daher. Thanks for listening.
[music]
I'm glad you were able to join us. Our engineer is Raul Rosa. Our theme was composed by John McKusick. Our graphic design is by Katharine Woodman-Maynard. Our host is coached by Grace Daher.